Review

Eleutherine bulbosa (Mill.) Urb.: Update Review of the Pharmacological Activities

Zuliar Permana1 Neng Fisheri Kurniati1 Muhamad Insanu1 Diky Mudhakir1

1
School of Pharmacy, Institut Teknologi Bandung (ITB), Bandung 40132
*
Corresponding author details
Diky Mudhakir, Ph.D.
Department of Pharmaceutics,
School of Pharmacy, Institut Teknologi Bandung (ITB)
Gedung Yusuf Panigoro, Laboratorium Teknologi VII
Jalan Ganesha No. 10, Bandung, Indonesia-40132
Phone: +62-22-2504852
Email: mudhakir@itb.ac.id
Abstract:

A valuable natural product with diverse therapeutic potential is E. bulbosa, a member of the Iridaceae family. The bulb of E.
bulbosa, traditionally used by the Dayak community as a folk medicine for various ailments, contains high levels of
phytochemicals such as phenolic and flavonoid derivatives, naphthalene, anthraquinone, and naphthoquinone. Through
scientific investigations, it has been discovered that the bulb possesses various pharmacological activities. To search
electronic databases for research on this valuable natural product, the interchangeably used scientific names of E . bulbosa
and related species, such as E. americana, E. palmifolia, and E. platifolia, were used. This study presents a comprehensive
review of the extensive pharmacological activities of E. bulbosa, including anti-cancer, anti-hypertensive, anti-diabetes, anti-
bacterial, anti-fungal, anti-virus, anti-inflammatory, dermatological problems, anti-oxidant, and anti-fertility, making it an
excellent candidate for alternative medicine for disease management.

Keywords: Eleutherine bulbosa; bul b, Iridaceae; pharmacology activities

1. Introduction
Eleutherine bulbosa, also known as Dayak onion, forest onion, or tiwai onion, is a perennial herbaceous
flowering plant belonging to the Iridaceae family. It is widely cultivated in Indonesia, South America, and
Africa, and commonly found in sulfur-containing soils in Indonesia at elevations between 600 to 2000
meters above sea level. The bulb of E. bulbosa has been traditionally used by the Dayak tribe in Kalimantan
to treat various ailments, including diabetes, breast cancer, hypertension, stroke, and sexual disorders, as
well as to enhance breast milk production [1,2,3,4] (Kamarudin, 2021; Kusuma, 2010; Insanu, 2014;
Ieyama, 2011). E. bulbosa has multiple scientific names, including E. americana, E. palmifolia, and E.
platifolia, but it has been proposed as an official scientific name by Kew and Missouri Botanic Garden [5]
(Couto, 2016). Morphologically, E. bulbosa has a red bulb resembling an onion and 25 cm long leaves with
five to six white flowers at the top [6] (Rivella, 2021). The bulb of E. bulbosa contains key constituents such
as naphthalene, anthraquinone, and naphthoquinone, which have demonstrated various pharmacological
properties, including anti-microbial, anti-inflammatory, anti-hypertensive, anti-cancer, anti-diabetic, and
anti-melanogenesis activities [1,2,3] (Kamarudin, 2021; Kusuma, 2010; Insanu, 2014). However,
scientific evidence regarding the biological activities of the bulb of E. bulbosa is limited. This study is the first
to highlight recent biological reviews of the E. bulbosa bulb.
2. Morphological Characteristics.

The Eleutherine genus is a perennial flowering plant characterized as herbaceous, rhizomatous, and
having predominantly red and wine-colored bulbs that resemble red onions (Figure 1). The bulbs are
typically around 20 to 30 cm in size (5,6) (Couto, 2016; Rivella, 2021). The plant has whole leaves,

Figure 1. The morphological characteristics of E. bulbosa. Note that it is a rhizomatous long, red bulb
that nearly mimics the red onion (a) and has a leaf in a pleated linear-lanceolate shape (b).

pleated at an average length of 25 cm, with a large panicle of white or pink flowers arranged at the top
of a long, dense scape above the foliage (5) (Couto, 2016). The pollen grain of the Eleutherine genus is
monosulcate and perforated on the proximal surfaces with heterogenous exine at different grain parts
(7) (Goldblatt, 1992). Microscopic examination of the E. americana bulb reveals varying sizes of
parenchymal cells and various shapes of calcium oxalate crystals, predominantly a styloid structure (8)
(Kuntorini, 2010). The bulb is derived from a thick petiole with similar vascular bundles as in the leaves,
and it lacks sclerenchyma cells for tissue support (8) (Kuntorini, 2010).

3. Traditional Uses
The traditional use of the bulb of E. bulbosa is widespread and diverse, with applications ranging from
carminative and anti-flatulent effects to treating various diseases such as diabetes, breast cancer, stroke,
hypertension, and fertility problems, among others (4,9) (Ieyama, 2011; Ifesan, 2009). The Dayak tribe has
specific uses for the bulb, including enhancing breast-milk production in women (4,9) (Ieyama, 2011;
Ifesan, 2009. Other areas also use it for the treatment of coronary disorders, menstrual pain, wound
healing, and as an anti-inflammatory, abortifacient, and emmenagogue (10-15) (Zhengxiong,1986;
Weniger,1982; Lans,2007; Lucena,2007; Tessele,2011; Villegas,1997). Additionally, the bulb's anti-
microbial and anti-inflammatory properties make it useful for treating pertussis, hemoptysis, and simple
coughs (16) (WHO,1990). The fresh bulb's juice or chew is used to manage various digestive disorders
such as diarrhea, dysentery, jaundice, and colitis. The bulb's effectiveness in managing colon cancer has
also been reported in some instances (16) (WHO,1990).
4. Phytochemical Constituents

Naphthalene, anthraquinone, and naphthoquinone are the three main chemical components found in the bulb of E. bulbosa. Numerous
compounds have been extracted from the bulb of E. bulbosa, including hongconin, eleutherin, eleutherol, isoeleutherol, isoeleutherine,
elecanacin, eleutherinoside A, eleuthoside B, and four polyketides, such as (R)-4-hydroxyeleutherin, eleuthone, eleutherinol-8-O-β-D-glucoside,
and isoeleuthoside C (dihydroisoeleutherin-5-O-β-D-gentiobioside) (10,17-19) (Zhengxiong,1986; Hara,1997; Bianch,1975; Gallo,2010). Additionally, 9,9′-
dihydroxy-8,8′-dimethoxy-1,1′-dimethyl-1H, 1H′-[4,4′]bis[naphtha[2,3-c]funanyl]-3,3′-dione, 6,8-dihydroxy-3,4-dimethoxy-1-methyl-
anthraquinone-2-carboxylic acid methyl ester, and 2-acetyl-3,6,8-trihydroxy-1-methyl anthraquinone were identified via bio-guided extraction
(20) (Xu,2006). Recent research also revealed eight bioactive compounds in the E. bulbosa bulb, including eleutherin, gallic acid, chlorogenic
acid, quercetin, kaempferol, rutin, epicatechin gallate, and myricetin (21) (Kamarudin,2020). Table 1 summarizes the major bioactive
constituents isolated from the E. bulbosa bulb.

Table 1. Chemical constituents isolated from Eleutherine bulbosa (Mill.) Urb. bulb.

Chemical Phytochemical IUPAC Names * Chemical Structures References

Constituents Family
(1R,3R)-5,10-dihydroxy-9- 10
Hongconin Naphthalene
methoxy-1,3-dimethyl-1H- Zhengxiong,1986
benzo[g]isochromen-4-one

Eleutherin Naphthoquinone (1R,3S)-9-methoxy-1,3-dimethyl- 18

3,4-dihydro-1H- Bianchi,1975
benzo[g]isochromene-5,10-dione

Eleutherol Naphthalene (3R)-4-hydroxy-5-methoxy-3- 18

methyl-3H- benzo[f][2]benzofuran- Bianchi,1975
1-one
 Table 1. Cont.

Chemical Phytochemical IUPAC Names * Chemical Structures References

Constituents Family
Eleutherol A Naphthoquinone 22
Chen,2018

Eleutherol B Naphthoquinone 22
Chen,2018

Eleutherol C Naphthoquinone 22
Chen,2018

Eleuthinones B Naphthoquinone 22
Chen,2018

Eleuthinones C Naphthoquinone 22
Chen,2018
 Table 1. Cont.

Chemical Phytochemical IUPAC Names * Chemical Structures References

Constituents Family
Eleutherinoside A Naphthalene 10-hydroxy-2,5-dimethyl-8- 23
[(2S,3R,4S,5S,6R)-3,4,5- Paramapojn, 2008
trihydroxy-6-(hydroxymethyl)oxan-
2- yl]oxybenzo[h]chromen-4-one

Eleuthoside B Naphthalene (3R)-5-methoxy-3-methyl-4 10,17

[(2S,3R,4S,5S,6R)-3,4,5- trihydroxy- Zhengxiong,1986
6-[[(2R,3R,4S,5S,6R)-3,4,5- Hara, 1997
trihydroxy-6-(hydroxymethyl)oxan-
2-yl]oxymethyl]oxan-2-yl]oxy-3H-
benzo[f][2]benzofuran-1-one

Naphthoquinone 6-methoxy-2-methyl-1,2,4,4a- 10,17

Elecanacin tetrahydro-3aH- Zhengxiong,1986
naphtho[2′,3′:2,3]cyclobuta[1,2- Hara, 1997
b]furan-5,10-dione
 Table 1. Cont.

Chemical Phytochemical Family IUPAC Names * Chemical Structures References

Constituents
Naphthoquinone 8-methoxy-1-methyl-1,3-dihydro- 24
Eleutherinone naphtho(2,3- c)furan-4,9-dione Alves, 2003

24
(1R,3R)-9-methoxy-1,3-dimethyl-3,4- Alves, 2003
Isoeleutherin Naphthoquinone
dihydro-1H-benzo[g]isochromene-5,10-
dione

Eleucanainones Naphthoquinone 25
A Chen,2020

Eleucanainones Naphthoquinone 25
B Chen,2020
5. Pharmacological Activities

The following is a description of various pharmacological activities of E. bulbosa (EB) from several studies presented in table form. There are
several advantages to presenting these activities in table format. First, it allows for easy comparison of different studies and their findings.
Second, it provides a clear and concise summary of the pharmacological properties of E. bulbosa. Third, it can aid in identifying potential
therapeutic applications for this plant. Finally, it can serve as a useful reference tool for researchers, clinicians, and others interested in the
pharmacological properties of E. bulbosa.

Table 2. Pharmacological Activity of E. bulbosa as Chemotherapeutics: Potential Cytotoxic Agent

Compound / Object of Test Dose/Amount Pharmacological Other Findings Ref.

Sample of EB Activity
E. bulbosa Retinoblastoma IC50 value of Markedly Compared to non-optimised extract (p < 26
ethanolic bulb cancer cells 15.7 μg/mL suppressed 0.01). Induced apoptosis-like membrane Kamarudin,
extract proliferation of blebbing, chromatin condensation, and 2021
cancer cells formation of apoptotic bodies in a dose-
dependent manner. Upregulation of Bax,
Bad, p53, Caspase 3, Caspase 8, and Caspase
9 genes, and downregulation of Bcl-2, BcL-xL,
Nrf-2, and HO-1 genes were observed.
Eleutherine Leukemia cells - Anticancer The IC50 value of the chloroform fraction on 27
bulbosa [Mill.] L1210 activity L1210 Leukemia cells was 9.56 ppm (very Lestari,2019
Urb. fractions strong category). GC-MS analysis of the
(ethanol chloroform fraction detected compounds
extract, n- such as hexadecanoic acid, 9,12-
hexane, octadecadienoic acid, linolenic acid,
chloroform, and octadecanoic acid, androstan-17-one, and 1-
water fraction) (2,3,5,6-tetramethylphenyl)- ethanone.
E. bulbosa bulb HeLa cervical cancer 10 ppm + 50 nM, Synergistic Good combinative index recorded 28
extract + cells 15 ppm + 50 nM cytotoxic effect Mutiah,2019
Doxorubicin
 Table 2. Cont.

Compound / Sample of Object of Test Dose/Amount Pharmacological Activity Other Findings Ref.
EB
E. palmifolia and HeLa cancer N/A Potent synergistic activity, Potential 29
Macrosolen cells induced cell cycle arrest and chemotherapeutic Mutiah,2018
cochinchinensis apoptosis agent
E. bulbosa bulb hexane Dalton’s Ascites LC50 67.97 µg/mL, Promising cytotoxic effects N/A 30
and ethyl acetate Lymphoma LC50 41.02 µg/mL Rani,2017
extracts (DLA) cell line
E. bulbosa bulb Adenocarcinoma IC50 56.15 µg/mL Selective cytotoxic effect Ethyl acetate and 31
n-hexane extract colon cancer ethanol extracts Lubis,2017
cells (WiDr) less effective
Eleutherinoside C and HCT116, DLD1, N/A Selective cytotoxic properties, Compared to 32
Isoeleutherin and SW480 inhibition of transcription of quercetin as Li,2009
compounds colon cancer TCF/ß-catenin positive control
cells

Endocrine Disorder: Diabetes Mellitus

Diabetes mellitus is a severe endocrine disorder characterized by chronic hyperglycemia, causing multiple vascular complications and cardiac
dysfunction (33) (Sharma,2020). In addition, studies have shown that the increased glucose level or hyperglycemia could lead to various
endothelial dysfunctions, e.g., dysregulation of endothelial proliferation, migration, and apoptosis (34) (Dong,2017). Therefore, therapeutic
approaches should be enhanced to prevent hyperglycemic-induced oxidative stress, to reduce the risk of diabetic complications (35)
(Teng,2018). Recent studies involving the E. bulbosa bulb would be discussed as a functional bioactive agent for diabetic research, in vitro and
in vivo.

Table 3. Pharmacological Activity of E. bulbosa on Endocrine Disorder: In Vitro Studies

Compound / Sample of EB Test Object Dose/Amount Pharmacological Other Information Ref.

Activity
New naphthalene derivatives Human N/A Protective effect Potential therapeutic effect 22
(eleutherol A, B, and C, umbilical vein against high against hyperglycemia Chen,2018
eleuthinone B, and C), endothelial glucose levels
hongconin, Karwinaphthol A, cells (HUVECs)
dihydroisoeleutherin

Table 3. Cont.

Compound / Sample Test Object Dose/Amount Pharmacological Other Information Ref.

of EB Activity
36
E. americana bulb N/A 50 µg/mL Insulin-induced Potential efficacy for diabetic
glucose uptake- treatment by promoting insulin Lahrita,2015
enhancing activity sensitivity
4
Eleutherinoside A, α-glucosidase IC50: 0.5 mM α-glucosidase Eleutherinoside A is the main
Eleutherol, (Eleutherinoside A), inhibition inhibitory compound for α-glucosidase Ieyama,2011
Eleuthoside B IC50 > 1.0 mM activity with relatively low inhibition
(Eleutherol, compared to acarbose. Potential for
Eleuthoside B) diabetic management.

Table 4. Pharmacological Activity of E. bulbosa on Endocrine Disorder: In Vivo Studies

Sample of EB Test Subject Dose/Amount Pharmacological Activity Other Findings Ref.
E. palmifolia Alloxan-induced Not specified Improved blood glucose levels in Did not affect 37
aqueous and rats diabetic rats; Reduced total overall body Febrinda,2014
ethanolic bulb cholesterol and LDL levels in diabetic weight
extracts rats; Increased serum albumin levels
in diabetic rats
Methanolic extract Swiss albino rats Not specified Reduced glucose tolerance level; Reflux and 38
of E. palmifolia bulb More effective than glibenclamide in maceration Ahmad,2018
reducing glucose levels methods were
most effective
E. bulbosa bulb Alloxan-induced 400 mg/kg Protected kidney from degeneration - 39
extract Wistar rats and necrosis compared to positive Nur,2017
control metformin
Infectious Disease: Microbial Activity
The infectious disease accounts for approximately a quadrant of overall mortality cases worldwide annually (40) (Fauci,2020). All infectious
pathogens like viruses, bacteria, fungi, protozoa, and worms, share a similar pathologic feature by colonizing the host cells. Therefore, natural
products have been extensively studied to overcome resistance and the newly emerging pathogens. For example, the bulb of E. bulbosa has been
reported as an excellent anti-microbial agent due to its leading bioactive compounds such as naphthalene, anthraquinone, and naphthoquinone.

Table 5. Pharmacological Activity of E. bulbosa as Anti-Bacterial

Sample of Test Object Dose / Pharmacological Activity Other Details Ref.
EB Amount Information
E. bulbosa Litopenaeus 12.5 g/kg Significant increase in immunity Increased total hemocyte count,
bulb vannamei response and resistance towards phenoloxidase activity, respiratory burst, total 41
extract Vibrio parahaemolyticus infection bacterial count, and gene expression activity Munaeni,
like prophenoloxidase (proPO), 2020
lipopolysaccharide- and β-1,3-glucan-binding
protein. The extract can suppress V.
parahaemolyticus in the intestines, hepato-
pancreas, and muscles, thus increasing the
survival rate of white shrimp. Inhibitory
against Vibrio harveyi.
E. bulbosa Staphylococcus - Moderate inhibitory activity Active fractions extracted from the E.
bulb aureus, against E. coli with MIC value of bulbosa bulb. Eleubosa A and B compounds 42
extract Escherichia 12.5 µg/mL. Mild inhibitory present. Jiang,2020
coli, and activity against S. aureus and P.
Pseudomonas aeruginosa with MIC values of 25
aeruginosa µg/mL
E. E. coli 10% - 100% Inhibited the growth of E. coli Compared to the positive control,
palmifolia concentration significantly with an inhibition ceftriaxone (35 mm). 43
bulb diameter of 6 mm at the lowest Mahmudah,
water concentration of 10% and 30 mm 2019
extract at the highest concentration of
 100%

Table 5. Cont.

Sample of EB Test Object Dose / Pharmacological Other Details Ref.

Amount Activity Information
E. americana Campylobacter spp. 250 µg/mL Prevented the No significant cytotoxic effects. The
bulb extract on colon cancer cells adhesion and invasion extract could be a valuable source of 44
(Caco-2) effects of food preservative to control Sirirak,2019
Campylobacter spp. on Campylobacter contamination. Good
the Caco-2 cells antibacterial activity against all tested
isolates. Inhibition diameter ranging
from 10 to 37 mm. The MIC values
recorded were 31.25 to 500 µg/mL
and 62.50 to 1000 µg/mL for human
and chicken isolates of Campylobacter
spp. Inhibitory against MRSA, Bacillus
cereus, Shigella sp., and Pseudomonas
aeruginosa. Ethyl acetate extract
displayed the highest inhibition (10
mg/mL) on the growth of P.
aeruginosa and S. aureus compared to
cefadroxil (30 mg/mL).
Rhodomyrtus Campylobacter spp. - Mild antimicrobial Percentage inhibition of 36% and 16%,
tomentosa activity against 46% and 16% against human and 45
(Aiton) Hassk. Campylobacter spp. chicken sample isolates, respectively. Siri,2011
extract, The E. americana ethanolic bulb
Quercus extract displayed good antibacterial
infectoria G. activity against all tested isolates, with
Oliver extract, an inhibition diameter ranging from 10
and E. to 37 mm. The MIC values recorded
 americana were 31.25 to 500 µg/mL and 62.50 to
Merr. extract 1000 µg/mL for human and chicken
isolates of Campylobacter spp.
Inhibitory against MRSA, Bac

Table 6. Pharmacological Activity of E. bulbosa as Anti-Fungal

Compound / Test Object Dose/Amount Pharmacological Other Observations Ref.

Sample of EB Activity
E. palmifolia Candida albicans 200 mg/mL and Strong inhibitory Induced a change in membrane 46
n-hexane bulb and Trichophyton 20 mg/mL activities against the permeability and damage the cell Masfria,2019
extract mentagrophytes pathogens membrane of pathogens
E. bulbosa essential Malassezia furfur Concentration Inhibitory activity Lower inhibition compared to the 47
oil range: 3.125% to against M. furfur positive control ketoconazole Hayati,2019
50%
Eleutherin isolated T. mentagrophytes Not specified Significant inhibition Believed to have fewer adverse 2
from E. bulbosa against T. effects in topical application Kusuma,201
bulb mentagrophytes compared to miconazole 0
E. bulbosa bulb Clasdosporium Not specified Potent inhibitory Four bioactive compounds, i.e., 24
extract sphaerospermum activity in eleutherinone, eleutherin, Alves,2003
bioautography assay isoeleutherin, and eleutherol,
were isolated and demonstrated
potent anti-fungal activities
except for eleutherinone, which
was inactive.

Table 7. Pharmacological Activity of E. bulbosa as Anti-Viral

Compound / Sample Test Subject Dose/Amount Pharmacological Other Information Ref.

of EB Activity
Isoeleutherine and HIV IC50 values of 8.5 µg/mL Potential anti-viral Isolated from the bulb of E. americana; 17
Isoeleutherol and 100 µg/mL, agent against HIV More studies needed to validate the Hara,1997
respectively replication effectiveness of the bulb extract as
anti-viral agents
 Table 8. Pharmacological Activity of E. bulbosa as Anti-Malarial
Compound / Test Object Dose/Amount Pharmacological Other Findings Ref.
Sample of EB Activity
Ethyl acetate Bulb of E. plicata 10.22 ± 2.32 µg/mL Good anti-plasmodial Compared to positive control (chloroquine) 48
extract activity Vale,2020
Eleutherin Bulb of E. plicata 10.45 ± 3.13 µg/mL Good anti-plasmodial Naphthaquinone compound responsible for 48
activity anti-plasmodial activity
Isoeleutherin Bulb of E. plicata 8.70 ± 2.45 µg/mL Good anti-plasmodial Naphthaquinone compound responsible for 48
activity anti-plasmodial activity
S2 fraction Bulb of E. plicata 3.67 ± 1.01 µg/mL Good anti-plasmodial Naphthaquinone compounds responsible for 48
(eleutherin + activity anti-plasmodial activity
isoeleutherin)
Note: In silico analysis through molecular docking suggested isoeleutherin and eleutherin as potential anti-malarial drugs causing mitochondrial damage
on the parasite

Table 9. Pharmacological Activity of E. bulbosa as an anti-hypertensive agent

Sample of EB Test Object Dose/Amount Pharmacological Activity Other Information Ref.
E. bulbosa or Hypertensive N/A or Supportive therapy to This study used a quasi-experimental research design
patients, 49
E. americana not specified reduce and stabilize blood pre-post-test with a control group design, involving
Merr Tablet Number of pressure 30 respondents. Data collection was carried out for 1 Waras,202
respondents: Significant decrease in month. Then blood pressure observations were 1
30 systolic and diastolic carried out every 1 week for a month after giving E.
blood pressure in americana tablets. The sampling technique was
patients with suspected purposive sampling method. The data analysis used
hypertension who was the Independent Sample T-Test with a
obtained E. americana significance level of p < 0.05.
tablets. Most respondents were in the elderly age range of
56-65 years old, and 60% were female. Majority had
hypertension Grade 1 (57%) and Grade II (43%). The
study found a significant difference in blood pressure
before and after taking E. americana tablets in
 hypertensive patients based on independent sample
t-test results (p < 0.005) with p-values of 0.029 for
systole and 0.000 for diastole.

Anti-Inflammatory Activities
Felix Hoffman was the first German chemist who created the world’s most usable therapeutic agent, aspirin, back in sesquicentennial (50)
(Dinarello,2010). It acts as an inhibitor of cyclooxy- genase (COX) enzymes like COX-1 and COX2 by blocking the inflammatory mediators, i.e.,
prostaglandins and thromboxane (50)( Dinarello,2010). Many inflammatory mediators occur during inflammatory responses upon harmful stimuli that
trigger the immune system’s alarm on the injured tissues. Pro-inflammatory cytokines like tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and
vascular endothelial growth factor (VEGF) are the primary drivers during the dynamic inflammatory responses (49)( Dinarello,2010). Alternative
approaches to current anti-inflammatory drugs for chronic diseases are necessary due to their concomitant side effects on the glucocorticoid hormone
cortisol in the long run. Plants, being abundant and cost-effective, could be a promising avenue in drug discovery.

Table 10. Pharmacological Activity of E. bulbosa as Anti-Inflammatory: Rheumatoid Arthritis

Sample of EB Test Subject Dose/Amount Pharmacological Activity Other Ref.
E. bulbosa Collagen antibody- 500 mg/kg Slight decrease in arthritis score No significant difference 51
ethanolic bulb induced arthritis compared to 1000 mg/kg after Hanh,2018
extract mice 10 days
E. bulbosa Collagen antibody- 1000 mg/kg Reduced incidence of arthritis, inflammation, No toxicity at highest dose of 51
ethanolic bulb induced arthritis swelling, and redness; reduced edema and 5000 mg/kg
extract mice infiltration of inflammatory cells in joints;
suppressed pro-inflammatory cytokines (TNF-α
and IL-6)
E. bulbosa LPS-induced RAW 27.30 µg/mL Potent inhibitory effect on nitric oxide production - 51
ethanolic bulb 264.7 macrophages
extract

Table 11. Pharmacological Activity of E. bulbosa as Anti-Inflammatory: Erythrocyte Membrane Stabilization

Sample of EB Test Subject Dose/Amount Pharmacological Activity Other Ref.
E. bulbosa In vitro: EC50 value of Potential anti-inflammatory -
ethanolic bulb Erythrocyte 52.87 µg/mL activity compared to 52
extract membrane indomethacin (EC50 value of Paramita,2018
stabilization 26.39 µg/mL)
 Table 12. Pharmacological Activity of E. bulbosa as Anti-Inflammatory: Lipopolysaccharide-Induced (LPO) Nitric Oxide Production

Compound / Sample of Test Object Dose/Amount Pharmacological Activity Other Information Ref.
EB
Isoeleutherin isolated LPS- Not specified Inhibition of NO production in a Cell viability recorded more than
from E. americana bulb stimulated dose-dependent manner, 95% survival, non-cytotoxic 53
Song,2009
RAW 264.7 inhibition of iNOS and pro-
macrophage inflammatory cytokines mRNA
cells expression, inhibition of NF-κB
transcriptional activity
Isoeleutherin, eleutherin, LPS-activated Not specified Potent inhibitory activity on NO Compounds with 54
hongconin, mouse production with IC50 values of naphthoquinone and Han,2008
dihydroeleutherinol, and macrophage 7.7-34.4 µM, stronger inhibitory naphthalene groups with pyran
eleutherinol isolated RAW 264.7 activity than positive control N- or lactone rings were excellent
from E. americana bulb cells methylarginine (L-NMMA) for inhibiting NO production

Table 13. Pharmacological Activity of E. bulbosa as Anti-Inflammatory: Activation of CD4+ T Helper (Th) Cells

Compound / Sample of Test Object Dose/Amount Pharmacological Activity Other Ref.

EB
Isoeleutherin T-cell receptor (TCR) 10 µM Increased interferon-gamma Did not affect IL-2 55
stimulated cells (IFNγ) production at 24 and 48 h production Hong,2008
post-stimulation; enhanced IFNγ
and T-bet expressions in a
concentration-dependent
manner; modulated IFNγ
production in a T-bet dependent
manner
Eleutherinol T-cell activation - Inhibited IFNγ and IL-2 - 55
 production in a semi-quantitative Hong,2008
RT-PCR significantly

Table 14. Pharmacological Activity of E. bulbosa on Wound Healing

Sample of EB Test Object Dose/Amount Pharmacological Other Findings Ref.

Activity
E. palmifolia Sprague–Dawley Not specified Gradual wound healing - Packed with granulated tissues like 56
gel extract mice with alveolar activity fibroblast and collagen on day 3. Rezandaru,2020
osteitis-induced - Trabecular teeth bone formed at
wound the apical edge, reaching the center
of the socket.
- Trabecular bone almost developed
and filled the socket on day 5.
- Trabecular bone covered nearly the
whole inflamed socket at day 10.
- Effectiveness significantly similar to
the positive control, iodoform paste.
Eleutherine Wistar rats with Not specified Safe for topical - Granulated connective tissues 57
indica cutaneous wound application with no noticeable after three days post- Upadhyay,2013
methanolic symptoms of irritation injury
bulb extract and inflammation - Wound contraction of 50% to 87%.
- Higher hydroxyproline level
compared to non-treated and vehicle
control
- Well-regulated wound healing
activity in treated groups compared
to non-treated and vehicle control.
- Increased collagen layering and
rapid keratinization with
intraepithelial cornification on day 15
- Increase in granulation proteins
responsible for connective tissue
 assembles caused by the E. indica
methanolic bulb extract.

Table 15. Pharmacological Activity of E. bulbosa as Anti-Melanogenesis

Compound / Test Object Dose/Amount Pharmacological Activity Other Findings Ref.
Sample of EB
Eleutherin from B16 melanoma 5-50 µg/mL Suppresses melanin Safe for further study 2
E. americana cells formation with 35-87% Kusuma,2010
inhibition
E. palmifolia B16 melanoma 50 µg/mL 57.3% inhibition of melanin Not toxic to cells; caused by high 58
bulb extract cells formation DPPH radical scavenging activity Arung,2009
E. palmifolia UV-induced - Low melanin index and H2O2 Increased erythema and 59
ethanolic bulb rats level tyrosinase index, potential anti- Biworo,2019
extract melanogenesis therapeutic agent

Table 16. Pharmacological Activity of E. bulbosa as Antioxidant

Sample of EB Test Object Dose/Amount Pharmacological Activity Others Ref.
Eleutherine bulbosa DPPH assay IC50 value of Antioxidant activity Very strong category 27
[Mill.] Urb. 19.694 ppm Lestari, 2019
chloroform fraction
E. bulbosa bulb DPPH assay IC50 1.48 Potent antioxidant activity, Strong antioxidant activity 60
µg/mL stimulated the growth of compared to ascorbic acid Munaeni,2020
probiotic bacteria
E. bulbosa bulb Probiotic - Prebiotic and antioxidant Extract could stimulate the 1
extract bacteria growth of probiotic Kamarudin,2021
bacteria
E. bulbosa bulb DPPH and ABTS - Antioxidant Strong antioxidant activity 21
extract assays under optimized Kamarudin,2020
extraction conditions
E. bulbosa bulb Mice - Antioxidant Antioxidant activity could 1
improve the quality of Kamarudin,2021
sperm in mice
E. bulbosa bulb Lead acetate- - Increased sperm concentration Significant increase in 61
induced mice sperm concentration Jayanti,2019
E. bulbosa bulb UV-induced skin - Antioxidant E. palmifolia increased 62
oxidative SOD level, while lowering Chiang,2014
damage in rats MDA and AOPP
production

Table 16. Cont.

Sample of EB Test Object Dose/Amount Pharmacological Activity Others Ref.

E. bulbosa bulb HepG2 cells - Antioxidant High peroxyl radical 63
scavenging capacity Shi,2019
E. bulbosa bulb HepG2 cells Dose-dependent High phenols and flavonoids Fluorescent intensity 1
contribute towards its potent emitted by the DCFH Kamarudin,2021
antioxidant activity probe increased in a dose-
dependent manner
E. bulbosa bulb Not specified Ethanolic extract: Higher total phenolic and Ethanolic extract showed 64
27.12 mg GAE/g DW; flavonoid content in ethanolic high antioxidant activity Morabandza,
Aqueous extract: extract (IC50) with 0.595 mg/mL 2016
not specified compared to aqueous
extract with 1.251 mg/mL.
Significant fungal
inhibition by ethanolic
extract compared to
fluconazole.
E. bulbosa bulb Not specified 70% methanol Most effective solvent for DPPH radical scavenging 65
extracting polyphenols with a activity revealed an IC50 Agustin,2016
phenol content of 20 mg value of 39.06 µg/mL
GAE/g DW and flavonoid
content of 15.03 mg QE/g DW
 Table 17. Pharmacological Activity of E. bulbosa on the Reproductive System Disorders
Compound / Test Object Dose/ Pharmacological Other Information Ref.
Sample of EB Amount Activity
E. bulbosa extract Menstrual pain and N/A Used in treating Further pharmacological studies should
66
certain female menstrual pain be investigated as the information to
complaints and certain female support the study is still scarce. Lans,2007
complaints
E. bulbosa bulb Mouse N/A Anti-fertility -
Weniger,1982
potential
E. bulbosa bulb and Ovariectomized N/A Elevated calcium Synergistic effect reported. Potential
68
cowpea extract rats level and weight of application could be further extrapolated
bone, alleviated in osteoporosis management in post- Bahtiar,2019
fat in bone menopausal women
marrow
E. bulbosa bulb Hypoestrogenic N/A Increased calcium -
69
rats level, weight, and
bone length Bahtiar,2018
E. bulbosa bulb Ovariectomized N/A Reduced lipids Other studies indicated this finding 70
rats Purnama,2018
Conclusions
This review provides an overview of E. bulbosa, including its botanical characteristics, phytochemistry, and pharmacological
properties presented in the form of a table. Multiple scientific names have been used in different countries to collect relevant
information. Pharmacological studies on the bulb of E. bulbosa have demonstrated potential cytotoxic, anti-hypertensive,
anti-diabetic, anti-microbial, anti-inflammatory, anti-melanogenesis, anti-oxidant, and reproductive system disorder
treatment effects, both in vitro and in vivo. The presence of bioactive compounds like naphthalene, anthraquinone, and
naphthoquinone may contribute to its potent pharmacological activities. However, further high-quality studies are needed
to understand the mechanism of action in greater depth, particularly in animal and human models.

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