Food Chemistry 338 (2021) 127773

Contents lists available at ScienceDirect

Food Chemistry
journal homepage: www.elsevier.com/locate/foodchem

Phytochemical and pharmacological review of Cinnamomum verum J. Presl-a T

versatile spice used in food and nutrition
Neetu Singha, Amrender Singh Raoa, Abhishek Nandala, Sanjiv Kumarb, Surender Singh Yadava, ,
⁎

Showkat Ahmad Ganaiea, Balasubramanian Narasimhanc

a
Department of Botany, Maharshi Dayanand University, Rohtak, Haryana 124001, India
b
Department of Pharmaceutical Sciences, Ch. Bansi Lal University, Bhiwani, Haryana 127021, India
c
Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, Haryana 124001, India

ARTICLE INFO ABSTRACT

Chemical compounds studied in this article: Cinnamomum verum is the widely used spice for its medicinal and culinary uses since ages. It is native to Sri
Cinnamaldehyde (Pubchem CID: 637511) Lanka and southern India but also distributed in many Asian, Caribbean, Australian and African countries. It is
Cinnamyl alcohol (Pubchem CID: 5315892) widely used in food preparations and industrial products like candies, chewing gums, mouthwash and tooth­
Eugenol (Pubchem CID: 3314) paste. It is also used to treat asthma, bronchitis, diarrhea, headache, inflammation and cardiac disorders.
Camphor (Pubchem CID: 2537)
Cinnamaldehyde, eugenol, caryophyllene, cinnamyl acetate and cinnamic acid are the major compounds found
Methoxycinnamaldehyde (Pubchem CID:
in its essential oil. These compounds exhibit a wide range of pharmacological activities including antioxidant,
4452795)
Cinnamyl acetate (Pubchem CID: 5282110) antimicrobial, anti-inflammatory, anticancer, antidiabetic, wound healing, anti-HIV, anti-anxiety and anti­
Linalool (Pubchem CID: 6549) depressant, etc. This review highlights its comprehensive and up-to-date information on taxonomy, ethnome­
Methyl cinnamate (Pubchem CID: 637520) dicinal uses, phytochemical composition, pharmacological and toxicity activities. Structure-activity relationship,
Cinnamic acid (Pubchem CID: 444539) mechanism of action and some research gaps has also been provided. Owing to its immense medicinal im­
portance, more well-designed in-vivo and clinical studies are required.
Keywords:
Cinnamomum verum
Cinnamaldehyde
Phytochemistry
Pharmacology
Spices
Medicinal food

1. Introduction various ailments of the human body.

Spices are one of the important food ingredients which play a car­
dinal role in food preparations. Over a hundred plant species are used
as spices and condiments across the globe. They are aromatic, dried
plant parts usually obtained from seeds, fruits, leaves, roots and bark,
etc. (Sangal, 2011). They are generally used to add flavor to the food­
stuffs and to enhance the quality of the food since ages (Aparna,
Narayanan, & Sarada, 2014). A large number of spices also act as ex­
cellent preservatives which increase the shelf life of the food items by
delaying the process of decaying (Asimi, Sahu, & Pal, 2013). Moreover,
spices being the rich reservoir of biologically active compounds, also
possess properties viz. antioxidant, antimicrobial, anti-inflammatory,
antidiabetic and anticancer, etc (Abeysekera, Premakumara, &
Ratnasooriya, 2013). These properties of spices help in combating
Cinnamomum is one of the oldest known spices used in cookery art
(Rao & Gan, 2014). Though numerous species of this genus are mar­
keted as cinnamon but the inner dried bark of Cinnamomum verum J.
Presl (belonging to family Lauraceae), has been considered as the true
cinnamon (Avula, Smillie, Wang, Zweigenbaum, & Khan, 2015). Its
medicinal and culinary uses are well reported in ancient literature since
4000 years dating back (Rao & Gan, 2014). The different plant parts
and its essential oil (EO) are predominantly used as a spice and fla­
voring agent all over the globe. It is also used as a condiment in sea­
sonings, sauces, bakery, confectionery and drinks for the preservation
of food products and to enhance their pharmacological activities
(Pittman, 2011). Due to its fragrance and flavoring properties, it has
also been used to embalm mummies in Egypt and Roman empires
(Ribeiro-Santos et al., 2017).

⁎
Corresponding author.
E-mail address: ssyadavindia@gmail.com (S.S. Yadav).

https://doi.org/10.1016/j.foodchem.2020.127773
Received 28 February 2020; Received in revised form 20 July 2020; Accepted 2 August 2020
Available online 04 August 2020
0308-8146/ © 2020 Elsevier Ltd. All rights reserved.
N. Singh, et al. Food Chemistry 338 (2021) 127773

Nomenclature DMBA 7, 12-Dimethylbenz[a]anthracene

PBMCs Peripheral blood mononuclear cells
CA Trans-cinnamaldehyde MDSCs Myeloid-derived suppressor cells
DART Direct analysis in real-time LPS Lipopolysacaride
CPE Cinnamon polyphenol extract IL-6 Interleukin-6
TTP Tristetraprolin TNF-α Tumor Necrosis Factor-α
FRAP Ferric reducing antioxidant power PM Phosphomolybdate
DPPH 2,2-Diphenyl-1-picrylhydrazyl TLR2 Toll-like receptors
ABTS 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) Akt AKT serine/threonine kinase
ORAC Oxygen radical absorbance capacity IκBα NF-κB inhibitor alpha
MIC Minimal inhibitory concentration FST Forced swim test
MBC Minimum bactericidal concentration EPM Elevated pulse maze
MBIC Minimum biofilm inhibitory concentration TST Tail suspension test
MBEC Minimum biofilm eradication concentration PAR Protease activity reduction
LOX Lipoxygenase EO Essential oil
HDL High-density lipoprotein BHA Butylated hydroxyl anisole
LDL Low-density lipoprotein OAT Open arms time
FBS Fasting blood sugar OAE Open arms entries
CEO Cinnamon essential oil T2D Type 2 Diabetes
ACD Allergic contact dermatitis GOD Glucose oxidase
Nrf2 Nuclear factor-E2-related factor 2 RIA Radioimmunoassay
ZI Zone of Inhibition ELISA Enzyme-linked immunosorbent assay
NF-κB Nuclear factor-kappa B AIDS Acquired immune deficiency syndrome
COX-2 Cyclooxygenase-2 AChE Acetylcholinesterase
PGE2 Prostaglandin E2 BChE Butyrylcholinesterase
2-MCA 2-Methoxycinnamaldehyde MMP Matrix metalloproteinase
VAC Volume of acidic compartment NO Nitric oxide
SRB Sulforhodamine B PI3K Phosphoinositide-3-kinase MAPK
STZ Streptozotocin IRS1 Mitogen activated protein kinase Insulin receptor sub­
IGF Insulin-like growth factor strate1
FGF Fibroblast growth factors eNOS NOX4 Aortic nitric oxide synthase 3
VEGF Vascular endothelial growth factor NADPH oxidase 4
MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium Keap1 Kelch-like ECH-associated protein 1
bromide GLUT4 Glucose transporter 4

Cinnamaldehyde, the major active constituent of cinnamon, is pri­
marily responsible for rendering taste, odour and flavour to the food­
stuffs (Isaac-Renton, Li, & Parsons, 2015). It also offers protection
against oxidative stress, microbial infection and other chronic diseases
(Ribeiro-Santos et al., 2017). In the present review, the comprehensive
information about the traditional uses, phytoconstituents and phar­
macological activities of Cinnamomum verum (C. verum) has been pre­
sented. An effort has also been made to explain the possible mechan­
isms of action, structure–activity relationship including safety and
toxicity aspects of this plant.
phytoconstituent, pharmacology, antimicrobial, antioxidant, anti-in­
flammatory, anticancer, anti-HIV, antidiabetic, antiparkinson and
wound healing etc. were used as the keywords. A total of 1230 articles
were available with the above-mentioned keywords out of which 119
research and review articles were selected based on the inclusion and
exclusion criteria. The articles dealing with ethnomedicine, phy­
tochemistry and pharmacological activities of C. verum were selected
for the present review while articles related to packaging, adulteration,
cosmetics, etc. were excluded.

2. Modology
The present review considered the literature published between
2011 and 2020. Recognized electronic databases viz. Google scholar,
Web of Science, Science Direct, Scopus and PubMed were searched.
Cinnamomum verum, phytochemical, C. verum essential oil,
3. Botanical description
3.1. Taxonomy
The genus Cinnamomum contains 250 species of trees and shrubs.
Cinnamomum verum J. Presl (Syn. Cinnamomum zeylanicum Blume) is an
important evergreen tree of family Lauraceae. It is also known as True

Bark Leaves Fruits

Fig. 1. Different parts of Cinnamomum verum J. Presl.

2
N. Singh, et al. Food Chemistry 338 (2021) 127773

Table 1
Chemical composition of C. verum.
S. No. Class of Name of the compound Plant part % Yield Structure of the compound Ref.
compounds used

1. Aldehydes Cinnamaldehyde (Pubchem CID: Bark EO 74.49 CHO Malsawmtluangi, Nautiyal, Hazarika,
637511) Chauhan, & Tava, 2016; Li, Kong, &
Wu, 2013b
Methoxycinnamaldehyde (Pubchem 3.96 CHO Kamaliroosta, Gharachorloo,
CID: 4452795) Kamaliroosta, & Alimohammad Zadeh,
2012; Wahab & Adzmi, 2017
OCH3
Hydrocinnamic aldehyde (Pubchem NR Choi et al. (2016)
CID: 7707) O

Benzaldehyde (Pubchem CID: 240) 0.29 O Kamaliroosta et al. (2012)

Vanillin (Pubchem CID: 1183) 0.01 OCH3 Nabavi et al., 2015; Gulcin et al., 2019

O
OH
H
Cuminaldehyde (Pubchem CID: 326) NR Tsai et al., 2016a; Yang et al., 2016
H CH3

O CH3
Benzenepropanal (Pubchem CID: 0.53 O Sohrabi et al. (2017)
7707)

H
2-Methyl-3-phenyl-propanal 0.30 O Sohrabi et al. (2017)
(Pubchem CID: 95593)

CH3
Citronellal (Pubchem CID: 7794) NR NR CHO Jayaprakasha and Rao (2011)

2. Alcohols Cinnamyl alcohol (Pubchem CID: Bark EO 1.87 CH2OH Choi et al., 2016; Wahab & Adzmi,
5315892) 2017

α-Terpineol (Pubchem CID: 17100) 0.76 Malsawmtluangi et al., 2016; Ribeiro-

HO
CH3 Santos et al., 2017

CH3
H3C
Linalool (Pubchem CID: 6549) 3.70 Chakraborty et al., 2015;
H3C Malsawmtluangi et al., 2016
CH2
CH3 HO CH3
α –Bisabolol (Pubchem CID: 0.18 Sohrabi et al. (2017)
1549992) H3C OH

CH3
H3C CH3
3. Esters Cinnamyl acetate (Pubchem CID: 8.78 Ribeiro-Santos et al. (2017)
5282110)
O

O CH3

(continued on next page)

3
N. Singh, et al. Food Chemistry 338 (2021) 127773

Table 1 (continued)

S. No. Class of Name of the compound Plant part % Yield Structure of the compound Ref.
compounds used

Cinnamaldehyde diethyl acetal 2.34 Sohrabi et al. (2017)

(Pubchem CID: 5356250)
CH3
O

O
CH3
Methyl cinnamate (Pubchem CID: 81.87 Jayaprakasha and Rao (2011)
COOCH3
637520)

Ethyl cinnamate (Pubchem CID: 0.16 Jayaprakasha and Rao (2011)

COOC2H5
637758)

Hydrocinnamyl acetate (Pubchem NR NR Choi et al. (2016)

O
CID: 31226)

O CH3

Eugenyl acetate (Pubchem CID: CH2 Nabavi et al. (2015)

7136) O

H3C O
OCH3
Benzyl benzoate (Pubchem CID: Leaf EO 6.01 Chakraborty et al., 2015;
2345)
O Malsawmtluangi et al., 2016

Bornyl acetate (Pubchem CID: 6448) 0.26 Malsawmtluangi et al. (2016)

O
O
4. Phenols Eugenol (Pubchem CID: 3314) 71 Azimi et al., 2014; Chakraborty et al.,
OH
2015; Sharma et al., 2016

H2C OCH3
Pyrogallol (Pubchem CID: 1057) Bark EO 0.026 Gulcin et al. (2019)
OH
HO OH

5. Acids Cinnamic acid (Pubchem CID: NR Durak et al., 2014; Williams et al.,
444539)
COOH 2015; Qabaha et al., 2017

Ferulic acid (Pubchem CID: 445858) 0.022 Nabavi et al., 2015; Gulcin et al., 2019
O
OH

HO
OCH3
Caffeic acid (Pubchem CID: 689043) 0.009 Nabavi et al., 2015; Gulcin et al., 2019
O
HO
OH

HO
(continued on next page)

4
N. Singh, et al. Food Chemistry 338 (2021) 127773

Table 1 (continued)

S. No. Class of Name of the compound Plant part % Yield Structure of the compound Ref.
compounds used

Gallic acid (Pubchem CID: 370) NR NR Nabavi et al. (2015)

O OH

HO OH
OH
Protocatechuic acid (Pubchem CID: Nabavi et al. (2015)
72)
O OH

OH
OH
Oleic Acid (Pubchem CID: 445639) H H Bhagavathy and Latha (2015)

H O
p-Hydroxybenzoic acid (Pubchem Bark EO 0.032 Gulcin et al. (2019)
OH
CID: 135)

HO
6. Monoterpenes p-Cymene (Pubchem CID: 7463) 1.91 Jayaprakasha & Rao, 2011;
CH3 Malsawmtluangi et al., 2016; Ribeiro-
H3C Santos et al., 2017
CH3
Limonene (Pubchem CID: 22311) 1.21 Malsawmtluangi et al., 2016; Ribeiro-
H2C Santos et al., 2017
CH3
H3C
α-Terpinene (Pubchem CID: 7461) 1.30 Ribeiro-Santos et al. (2017)
CH3
H3C
CH3
α-Pinene (Pubchem CID: 440967) 3.34 Malsawmtluangi et al., 2016; Ribeiro-
H3C Santos et al., 2017
H3C

CH3
Camphene (Pubchem CID: 6616) 0.50 CH2 Malsawmtluangi et al., 2016; Ribeiro-
Santos et al., 2017

CH3
H3C
Camphor (Pubchem CID: 2537) 0.53 Li et al., 2013b; Rao & Gan, 2014;
O Goyal et al., 2018

(1,4)-Cineole (Pubchem CID: 10106) 4.60 Jayaprakasha and Rao (2011)

O

(continued on next page)

5
N. Singh, et al. Food Chemistry 338 (2021) 127773

Table 1 (continued)

S. No. Class of Name of the compound Plant part % Yield Structure of the compound Ref.
compounds used

β-Pinene (Pubchem CID: 440967) Leaf EO 1.09 Malsawmtluangi et al., 2016; Ribeiro-
H3C
CH2 Santos et al., 2017
H3C

β –Phellandrene (Pubchem CID: 2.01 Malsawmtluangi et al., 2016; Ribeiro-

443160)
CH3 Santos et al., 2017
H2C
CH3
α –Phellandrene (Pubchem CID: NR NR Jayaprakasha & Rao, 2011; Ribeiro-
443160)
CH3 Santos et al., 2017
H3C
CH3
3-Carene (Pubchem CID: 26049) Choi et al. (2016)
H
CH3
H3C

H3C H
7. Diterpenes Cinnzeylanine (Pubchem CID: Jayaprakasha and Rao (2011)
85379763)
OAc
OH
OH
HO O

HO OH
Cinnzeylanol (Pubchem CID: Jayaprakasha and Rao (2011)
44559448)
OH
OH
OH
HO O

HO OH
8. Sesquiterpenes Humulene (Pubchem CID: 5281520) CH3 Choi et al., 2016; Ribeiro-Santos et al.,
2017
CH3
CH3

H3C
Caryophyllene oxide (Pubchem CID: Leaf EO 0.34 Malsawmtluangi et al., 2016; Ribeiro-
H3C
1742210) H Santos et al., 2017
CH3
H3C
O

H
H2C
β-Caryophyllene (Pubchem CID: Bark EO 8 CH3 Jayaprakasha & Rao, 2011;
5281515) Kamaliroosta et al., 2012

H2C
H H
CH3
H3C
(continued on next page)

6
N. Singh, et al. Food Chemistry 338 (2021) 127773

Table 1 (continued)

S. No. Class of Name of the compound Plant part % Yield Structure of the compound Ref.
compounds used

α –Muurolene (Pubchem CID: 1.83 Kamaliroosta et al. (2012)

12306047)
H

H
α –Copaene (Pubchem CID: 19725) 3.86 Kamaliroosta et al. (2012)
H

Cedrene (Pubchem CID: 6431015) 0.44 Bhagavathy and Latha (2015)

H
α –Tumerone (Pubchem CID: 0.38 CH3 O CH3 Sohrabi et al. (2017)
558173)
CH3

H3C
β –Tumerone (Pubchem CID: 3.31 Sohrabi et al. (2017)
558173)
CH3 O CH3

CH3

H2C
α –Cadinol (Pubchem CID: 0.18 Sohrabi et al. (2017)
12302222)
HO H

H
t-Cadinol (Pubchem CID: 160799) 0.81 Sohrabi et al. (2017)
OH

Calamenene (Pubchem CID: 10224) 0.35 Sohrabi et al. (2017)

α –Ylangene (Pubchem CID: NR Jayaprakasha and Rao (2011)

6432119)

9. Benzopyrones Coumarin (Pubchem CID: 323) 0.029 Azimi et al., 2014; Goyal et al., 2018

O O
10. Hydrocarbons δ-Cadinene (Pubchem CID: 441005) 0.45 Sohrabi et al. (2017)

(continued on next page)

7
N. Singh, et al. Food Chemistry 338 (2021) 127773

Table 1 (continued)

S. No. Class of Name of the compound Plant part % Yield Structure of the compound Ref.
compounds used

Myrcene (Pubchem CID: 31253) 2.70 Malsawmtluangi et al. (2016)

CH3 CH2
CH2
H3C
Styrene (Pubchem CID: 7501) 0.14 Li et al., 2013b; Malsawmtluangi et al.,
CH2
HC 2016

11. Flavonoids A-type procyanidin dimer Bark 24.2 HO OH Azimi et al., 2014; Williams et al.,
aqueous 2015
extract
HO O

OH O
OH

O OH

HO

HO OH

B-type procyanidin dimer (Pubchem NR HO OH Azimi et al., 2014; Williams et al.,

CID: 30848127) 2015
OH
O

OH
HO OH OH

HO O

OH
OH

NR* = Not reported.

cinnamon, Ceylon cinnamon, Mexican cinnamon, Dalchini, Qirfa,
Darchini (Ribeiro-Santos et al., 2017). Earlier it was known as “Cin­
namomum zeylanicum”, the name was derived from Ceylon (the oldest
name of Sri Lanka). This is the reason why true cinnamon is also known
as Sri Lankan cinnamon or Ceylon cinnamon (Chen, Sun, & Ford, 2014).
C. verum attains a height of 10–15 m long. Its leaves are opposite,
ovate to oblong in shape, glabrous and usually have leathery texture on
both surfaces. The dark green leaves are 7–18 cm long with pointed
tips. The lamina is greenish-white abaxially and shiny green adaxially
(Chakraborty, Sankaran, Ramar, & Chellappan, 2015). The greenish or
yellowish-white flowers are arranged in panicles with a unique odour.
Its fruit is one cm long berry which contains a single seed (Ribeiro-
Santos et al., 2017). Its bark is known as milled bark and is of great
economic importance (Cardoso-Ugarte, López-Malo, & Sosa-Morales,
2016). The right time for peeling off the bark is when the red flush of
the young leaves turn to green (Balasubramanian, Singh, Mohite, &
Zachariah, 2012). The dried bark turned into a tubular form known as
quill or cinnamon stick is chiefly used in food preparation (Hamidpour,
Hamidpour, Hamidpour, & Shahlari, 2015). The different parts of C.
verum are depicted in Fig. 1.
3.2. Distribution
C. verum is native to Sri Lanka and southern India but also dis­
tributed in South-east Asia, China, Burma, Indonesia, Madagascar,
Caribbean, Australia and Africa (Abeysekera et al., 2013; Goyal et al.,
2018) as shown in Fig. 2 (provided as Supplementary file). It commonly
grows in tropical rain forests, marshy places and well-drained soils. C.
verum is the most harvested species of cinnamon and it can be harvested
after 3 years of its cultivation (Ribeiro-Santos et al., 2017). During the
17th century, Java had started the cultivation of cinnamon and at the
same time East India Company had become the largest exporter of
cinnamon to European nations. Now-a-days, Sri Lanka followed by
China, Vietnam and Madagascar are the leading exporters of cinnamon.
4. Ethnomedicinal uses
C. verum has a long history of uses in various ethnomedicinal for­
mulations and food items. It was the first aromatic plant reported to
have antibronchitis potential (Ribeiro-Santos et al., 2017). It is used by
rural people in curing various ailments viz. bronchitis, asthma, cepha­
lalgia, odontalgia, cardiac diseases, diarrhea, uropathy, nausea, vo­
miting, flatulence, fever, halitosis, arthritis, coughing, hoarseness, im­
potence, frigidity, eye inflammation, cramps, intestinal spasms,
vaginitis, neuralgia, rheumatism and sore throats, etc (Abeysekera
et al., 2013; Gulcin et al., 2019; Hamidpour et al., 2015; Khasnavis &
Pahan, 2014; Mariappan, Sabesan, Koilpillai, Janakiraman, & Sharma,
2013). It also improves blood circulation in the uterus. It is also used
during the preparation of candy, chewing gum, mouthwash, lip sunsc­
reen, fragrance, cinnamon toast, volatile oils and toothpaste, etc (Isaac-
Renton et al., 2015). It also possesses tissue regenerative, coagulant and
wound healing properties (Rao & Gan, 2014). Cinnamon essential oil
(CEO) can be used for curing biliousness, headache, piles, parched
mouth, bronchitis, diarrhea, itching, heart and urinary disease
(Farahpour & Habibi, 2012). Cardoso-Ugarte et al. (2016) reported the
aphrodisiac and anthelmintic use of the CEO along with its uses for
removing the harmful pathogens like termites, bacteria, mildew and
mosquitoes, etc.

8
 Table 2
Summary of antimicrobial activity by the various active constituents of C. verum.
Pharmacological active Plant Extract Assay Concentration Bacteria/Fungal species Screening results Reference
N. Singh, et al.

constituent part
used

Cinnamaldehyde Bark Steam distillation Quorum sensing 8 mg/ml Serratia marcescens PAR = 54.9% Aparna et al. (2014)
activity (Protease
activity reduction
(PAR)
Pseudomonas aeruginosa PAR = 20.9%
Disc diffusion assay 10 µl Streptococcus mutans and ZI = 4.0 – 4.6 cm Choi et al. (2016)
Streptococcus sobrinus
−1
40% (µL mL ) Staphylococcus aureus(ATCC ZI = 5.43 cm Freire, Cardoso, Batista,
25923) and Andrade (2011)
−1
50% (µL mL ) Escherichia coli(ATCC 25992) ZI = 3.05 cm
0.005 Aspergillus flavus ZI = 3.99 cm
0.25 Aspergillus Parasiticus ZI = 100%
5 μl Listeria innocua (ATCC 33090) ZI = 21.3 ± 0.6 mm Evrendilek (2015)
Coagulase-negative Staphylococci ZI = 21.2 ± 0.3 mm
(P-13)
Staphylococcus aureus(OSU 137) ZI = 52.2 ± 6.0 mm
Bacillus subtilis(OSU 494) ZI = 27.9 ± 4.8 mm
Broth microdilution 62.5 μg/ml Candida albicans (ATCC 10231) 66.4% (killing rate) Essid et al. (2017)
assay (MIC)
20 µl Candida albicans MIC = 231.37 ± 51.03 μg/mL Ainane, Khammour,
and Merghoub (2019)
Aspergillus niger MIC = 119.26 ± 25.78 μg/mL
Escherichia coli MIC = 265.44 ± 53.56 μg/mL

9
Methanol, ethanol, petroleum
ether (P.E.) and ethyl acetate
(E.A.)
Methanol
NR EthanolMethanolAcetone
Liposome-encapsulated
Steam distillation
Pseudomonas aeruginosa
Staphylococcus aureus
NR Pseudomonas aeruginosa (PAO1)
Agar streak dilution 0–7 μg/mL Candida albicans
method
Agar well-diffusion 100 mg/ml Staphylococcus aureus (ATCC
method 25923)
Bacillus subtilis (NCTC 8236)
Escherichia coli (ATCC 25922)
Pseudomonas aeruginosa (ATCC
27853)
0.5 to 5 mg/ml Malassezia globosa
Malassezia sympodialis
Malassezia furfur
Disc diffusion assay 50 mg Aeromonas hydrophila
Well-diffusion method 20 µl Vibrio sp.
−1
Broth dilution method 1.0 mg ml Staphylococcus aureus
Macrophage growth 1% Brucella abortus (544)
assays
Disc diffusion assay 5 mg/ml Klebsiella pneumoniae (ATCC
13047)
Proteus vulgaris (KZN)
Staphylococcus aureus (OK 2b)
MIC = 335.34 ± 68.06 μg/mL
MIC = 576.71 ± 112.52 μg/mL
MIC = 0.0562–0.225 %MBC = 0.1125–1.8% Utchariyakiat et al.
(2016)
MIC = 1.8 μg/mL Elgendy et al. (2016)
ZI = 26 ± 4.0 mm (E.A.) Abdalla and Abdelgadir
(2016)
ZI = 26 ± 5.0 mm (P.E.)
ZI = 32 ± 7.0 mm (E.A.)
ZI = 30 ± 8.5 mm (E.A.)
MIC = 0.75 mg/ml Mariappan et al. (2013)
MIC = 1.5 mg/ml
MIC = 1.1 mg/ml
ZI = 10.36 mm Ramena, Ramena, and
Challa (2018)
Best ZI = 25 mm with acetone Srivastava, Singh, and
Singh (2016)
MIC = 0.25MBC = 0.25MBIC = 1.0 MBEC = 1.0 Cui, Li, Li,
Vittayapadung, and Lin
(2016)
Strong inhibitory effect Al-Mariri, Saour, and
Hamou (2012)
ZI = 6.1 mm Fapohunda, Mmom,
and Fakeye (2012)
ZI = 5.5 mm
ZI = 4.5 mm
(continued on next page)
Food Chemistry 338 (2021) 127773
 Table 2 (continued)

Pharmacological active Plant Extract Assay Concentration Bacteria/Fungal species Screening results Reference
constituent part
N. Singh, et al.

used

15% v/v Staphylococcus aureus ZI = 100% Hussien, Teshale, and

Mohammed (2011)
Escherichia coli ZI = 36.36 ± 0.6%
Pseudomonas aeruginosa ZI = 10.0 ± 0.6%
Salmonella typhi ZI = 100.0%
Micro-broth dilution 0.01–1.5 μl/ml Pseudomonas aeruginosa (PAO1) MIC = 1 μl/ml Kalia et al. (2015)
assay
Microplate dilution 5% to 0.0195% Solobacterium moorei (CH8-20) MIC = 0.039% MBC = 0.156% LeBel et al. (2017)
assay v:v
Agar dilution method 0.1 to Bacillus subtilis (ATCC6633) MIC = 0.2 μl/ml Fei, Ding, Ye, and Ding
0.4 μl mL−1 (2011)
Bacillus cereus (ATCC10876) MIC = 0.1 μl/ml
Staphylococcus aureus (ATCC6538) MIC = 0.1 μl/ml
Escherichia coli (ATCC11229) MIC = 0.4 μl/ml
Salmonella typhimurium MIC = 0.4 μl/ml
(ATCC14028)
Cinnamaldehyde (cinn.) and Methanol and ethylacetate 100 µg/mL Staphylococcus aureus (ATCC ZI-LM = 11 mm ZI –SBM = 9 mm MIC-LM and Mazimba et al. (2015)
eugenol (eug.) 25923) SBM = 2.5 μl/ml
Bacillus subtilis (NCIB 3610) ZI-LE = 10 mm ZI-LM = 9 mm MIC-LM and
MIC-SBM = 2.5 μl/ml
Escherichia coli (ATCC 8739) ZI-LM = 9 mm ,
ZI-SBM = 10 mm and MIC-
LM and SBM = 2.5 μl/ml
Pseudomonas aeruginosa (NCIMB ZI-SBM = 9 mm MIC- SBM = 2.5 μl/ml

10
8295)
Candida albicans ZI-LE = 12 mmZI-LM = 10 mm ZI-SBM = 9 mm
MIC = 2.5 µg/mL
NR NR Disc diffusion assay 20 μl Bacillus cereus (MTCC 6840) ZI = 30 mm (cinn.) Sharma et al. (2016)
ZI = 12 mm (eug.)
Streptococcus mutans (MTCC 497) ZI = 30 mm (cinn.)
ZI = 9 mm (eug.)
Proteus vulgaris (MTCC 7299) ZI = 22 mm (cinn.)
ZI = 10 mm (eug.)
Salmonella typhi (MTCC 3917) ZI = 27 mm (cinn.)
ZI = 10 mm (eug.)
Bordetella bronchiseptica (MTCC ZI = 26 mm (cinn.)
6838)
ZI = 10 mm (eug.)
Cinnamaldehyde and benzyl Steam distillation 200–6.25 µl/ml Bacillus cereus (ATCC11778) ZI = 39.5 mm Padalia et al. (2017)
alcohol
Bacillus subtilis (ATCC6633) ZI = 15.2 mm
Staphylococcus aureus ZI = 17.1 mm
(ATCC29737)
Corynebacterium rubrum ZI = 13.8 mm
(ATCC14898)
Escherichia coli (NCIM2931) ZI = 15 mm
Pseudomonas aeruginosa ZI = 10.2 mm
(ATCC9027)
Klebsiella pneumoniae (NCIM2719) ZI = 14.1 mm
Salmonella typhimurium ZI = 12.4 mm
(ATCC23564)
Candida glabrata (NCIM3448) ZI = 34.1 mm
Candida albicans (ATCC2091) ZI = 38.5 mm
Food Chemistry 338 (2021) 127773

(continued on next page)

 Table 2 (continued)

Pharmacological active Plant Extract Assay Concentration Bacteria/Fungal species Screening results Reference
constituent part
N. Singh, et al.

used

Cryptococcus neoformans ZI = 30.1 mm

(ATCC34664)
Candida epicola (NCIM3367) ZI = 29 mm
Cinnamaldehyde, linalool 10 μl/mL Staphylococcus aureus, Escherichia MIC = 0.5 μl/mL and MBC = 1 μl/mL except Vazirian et al. (2015)
coli, Bacillus cereus and Salmonella Staphylococcus aureus
typhimurium
Candida albicans MIC = 0.5 μl/mL MBC = 1 μl/mL
Cinnamaldehyde and CEO Bark Resazurin microtiter 100 μl Mycobacterium tuberculosis H37Rv MIC = 19.5 μg/mL Mota, Campelo, and
assay Frota (2019)
NR Bark EO, methanol, chloroform and Well diffusion method 1 ml Klebsiella pneumonia ZI = 22 mm (EO) Shreya, Manisha, and
and leaf aqueous Sonali (2015)
Escherichia coli ZI = 29 mm (EO)
0.1 ml Aspergillus niger 100% inhibition with CEO
Acetone Quantitative 10 mg/ml Aeromonas hydrophila (MTCC646) MIC = 0.3125 mg/ml Parasa, Tumati, Prasad,
antibacterial activity and Kumar (2012)
assay
Aeromonas salmonicida MIC = 0.078 mg/ml
(MTCC1522)
Edwardsiella tarda (MTCC2400) MIC = 0.078 mg/ml
Bark Hydro-distillation Disc diffusion method – Staphylococcus aureus ZI = 20.00 ± 0.20 mm Ahmadi et al. (2019)
MIC = 1.90 ± 0.17 mg/mL
MBC = 3.30 ± 0.35 mg/mL
Pseudomonas aeruginosa ZI = 16.00 ± 0.10 mm
MIC = 2.70 ± 0.03 mg/mL

11
MBC = 4.50 ± 0.35 mg/mL
6 µl Streptococcus pyogenes ZI = 48 mm Sfeir, Lefrançois,
Baudoux, Derbré, and
Licznar (2013)
Well diffusion method 5 mg to 100 µl Klebsiella pneumonia ZI = 19.33 ± 1.52 mmMIC = 1 mg/ml Garg and Kumar (2019)
and Broth dilution
method
Enterobacter aerogenes ZI = 18.66 ± 2.08 mmMIC = 0.7 mg/ml
Escherichia coli ZI = 18.33 ± 1.52 mmMIC = 0.5 mg/ml
PseudomonasAeruginosa ZI = 14.66 ± 2.08 mmMIC = 2.5 mg/ml
ProteusMirabilis ZI = 13.66 ± 0.57 mmMIC = 2 mg/ml
0.2–0.73 mg/mL Staphylococcus aureus MIC = 0.2466 mg.ml−1 No ZI Rakshit and
Ramalingam (2011)
Bacillus cereus MIC = 0.6165 mg.ml−1 ZI = 1.2 cm
Enterococcus faecalis MIC = 0.1233 mg.ml−1 ZI = 0.8 cm
Escherichia coli MIC = 0.6165 mg.ml−1 No ZI
Proteus mirabilis MIC = 0.1233 mg.ml−1 ZI = 1.3 cm
Poison food method 500 mg/mL Aspergillus flavus ZI = 100% Lakshmeesha, Sateesh,
Vedashree, and Sofi
(2014)
Agar streak dilution 0–25 μg/mL Staphylococcus aureus MIC = 1 μg/mL Elgendy et al. (2016)
method
Escherichia coli MIC = 3 μg/mL
Broth microdilution 60 μl Salmonella typhi (D1Vi -positive) ZI = 24.6 ± 0.33 mm Naveed et al. (2013)
assay
MIC = 3.8 ± 0.96 mg/ml
Salmonella typhi (G7Vi-negative) ZI = 26.5 ± 0.28 mm
MIC = 2.9 ± 0.11 mg/ml
Salmonella para typhi A ZI = 25.5 ± 0.28
Food Chemistry 338 (2021) 127773

(continued on next page)

 Table 2 (continued)

Pharmacological active Plant Extract Assay Concentration Bacteria/Fungal species Screening results Reference
constituent part
N. Singh, et al.

used

MIC = 3.8 ± 0.96 mg/ml

Ethanol
Methanol (M) and water (W)
Escherichia coli (SS1)
Staphylococcus aureus
Bacillus licheni formis (14580)
Pseudomonas fluorescens
Disc diffusion method 2–10 mg/mL Staphylococcus aureus
Escherichia coli
Well-diffusion method 50 µl Bacillus subtilis
Candida albicans
0.4 g/ml Staphylococcus aureus
Escherichia coli
Klebsiella pneumonia
Pseudomonas aeruginosa
Bacillus cereus
Enterobacter aerogenes
MIC = 3.8 ± 0.96 mg/ml
ZI = 23.5 ± 0.28 mm
MIC = 4.8 ± 0.96 mg/ml
ZI = 32.6 ± 1.20 mm
MIC = 3.8 ± 0.96 mg/ml
ZI = 15 ± 0.57 mm
MIC = 2.9 ± 0.12 mg/ml
MIC = 6 mg/mL ZI = 1.25 mm Husain et al. (2018)
No significant activity
ZI = 5. 8 ± 0. 2 mmMIC = 6.25 µg/ml Ababutain (2011)
ZI = 3. 8 ± 0. 3 mmMIC = 25 µg/ml
ZI = 21.5 ± 1.0 mm (W) Bello and Osho (2012)
ZI = 23.0 ± 1.0 mm (M)
ZI = 16.8 ± 0.7 mm (W)
ZI = 17.8 ± 1.0 mm (M)
ZI = 18.0 ± 0.7 mm (W)
ZI = 22.0 ± 0.7 mm (M)
ZI = 17.0 ± 0.8 mm (W)
ZI = 21.0 ± 1.0 mm (M)
ZI = 13.5 ± 0.7 mm (W)
ZI = 24.5 ± 1.0 mm (M)
ZI = 14.0 ± 0.7 mm (W)
ZI = 22.0 ± 1.0 mm (M)

12
Proteus mirabilis ZI = 16.7 ± 0.9 mm (W)
ZI = 25.7 ± 1.2 mm (M)

*LM-Leaf methanol; *SBM-Stem bark methanol; *LE-Leaf ethylacetate, NR*-Not reported.

Food Chemistry 338 (2021) 127773
N. Singh, et al.
5. Phytochemical analysis
C. verum is a rich reservoir of diversified phytocompounds as
modern analytical techniques have enabled the identification and iso­
lation of its individual phytocompunds. Its essential oil contains various
classes of compounds like monoterpenes, diterpenes, sesquiterpenes,
oxygenated hydrocarbons and polyphenols, etc. (Cardoso-Ugarte et al.
2016). With the help of Gas Chromatography-Mass Spectrometry
(GC–MS), Azeredo, Santos, de Noronha Sales, and Soares (2014) iden­
tified (E)-cinnamaldehyde, eugenol, (E)-caryophyllene, (E)-cinnamyl
acetate and α-humulene as the five major compounds of CEO out of
which (E)-cinnamaldehyde was reported to be predominant. Choi, Cho,
Kim, Park, and Kim (2016) also investigated the CEO through Gas
Chromatography – flame ionization detector, GC–MS analyses and
chemical synthesis and found a total of 27 compounds, out of them only
24 compounds were identified. Williams et al. (2015) isolated trans-
cinnamaldehyde along with cinnamic acid and A-type and B-type pro­
cyanidins via LC-MS analysis of cinnamon bark extract. Chakraborty
et al. (2015) reported eugenol (70–95%) as the major compound of
cinnamon leaf EO while Nabavi et al. (2015) reported (E)-cinnamyl
acetate and caryophyllene as the main component of cinnamon fruits
and flowers EO. The various chemical compounds derived from C.
verum are shown in Table 1.
6. Pharmacological activity
Different plant parts of cinnamon and its EO are predominantly used
as a spice and condiment to flavor seasonings, sauces, bakery, con­
fectionery and drinks. They also added as a food additive in different
food items due to their food preserving potential (Pittman, 2011). In
addition to being used as a food additive, C. verum is one of the potent
medicinal plants used for healthcare purposes. It possesses various
pharmacological activities viz. antioxidant, antibacterial, antifungal,
Fig. 3A. Mechanism of action for the antimicrobial activity.
13
Food Chemistry 338 (2021) 127773
antiviral, antiulcer, antilipidemic, anticancer, antipyretic, antiplatelet,
antiallergic, antihypertensive, insecticidal, nematicidal, antidiabetic
and anesthetic activities, etc (Farahpour & Habibi, 2012; Gulcin et al.,
2019; Mariappan et al., 2013; Ribeiro-Santos et al., 2017; Shrishrimal,
Sharma, Sonawane, Sonawane, & Varpe, 2016; Wisal, 2018). It also
possesses gastroprotective, cardioprotective, immunomodulatory and
cognitive function boosting activities (Gopinath, Vidya, & Narasimha
Murthy, 2014). Its effective usefulness was also reported during flatu­
lence, diarrhea, amenorrhea, toothache, fever, leucorrhea, common
cold, headache and blood pressure control (Azimi et al., 2016;
Hajimonfarednejad et al., 2019). Gulcin et al. (2019) have opined that
enzymatic inhibition is the most studied therapeutic approach for
combating various health problems like obesity, diabetes, alzheimer’s,
etc. The α-amylase, α-glycosidase, acetylcholinesterase (AChE) and
Butyrylcholinesterase (BChE) inhibition potential of cinnamon is highly
explored in pharmaceutical, cosmeceutical and food industries. Some of
the major pharmacological activities of C. verum are described as
under:-
6.1. Antimicrobial activity
Antibiotic resistance is the failure of available antibiotics to exert
their desired pharmacological effects. The failure of chemotherapeutic
drugs such as adriamycin and paclitaxel are the well-known examples
of antibiotic resistance. Worldwide, pathogenic micro-organisms are
causing tremendous cellular and molecular changes that are difficult to
detect (Padalia, Rathod, Moteriya, & Chanda, 2017). Now-a-days, the
growing antibiotic resistance of microbes has become a global concern.
However, plenty of effective antibiotics are available to counteract the
pathogenic microbes but they are also associated with some negative
effects. As a result, the relatively safe nature of herbal formulations and
essential oils has led to their extensive use for developing new ther­
apeutic agents. Thus, researchers are trying to search novel antibiotics
N. Singh, et al. Food Chemistry 338 (2021) 127773

from natural resources, which can invade the bacterial cell membrane
and can stop their further growth without any adverse effect. Cinnamon
is one of the well documented natural antimicrobial agent
(Vasconcelos, Croda, & Simionatto, 2018; Wisal, 2018). It possesses
strong hydrophobic nature which renders its antibacterial action and
enables it to penetrate the biofilms which resultantly inhibit bacterial
cell colonization and growth. It also reduces the bacterial cell meta­
bolism, coagulates cellular materials and restricts the replication rate
(Kothiwale, Patwardhan, Gandhi, Sohoni, & Kumar, 2014). All these
qualities are unique to cinnamon and make it superior to antibiotics.
Naveed et al. (2013) screened the antibacterial activity of C. verum EO
along with the EO extracted from three other spices (Cuminum cyminum,
Amomum subulatum and Syzygium aromaticum) via broth micro-dilution
method against Salmonella typhi, Salmonella typhi, Salmonella para­
typhoid, Escherichia coli, Staphylococcus aureus, Bacillus licheniformis
and Pseudomonas fluorescens. They reported CEO as most potent anti­
bacterial agent among all the selected EO. Abdalla and Abdelgadir
(2016) studied the antibacterial effect of methanol, ethanol, petroleum
ether and ethyl acetate extracts of C. verum against Staphylococcus
aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa.
Ethyl acetate extract was reported to possess the strongest antibacterial
activity against Staphylococcus aureus, Escherichia coli and Pseudomonas
aeruginosa while Bacillus subtilis had shown the maximum sensitivity
towards petroleum ether extract. Mith et al. (2014) screened 15 EO

Table 3
Summary of antioxidant activity by the various active constituents of C. verum.
Pharmacological active Plant part Extract Assay Dosage Screening results Reference
constituent used

Phenolics Bark Aqueous (A)Ethanol (E) DPPH 1.5 ml 21. 25 µg/mL (E) Gulcin et al. (2019)
15.71 µg/mL (A)
ABTS 3.0 ml 5.79 μg/mL (E)
6.52 μg/mL (A)
2-(Cinnamyl) Distilled water DPPH 2.5 ml IC50 = 14.15 ppm Kankeaw and
hydroquinone Masong (2015)
Cinnamic acid ABTS 0.04 ml 119.70 µg/mL Durak et al. (2014)
Cinnamaldehyde and DPPH 1.0 ml 81% radical scavenging with eugenol Sharma et al. (2016)
eugenol
57% radical scavenging with cinnamaldehyde
Cinnamaldehyde 1 ml EC50 value = 0.321 mg/ml Rakshit and
Ramalingam (2011)
0.1 ml Antioxidant capacity = 72.2 ± 0.2% Evrendilek (2015)
ABTS 50 ml 81.7% with CEO Elgendy et al. (2016)
Ethanol and methanol 40 μl 100% inhibition with ethanol at a concentration of 200 μg/ Bhagavathy and
mL Latha (2015)
Methanol, chloroform and DPPH 250 μg/ml 82–91% Goyal et al. (2018)
dichloromethane
Methanol DPPH 10 μg/ml 85.98% Yousefifar and
Imungi (2018)
20 μg/ml 90.33%
30 μg/ml 89.81%
0.5 gm 11.9 μg mL−1 Saranya et al. (2017)
FRAP 0.5 ml 1.56 MAAE g−1
PM NR 2.34 MAAE g−1
Hexane DPPH 0.5 gm 689.2 μg mL−1
FRAP 0.5 ml 0.27 MAAE g−1
PM NR 0.86 MAAE g−1
Chloroform DPPH 0.5 gm 166.3 μg mL−1
FRAP 0.5 ml 0.37 MAAE g−1
PM NR 11.9 MAAE g−1
NR Bark (B) Dichloromethane: Methanol FRAP 20 µl 125.71 ± 3.21 mg (EL) Abeysekera et al.
and leaf (DCM: M) and ethanol (E) (2013)
(L)
73.02 ± 2.81 mg (EB)
65.17 ± 2.33 mg (DCM: M:L)
44.63 ± 1.85 mg (DCM: M:B)
DPPH 50 µl 33.96 ± 0.47 mg (EL)
107.69 ± 2.01 mg (EB)
14.41 ± 0.98 mg (DCM: M:L)
60.49 ± 0.48 mg (DCM: M:B)
ABTS 121.78 ± 3.20 mg (EL)
89.09 ± 2.87 mg (EB)
113.45 ± 4.29 mg (DCM: M:L)
62.88 ± 5.35 mg (DCM: M:B)
ORAC 44.74 ± 0.36 mg (EL)
22.14 ± 1.04 mg (EB)
21.17 ± 0.24 mg (DCM: M:L)
12.03 ± 0.36 mg (DCM: M:B)
Methanol (M) and ethyl DPPH 1.5 ml 76.5 µg/mL (MB)100.2 µg/mL (ML) Mazimba et al.
acetate (EA) (2015)
Methanol (M), Choloroform 2 ml 111.5 ± 0.62 μg/mL (M−B)175 ± 0.32 μg/mL Sudan, Bhagat,
(C), Aqueous (A) (M−L)289.5 ± 0.4 μg/mL (C-B)299 ± 0.21 μg/mL Gupta, and Devi
(C-L)122 ± 0.5 μg/mL (A-B)245.9 ± 0.4 μg/mL (A-L) (2013)
Essential oil, methanol, FRAP 0.1 ml 2.0 ± 4 μg/mL (the best activity with methanol extract) Shreya et al. (2015)
choloroform and aqueous

*NR – Not reported.

14
N. Singh, et al.
extracted from different plants and found that among them CEO was
the strongest antibacterial agent with a MIC of ≥0.125 µl/mL and
MBC ≥ 0.25 µl/mL against tested bacterial strains. Utchariyakiat,
Surassmo, Jaturanpinyo, Khuntayaporn, and Chomnawang (2016)
evaluated the antibacterial activity of cinnamon extract via agar well
diffusion assay. They revealed chloroform extract as a more potent
antibacterial agent than methanol extract. The various antimicrobial
studies of C. verum and its phytoconstituents are summarized in Table 2.
6.1.1. Antimicrobial mechanism of action
The antibacterial activity of the CEO is mainly due to its hydro­
phobic nature. The hydrophobicity of CEO increases the bacterial cell
membrane permeability which resultantly releases the cellular contents
outside the cell and causes cell mortality (Fig. 3A). However, it exerts
diverse action against different pathogens. For instance, the S. aureus
cells treated with the CEO observed with reduced metabolic and re­
plication rates while in case of P. aeruginosa, the cells were found with
decreased cellular membrane potential and selective membrane per­
meability. Apart from these modifications, it also induces oxidative
stress and membrane disruption as in case of KPC-KP cells of K. pneu­
monia bacteria (Yang et al., 2019). In multidrug-resistant E. coli strain
CEO has inhibited the biofilm formation and bacterial quorum sensing
(QS) ability of bacterial pathogen along with its membrane disruption
(Yap, Krishnan, Chan, & Lim, 2015) while it reduced the synthesis of
ergosterol up to 83% and hinder the fungal cell membrane formation
(Essid et al., 2017). Along with CEO, Cinnamaldehyde also individually
causes many morphological alterations to various foodborne bacterial
pathogens (e.g. S. aureus, S. anatum and B. cereus) and halted their
growth (Kothiwale et al., 2014). Hence, it can be concluded that the
CEO causes microbial membrane deterioration which resultantly makes
it a good antimicrobial agent.
6.2. Antioxidant activity
Generation of excess free radicals creates redox imbalance which
resultantly disturbs the cellular functions and may even accelerate the
cell mortality rate (Durak, Gawlik-Dziki, & Pecio, 2014). Medicinal
plants particularly spices and aromatic herbs are used as natural anti­
oxidants since antiquity. Phenolic compounds of cinnamon exhibit good
Fig. 3B. Mechanism of action for the antioxidant activity.
15
Food Chemistry 338 (2021) 127773
antioxidant potential. Elgendy, Ibrahim, Elmeherry, Sedki, and
Mekhemer (2016) reported that the CEO possesses stronger antioxidant
activity than lemon oil. Saranya et al. (2017) investigated the anti­
oxidant efficacy of hexane, chloroform and methanol extracts of cin­
namon, black pepper, ginger and turmeric via DPPH, phosphomo­
lybdate (PM) and ferric reducing antioxidant power (FRAP) assay. They
observed that methanol extract of cinnamon exhibited the strongest
antioxidant potential as compared to others as shown in Table 3. Beji,
Khemir, Wannes, Ayari, and Ksouri (2018) examined the antioxidant
effect of cinnamon powder in alloxan-induced diabetic rats and found
that the cinnamon powder significantly enhanced the level of anti­
oxidant enzymes such as glutathione peroxidase, catalase and super­
oxide dismutase, etc. Noorolahi, Sahari, Barzegar, Doraki, and Naghdi
Badi (2013) evaluated the antioxidant potential of the CEO and re­
ported that the CEO possesses the antioxidant activity comparable to
the synthetic antioxidant butylated hydroxyl anisole (BHA). Different
solvents used for extraction show different antioxidant activity.
Mazimba, Wale, Tebogo, Tebogo, and Kwape Shetonde (2015) observed
that ethyl acetate extract of cinnamon possess less antioxidant activity
as compared to its methanol extract. The various antioxidant studies of
C. verum extracts, its phytoconstituents and EOs are summarized in
Table 3.
6.2.1. Antioxidant mechanism of action
Gulcin et al. (2019) stated that cinnamon and its active components
has the ability to donate a hydrogen atom to the free radicals. After
gaining the hydrogen atom, the free radicals get stabilized and relieve
the cell from further oxidative stress. Li et al. (2016) reported that
cinnamaldehyde can enhance the release of cytochrome C from mi­
tochondria and upregulate the activity of caspase-9 and −3. It also
upregulates the expression of the pro-apoptotic factors (Bax gene) while
downregulates the expression of apoptotic inhibitors (Bcl-2) to induce
apoptosis and protect the cell from oxidative stress (Ezzat, Abu Elkhair,
Mourad, Helal & Grawish, 2017). Long et al. (2015) reported cinna­
maldehyde as the activator of the nuclear factor erythroid 2-related
factor (Nrf2), which is the master regulator of the cellular antioxidant
defense system. Cinnamaldehyde intervention leads to the ubiquitina­
tion of its negative regulator Kelch-like ECH-associated protein 1
(Keap1) and its nuclear translocation where it upregulated the
N. Singh, et al.
expression phase II antioxidant enzyme and reduced the oxidative
stress. Thus, the cinnamon reduces the generation of free radicals and
minimizes oxidative stress. The signaling pathway involved by cin­
namon to reduce oxidative stress is depicted in Fig. 3B.
6.3. Anti-inflammatory activity
The extracts and essential oil of C. verum, also possesses good anti-
inflammatory activity. Its aqueous extract showed significant anti-in­
flammatory activity by inhibiting the lipoxygenase (LOX) enzyme ac­
tivity (Durak et al., 2014). Qadir et al. (2018) investigated the anti-
inflammatory role of C. verum methanolic and ethanolic extract. The
BALB/c mice were induced with collagen mediated arthritis and were
treated with cinnamon extract. The treated mice were observed with
cinnamon mediated anti-inflammatory key markers like high immune
tolerance, reduced carbonic anhydrase expression and reduced arthritic
inflammation. The extract has also inhibited the production of pro-in­
flammatory cytokines, etc. Qabaha, Abu-Lafi, and Al-Rimawi (2017)
examined the anti-inflammatory effect of ethanolic extract of C. verum
along with C. longa on lipopolysaccharide (LPS)-induced interleukin-6
(IL-6) and tumor necrosis factor-α (TNF-α) of polymorphonuclear cells
isolated from blood. Cinnamic acid isolated from cinnamon has sig­
nificantly reduced the level of IL-6 and TNF-α in the studied cells.
Schink et al. (2018) evaluated the anti-inflammatory effect of the cin­
namon ethanolic extract on the suppression of toll-like receptors (TLR2)
and TLR4 signaling pathway involved in inflammation. They treated
THP-1 monocyte-macrophage cell lines with the cinnamon hydroalco­
holic extract with a concentration ranged from 0.03% to 3% and ob­
served a positive effect on the inhibition of inflammation signaling
pathways. They further revealed that trans-cinnamaldehyde and p-
cymene as the main compounds which acts as anti-inflammatory agents
and work synergistically. The compounds leads to the deficit secretion
of LPS induced IL-8 and reduced the phosphorylation of AKT serine/
threonine kinase (Akt) and expression of NF-κB inhibitor alpha (IκBα)
signaling pathways, which act as pro-inflammatory markers. Gawlik-
Dziki et al. (2013) reported LOX as an enzyme responsible for arachi­
donic acid metabolism. As a result, arachidonic acid gets converted into
Fig. 3C. Mechanism of action for the anti-inflammatory activity.
16
Food Chemistry 338 (2021) 127773
reactive oxygen species and other arachidonic acid products which
might be responsible for inflammation and carcinogenesis. This ara­
chidonic acid metabolism may be prevented by the CEO. Thus, cin­
namon and its bioactives can be used as an antioxidant and anti-in­
flammatory supplement.
6.3.1. Anti-inflammatory mechanism of action
Inflammation is mainly caused by the increased level of nitric oxide
(NO). Therefore, the reduction of NO production is essential to anti-
inflammation. The anti-inflammatory mechanism of action of C. verum
and its bioactives drawn from the above data suggested that C. verum
and its bioactives can decrease NO production (regulated by NF-kB
upregulation). NF-kB expression is antagonistic to the upregulation of
p53 (major tumour suppressor) expression. Cinnamaldehyde sig­
nificantly inhibits NF-kB expression and upregulates p53, consistent
with its anti-inflammatory action (Schink et al., 2018). In another
study, it was found that cinnamaldehyde down-regulates the expression
of many pro-inflammatory markers such as iNOS, COX-2, IL, TNF-α,
Akt, MAPKs and NF-kB signaling involved in nitric oxide production.
The suppression of these pro-inflammatory markers reduced the NO
level and finally prevented inflammation. The various signaling in­
volved in cinnamon mediated anti-inflammation action, are depicted in
Fig. 3C.
6.4. Anticancer activity
The use of C. verum is increasing in the treatment of various types of
ulcers and cancers (Bhagavathy & Latha, 2015). Ezzat, AbuElkhair,
Mourad, Helal, and Grawish (2017) evaluated the anticancer effect of
cinnamon bark aqueous extract on 7, 12-dimethylbenz[a]anthracene
(DMBA) induced oral cancer in sixty male Syrian hamster’s cheek pouch
(HCP) mucosa via different cytotoxicity assays such as 3-(4,5-di­
methylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay,
DNA fragmentation assay, etc. Cancer-induced hamsters supplemented
with cinnamon aqueous extract were noticed with significantly sup­
pressed oral cancer progression. Goyal et al. (2018) compared the im­
munomodulatory effects of water-soluble polysaccharides and other
 Table 4
Summary of anticancer activity by the various active constituents of C. verum.
Pharmacological active Plant Doses Assay Mechanism of action Model organism Cancer type Cell analyzed Ref.
N. Singh, et al.

constituent part
used

Cinnamaldehyde Bark 10 mmol/L Glutathione assay, viability Enhanced Nuclear factor-E2–related Murine colorectal cancer model Colorectal cancer HCT116 Long et al.
assay factor 2 (Nrf2) protein half-life and (2015)
glutathione
50–250 μg/ml Cytotoxicity assay, DNA Nuclear fragmentation, cytotoxic effects, In-vitro Leukemia HL 60 Bhagavathy
fragmentation assay, cell induced apoptosis and Latha
morphology assay and MTT (2015)
assay
1.56–100 μg/ml MTT assay and Anti- Cytotoxicity Hepatocellular and HePG-2 and Elgendy et al.
Proliferative Activity Assay colorectal cancer HCT-116 (2016)
10–100 μg/mL Trypan Blue Dye Exclusion Induced cytotoxicity and obtained an IC50 Breast and kidney MDA-MB-231 Husain et al.
Assay, DNA fragmentation assay value of 25 μg/mL cancer (2018)
and MTT assay
100 μl Sulforhodamine B (SRB) assay 43–46% antiproliferative activity with Breast, lung and T47D, NCI- Sharma et al.
cinn. While 39, 17 and 13% with eugenol prostate cancer H322 and PC-3 (2016)
against Breast, lung and prostate cancer,
respectively
500 mg Immunohistochemical staining Increased T lymphocytes, expressed CD3, Hamsters Oral cancer Epithelial cells Ezzat et al.
inhibited anti-CD3 and other (2017)
immunomodulatory effects
0–4 μg/mL Apoptosis assay, MTT assay and Induced apoptosis, anti-MDSC activity Male nude mice (BALB/c mice) Colon cancer Myeloid- He et al. (2019)
Western blotting derived
suppressor cells
(MDSCs)

17
2-Methoxycinnamaldehyde (2- 20 μmol/L XTT assay for cell viability, LDH Induced apoptosis, cytotoxicity, Lung cancer NCIH520 Liu et al. (2017)
MCA) cytotoxicity assay, Nuclear fragmentation increased lysosomal vacuolation
assay, Assay for the volume of the acidic (LV), increased volume of the
compartment, Mitochondrial membrane acidic compartment (VAC),
potential assay, Assay for caspase activity, suppressed NF-κB, cyclooxygenase-
Assay for topoisomerase I and II activities, 2 (COX-2) and prostaglandin E2
Flow cytometric analysis, (PGE2), and inhibited both
immunoprecipitation assay, Colorimetric topoisomerase I and II activity
assay and Comet assay
32 μM Human lung A549 Wong et al.
adenocarcinoma (2016)
0–20 μM Hepatocellular SK-Hep-1 Perng et al.,
carcinoma 2016a
10–30 μM Hep 3B Perng et al.
(2016b)
Cuminaldehyde 33.29 μM Human Lung NCI-H520 Yang et al.
squamous cell (2016)
cancer
0–20 μM Human colorectal COLO 205 Tsai et al.
adenocarcinoma (2016a, 2016b)
NR 100 mg/Ml SRB assay and colorimetric Induced 90% and 78% cytotoxicity in PC- In-vitro Prostrate and PC-3 and T98G Sudan et al.
method 3 and T98G cells, respectively glioblastoma (2013)
0–400 μl/mL MTT assay Decreased cell viability Breast cancer MCF-7 Wahab and
Adzmi (2017)
Polysaccharides 250 μg/ml Improved leukocyte counts and Mouse Leukemic RAW 264.7 Goyal et al.
peripheral blood mononuclear cells macrophage (2018)
(PBMCs) proliferation

NR*-Not reported.
Food Chemistry 338 (2021) 127773
N. Singh, et al.
different extracts of cinnamon against leukemic macrophage cell lines.
It was observed that cinnamon polysaccharide fraction possesses more
immunostimulatory effects as compared to other solvent extracts. Cell
proliferation assay further revealed the improved leukocyte counts and
peripheral blood mononuclear cells (PBMCs) proliferation in the stu­
died cell lines. He et al. (2019) reported that cinnamaldehyde treated
myeloid-derived suppressor cells (MDSCs) have positively inhibited the
antitumor immune system by suppressing the T-cells proliferation.
Mehrim and Salem (2013) screened various medicinal plants including
C. verum for their antiaflatoxin (a heptocarcinogen) activity on 360
randomly selected fishes and observed that among studied plants, C.
verum has shown a significant effect against aflatoxin. Morimoto,
Mitsukawa, Fujiwara, Kawamura, and Masuda (2019) evaluated and
observed good anti-mRNA processing activity in U2OS cell lines of
human bone osteosarcoma. The various other anticancerous studies of
C. verum extracts and its phytoconstituents are summarized in Table 4.
6.4.1. Anticancer mechanism of action
Li et al. (2016) evaluated the apoptosis-inducing mechanism of
cinnamaldehyde in tumour cells. They reported that phosphoinositide-
3-kinase (PI3K)/ AKT signaling pathway is indispensable for various
types of carcinogenesis. Cinnamaldehyde upregulates the expression of
pro-apoptotic factors such as E-cadherin, Bax and suppresses the ex­
pression of apoptotic inhibitors such as Bcl-2, matrix metalloproteinase-
2 (MMP-2), MMP-9, mTOR, IGF-1 and PI3K/ AKT signaling pathway
(He et al., 2019; Liu et al., 2017). In another study, Long et al. (2015)
reported that cinnamaldehyde eventually enhanced the expression of
phase II antioxidant enzyme via the activation of ERK1/2, Akt and JNK
signaling pathways. It also activated the Nrf2 by the ubiquitination of
its negative regulator Keap1. Keap1 degradation subsequently facil­
itates the Nrf2 nuclear translocation where it activates the cytoprotec­
tive genes and antioxidant response elements such as phase II enzymes.
These antioxidant enzymes relieve oxidative stress and play a critical
role in cancer prevention. It was also observed that PI3K/AKT and Nrf2
signaling as the major pathway involved by cinnamon to exert its an­
ticancer potential (as shown in Fig. 3D).
Fig. 3D. Mechanism of action for the anticancer activity.
18
Food Chemistry 338 (2021) 127773
6.5. Antidiabetic activity
Diabetes is the condition characterized by insulin resistance and
hyperglycemia and is mainly caused by increased oxidative stress and
inflammation. Nowadays, herbal formulations are preferred for treating
diabetes as compared to conventional synthetic drugs. Cinnamon is
reported as one of the most potent antidiabetic plant (Costello et al.,
2016; Gulcin et al., 2019). Azimi, Ghiasvand, Feizi, Hariri, and Abbasi
(2014) evaluated the antidiabetic effect of cinnamon and observed
significant results on total cholesterol, low-density lipoprotein (LDL)
and high-density lipoprotein (HDL) levels and proved the antidiabetic
effect of cinnamon. Shokri, Fathi, Jafari Sabet, Nasri Nasrabadi, and
Ataee (2015) evaluated the antidiabetic role of methanol extracts of
cinnamon along with green tea on 50 streptozotocin (STZ) induced
diabetic Wistar rats. After the 6th week of treatments, the rats were
observed with a significant reduction in glucose level and body weight.
Both the extracts have shown a synergistic effect to control diabetes.
Joshi, Jain, and Sharma (2017) evaluated the hypolipidaemic and an­
tiatherosclerotic effects of methanolic extract of cinnamon bark on male
rabbits. Biochemical and histological studies revealed that cinnamon
administration significantly reduced the high cholesterol level and re­
stored the normal arteries without any sign of abnormality. Sangi and
Elwahab (2017) investigated the antihyperglycemic, antihyperlipe­
demic and renoprotective action of C. verum along with ginger on forty
adult albino male rats and observed that C. verum was more effective
against the studied unusual health issues of an albino rat than Z. offi­
cinale. Yousefifar and Imungi (2018) studied the antidiabetic effect of
cinnamon methanol extract and observed inhibition of α-amylase and α-
glucosidase activity. El-Desoky, Aboul-Soud, and Al-Numair (2012)
screened the aqueous extract of cinnamon for antidiabetic potential on
alloxan-induced diabetic rats. The rats were administrated with dif­
ferent doses (200, 400, 600 and 1200 mg/kg) of cinnamon aqueous
extract for 30 days. After completion of 30 days of cinnamon admin­
istration, the rats were observed with antidiabetic symptoms like de­
creased FBS, HDL cholesterol, LDL cholesterol, triglycerides and serum
contents of total cholesterol. The rat supplemented with the lowest dose
of cinnamon extract i.e. 200 mg/kg was reported with the highest
N. Singh, et al.
antidiabetic effects. Beji et al. (2018) examined the antidiabetic effect
of cinnamon powder on alloxan-induced diabetic rats. It was observed
that cinnamon powder significantly reduced the FBS, serum levels of
total cholesterol, triglycerides and improved the hyperglycemia and
lipid profile of diabetic rats. Beejmohun et al. (2014) examined the
antidiabetic effect of hydro-alcoholic extract of Ceylon cinnamon on
post-meal glycemia. The rats were administrated with 1 g of Ceylon
cinnamon hydro-alcoholic extract after a standardized meal. The rats
were analyzed via in-vitro enzymatic assay and in- vivo starch tolerance
tests. In-vitro and in- vivo studies suppressed α- amylase activity and
acutely reduced glycemic response to starch, respectively. They also
revealed that cinnamon hydro-alcoholic extract is a more potent anti­
diabetic agent than its aqueous extract. Li et al. (2013) examined the
antidiabetic role of cinnamon in diabetic mice induced with STZ and
fed with high sugar. The diabetic mice were fed with cinnamon for
14 days. Later on, diabetic mice were evaluated via glucose oxidase
(GOD) and radioimmunoassay (RIA). These assays revealed sig­
nificantly reduced blood glucose and insulin level. Enzyme-linked im­
munosorbent assay (ELISA) revealed a significantly reduced level of
oxidative stress markers. They suggested that cinnamon polyphenols
help in repairing the pancreatic beta cells which further exerts the
hypoglycemic and hypolipidemic effects. Couturier et al. (2011) in­
vestigated the effect of cinnamon on glycogen synthesis, associated
gene expression and protein level on insulin-resistant male Wister rats
and observed that addition of cinnamon in the high fat and high fruc­
tose diet increased the glycogen synthesis. Tulini et al. (2016) reported
that solid lipid microparticles (SLM) of proanthocyanidin rich cin­
namon extract enhance the antioxidant and antidiabetic potential of the
food. All the above-mentioned studies clearly indicate the antidiabetic
effect of cinnamon. Out of different extracts, methanol (precisely more)
and aqueous extract were found to be highly useful for their anti­
diabetic potential. They mainly act on reducing oxidative stress, TC,
LDL, HDL, FBS, triglycerides level and help in restoring the normal
insulin level which ultimately resulted in normal glucose levels. Santos
and da Silva (2018) reviewed the role of cinnamon in diabetes control.
They also observed that a 1–6 g/d of cinnamon powder can be used
safely to cure T2D mellitus and hyperglycemic conditions. They sug­
gested that more clinical studies are required to establish the anti­
diabetic activity of cinnamon. Thus, cinnamon can be used for the
preparation of new antioxidants and antidiabetic rich functional foods.
Fig. 3E. Mechanism of action for the antidiabetic activity.
19
Food Chemistry 338 (2021) 127773
6.5.1. Antidiabetic mechanism of action
Zare, Nadjarzadeh, Zarshenas, Shams, and Heydari (2019) reported
that cinnamon improves insulin sensitivity via upregulating the ex­
pression of insulin receptor kinases while suppressing the depho­
sphorylation of insulin receptors. Furthermore, it reduces the uptake of
glucose by inhibiting the enzyme glycogen synthase kinase-3 and in­
creasing the expression of UCP3 genes of fatty acid metabolism. Cin­
namon also increases the glucose uptake by increasing the amount of
glucose transporter 4 (GLUT4) and insulin receptors and activating
glycogen synthase to reduce glucose concentration. Cinnamaldehyde
treatment upregulated the insulin receptor substrate1 (IRS1), p-85
regulatory subunit of PI3K (PI3K-P85), AKT2 and aortic nitric oxide
synthase 3 (eNOS) while reduced the expression of NADPH oxidase 4
(NOX4) and ultimately optimized the elevated glucose level (as shown
in Fig. 3E).
6.6. Wound healing
Wounds are an inescapable event for living beings, which can’t be
prevented but can be cured. Farahpour and Habibi (2012) investigated
the wound healing activity of the cinnamon ethanolic extract in the
mice. The different mice were supplemented with 1.5% and 3% of
cinnamon extract for 14 days. It was reported that the extract inter­
vention has stimulated collagenation, wound contraction and epitheli­
zation and other crucial steps for wound healing. It was also noticed
that 3% cinnamon extract exerted better wound reducing action.
Ahmadi, Farahpour, and Hamishehkar (2019) investigated the wound
healing efficacy of the CEO in wound-induced mice model (BALB/c
mice model). The 5 mm circularly induced wound lesions were in­
oculated with 107 CFU of two bacterial strains viz. S. aureus and P.
aeruginosa. The mice were treated with ointments containing 2% and
4% of the CEO and were observed with reduced inflammatory phase,
enhanced fibroblast distribution, accelerated cellular proliferation,
collagen deposition, keratin synthesis and reepithelialization. CEO has
also enhanced the mRNA levels of insulin-like growth factor (IGF-1),
fibroblast growth factors (FGF-2) and vascular endothelial growth
factor (VEGF). Yuan et al. (2018) reported that cinnamaldehyde at a
dose of 10 μM can stimulate endothelial cell proliferation, as an early
approach to angiogenesis in wound healing without any cytotoxicity.
N. Singh, et al.
6.6.1. Wound healing mechanism of cinnamon
Angiogenesis is a crucial step to the wound healing process. Yuan
et al. (2018) reported the angiogenesis promoting the potential of
cinnamaldehyde in wound healing. Cinnamaldehyde upregulated the
expression of PI3K signaling and mitogen-activated protein kinases
(MAPK) such as Erk1/2, P38, and JNK/ SAPK and stimulated the pro­
cess of angiogenesis. It also induces the phosphorylation of AKT, Erk1/
2, and P38, indispensable to angiogenesis. Furthermore, Ahmadi et al.
(2019) reported that the CEO enhances the release of VEGF and Flk-1/
KDR expression, to stimulate angiogenesis during wound healing. The
signaling pathway involved by cinnamon for healing wound is pre­
sented in Fig. 3F.
6.7. Anti-HIV activity
Semenya, Potgieter, and Erasmus (2013) reported the anti-human
immunodeficiency virus (HIV) activity of C. verum for curing acquired
immune deficiency syndrome (AIDS). Gopinath et al. (2014) in­
vestigated the anti-HIV activity of cinnamon extract via Pepsin assay.
The extract has significantly inhibited the pepsin enzyme which further
upregulated the inhibition of HIV protease. A significant IC50 value
obtained at the concentration of 56.08 ± 0.87 µg/ml indicated the
anti-HIV activity of C. verum.
6.8. Antianxiety and antidepressant
Sohrabi, Pazgoohan, Seresht, and Amin (2017) investigated the
anti-anxiety and antidepressant effect of the CEO. They carried out
forced swim test (FST) and tail suspension test (TST) to determine the
antidepressant role; elevated plus-maze test (EPM) and elevated open
field tests to determine the anti-anxiety activity of different doses (0.5,
1 and 2 mg/kg) of CEO. After 14 days of supplementation, the CEO has
significantly improved the anti-anxiety and antidepressant symptoms in
the studied mice. The 2 mg/kg dose of the CEO was found to be more
effective. Fadaei and Asle-Rousta (2018) evaluated the anti-anxiety and
antidepressant role of cinnamon hydroalcoholic extract in lead acetate
treated male rats. The rats were administrated with 200 mg/kg cin­
namon extract for 30 days and thereafter EPM and FST tests were
conducted to assess the anxiety and depression levels, respectively. FST
Fig. 3F. Mechanism of action for wound healing.
20
Food Chemistry 338 (2021) 127773
test revealed that cinnamon administration has significantly reduced
the immobility time delay and enhanced the total time of immobility
while the EPM test has revealed the significant reduction of open arms
entries (OAE) and open arms time (OAT).
6.9. Anti-Parkinson effects
Khasnavis and Pahan (2014) evaluated the antiparkinson activity of
cinnamon on MPTP-intoxicated mice. The mice were supplemented
with 100 μl of cinnamon powder solubilized in 0.5% methylcellulose
(MC). It was found that cinnamon administration has stimulated the
sodium benzoate production in the brain and blood cells of mice
models, which further increased the synthesis of Parkin and DJ-1 pro­
teins and inhibit their subsequent loss. The cinnamon intervention also
protected the dopaminergic neurons, optimized striatal neuro­
transmitters and improved motor functions.
7. The basic reason for several pharmacological activities of
cinnamon
Cinnamon finds ample importance in different pharmacological
actions. Its diverse medicinal properties are mainly atrributed to its
principal compound “cinnamaldehyde”. Cinnamaldehyde contains an
aldehydic (–CHO) functional group which decides its pharmacological
action. It donates hydrogen atom to the free radicals and prevents
oxidative stress and the associated disorders such as inflammation,
diabetes, cancer and many others. The compound “cinnamaldehyde”
also has the metal chelating power and can activate many signaling
pathways. Each signaling pathway mediated via cinnamon is involved
in combating more than one disorder. For instance, Nrf2 signaling is
involved in both cancers as well as oxidative stress (as shown in Fig. 3).
Likewise, MAPK signaling involved in inflammation also activated
during wound healing and PI3k/Akt signaling involved in both wound
healing and cancer. This common signaling also makes the basis for a
broad range of pharmacological activities rendered by cinnamon.
Cinnamaldehyde, due to its functional group is also evaluated for its
structure–activity relationship as well as for modulating the pharma­
cological action. Among the aforementioned physiological activities,
antimicrobial and antidiabetic activities are more studied. Clinical
N. Singh, et al.
studies have also been conducted which provide solid shreds of evi­
dence and well demonstrate the antidiabetic action of cinnamon.
8. Advantages of cinnamon over chemical drugs
Though plenty of chemical drugs are available against different
disorders but still, the research is always focused on the invention of
natural drugs. This is because the chemical drugs are action-oriented for
a specific disorder, while plant extracts work synergistically and render
more than one pharmacological effect. In Fig. 2, it was found that one
signaling pathway activated via cinnamon or its bioactives is involved
in other complications too, so treatment of one disease can prevent the
occurrence of other diseases too. Ahmadi et al. (2019) also supported
this view and stated that the antioxidant and antibacterial properties of
the CEO may also serve to its wound-healing action. Farahpour and
Habibi (2012) reported that treatment of diabetes and inflammation
can also prevent the occurrence of complications in other systems of the
body. Moreover, cinnamon is well established as one of the safe tradi­
tional medicine as compared to the chemical drugs (Sharma, Sharma, &
Pandey, 2016).
9. Structure-activity relationship
Cinnamaldehyde due to its functional group provides a basis for the
design of compounds in which different pharmacophores can be added
in one structure, which leads to an increase in the pharmacological
effect (Sharma et al., 2013). They synthesized different cinnamalde­
hyde derivatives via the functional group modification and evaluated
these compounds for their antibacterial and antioxidant activity via
broth dilution and DPPH assay, respectively. The dose of test com­
pounds ranged from 4000 to 3.9 µg/ml and 0.1 ml for antibacterial and
antioxidant assay, respectively. They noticed that some of these syn­
thetic compounds showed significantly improved activities with a MIC
of 0.01 mM against P. aeruginosa along with 80.71% of DPPH radical
inhibition but some of the compounds also showed considerable de­
creased or moderate activity. Therefore, they also reported that the
activity of these synthetic compounds decided by their functional group
modification. Kankeaw and Masong (2015) modified the structure of
cinnamaldehyde to enhance its antioxidant power. They synthesized
hydroquinone via the aldol condensation reaction between 1,4-cyclo­
hexanedione and cinnamaldehyde and studied the antioxidant potential
of resulted 2-(cinnamyl) hydroquinone via DPPH assay. Results showed
that the derivative is given less IC50 value (as shown in Table 3) than
the gallic acid standard. Wang et al. (2017) synthesized 24 cinna­
maldehyde amino acid schiff bases and evaluated the antifungal activity
via disc diffusion assay. They used a concentration of 0.125 mol/L of
the test solution and noticed two compounds with excellent antifungal
activity as compared to the existing compounds. Above data represent
cinnamaldehyde as a good agent for the structure–activity relationship
studies which can be further used to form new natural and safe com­
pounds with improved pharmacological effects.
10. Mechanism of action
Cinnamon and its bioactives activate various signaling pathways as
already discussed with respective pharmacological activity in Fig. 2. It
was found that Nrf2, PI3K/Akt and MAPK are the major signaling
pathways activated by cinnamon. These signaling pathways are in­
volved in more than one pharmacological effect. Due to the involve­
ment of these signaling pathways in more than one disorder, it can
interfere that the activation of one signaling pathway can be used to
prevent the occurrence of other disorders too.
11. Toxicological studies
Herbal products are generally labeled as safe and have lesser side
21
Food Chemistry 338 (2021) 127773
effects. Though, Farahpour and Habibi (2012) reported cinnamon as
quite safe for food preparation but, some occasional instances of skin
allergies have also been reported. Isaac-Renton et al. (2015) reported
the intraoral allergic contact dermatitis (ACD) associated with cin­
namon consumption. Cardoso-Ugarte et al. (2016) reported the toxicity
of cinnamic acid, a compound derived from the CEO. This compound
promoted dermatitis and oral sensitivity when added to perfumery and
oral care products, respectively. Limonene, linalool, terpineol, geraniol,
phellandrene, borneol, cymene, decanal and furfural compounds de­
rived from CEO were reported as toxic compounds but the toxicity of
these compounds was dose-dependent. Silva, Bernardo, Singh, and de
Mesquita (2019) reported the dose-dependent hepatotoxic effects of
coumarin compound derived from the cinnamon plant. Zare et al.
(2019) reported allergic symptoms in a patient during the investigation
of cinnamon efficacy in Type 2 Diabetes (T2D) treatment. They further
observed that these allergic symptoms get vanished within one week
after stoppage the cinnamon administration without any treatment.
Apart from this, no serious ill-effects were reported by other patients.
Food and Drug Administration also granted cinnamon as a safe food
additive (Cardoso-Ugarte et al., 2016; Long et al., 2015). It was also
noticed that the toxicity of cinnamon is only due to some selected
compounds and these compounds exert their toxic effect only at a
concentration higher than 3 g/3kg. Biron, Iovino, Bailey, and Brown
(2013) also reported that the CEO possesses almost negligible toxic
effects and can be used safely as a food preservative in a dose-depen­
dent manner. Thus, a suitable dose of cinnamon should be decided, at
which the toxicity of these toxic compounds becomes negligible and
cinnamon only render their pharmacological effect. After analyzing the
whole data of the present study regarding the safe dose of cinnamon
used for various pharmacological activities as well as for food pre­
paration, it was interpreted that 1–2 g/day dose of cinnamon can be
recommended as safe.
12. Clinical studies
Azimi et al. (2014) evaluated the antidiabetic role of an herbal
formulation containing cinnamon as a constituent. They carried out a
clinical trial on 204 patients suffering from Type 2 Diabetes (T2D).
They observed promising results of this formulation on total choles­
terol, LDL and HDL levels. Cinnamon also significantly reduced fasting
blood sugar (FBS). Dugoua et al. (2012) examined the antidiabetic role
of C. verum in combination with C. aromaticum on fifty patients of T2D
and found no significant improvement in patients. Magistrelli and
Chezem (2012) examined the cinnamon effect in thirty adults of normal
weight and obesity. They observed that cinnamon has decreased blood
sugar concentration and induced more insulin sensitivity during the
postprandial period. Zare et al. (2019) carried out a clinical trial on the
patients suffering from T2D to investigate the antidiabetic role of cin­
namon. The cinnamon intervention significantly reduced glycemic in­
dices and improved the anthropometric parameters and lipid profile.
13. Conclusion and future prospective
The bark of C. verum is used as an excellent health booster in cu­
linary and other products. From the present study, it is also evident that
it is also of great medicinal importance in curing microbial infections,
oxidative stress, diabetes, inflammation, wound healing, cancer, an­
xiety and depression, etc. The ethnomedicinal data reveals plant is a
potential source for the treatment of bronchitis, cardiac disorder, ce­
phalalgia, cardiac diseases, diarrhea, uropathy, fever, arthritis,
coughing, impotence, frigidity, intestinal spasms, vaginitis, neuralgia,
rheumatism. Cinnamaldehyde is the principal phytoconstituent of the
CEO responsible for almost all the pharmacological activities exerted by
cinnamon. The common signaling pathway and the cinnamaldehyde'
functional group is the basic reason for a broad spectrum of its med­
icinal attributes. The plant is extensively studied for its anti-diabetic
N. Singh, et al.
potential followed by antimicrobial, antioxidant, anti-inflammation and
anticancer, etc. It has been observed that it is not yet fully explored for
its anti-HIV, antiparkinson and other emerging infectious and life style
diseases. Unfortunately, the pharmacological studies in these areas are
still insufficient to substantiate these preventive effects and the phar­
macological studies are still insufficient to substantiate in these areas. It
has also been observed that cinnamaldehyde has been widely explored
for its pharmacological actions but its other phytoconstituents have not
yet been investigated as frequently and as deep as cinnamaldehyde.
These less explored compounds like cinnzeylanine, cinnzeylanol and
humulene etc. from cinnamon can be evaluated for their pharmacolo­
gical efficacy. Further, the clinical studies of the plant have been re­
stricted to diabetes only and other disorders have been neglected de­
spite of having plenty pharmacological pieces of evidence in the
literature, therefore it is recommended to conduct controlled clinical
studies in other pharmacological aspects as well. It is also crucial to
elucidate in-depth molecular mechanisms, structure–activity relation­
ships and potential synergistic and antagonistic effects of its bioactive
constituents.
Declaration of Competing Interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influ­
ence the work reported in this paper.
Acknowledgment
Financial assistance from the Council for Scientific and Industrial
Research (CSIR), New Delhi and Haryana State Council for Science and
Technology (HSCST), Panchkula, Haryana; Fund for Improvement of S&
T infrastructure in universities & higher educational institutions (FIST),
Department of Science and Technology, Govt. of India, New Delhi is
thankfully acknowledged.
Appendix A. Supplementary data
Supplementary data to this article can be found online at https://
doi.org/10.1016/j.foodchem.2020.127773.
References
Ababutain, I. M. (2011). Antimicrobial activity of ethanolic extracts from some medicinal
plant. Australian Journal of Basic and Applied Sciences, 5(11), 678–683.
Abdalla, R. M., & Abdelgadir, A. E. (2016). Antibacterial activity and phytochemical
constituents of Cinnamomum verum and Matricaria chamomilla from Sudan. Bio
Bulletin, 2(2), 08–12.
Abeysekera, W. P. K. M., Premakumara, G. A. S., & Ratnasooriya, W. D. (2013). In vitro
antioxidant properties of leaf and bark extracts of Ceylon cinnamon (Cinnamomum
zeylanicum Blume). Tropical Agricultural Research, 24(2), 128–138.
Ahmadi, S. G. S., Farahpour, M. R., & Hamishehkar, H. (2019). Topical application of
Cinnamon verum essential oil accelerates infected wound healing process by in­
creasing tissue antioxidant capacity and keratin biosynthesis. The Kaohsiung journal of
medical sciences, 35(11), 686–694.
Ainane, T., Khammour, F., & Merghoub, N. (2019). Cosmetic bio-product based on cin­
namon essential oil “Cinnamomum verum” for the treatment of mycoses: Preparation,
chemical analysis and antimicrobial activity. MedCrave Online Journal of Toxicology,
5(1), 5–8.
Al-Mariri, A., Saour, G., & Hamou, R. (2012). In vitro antibacterial effects of five volatile
oil extracts against intramacrophage Brucella abortus 544. Iranian Journal of Medical
Sciences, 37(2), 119.
Aparna, Y., Narayanan, L., & Sarada, J. (2014). Quorum quenching ability of dietary spice
Cinnamomum verum on pathogenic bacteria. International Journal of Pharmaceutical
Sciences and Research, 5(12), 5216.
Asimi, O. A., Sahu, N. P., & Pal, A. K. (2013). Antioxidant activity and antimicrobial
property of some Indian spices. International Journal of Scientific and Research
Publications, 3(3), 1–8.
Avula, B., Smillie, T. J., Wang, Y. H., Zweigenbaum, J., & Khan, I. A. (2015).
Authentication of true cinnamon (Cinnamon verum) utilising direct analysis in real
time (DART)-QToF-MS. Food Additives & Contaminants: Part A, 32(1), 1–8.
Azeredo, C. M. O., Santos, T. G., de Noronha Sales, B. H. L., & Soares, M. J. (2014). In
vitro biological evaluation of eight different essential oils against Trypanosoma cruzi,
22
Food Chemistry 338 (2021) 127773
with emphasis on Cinnamomum verum essential oil. BMC complementary and alter­
native medicine, 14(1), 309.
Azimi, P., Ghiasvand, R., Feizi, A., Hariri, M., & Abbasi, B. (2014). Effects of cinnamon,
cardamom, saffron, and ginger consumption on markers of glycemic control, lipid
profile, oxidative stress, and inflammation in type 2 diabetes patients. The Review of
Diabetic Studies: RDS, 11(3), 258.
Azimi, P., Ghiasvand, R., Feizi, A., Hosseinzadeh, J., Bahreynian, M., Hariri, M., &
Khosravi-Boroujeni, H. (2016). Effect of cinnamon, cardamom, saffron and ginger
consumption on blood pressure and a marker of endothelial function in patients with
type 2 diabetes mellitus: A randomized controlled clinical trial. Blood Pressure, 25(3),
133–140.
Balasubramanian, S., Singh, K. K., Mohite, A. M., & Zachariah, T. J. (2012). Physical
properties of cinnamon bark. Journal of Spices and Aromatic Crops, 21(2), 161–163.
Beejmohun, V., Peytavy-Izard, M., Mignon, C., Muscente-Paque, D., Deplanque, X., Ripoll,
C., & Chapal, N. (2014). Acute effect of Ceylon cinnamon extract on postprandial
glycemia: Alpha-amylase inhibition, starch tolerance test in rats, and randomized
crossover clinical trial in healthy volunteers. BMC Complementary and Alternative
Medicine, 14(1), 351.
Beji, R. S., Khemir, S., Wannes, W. A., Ayari, K., & Ksouri, R. (2018). Antidiabetic, an­
tihyperlipidemic and antioxidant influences of the spice cinnamon (Cinnamomum
zeylanicum) in experimental rats. Brazilian Journal of Pharmaceutical Sciences,
54(2), 1–8.
Bello, O. O., & Osho, A. (2012). Antimicrobial effects of spices on spoilage organisms of
moin-moin. Advances in Bioresearch, 3(2), 60–65.
Bhagavathy, S., & Latha, S. (2015). Anticarcinogenic effects of Cinnamomum verum on
HL60 leukemia cell lines. Journal of Pharmacy Research, 9(12), 650–661.
Biron, J. F., Iovino, J. P., Bailey, J. R., & Brown, R. S. (2013). Cinnamon-induced oral
contact stomatitis. Dentistry Today, 32(2), 82.
Cardoso-Ugarte, G. A., López-Malo, A., & Sosa-Morales, M. E. (2016). Cinnamon
(Cinnamomum zeylanicum) essential oils. In Essential Oils in Food Preservation,
Flavor and Safety, 339-347.
Chakraborty, A., Sankaran, V., Ramar, M., & Chellappan, D. R. (2015). Chemical analysis
of leaf essential oil of Cinnamomum verum from Palni hills, Tamil Nadu. Journal of
Chemical and Pharmaceutical Sciences, 8(3), 476–479.
Chen, P., Sun, J., & Ford, P. (2014). Differentiation of the four major species of cinnamons
(C. burmannii, C. verum, C. cassia, and C. loureiroi) using a flow injection mass
spectrometric (FIMS) fingerprinting method. Journal of agricultural and food chem­
istry, 62(12), 2516-2521.
Choi, O., Cho, S. K., Kim, J., Park, C. G., & Kim, J. (2016). In vitro antibacterial activity
and major bioactive components of Cinnamomum verum essential oils against cario­
genic bacteria, Streptococcus mutans and Streptococcus sobrinus. Asian Pacific Journal of
Tropical Biomedicine, 6(4), 308–314.
Costello, R. B., Dwyer, J. T., Saldanha, L., Bailey, R. L., Merkel, J., & Wambogo, E. (2016).
Do cinnamon supplements have a role in glycemic control in type 2 diabetes? A
narrative review. Journal of the Academy of Nutrition and Dietetics, 116(11),
1794–1802.
Couturier, K., Qin, B., Batandier, C., Awada, M., Hininger-Favier, I., Canini, F., &
Anderson, R. A. (2011). Cinnamon increases liver glycogen in an animal model of
insulin resistance. Metabolism, 60(11), 1590–1597.
Cui, H., Li, W., Li, C., Vittayapadung, S., & Lin, L. (2016). Liposome containing cinnamon
oil with antibacterial activity against methicillin-resistant Staphylococcus aureus
biofilm. Biofouling, 32(2), 215–225.
Dugoua, J., Perri, D., Seely, D., Ardilouze, J., Ridout, R., Bowers, K., & Koren, G. (2012).
The antidiabeticand cholesterol-lowering effects of common and cassia cinnamon
(Cinnamomum verum and C. aromaticum): A randomized controlled trial. BMC
Complementary and Alternative Medicine, 12(1), P179.
Durak, A., Gawlik-Dziki, U., & Pecio, Ł. (2014). Coffee with cinnamon–Impact of phy­
tochemicals interactions on antioxidant and anti-inflammatory in vitro activity. Food
Chemistry, 162, 81–88.
El-Desoky, G. E., Aboul-Soud, M. A., & Al-Numair, K. S. (2012). Antidiabetic and hypo­
lipidemic effects of Ceylon cinnamon (Cinnamomum verum) in alloxan-diabetic rats.
Journal of Medicinal Plants Research, 6(9), 1685–1691.
Elgendy, E. M., Ibrahim, H. S., Elmeherry, H. F., Sedki, A. G., & Mekhemer, F. U. (2016).
Chemical and biological comparative in vitro studies of cinnamon bark and lemon
peel essential oils. Food and Nutrition Sciences, 8(1), 110–125.
Essid, R., Hammami, M., Gharbi, D., Karkouch, I., Hamouda, T. B., Elkahoui, S., &
Tabbene, O. (2017). Antifungal mechanism of the combination of Cinnamomum verum
and Pelargonium graveolens essential oils with fluconazole against pathogenic Candida
strains. Applied Microbiology and Biotechnology, 101(18), 6993–7006.
Evrendilek, G. A. (2015). Empirical prediction and validation of antibacterial inhibitory
effects of various plant essential oils on common pathogenic bacteria. International
Journal of Food Microbiology, 202, 35–41.
Ezzat, S. K., AbuElkhair, M. T., Mourad, M. I., Helal, M. E., & Grawish, M. E. (2017).
Effects of aqueous cinnamon extract on chemically-induced carcinoma of hamster
cheek pouch mucosa. Biochemistry and Biophysics Reports, 12, 72–78.
Fadaei, S., & Asle-Rousta, M. (2018). Anxiolytic and antidepressant effects of cinnamon
(Cinnamomum verum) extract in rats receiving lead acetate. Scientific Journal of
Kurdistan University of Medical Sciences, 22(6), 31–39.
Fapohunda, S. O., Mmom, J. U., & Fakeye, F. (2012). Proximate analyses, phytochemical
screening and antibacterial potentials of bitter cola, cinnamon, ginger and banana
peel. Academia Arena, 4(8), 8.
Farahpour, M. R., & Habibi, M. (2012). Evaluation of the wound healing activity of an
ethanolic extract of Ceylon cinnamon in mice. Veterinarni Medicina, 57(1), 53–57.
Fei, L. U., Ding, Y. C., Ye, X. Q., & Ding, Y. T. (2011). Antibacterial effect of cinnamon oil
combined with thyme or clove oil. Agricultural Sciences in China, 10(9), 1482–1487.
Freire, J. M., Cardoso, M. G., Batista, L. R., & Andrade, M. A. (2011). Essential oil of
N. Singh, et al.
Origanum majorana L., Illicium verum Hook. f. and Cinnamomum zeylanicum Blume:
Chemical and antimicrobial characterization. Revista Brasileira de Plantas Medicinais,
13(2), 209–214.
Garg, S., & Kumar, G. (2019). Phytochemical composition and antimicrobial activity of
Cinnamomum verum bark against UTI causing bacteria. Think India Journal, 22(17),
768–773.
Gawlik-Dziki, U., Świeca, M., Sułkowski, M., Dziki, D., Baraniak, B., & Czyż, J. (2013).
Antioxidant and anticancer activities of Chenopodium quinoa leaves extracts–in vitro
study. Food and Chemical Toxicology, 57, 154–160.
Gopinath, S. M., Vidya, G. M., & Narasimha Murthy, T. P. (2014). Isolation, character­
ization and purification of bio-active compounds from Andrographis paniculata and
Cinnamon verum for anti-HIV activity. International Journal of Innovative Research in
Science, Engineering and Technology, 3(6), 13777–13783.
Goyal, M., Kaur, H., Bhandari, M., Rizvanov, A. A., Khaiboullina, S. F., & Baranwal, M.
(2018). Antioxidant and immune effects of water soluble polysaccharides isolated
from Cinnamomum verum bark. Bio Nano Science, 8(3), 935–940.
Gulcin, I., Kaya, R., Goren, A. C., Akincioglu, H., Topal, M., Bingol, Z., & Alwasel, S.
(2019). Anticholinergic, antidiabetic and antioxidant activities of cinnamon
(Cinnamomum verum) bark extracts: Polyphenol contents analysis by LC-MS/MS.
International Journal of Food Properties, 22(1), 1511–1526.
Hajimonfarednejad, M., Ostovar, M., Raee, M. J., Hashempur, M. H., Mayer, J. G., &
Heydari, M. (2019). Cinnamon: A systematic review of adverse events. Clinical
Nutrition, 38, 594–602.
Hamidpour, R., Hamidpour, M., Hamidpour, S., & Shahlari, M. (2015). Cinnamon from
the selection of traditional applications to its novel effects on the inhibition of an­
giogenesis in cancer cells and prevention of Alzheimer's disease, and a series of
functions such as antioxidant, anticholesterol, antidiabetes, antibacterial, antifungal,
nematicidal, acaracidal, and repellent activities. Journal of Traditional and
Complementary Medicine, 5(2), 66–70.
He, W., Zhang, W., Zheng, Q., Wei, Z., Wang, Y., Hu, M., & Luo, C. (2019).
Cinnamaldehyde causes apoptosis of myeloid–derived suppressor cells through the
activation of TLR4. Oncology Letters, 18(3), 2420–2426.
Husain, I., Ahmad, R., Chandra, A., Raza, S. T., Shukla, Y., & Mahdi, F. (2018).
Phytochemical characterization and biological activity evaluation of ethanolic ex­
tract of Cinnamomum zeylanicum. Journal of Ethnopharmacology, 219, 110–116.
Hussien, J., Teshale, C., & Mohammed, J. (2011). Assessment of the antimicrobial effects
of some Ethiopian aromatic spice and herb hydrosols. International Journal
Pharmacology, 7(5), 635–640.
Isaac-Renton, M., Li, M. K., & Parsons, L. M. (2015). Cinnamon spice and everything not
nice: Many features of intraoral allergy to cinnamic aldehyde. Dermatitis, 26(3),
116–121.
Jayaprakasha, G. K., & Rao, L. J. M. (2011). Chemistry, biogenesis, and biological ac­
tivities of Cinnamomum zeylanicum. Critical reviews in food Science and Nutrition, 51(6),
547–562.
Joshi, S. C., Jain, P. K., & Sharma, Priyanka (2017). Antiatherosclerotic and lipid-low­
ering effects of Cinnamomum verum in cholesterol-fed rabbits. International Journal
Curentr Pharmaceutical Research, 9(1), 75–80.
Kalia, M., Yadav, V. K., Singh, P. K., Sharma, D., Pandey, H., Narvi, S. S., & Agarwal, V.
(2015). Effect of cinnamon oil on quorum sensing-controlled virulence factors and
biofilm formation in Pseudomonas aeruginosa. PLoS one, 10(8).
Kamaliroosta, L., Gharachorloo, M., Kamaliroosta, Z., & Alimohammad Zadeh, K. H.
(2012). Extraction of cinnamon essential oil and identification of its chemical com­
pounds. Journal of Medicinal Plants Research, 6(4), 609–614.
Kankeaw, U., & Masong, E. (2015). The Antioxidant Activity from Hydroquinone
Derivatives by the Synthesis of Cinnamomum verum J. Presl Bark's Extracted.
International Journal of Chemical Engineering and Applications, 6(2), 91.
Khasnavis, S., & Pahan, K. (2014). Cinnamon treatment upregulates neuroprotective
proteins Parkin and DJ-1 and protects dopaminergic neurons in a mouse model of
Parkinson’s disease. Journal of Neuroimmune Pharmacology, 9(4), 569–581.
Kothiwale, S. V., Patwardhan, V., Gandhi, M., Sohoni, R., & Kumar, A. (2014). A com­
parative study of antiplaque and antigingivitis effects of herbal mouthrinse con­
taining tea tree oil, clove, and basil with commercially available essential oil mou­
thrinse. Journal of Indian Society of Periodontology, 18(3), 316.
Lakshmeesha, T. R., Sateesh, M. K., Vedashree, S., & Sofi, M. S. (2014). Antifungal activity
of Cinnamomum verum on Soybean seed-borne Aspergillus flavus. International Journal
of Advanced Research, 2(5), 1167–1172.
LeBel, G., Haas, B., Adam, A. A., Veilleux, M. P., Lagha, A. B., & Grenier, D. (2017). Effect
of cinnamon (Cinnamomum verum) bark essential oil on the halitosis-associated
bacterium Solobacterium moorei and in vitro cytotoxicity. Archives of Oral Biology, 83,
97–104.
Li, J., Teng, Y., Liu, S., Wang, Z., Chen, Y., Zhang, Y., & Zou, X. (2016). Cinnamaldehyde
affects the biological behavior of human colorectal cancer cells and induces apoptosis
via inhibition of the PI3K/Akt signaling pathway. Oncology Reports, 35(3),
1501–1510.
Li, R., Liang, T., Xu, L., Li, Y., Zhang, S., & Duan, X. (2013). Protective effect of cinnamon
polyphenols against STZ-diabetic mice fed high-sugar, high-fat diet and its underlying
mechanism. Food and Chemical Toxicology, 51, 419–425.
Li, Y. Q., Kong, D. X., & Wu, H. (2013). Analysis and evaluation of essential oil compo­
nents of cinnamon barks using GC–MS and FTIR spectroscopy. Industrial Crops and
Products, 41, 269–278.
Liu, Y. H., Tsai, K. D., Yang, S. M., Wong, H. Y., Chen, T. W., Cherng, J., & Cherng, J. M.
(2017). Cinnamomum verum ingredient 2-methoxycinnamaldehyde: A new anti­
proliferative drug targeting topoisomerase I and II in human lung squamous cell
carcinoma NCI-H520 cells. European Journal of Cancer Prevention, 26(4), 314–323.
Long, M., Tao, S., De La Vega, M. R., Jiang, T., Wen, Q., Park, S. L., & Wondrak, G. T.
(2015). Nrf2-dependent suppression of azoxymethane/dextran sulfate
23
Food Chemistry 338 (2021) 127773
sodium–induced colon carcinogenesis by the cinnamon-derived dietary factor cin­
namaldehyde. Cancer Prevention Research, 8(5), 444–454.
Magistrelli, A., & Chezem, J. C. (2012). Effect of ground cinnamon on postprandial blood
glucose concentration in normal-weight and obese adults. Journal of the Academy of
Nutrition and Dietetics, 112(11), 1806–1809.
Malsawmtluangi, L., Nautiyal, B. P., Hazarika, T., Chauhan, R. S., & Tava, A. (2016).
Essential oil composition of bark and leaves of Cinammoum verum Bertch. & Presl
from Mizoram, North East India. Journal of Essential oil research, 28(6), 551–556.
Mariappan, P. M., Sabesan, G., Koilpillai, B., Janakiraman, S., & Sharma, N. K. (2013).
Chemical characterisation and antifungal activity of methanolic extract of
Cinnamomum verum J. Presl bark against Malassezia spp. Pharmacognosy Journal,
5(5), 197–204.
Mazimba, O., Wale, K., Tebogo, E., Tebogo, E., & Kwape Shetonde, O. (2015).
Cinnamomum verum: Ethylacetate and methanol extracts antioxidant and anti­
microbial activity. Journal of Medicinal Plants Studies, 3(3), 28–32.
Mehrim, A. I., & Salem, M. F. (2013). Medicinal herbs against aflatoxicosis in Nile tilapia
(Oreochromis niloticus): Clinical signs, postmortem lesions and liver histopatholo­
gical changes. Egyptian Journal of Aquatic Research, 3, 13–15.
Mith, H., Dure, R., Delcenserie, V., Zhiri, A., Daube, G., & Clinquart, A. (2014).
Antimicrobial activities of commercial essential oils and their components against
food-borne pathogens and food spoilage bacteria. Food Science & Nutrition, 2(4),
403–416.
Morimoto, M., Mitsukawa, M., Fujiwara, C., Kawamura, Y., & Masuda, S. (2019).
Inhibition of mRNA processing activity from ginger-, clove-and cinnamon-extract,
and by two ginger constituents, 6-gingerol and 6-shogaol. Bioscience, Biotechnology,
and Biochemistry, 83(3), 498–501.
Mota, A. P. P., Campelo, T. A., & Frota, C. C. (2019). Evaluation of the antimicrobial
activity of Cinnamomum zeylanicum essential oil and trans-cinnamaldehyde against
resistant Mycobacterium tuberculosis. Bioscience Journal, 35(1), 296–306.
Nabavi, S. F., Di Lorenzo, A., Izadi, M., Sobarzo-Sánchez, E., Daglia, M., & Nabavi, S. M.
(2015). Antibacterial effects of cinnamon: From farm to food, cosmetic and phar­
maceutical industries. Nutrients, 7(9), 7729–7748.
Naveed, R., Hussain, I., Tawab, A., Tariq, M., Rahman, M., Hameed, S., & Iqbal, M.
(2013). Antimicrobial activity of the bioactive components of essential oils from
Pakistani spices against Salmonella and other multi-drug resistant bacteria. BMC
Complementary and Alternative Medicine, 13(1), 265.
Noorolahi, Z., Sahari, M. A., Barzegar, M., Doraki, N., & Naghdi Badi, H. (2013).
Evaluation antioxidant and antimicrobial effects of cinnamon essential oil and
echinacea extract in Kolompe. Journal of Medicinal Plants, 1(45), 14–28.
Padalia, H., Rathod, T., Moteriya, P., & Chanda, S. (2017). Antimicrobial efficacy of
Cinnamonum verum essential oil alone and in combination with antibiotics and other
essential oils. International Journal of Current Microbiology and Applied Sciences, 6(11),
3377–3395.
Parasa, L. S., Tumati, S. R., Prasad, C. S., & Kumar, L. C. A. (2012). In vitro antibacterial
activity of culinary spices aniseed, star anise and cinnamon against bacterial patho­
gens of fish. International Journal of Pharmaceutical Science, 4, 667–670.
Perng, D. S., Tsai, Y. H., Cherng, J., Kuo, C. W., Shiao, C. C., & Cherng, J. M. (2016).
Discovery of a novel anti-cancer agent targeting both topoisomerase I and II in he­
patocellular carcinoma Hep 3B cells in vitro and in vivo: Cinnamomum verum com­
ponent 2-methoxycinnamaldehyde. Journal of drug targeting, 24(7), 624–634.
Perng, D. S., Tsai, Y. H., Cherng, J., Wang, J. S., Chou, K. S., Shih, C. W., & Cherng, J. M.
(2016). Discovery of a novel anticancer agent with both anti-topoisomerase i and ii
activities in hepatocellular carcinoma sK-hep-1 cells in vitro and in vivo:
Cinnamomum verum component 2-methoxycinnamaldehyde. Drug Design, Development
and Therapy, 10, 141.
Pittman, S. (2011). Cinnamon: It's not just for making cinnamon rolls. Ethnobotanical
Leaflets, 2000(2), 11.
Qabaha, K., Abu-Lafi, S., & Al-Rimawi, F. (2017). Anti-inflammatory Activities of
Ethanolic Extracts of curcuma Longa (Turmeric) and cinnamon (Cinnamomum verum).
Journal of Food and Nutrition Research, 5(9), 668–673.
Qadir, M. M. F., Bhatti, A., Ashraf, M. U., Sandhu, M. A., Anjum, S., & John, P. (2018).
Immunomodulatory and therapeutic role of Cinnamomum verum extracts in collagen-
induced arthritic BALB/c mice. Inflammopharmacology, 26(1), 157–170.
Rakshit, M., & Ramalingam, C. (2011). In-vitro antibacterial and antiodixant activity of
Cinnamomum verum (Cinnamon) aqueous bark extract in reference to its total phenol
content as natural preservative to food. International Journal of Biotechnology, 8(4),
529–537.
Ramena, G., Ramena, Y., & Challa, N. (2018). Identification and determination of
minimum inhibitory concentrations of plant extracts having antimicrobial activity as
potential alternative therapeutics to treat Aeromonas hydrophila infections. Journal of
Microbial Pathogenesis, 2(1), 1–9.
Rao, P. V., & Gan, S. H. (2014). Cinnamon: A multifaceted medicinal plant. Evidence-Based
Complementary and Alternative Medicine, 2014, 1–12.
Ribeiro-Santos, R., Andrade, M., Madella, D., Martinazzo, A. P., Moura, L. D. A. G., de
Melo, N. R., & Sanches-Silva, A. (2017). Revisiting an ancient spice with medicinal
purposes: Cinnamon. Trends in Food Science & Technology, 62, 154–169.
Sangal, A. (2011). Role of cinnamon as beneficial antidiabetic food adjunct: A review.
Advances in Applied Science Research, 2(4), 440–450.
Sangi, S. M. A., & Elwahab, M. F. A. (2017). Experimental evaluations of the ne­
phroprotective properties of ginger (Zingiber officinale), Cinnamomum verum and
Nigella sativa in STZ induced diabetic rats. International Journal of Biology, Pharmacy
and Allied Sciences, 6(6), 1195–1209.
Santos, H. O., & da Silva, G. A. (2018). To what extent does cinnamon administration
improve the glycemic and lipid profiles? Clinical Nutrition ESPEN, 27, 1–9.
Saranya, B., Sulfikarali, T., Chindhu, S., Muneeb, A. M., Leela, N. K., & Zachariah, T. J.
(2017). Turmeric and cinnamon dominate in antioxidant potential among four major
N. Singh, et al.
spices. Journal of Spices and Aromatic Crops, 26(1), 27–32.
Schink, A., Naumoska, K., Kitanovski, Z., Kampf, C. J., Fröhlich-Nowoisky, J., Thines, E.,
& Lucas, K. (2018). Anti-inflammatory effects of cinnamon extract and identification
of active compounds influencing the TLR2 and TLR4 signaling pathways. Food &
Function, 9(11), 5950–5964.
Semenya, S. S., Potgieter, M. J., & Erasmus, L. J. C. (2013). Ethnobotanical survey of
medicinal plants used by Bapedi traditional healers to manage HIV/AIDS in the
Limpopo Province, South Africa. Journal of Medicinal Plants Research, 7(8), 434–441.
Sfeir, J., Lefrançois, C., Baudoux, D., Derbré, S., & Licznar, P. (2013). In vitro antibacterial
activity of essential oils against Streptococcus pyogenes. Evidence-based Complementary
and Alternative Medicine, 1–9.
Sharma, U. K., Sharma, A. K., & Pandey, A. K. (2016). Medicinal attributes of major
phenylpropanoids present in cinnamon. BMC Complementary and Alternative Medicine,
16(1), 1–11.
Sharma, U. K., Sood, S., Sharma, N., Rahi, P., Kumar, R., Sinha, A. K., & Gulati, A. (2013).
Synthesis and SAR investigation of natural phenylpropene-derived methoxylated
cinnamaldehydes and their novel Schiff bases as potent antimicrobial and antioxidant
agents. Medicinal Chemistry Research, 22(11), 5129–5140.
Shokri, G., Fathi, H., Jafari Sabet, M., Nasri Nasrabadi, N., & Ataee, R. (2015). Evaluation
of antidiabeticeffects of hydroalcoholic extract of green tea and cinnamon on strep­
tozotocin-induced diabetic rats. Pharmaceutical and Biomedical Research, 1(2), 20–29.
Shreya, Ahuja, Manisha, Dharmadikari, & Sonali, J. (2015). Phytochemical screening and
anti-microbial activity of cinnamon spice against urinary tract infection and fungal
pathogens. International Journal of Life Science & Pharma Research, 5(4), 30–38.
Shrishrimal, R. P., Sharma, K. S., Sonawane, S., Sonawane, P., & Varpe, V. V. (2016). On
barks of Cinnamomomum zeylanicum Nees. International Journal of Research in
Pharmacy and Pharmaceutical Sciences, 1(5), 1–9.
Silva, M. L. T., Bernardo, M. A. S., Singh, J., & de Mesquita, M. F. (2019). Beneficial Uses
of Cinnamon in Health and Diseases: An Interdisciplinary Approach. In R. R. Watson,
R. B. Singh, & T. Takahashi (Eds.), The Role of Functional Food Security in Global
Health, (565-576). Academic Press.
Sohrabi, R., Pazgoohan, N., Seresht, H. R., & Amin, B. (2017). Repeated systemic ad­
ministration of the cinnamon essential oil possesses anti-anxiety and anti-depressant
activities in mice. Iranian Journal of Basic Medical Sciences, 20(6), 708.
Srivastava, A., Singh, A. N., & Singh, M. (2016). Antibacterial activity of spices against
Vibrio species isolated from pond water. European Journal of Experimental Biology,
6(2), 21–25.
Sudan, R., Bhagat, M., Gupta, S., & Devi, T. (2013). Comparative analysis of cytotoxic and
antioxidant potential of edible Cinnamomum verum (bark) and Cinnamomum tamala
(Indian bay leaf). Free Radicals and Antioxidants, 3, 70–73.
Tsai, K. D., Cherng, J., Liu, Y. H., Chen, T. W., Wong, H. Y., Yang, S. M., & Cherng, J. M.
(2016). Cinnamomum verum component 2-methoxycinnamaldehyde: A novel anti­
proliferative drug inducing cell death through targeting both topoisomerase I and II
in human colorectal adenocarcinoma COLO 205 cells. Food & nutrition research, 60(1),
31607.
Tsai, K. D., Liu, Y. H., Chen, T. W., Yang, S. M., Wong, H. Y., Cherng, J., & Cherng, J. M.
(2016). Cuminaldehyde from Cinnamomum verum induces cell death through tar­
geting topoisomerase 1 and 2 in human colorectal adenocarcinoma COLO 205 cells.
Nutrients, 8(6), 318.
Tulini, F. L., Souza, V. B., Echalar-Barrientos, M. A., Thomazini, M., Pallone, E. M., &
Favaro-Trindade, C. S. (2016). Development of solid lipid microparticles loaded with
24
Food Chemistry 338 (2021) 127773
a proanthocyanidin-rich cinnamon extract (Cinnamomum zeylanicum): Potential for
increasing antioxidant content in functional foods for diabetic population. Food
Research International, 85, 10–18.
Utchariyakiat, I., Surassmo, S., Jaturanpinyo, M., Khuntayaporn, P., & Chomnawang, M.
T. (2016). Efficacy of cinnamon bark oil and cinnamaldehyde on anti-multidrug re­
sistant Pseudomonas aeruginosa and the synergistic effects in combination with other
antimicrobial agents. BMC Complementary and Alternative Medicine, 16(1), 158.
Vasconcelos, N. G., Croda, J., & Simionatto, S. (2018). Antibacterial mechanisms of
cinnamon and its constituents: A review. Microbial pathogenesis, 120, 198–203.
Vazirian, M., Alehabib, S., Jamalifar, H., Fazeli, M. R., Najarian Toosi, A., & Khanavi, M.
(2015). Antimicrobial effect of cinnamon (Cinnamomum verum J. Presl) bark essential
oil in cream-filled cakes and pastries. Research Journal of Pharmacognosy, 2(4), 11–16.
Wahab, W. A., & Adzmi, A. N. (2017). The investigation of cytotoxic effect of
Cinnamomum zeylanicum extracts on human breast cancer cell line (Mcf-7). Science
Heritage Journal, 1(2), 23–28.
Wang, H., Jiang, M., Li, S., Hse, C. Y., Jin, C., Sun, F., & Li, Z. (2017). Design of cinna­
maldehyde amino acid Schiff base compounds based on the quantitative structure–­
activity relationship. Royal Society Open Science, 4(9), Article 170516.
Williams, A. R., Ramsay, A., Hansen, T. V., Ropiak, H. M., Mejer, H., Nejsum, P., &
Thamsborg, S. M. (2015). Anthelmintic activity of trans-cinnamaldehyde and A-and
B-type proanthocyanidins derived from cinnamon (Cinnamomum verum). Scientific
Reports, 5, 14791.
Wisal, G. A. (2018). Antibacterial and Antifungal Effect of Cinnamon. Microbiology
Research Journal International, 23(6), 1–8.
Wong, H. Y., Tsai, K. D., Liu, Y. H., Yang, S. M., Chen, T. W., Cherng, J., & Cherng, J. M.
(2016). Cinnamomum verum component 2-methoxycinnamaldehyde: A novel antic­
ancer agent with both anti-topoisomerase I and II activities in human lung adeno­
carcinoma a549 cells in vitro and in vivo. Phytotherapy Research, 30(2), 331–340.
Yang, S. K., Yusoff, K., Ajat, M., Thomas, W., Abushelaibi, A., Akseer, R., & Lai, K. S.
(2019). Disruption of KPC-producing Klebsiella pneumoniae membrane via induction
of oxidative stress by cinnamon bark (Cinnamomum verum J. Presl) essential oil. PloS
One, 14(4), Article e0214326.
Yang, S. M., Tsai, K. D., Wong, H. Y., Liu, Y. H., Chen, T. W., Cherng, J., & Cherng, J. M.
(2016). Molecular mechanism of Cinnamomum verum component cuminaldehyde
inhibits cell growth and induces cell death in human lung squamous cell carcinoma
NCI-H520 cells in vitro and in vivo. Journal of Cancer, 7(3), 251.
Yap, P. S., Krishnan, T., Chan, K. G., & Lim, S. H. (2015). Antibacterial mode of action of
Cinnamomum verum bark essential oil, alone and in combination with piperacillin,
against a multi-drug-resistant Escherichia coli strain. Journal of Microbiology and
Biotechnology, 25(8), 1299–1306.
Yousefifar, H., & Imungi, C. N. K. J. K. (2018). Antidiabetic and antioxidant properties of
methanolic extract for a diabetic supplement developed from drumsticks leaves
(Moringa oleifera), garlic (Allium sativum) and cinnamon (Cinnamomum verum) pow­
ders. Food Science and Quality Management, 79, 9–16.
Yuan, X., Han, L., Fu, P., Zeng, H., Lv, C., Chang, W., & Fan, T. (2018). Cinnamaldehyde
accelerates wound healing by promoting angiogenesis via up-regulation of PI3K and
MAPK signaling pathways. Laboratory Investigation, 98(6), 783–798.
Zare, R., Nadjarzadeh, A., Zarshenas, M. M., Shams, M., & Heydari, M. (2019). Efficacy of
cinnamon in patients with type II diabetes mellitus: A randomized controlled clinical
trial. Clinical Nutrition, 38(2), 549–556.