A REVIEW: HERBAL ANTI-CANCER DRUGS

Minor Project Report

submitted to

RAJIV GANDHI PROUDYOGIKI VISHWAVIDYALAYA, BHOPAL

(State Technological University of Madhya Pradesh, India)

in partial fulfillment of the requirement for the award of the degree of

BACHELOR OF PHARMACY

Submitted by

Alok Pandey
B.Pharm VII semester
Enrollment No.:
Under the Guidance of

Mr. G.K.Pandey
Associate Professor, Dept. of Pharmaceutics

TECHNOCRATS INSTITUTE OF TECHNOLOGY – PHARMACY EDUCATION & RESEARCH

ANAND NAGAR ,BHOPAL –21. MADHYA PRADESH

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 TECHNOCRATES INSTITUTE OF TECHNOLOGY PHARMACY
EDUCATION AND RESEARCH, BHOPAL

(Approved by AICTE, New Delhi)

(Affiliated to Rajiv Gandhi Proudhyogiki Vishwavidyalaya, Bhopal)

CERTIFICATE

This is to certify that the work embodied in this thesis entitled, A REVIW: HERBAL
ANTI-CANCER DRUG is prepared by ALOK PANDEY and submitted to R.G.P.V.,
Bhopal Under my Guidance in the Technocrates Institute of Technology Pharmacy Education
and Research, Bhopal for the partial fulfillment for the degree of BACHELOR OF
PHARMACY under my supervision.

This work is original has not been previously formed the basis for the award of other degree,
diploma, associate ship, fellowship or any other similar title and the dissertation represent
entirely an independent work on the part of the Candidate.

Principal Mr. G. K. Pandey

T.I.T. P.E.R Asst. Professor,

Bhopal Dept. of Pharmaceutics,

Technocrats Institute of Technology

Pharmacy Education and Research
Bhopal

Place: Bhopal
Date:

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 TECHNOCRATES INSTITUTE OF TECHNOLOGY PHARMACY
EDUCATION AND RESEARCH, BHOPAL

(Approved by AICTE, New Delhi)

(Affiliated to Rajiv Gandhi Proudhyogiki Vishwavidyalaya, Bhopal)

DECLARATION

The work presented in this thesis entitled “A REVIEW: HERBAL ANTI-CANCER

DRUGS” was carried out by me at Technocrats Institute of Technology Pharmacy Education
and Research, Bhopal under the supervision of Mr. G. K. Pandey, Asst. Prof., Dept. of
Pharmaceutics, T.I.T.P.E.R , Bhopal. This work is original & has not been submitted in part
or full for the award of other degree or diploma of any other university.

Place: Bhopal

Date

Alok Pandey

VII Semester

T.I.T.P.E.R, Anand Nagar

Bhopal

AKNOWLEDGMENT
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First, I would like to express my salutation to God for giving me the strength, confidence in
moral boost to successful completion of this project.

Numerous people have been instrumental in enabling me to give a concrete shape to my

thesis. However, I must mention the names of few people who have made catalytic impact on
the development of this project.

First and foremost, I would like to acknowledge the continuous encouragement and help
extended to me by Mr. G.K.Pandey sir , for preparing this project. He has been my soul guide
and philosopher throughout the period of my work. His extensive knowledge of the subject
and the way he imparted the same to me has enabled me to develop the thesis in a cohesive
manner and kindled within me a passion for the subject.

I wish to thank Mr. Amit JAIN sir for providing the necessary facilities and constant
inspiration throughout my studies of B. Pharm. I take this opportunity to place on record my
indepthness to Mr .Salaj Khare sir for helping me when I needed.

I am also thankful to my parents who lead me from darkness to light, ignorance to enlighten,
confusion to clarity throughout my life.

I am specially thankful to my friends and classmates for their tremendous corporation

throughout my studies.

Date: ……………… Student’s Name: Alok Pandey

Place: Bhopal Enrollment no:

TABLE OF CONTENT

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 PARTICULARS PAGE NO.
S.NO.
1. Acknowledgment
2. Abstract
3. Chapter-I
Introduction
1.1Causes of Cancer
1.2 Environmental Factors
1.3 Ayurvedic Concept of Cancer
4. Chapter-II
Plants used for cancer treatment
2.1 Anticancer Herbs
2.1.1 Autumn Crocus
2.1.2 Birch
2.1.3 Camptotheca
2.1.4 Hemp
2.1.5 Curcumin from turmeric
2.1.6 Cyanidins from Grapes
5. Chapter-III
Future Developments
3.1 WHO Role in developing Herbal Medicines
6. Chapter-IV
Conclusion
7. Chapter V
Refrences

ABSTRACT

This article has been made to review some medicinal plants used for the treating cancer
disease. The plant sources of India are likely to provide effective anticancer agents. Herbs
have a vital role in the prevention and treatment of cancer.

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Examples are provided in this review of promising bioactive compounds obtained from
various plants with medicinal and other therapeutic uses. The photochemical exploration of
these herbs has contributed to some extent in this race for the discovery of new anticancer
drugs. In recent years owing to the fear of side effects people prefer to use of natural plant
products for cancer treatment.

This review also helps to summarize the diverse methodologies and various ways to evaluate
the potential natural compounds having anticancer activity. Although drug discovery from
medicinal plants continues to provide an important source of new drug leads, numerous
challenges are encountered including the procurement of plant materials and their selection.

Keywords: Medicinal plants, Anticancer agents, Bioactive compounds.

Literature Review:

1. Medicinal Plants as Potential Source of Anticancer Agents: A Review, Journal of

Pharmacognosy and Phytochemistry, Author-A M Shaikh, Dr B Shrivastava, Dr
K G Apte, S D Navale

The authors of this research paper concluded that herbal medicinal plants and its derivatives
are active against different type of cancers like lymphomas, breast, ovarian, lung, liver,
stomach, prostate and testicular cancers. The cheap herbal drug treatment may highly be
recommended to the rural and poor people to treat effectively the cancers of various type is
an ideal choice. The authors of this research paper also revealed the role of Indian medicinal
plants and the various phytochemicals may be treated effectively for cancer. In an attempt of
screening the traditional medicinal plants for anticancer activity the presence of several
bioactive compounds such as flavonoids, polyphenols, saponins, etc. with specific anticancer
activity against particular type of cancer, hence the huge space are available for development
of strong anticancer agents from plant derivatives.

2. A review of Anticancer Properties of Herbal Medicines, Authored by Alireza

Shabani

The author of this research paper explained that today, more than 50% of drugs are derived
from plants so it is crystal clear that natural resources, especially plants could be drastically
used to find effective drugs for cancer treatment.

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Author in this research paper concluded the research paper on the note that today using new
techniques have been accelerated active plant compounds extraction and this in turn has been
recycled medicinal plants. The rebirth of medicines that originated in plants especially ones
used for cancer treatment and autoimmunity is remarkable. Author suggested that since there
is little information about the usefulness and safety of plant production compared to products
commonly consumed more research can improve the appropriate use of herbal preparations.

3. Important herbs in treatment of cancer, international journal of research and

development in pharmacy and life sciences, authored by R Das, D.K. Mehta, A.K
Chaudhary and M.U. Khan

From the present review, it can be concluded that cancer is the leading cause of death in
developing countries like India. As there is an enormous increase in the population day by
day, the alternative therapy in the market is getting its glimpse. The cheap herbal drug
treatment may highly be recommended to the rural and poor people to treat effectively the
cancers of various type is an ideal choice. Based on that the siddha medicines are coming up
in combination with metals and other essential supplements to improve the immune status of
the cancer patients in India. The above survey reveals the role of Indian medicinal plants and
the various phytochemicals that may be used effectively for cancer treatment. The available
literature finds to be very impressive which may give an indication for the therapeutic
usefulness. Only few of the plants listed here and there are hundreds of plants unexplored
need much detailed survey. The isolation, identification of active principles and
pharmacological studies of the active phytoconstituents may be considered and studied
elaborately to treat effectively various types of cancer.

RESEARCH METHODOLOGY

I have analyzed Herbal Anticancer Drugs based on information obtained from internet,
studied concerned articles and journal and creating database from secondary data processing.
This chapter of the thesis describes the population & the subjects of the study, data collection,
the measuring instrument, tool, & the analysis method.

The study has been done on the basis of secondary data collected from internet search and
literature survey, analyzed the data of national drug regulatory authority, world health
organization.

OBJECTIVE OF THE STUDY

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The main objective of the present study is to isolate the potent anticancer compound from the
anti-cancer drugs. To study the effectiveness of herbal anti-cancer drugs. To determine the
toxic potential and safety of active compound present in herbal anticancer drug.

HYPOTHESIS OF THE STUDY

“Natural” and Herbal Anticancer Drug therapies should be regarded with great caution
because most are unsupported by evidence. Many people offering testimonials to the
effectiveness of such treatments may attribute benefits to them simply because their condition
improved after using them — when the actual cause for the improvement is unrelated.

CHAPTER-I

INTRODUCTION

Cancer is a leading cause of mortality, and it strikes more than one-third of the world’s
population and it’s the cause of more than 20% of all deaths. It has been a constant battle
globally with a lot of development in cures and preventative therapies. The disease is
characterised by cells in the human body continually multiplying with the inability to be
controlled or stopped. Consequently, forming tumours of malignant cells with the potential

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to be metastatic1. Current treatments include chemotherapy, radiotherapy and chemically
derived drugs. Treatments such as chemotherapy can put patients under a lot of strain and
further damage their health. Therefore, there is a focus on using alternative treatments and
therapies against cancer2.
For many years herbal medicines have been used and are still used in developing countries as
the primary source of medical treatment. Plants have been used in medicine for their natural
antiseptic properties. Thus, research has developed into investigating the potential properties
and uses of terrestrial plants extracts for the preparation of potential nanomaterial based drugs
for diseases including cancer. Many plant species are already being used to treat or prevent
development of cancer. Multiple researchers have identified species of plants that have
demonstrated anticancer properties with a lot of focus on those that have been used in herbal
medicine in developing countries.
Compounds which are characteristic to the plant kingdom and are necessary for plant survival
and “housekeeping” of the organism are being investigated for their ability to inhibit growth
and initiate apoptosis of cancerous cells. This article aims to take an overview of current plant
derived compounds that have anticancer therapeutic properties and their developments in the
field.
Among the causes for cancer are tobacco, viral infection, chemicals, radiation, environmental
factors, and dietary factors.3Surgery, chemotherapy and radiotherapy are the main
conventional cancer treatment often supplemented by other complementary and alternative
therapies in China.4 Plants has been used as an age old remedy of cancer history of use in the
treatment of cancer. Extensive
research at Sandoz laboratories in Switzerland in the 1960s and 1970s led to the development
of etoposide and teniposide as clinically effective agents which are used in the treatment of
lymphomas, bronchial and testicular cancer.5These plants may promote host resistance
against infection by re-stabilizing body equilibrium and conditioning the body tissues.
Several reports describe that the anticancer activity of medicinal plants is due to the presence
of antioxidants present in them. In fact, the medicinal plants are easily available, cheaper and

1
Ochwang’I DO, Kimwele CN, Oduma JA, Gathumbi PK, Mbaria JM, Kiama SG. Medicinal plants used in
treatment and management of cancer in Kakamega County Kenya. Journal of Ethnopharmacology.(2014) Pg
No. 1040–1055. Last visited on 21.11.2018 at 3:30 P.M.
2
 Cancer Research UK ,What is cancer? (2014 ) Available http://www.cancerresearchuk.org/about-cancer/what-
is-cancer. Last Visited on 23 November, 2018 at 2:19 P.M.
3

4
Freiburghaus F, Kaminsky R, Nkunya MHH, Brun R. Evaluation of African plants for their in
vitrotrypanocidal activity. Journal of Ethnopharmacology. 1996;55:1–11.
5
Jena J. A Study on Natural Anticancer Plants. Int J Pharmaceut Chem Sci . 2012;1(1):365–8.

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possess no toxicity as compared to the modern (allopathic) drugs. 6The development of novel
plant- derived natural products and their analogs for anticancer activity details efforts to
synthesize new derivatives based on bioactivity- and mechanism of action-directed isolation
and characterization coupled with rational drug design – based modification.

Oncogenes are regulators of cellular communication with the outside environment. They are
derived through the mutation of proto-oncogenes. Mutated oncogenes are stimulated by
exposure to chemical, environment or viral carcinogens, which leads to cell changes and they
produce proteins which are either wrongly expressed within their normal cell or expressed in
inappropriate tissue which leads to cellular proliferation and there by result in cancer
formation . Tumor suppressor genes are intended to keep oncogenes in check by halting
uncontrolled cellular growth. In direct opposition of oncogenes, which induce cancer when
stimulated and amplified, tumour suppressors genes promote cancer when inactivated or
attenuated. Two of the most prevalent tumours suppressors genes involved in the generation
of cancer are p53 and retinoblastoma or Rb.7

1.1 WHAT CAUSES CANCER?

Cancer begins with mutations in DNA, which instructs the cells how to grow and divide.
Normal cells have the ability to repair most of the mutations in their DNA, but the mutation
which is not repaired and causing the cells to grow becomes cancerous 8.

1.2 ENVIRONMENTAL FACTORS

Environmental factors which, from a scientist’s standpoint, include smoking, diet, and
infectious diseases as well as chemicals and radiation in our homes and workplace along with
trace levels of pollutants in food, drinking water and in air. Other factors which are more

6
Dhorajiya BD, Patel JR, Malani MH, Dholakiya BZ. Plant product (R)- Roscovitine valuable inhibitor of
CDKs as An anti-cancer agent. Der Pharmacia Sinica . 2012;3(1):131–43.
7
Pal SK, Shukla Y. Herbal medicine: current status and the future. Asian Pac J Cancer Prev . 2003;4(4):281–8
8
Krishnamurthi K. Screening of natural products for anticancer and antidiabetic properties. Health
Administrator. XX (1&2): 69, (2000).

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likely to affect are tobacco use, unhealthy diet, not enough physical activity, however the
degree of risk from pollutants depends on the concentration, intensity and exposure. The
cancer risk becomes highly increased where workers are exposed to ionizing radiation,
carcinomas chemicals, certain metals and some other specific substances even exposed at low
levels. Passive tobacco smoke manifold increase the risk in a large population who do not
smoke but exposed to exhaled smoke of smokers9.

1.3. AYURVEDIC CONCEPT OF CANCER

Charaka10 and Sushruta Samhita11 both described the equivalent of cancer as “granthi” and
“arbuda” “Granthi”and “Arbuda” can be inflammatory or devoid of inflammation, based on
the doshas involved . Three doshas “Vata, Pitta and Kapha”in body are responsible for
disease and the balanced coordination of these doshas in body, mind and consciousness is the
Ayurvedic definition of health12. Tridoshicarbudasare usually malignant because all three
major body humors lose mutual coordination, resulting in a morbid condition 13. Neoplasm
can be classified in Ayurveda depends upon various clinical symptoms in relation to
tridoshas.

Group I: Diseases that can be named as clear malignancies, including arbuda and granthi,
such as mamsarbuda (sarcomas) and raktarbuda (leukaemia), mukharbuda (oral cancer), and
asadhya vrana (incurable or malignant ulcers).

Group II: Diseases that are not cancers but can be considered probable malignancies, such as
ulcers and growths. Examples of these are mamsaja oshtharoga (growth of lips), asadhya
galganda (incurable thyroid tumour), tridosaja gulmas, and asadhya udara roga, (abdominal
tumours like carcinomas of the stomach and liver or lymphomas).

Group III: Diseases in which there is a possibility of malignancy, such as visarpa, asadhya
kamala (incurable jaundice), asadhya pradara (intreatable sinusitis).

9
Ibid.
10
Charaka. Charaka Samhita. Chaukhamba Publications, Varanasi, India; 700 BC: 215.
11
Susruta. Susruta Samhita. Chaukhamba Publications, Varanasi, India ; 700 BC: 520.
12
Balachandran P, Govindarajan R., Cancer- an ayurvedic perspective. Pharmacology Research, 51. 19. 2005.
13
Singh R. H., An assessment of the ayurvedic concept of cancer and a new paradigm of anticancer treatment in
Ayurveda. Journal of Alternative & Complementary Medicine, 8. 609. 2002

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 CHAPTER-II

PLANTS USED FOR CANCER TREATMENT

Cancer is often deadly and affects a considerable number of people worldwide. Ongoing
research is being done throughout the world to seek out effective treatments for cancer,
including the use of plants to relieve and treat cancer patients. This treatment makes use of
the compounds naturally present in plants that are known to inhibit or kill carcinogenic cells.
An alternative to chemotherapy, which is the most common means by which doctors and
specialists treat cancer, organically based treatments may not have the severe side effects that
radial treatments and chemotherapy has.

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The harsh side effects of cancer treatments is one motivating factor to finding alternative
methods. The use of botanical when treating cancer patients is considered a natural
alternative, because some plants may contain properties that naturally have the ability to
prevent the spread or risk of developing various forms of cancer. As in all medical testing,
careful precautions and considerations are taken when studying the different compounds
present in plants that are known to treat cancer 14. Some examples of plants that may be used
for cancer treatment are discussed below with their respective advancements. Some side
effects are still expected, and it is important that any patient interested in exploring botanical
treatment seek the advice of a licensed medical professional. There are around 460 species of
plants that can be used as herb for remedy, including plant healer various types of cancer.
Various types of anti-cancer plant are Zedoary (Curcuma zedoaria), Rodent Tuber
(Typhonium flagelliforme), God’s Crown (Phaleria macrocarpa), Madagaskar Periwinkle
(Catharanthus rosens), Artocarpus Integer (Selaginella corymbosa), Bamboo Grass
(Loathatreum Gràcies) , handsome (Taraxacum mongolicum), fruit makasar (Brucca
javanica), Garlic (Allium sativum), Echo China (Smilax china), Sunflower (Helianthus
annus), Leunca (Solanum nigrum), Job’s Tears (Coix Lachryma-Jobi), Bamboo Rope
(Asparagus cochinchinensis), and others.

2.1 ANTICANCER HERBS

Anticancer herbs, there are many different anticancer herbs that have been used by different
cultures throughout time for medicinal purposes. In fact, much of modern medicine owes
itself to plants and herbs. With such a wide variety of herbs in the world it’s no surprise that
there are quite a few anticancer herbs that can really help with cancer prevention. There are
also many other anticancer herbs which will help to alleviate the symptoms if you already
suffer from cancer treatments.One of the many anticancer herbs is Alfalfa.15

14
Naveen Kumar DR, Cijo George V, Suresh PK, Ashok Kumar R. Cytotoxicity, apoptosis induction and anti-
metastatic potential of Oroxylum indicum in human breast cancer cells. Asian Pac J Cancer Prev
2012;13(6):2729–34.

15
Mukherjee AK, Basu S, Sarkar N, Ghosh AC. Advances in cancer therapy with plant based natural
products. Curr Med Chem . 2001;8(12):1467–86.

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Considered one of the most nutritious foods available, Alfalfa has very important uses for
counteracting the effects of chemotherapy. Alfalfa contains antibacterial and anti fungal
properties that make it a great body cleanser and infection fighter. It works to increase the
production of white blood cells and replace those lost during treatments. The large amount of
nutrients in these anticancer herbs makes them invaluable in restoring healthy levels of
vitamins in the blood stream. Alfalfa has been researched and found to help lower cholesterol
levels and neutralize cancer.Another anticancer herb is Andrographis. It is an ancient
medicinal herb and is an annual plant that grows in the wastelands and forests of Asia.

There have been many conclusive studies of its use against cancer, AIDS and both bacterial
and viral infections. This herb has been shown to have a dramatic effect in maturing cancer
cells, a process which seems to stop the cancer cells growing out of control. In addition,
extracts from Andrographis leaves have been recorded as being able to kill cancer cells.
Research done in Japan has reportedly found that Andrographis reduced the likelihood of
cancer cells in the stomach multiplying. Many independent studies have also discovered
impressive results with other cancers including prostate and breast cancer16.

Anticancer herbs come in many forms one of which is a type of thistle plant. Blessed thistle
has a hugely positive effect on the reduction in size of tumors due to its main component
cnicin. This has the effect of reducing fluid around the tumor, cooling any inflammation in
the body as well as fighting off bacteria. Not only this but the anti-inflammatory properties
help rejuvenate the body and speed up recovery one of the more well-known anticancer herbs
is Burdock. The root has been used in natural medicine for centuries.

Although it was originally used for liver function, joint pain and skin health burdock root has
been discovered to have anti-tumor effects alongside its detoxifying qualities. This has been
shown in animal studies where it was discovered that this anticancer herbs inhibits mutations
in cells that are exposed to mutation causing chemicals that can lead to cancer. Mushrooms,
although not really an herb, are still a very natural cure. As a fungus there are many qualities
that certain types of mushrooms possess that aren’t found in herbs. For example the Maitake
mushroom has excellent healing properties. Extracts of the mushroom are most effective
when used as Maitake D-fraction and is available in capsule or tablet form. Maitake is a
proven cancer fighter.

16
Roy MK, Kobori M, Takenaka M, Nakahara K, Shinmoto H, et al. (2007)Antiproliferative effect on human
cancer cell lines after treatment nimbolide extracted from an edible part of the neem tree. Phytother Res 21: 245-
250.

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The FDA has recently approved clinical studies of a Maitake extract on participants with
advanced breast and prostate cancer. American studies also show positive results on
colorectal cancer and Chinese studies show positive results with liver, lung, stomach cancer
and leukemia. These mushrooms should be used as a complementary therapy for such
conditions and not be a substitute for standard treatments. Anticancer herbs include the
garden variety rosemary that is found all over the place. Rosemary is a potent antioxidant,
antispasmodic and antiseptic. It is rarely respected for its powerful effect on the body.
Rosemary helps to prevent cancer from ever forming in the first place. It does this by helping
to prevent carcinogenic chemicals from attaching themselves to cells and causing the
mutations that lead to cancer. A number of green tea blends are also anticancer herbs and act
in a very similar way to rosemary.17

To make a tea infusion of Rosemary, pour 1 cup boiling water over 1 teaspoon of rosemary
leaves and steep for 15 minutes. Strain and drink. Half a teaspoon of cinnamon spice is also
known to aid the fight against cancer. These anticancer herbs are just a small percentage of
the plants that can benefit the body through healing. These herbs can be a preventative
measure to ensure the body has everything it needs to stop mutations from occurring in the
first place. They can also be used to lessen the horrible side effects when taken alongside
chemotherapy treatments. But most importantly they have been shown to reduce the effects
of cancerous cells and even reduce the size of tumors.18 With all the benefits these anticancer
herbs can provide you may want to start growing some in your own garden.

2.1.1 AUTUMN CROCUS

Species Name – Colchicum Autumnale

Common Names – Naked Ladies, Colchicum, and Meadow Saffron

The Autumn Crocus, of the Lily Family (Liliaceae), is a plant with small flowers of varying
colors. This plant is indigenous to Europe, Northern African, and Asian continents. Being a
plant with a history of medicinal use, records have shown that it had been used in Ancient
Greece, India, and Egypt with records being stored in the oldest medical text, known as the
Ebers Papyrus. At present, it is used to treat inflammatory disorders. 19 The Autumn Crocus is
also valued for its' chemotherapeutic properties. Compound – Colchicine
17
Paul SM, Mytelka DS, Dunwiddie CT, Persinger CC, Munos BH, Lindborg SR, Schacht AL. How to improve
R&D productivity: the pharmaceutical industry's grand challenge. Nat Rev Drug Discov. 2010;9(3):203–214.
18
Rajendran L, Knolker HJ, Simons K. Subcellular targeting strategies for drug design and delivery. Nat Rev
Drug Discov. 2010;9(1):29–42. doi: 10.1038/nrd2897.

15
Otherwise known as the alkaloid colchicine, its medicinal use was in the treating gout, a
painful disease that is the result of the joints being inflamed. The other major use of
colchicine is in its effect on the mitosis of animal and plant cells; it works by interrupting the
process altogether, especially in the division of cancerous cells. Some common reactions to
using cochicine are diarrhea and reversible malabsorption syndrome.

2.1.2 BIRCH

Species Name – Betula Alba

Common Name – Birch

The Birch or Betula Alba plant has a variety of different uses. Its medicinal use include
diuretic, anti-inflammatory, and a general pain reliever. There are currently several side
effects associated with the use of the birch leaf, including chest pains, tightness in the chest or
that that may cause breathing problems, and skin irritation. The Birch has sixty species
throughout the world, ten of which are native to Canada and the northern part of the United
States.20

Compound – Betulinic Acid

The effects of Betulinic Acid, as studied by Dr. Brij Saxena of Weill Cornell Medical
College, has been known to kill cancerous cells, and has been especially effective in the
treatment of prostate cancer patients. This compound does not cause side effects, in typical
patients. However the compound is being researched furhter for it's compatibility with
patients suffering from HIV.

2.1.3 CAMPTOTHECA

Species Name – Camptotheca Acuminata

Common Names – Xi Shu, Happy Tree

The Camptotheca, otherwise known as the Happy Tree, is a fern-like deciduous tree with a
variety of medicinal uses. From its scientific name, Camptotheca Acuminata , its genus
"Camptotheca" is Greek for "curved sheath" which resembles the pods that are formed in a
curve found in the plant. Although its used medically, Camptotheca is very unstable. It isn't
19
Sairam K, Rao CV, Babu MD, Kumar VK, Agarwal VK and Goel RK. Antiulcerogenic effect of ethanolic
extract of Emblica officinalis: An experimental study. J Ethnopharmacol. 2002;82:1-9.
20
Indian Medicinal Plants. Vol 2. New Delhi: Indian Council of Medical Research; 2004.

16
soluble in water and can be highly toxic, so special care should be taken to observe any
dangerous side effects and a patient's health should be carefully monitored by a medical
professional. Although Camptotheca has been used medically, it has since been discontinued
by many professionals due to the development of treatments with less sever side effects. The
side effects of Camptotheca are attributed to its compounds.21

Compound – Camptothecia, Topotecan, CPT-11, 9-Aminocamptothecin

Extracted from the Camptotheca Acuminata plant, CPT-11 is a compound administered in

patients with brain tumors through the drug Irinotecan. It contains antineoplastic, used to
prevent the mutation of cells into cancerous cells with the possibility of preventing or
reducing the disease into one that is benign. Some common side effects of this compound
include diarrhea, alopecia or hair loss, vomiting, weakness, and lowering of white and red
blood cells.

Species Name – Taxus Baccata

Common Name – Yew

The English Yew is an evergreen tree that flowers from March to April. Not selffertile, the
yew is known for attraction of wildlife. This plant can grow in almost any soil, but it is most
prominent in groups. This tree has known to be used in wood furniture, especially cabinets.
English Yew can also be used medicinally to treat chest pains. English Yew is also valued for
it's 'taxol' that has been found to effectively been used as treatment for ovarian cancer, as well
as less serious aliments.

Compound – Docetaxel, Taxol

Although toxic, the occasional use of the docetaxel in medicine has shown potential in being
an anti-cancer drug, especially in breast cancer cases. The toxicity of the compound requires
proper management to avoid the worsening of the situation. Other treatments that are possible
are cystitis, heart and kidney problems, and others. Common side effects of docetaxel are
constipation, dizziness, diarrhea, hair loss, loss of appetite, joint pain, as well as weakness in
different parts of the body. When these side effects persist, medical attention should be
sought right away.

21
Garg GP, Nigam SS and Ogle CW. The gastric antiulcer effects of the leaves of the neem tree. Planta Medica.
1993; 59:215-7.

17
2.1.4 HEMP

Species Name – Cannabis Sativa

Common Names – Marijuana, Bhang, Ganja, and Hashish

The Hemp is an annual herb that may reach 5 meters in height with leaves that form a fan-
like structure with jagged edges. This plant is native to central Asia and as a result of
importation, has expanded toward Europe and the Americas. This plant has many uses, some
of which are furnishing fiber, oil, in medicine, and narcotics. Commonly referred to as
Cannabis, Hemp is a very versatile material and is frequently used to relieve cancer pain,
treat depression, and hypothermia, it also works as an appetite suppressant. A controversial
plant in the field of medicine, it has been up for the debate of its use being an abused or
medically prosperous drug.22

Compound – Delta-9-Tetrahydrocannabinol Research has shown that the administering of

smoked marijuana helped treated the nausea that was caused by cancer chemotherapy,
thereby being an aid to the cancer treatment process. Side effects of this compound are not
often seen in the physical aspect, rather in the mental or cognitive domain such as inability to
distinguish space distances and time intervals, vigilance, and memory processes.

2.1.5 CURCUMIN FROM TURMERIC

Curcumin (diferuloylmethane) is the major components of popular Indian spice

turmeric, Curcuma longa L., a member of the ginger family. Its anti-cancer effects have been
studied for colon cancer, breast cancer lung metastases, and brain tumor.

Curcumin’s anticancer effect is attributed to its ability to induce apoptosis in cancer cells
without cytotoxic effects on healthy cells, which is very attractive to cancer research
scientists. Curcumin interferes with NF-κB, which connects with inflammatory diseases
including cancer. Curcumin was able to dissociate raptor from mTOR, inhibit mTOR
complex I and might represent a new class of mTOR inhibitor. It is suggested that curcumin
modulates growth of tumor23 cells through regulation of multiple cell signaling pathways

22
Rao CV, Sairam K and Goel RK. Experimental evaluation of Bacopa monniera on rat gastric ulceration and
secretion. Indian J Physiol Pharmacol. 2000; 44:435.
23
Banasenthil S, Ramachandran CR and Nagini S: Prevention of 4-nitroquinoline-1-oxide induced rat tongue
carcinogenesis by garlic, Fitoterapia 2001; 72: 524.

18
including cell proliferation pathway (cyclin D1, c-myc), cell survival pathway (Bcl-2, Bcl-x,
cFLIP, XIAP, c-IAP1), caspase activation pathway (caspase-8, 3, 9), tumor suppressor
pathway (p53, p21), death receptor pathway (DR4, DR5), mitochondrial pathways, and
protein kinase pathway (JNK, Akt, and AMPK).

Curcumin inhibits p65 and cell invasion by downregulation of COX-2 and MMP-2
expression; by suppression of gene expression of EGFR and modulation of Akt/mTOR
signaling, and inhibition of cell growth . It has also been reported that curcumin suppresses
p38 mitogen-activated protein kinase (MAPK) activation, reduces IL-1 beta and matrix
metalloproteinase-3, and enhances IL-10 in the mucosa of children and adults with
inflammatory bowel disease24. Epstein and co-workers had a thorough review on in vitro,
animal and clinical studies.

In that review, curcumin is cited as non-toxic to human subjects at a high oral dose of up to
12 g/day, and it has anti-inflammatory, antioxidant and anti-cancer properties, however,
under some circumstances, its effects can be contradictory as the first clinical trial failed to
show benefit, which may be due to an unexpected lack of cognitive decline in placebo group.
In our lab, curcumin was studied for modulating AP-1 in human colon HT-29 cancer cell line
and was found increasing AP-1-luciferase activity dose-dependently from 1 to 25 μM, and
the expression of endogenous cyclin D1 protein was well correlated with those of AP-1-
luciferase assay. It inhibited NF-κB stimulator lipopolysaccharide (LPS)-induced
inflammation, reduced LPS-induced IκB phosphorylation, and potently inhibited cell growth
in MTS assay.

Caspase-3 activity was also induced by curcumin. Among our other studies, Affymetrix
mouse genome 430 array (45K) was used to analyze mouse liver and intestine mRNA after
oral dose of curcumin at 1,000 mg/kg. Our results showed that 822 (664 induced and 158
suppressed) and 222 (154 induced and 68 suppressed) genes in the liver and small intestine,
respectively, were curcumin-regulated Nrf2 dependent, which can be classified as
ubiquitination and proteolysis, electron transport, detoxification, transport, apoptosis and cell
cycle control, cell adhesion, kinase and phosphatase, and transcription factor.

24
Ketan VK, Dubey H, Chandrashekhar RT, Pramod GY and Angad MP: Anticancer activity of the ethanolic
extracts of Agave americana leaves, Pharmacologyonline 2011; 2: 53-68

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2.1.6 CYANIDINS FROM GRAPES

Cyanidin is an extract of pigment from red berries such as grapes, blackberry, cranberry,
raspberry, or apples and plums, red cabbage and red onion. It possesses antioxidant and
radical-scavenging effects which may reduce the risk of cancer. It is reported to inhibit cell
proliferation, and iNOS and COX-2 gene expression in colon cancer cells.

Another study shows that cyanidin-3-glucoside (C3G) attenuated the benzo[a]pyrene-7,8-

diol-9,10-epoxide-induced activation of AP-1 and NF-κB and phosphorylation of MEK,
MKK4, Akt, and MAPKs, blocked the activation of the Fyn kinase signaling pathway, which
may contributed to its chemopreventive potential . C3G blocks ethanol-induced activation of
the ErbB2/cSrc/FAK pathway in breast cancer cells and may prevent/reduce ethanol-induced
breast cancer metastasis25.

Cyanidin-3-O-glucoside, cyanidin-3-O-rutinoside, and the ethanol extract of their source of

freeze-dried black raspberries selectively caused significant growth inhibition and induction
of apoptosis in a highly tumorigenic rat esophagus cell line (RE-149 DHD) but not in a
weakly tumorigenic line (RE-149). Cyanidin markedly inhibited UVB-induced COX-2
expression and PGE2 secretion in the epidermal skin cell line by suppressing NF-κB and AP-
1 which are regulated by MAPK. In that study, MKK-4, MEK1 and Raf-1 are targets of
cyanidin for the suppression of UVB-induced COX-2 expression. Cyanidin-3-galactoside and
cyanidin-3-glucoside are found to be BCRP substrates, and cyanidin, cyanidin-3,5-
diglucoside, and cyanidin-3-rutinoside are potential BCRP inhibitors but their effects on
MDR1 were weak. This finding may be helpful for the further development of these
compounds for clinical studies and may explain their pharmacokinetic performance in vivo.

25
Ghosh A, Das B, Roy A, Mandal B and Chandra G: Antibacterial activity of some medicinal plant extracts,
Journal of Natural Medicines 2008; 62: 259-262.

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 CHAPTER III

FUTURE DEVELOPMENTS

For centuries if not millennia, various plants (many systematized in traditional Chinese
medicine) have been used as medicines and disease therapeutics in most human cultures. As
exemplified in this review, over the last two decades renewed public interest and research
efforts from scientific and medical communities worldwide have generated a large volume of
information including clinical studies and trials on the pharmacological effects, usage, and
the development into future medicines of herbs and derivative medicinal phyto chemicals as
anti-tumor and chemoprevention agents26.
26
Jaju SB, Indurwade NH, Sakarkar DM, Fuloria NK, Ali MD, Das S and Basu SP: Galango flavonoid Isolated
from Rhizome of Alpinia galanga (L) Sw (Zingiberaceae), Tropical Journal of Pharmaceutical Research 2009;

21
Although considerable effort has been put into the verification and upgrade of many
traditional remedies or multiple- herb formulations, systematic, standardized research and the
use of FDA regulatory protocols and defined clinical trials are still quite limited and need to
be actively pursued.27 At the same time, it is necessary for scientists, clinicians, and
regulatory agencies to actively consider how to create novel, improved, or modified clinical
surveys, studies, and trial mechanisms that employ the stringent trial standards of the 21st
century but also incorporate, at the international level, the wealth of old empirical but
incomplete data from various records and documents accumulated by traditional medicine
practices worldwide, to expedite the discovery and development of new phyto medicines and
botanical drugs.

While continuous and systematic effort is needed, a number of notable “breakthroughs” have
occurred in the field of medicinal plant research and botanical drugs in the last few years. In
April2008, the FDA approved the very first botanical drug, Veregen, a partially purified
fraction of the water extract of green tea leaves from Camellia sinensis, for topical treatment
of external genital and perianal warts. Very recently (January 2013), the FDA approved, for
the first time, an oral botanical drug, Crofelemer (a purified oligomeric proanthocyanidin
from the latex of the South American Croton lechleri tree), for treatment of diarrhea in
HIV/AIDS patients. Although these two pioneer FDA-approved botanical drugs are not
therapies for cancer, they certainly pave way for such future developments. One possible
example is the ongoing (2013) FDA clinical trial on “PHY906.” This four- herbal-plant-
composed TCM formulation has been shown to confer with good evidence. It is our hope that
the phase III clinical trial of this formula will lead the way in the development of CAM for
cancer patients. With the various other new clinical trials ongoing, CAM may start playing
critical roles in future health care of aging populations.

3.1 WHO ROLE IN DEVELOPING HERBAL MEDICINES

WHO has recently considered herbal medicine as a holistic treatment approach? 28 According
to this hypothesis, a disease can be created following body immunity system imbalance and it
is not necessarily due to external and pathologic elements. Hence, endogen herbal systems

8(6): 545-550.

27
Ketan VK, Dubey H, Chandrashekhar RT, Pramod GY and Angad MP: Anticancer activity of the ethanolic
extracts of Agave americana leaves, Pharmacologyonline 2011; 2: 53-68.

28
http://apps.who.int/medicinedocs/en/d/Jh2945e/2.1.html last accessed on 22 November, 2018 at 5 P.M

22
can improve these disorders and balance body immunity system. In 1991, WHO introduced
some guidelines to evaluate herbal medicine? According to this guideline, herbal medicines
are to pass approval processes as follows: quality control (raw herbal complexes, Plant
preparation, and final products), Stability and safety assessment and providing needed
documents in this regard, and evaluating medicine efficacy.

CHAPTER 4

CONCLUSION

The most ancient wisdom and science of life, Ayurveda, has a long history and its basic
principles are valid even today. Less or minimal effectiveness and severe toxic side effects of
current cancer therapies draw the global attention towards herbal medicine to arrest the
insidious nature of this disease. In addition, more than 80% of the world’s population cannot
afford modern medicines. Western medicine provides symptomatic treatment and largely
ignores the underlying conditions, whereas Ayurveda treats the disease from root of origin.
Ayurveda plays an important complementary role to western medicine in treatment
efficiency. In addition, most of the lowest economic strata can benefit by choosing Ayurveda
instead of western medicine as Ayurveda provides cost-effective treatments. Principally, the

23
long-term wellbeing is important for vulnerable communities, who rely on healthy bodies for
a steady income, which can be achieved by opting Ayurveda treatment. Ayurvedic
supplements protect healthy cells, regulate body metabolism and treats the disease, e.g., halts
cancer progression or acceleration.

Ayurveda is critically patient oriented, i.e., the Ayurvedic physician diagnoses, treats and
dispenses medicine to every individual patient. This vital principle can form the basis for
personalized western medicine. Western medicine is constantly seeking novel compounds
for better treatment of various disease conditions. The collaboration between traditional
medicinal systems such as Ayurveda and contemporary western biomedicine would be more
advantageous for treating complex disease such as cancer in a more efficient manner. A
noteworthy point is that many Ayurveda concepts have not yet been sufficiently scientifically
validated. Hence, collaborations between these two medicinal systems would be mutually
beneficial. Amalgamating the best of eastern traditional knowledge such as Ayurveda and
western biomedicine has contemporary significance and will help to deal with the challenges
in the global health care sector. Even though not authenticated by research, the ancient
knowledge of holistic Ayurvedic medicine immersed in wisdom of nature may one day bring
an end to suffering.

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