The Pharma Innovation Journal 2014; 3(7): 60-66

ISSN: 2277- 7695

TPI 2014; 3(7): 60-66 A review of traditional anticancer nano-medicine:
© 2013 TPI
www.thepharmajournal.com triphala
Received: 24-07-2014
Accepted: 28-08-2014 Amit Kumar
Amit Kumar Abstract
Regional Drugs Testing Laboratory, Ayurveda, the science of life, prevention and longevity is the oldest and most holistic medical system
Government of India, Ministry of available. In the last few years there has been an exponential growth in the field of herbal medicine and
Health and Family Welfare, Sec-39C, these drugs are gaining popularity both in developing and developed countries because of their natural
Chandigarh-160036, India origin and less side effects. Many traditional medicines in use are derived from medicinal plants,
minerals and organic matter .The World Health Organization (WHO) has listed 21,000 plants, which are
used for medicinal purposes around the world. It has recently come to the attention of western medical
researchers seeking novel therapeutic compounds. The present study was performed to evaluate, the anti-
cancer herbal drug (Triphala) preparations. The screening a number of traditional Vedic formulas
scientists discovered that one of the most revered of all Ayurvedic combination - Triphala (Harad,
Bahada & Amala) in different ratios exhibits a number of health benefits, including: Anti-cancerous,
Antipyretic, Antiulcer, Antidiabetic etc. activities.

Keywords: Triphala, Anti-cancer, Antiulcer, Anti-diabetic etc.

1. Introduction
Ayurveda, the science of life, prevention and longevity is the oldest and most holistic medical
system available. It is known to have evolved over thousands years ago in the far reaches of
the Himalaya in India from the deep wisdom of spiritually enlightened prophets, the Rishis.
Their wisdom was transmitted orally from teacher to disciple, and eventually set down in
Sanskrit poetry known as the Vedas. Before the advent of writing, the ancient wisdom of
healing, prevention and longevity was a part of the spiritual tradition of a universal religion.
When world is burning for the cure of a giant cancer disease the Indian well known medicine
used since our ancient period (Vedas) as a tonic is the ray of hope. When we are going in the
21st century but today no permanent treatment of cancer available.
Herbal care or traditional system of medicine are used throughout the world and from century's
herbs have been the original source for most of the drugs. Medicinal plants contain so many
chemical compounds which are the major source of therapeutic agents i.e. active phyto-
chemical ingredients (API) to cure human diseases. Recent discovery and advancement in
medicinal and aromatic plants have lead to the enhancement of health care of mankind.
Various medicinal plants like Neem, Arjuna, Ashwagandha, Tulsi, etc. traditionally used for
treating fever. The combination of three medicinal fruits is triphala used in many diseases and
cure the effectively the cancerous part in human and animal body. Our ancestors did used this
medicine since old ages and were free from cancer and other like death cause.
Triphala is an old Ayurvedic herbal formula prepared by three plants: Haritake (Harad)
Bibhitaki (Bahada) and Amalki (Amla). Triphala has antioxidant properties and is promoted as
an herbal combination for good digestion. Triphala has historically been used as a digestive aid
for constipation. Triphala triggered the cancerous cells to die off and significantly reduced the
size of the tumours.

Correspondence:
Amit Kumar
Regional Drugs Testing Laboratory,
Government of India, Ministry of
Health and Family Welfare, Sec-
39C, Chandigarh-160036, India
Triphala
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Amala or Amalaki (Emblica officinalis)

Harad/Haritaki (Terminalia chebula)

Baheda/Bibhitaki (Terminalia belerica).

Table 1: Triphala phytochemicals and theruptic uses described in Ayurvedic literature

Sanskrit/Hindi Name
Phytochemicals [13] Theruptic effect [5, 13]
(English) Botanical
Amalaki/Amala (Emblic Vitamin C, Nicotinic acid, Tannins, Gallic Diabetes, Hysteria, Jaundice, Eczema, Piles, Diarrhoea,
Myrobalan) Emblica officinalis acid, Ellagic acid, Linoleic acid, Linolenic Menorrhagia, Scurvy, Rebuilds and maintains new tissues
acid, Oleic acid. and increases red blood counts,

Cough, Asthma, Anorexia, Vomiting, Arthritis, Throat

Bibhitaki/Baheda (Belliric }-sitosterol, gallic acid, Ellagic acid, disorder, Fever, Epilepsy, Splenomegaly, Piles,
Myrobalan) Terminalia Chebulic acid, Mannitol, Oxalic acid, Galloyl, Diarrhoea, Leprosy, Brain tonic and laxative.
belerica Galactose, Fructose.
Constipation, Haemorrhoid, Skin disease, Asthma,
Haritaki/Harad (Chebulic Tannic acid, Gallic acid, Chebulinic acid, Dysentery, Uterine debility, Anaemia, Diabetes,
Myrobalan) Terminalia Anthraquinone, phosphoric acid, Succinic Leucoderma, Tumors and Heart disease.
chebula acid.

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1.1 Definition of Cancer Colon Liver, peritoneum, lungs

Cancer is a term used for diseases in which abnormal cells Kidney Lungs, liver, bones
divide without control and are able to invade other tissues. Lungs Adrenal gland, liver, lungs
Cancer cells can spread to other parts of the body through Melanoma Lungs, skin/muscle, liver
Ovary Peritoneum, liver, lungs
the blood and lymph systems. Cancer is not just one disease Pancreas Liver, lungs, peritoneum
but many diseases. There are more than 100 different types Prostate Bones, lungs, liver
of cancer. Most cancers are named for the organ or type of Rectum Liver, lungs, adrenal gland
cell in which they start. Cancer types can be grouped into Stomach Liver, peritoneum, lungs
broader categories. The main categories of cancer include: Thyroid Lungs, liver, bones
Uterus Liver, lungs, peritoneum
1. Carcinoma - cancer that origins in the skin or in tissues
In local invasion cancer cells invade nearby normal tissue. In
that line or cover internal organs.
extravasation cancer cells invade and move through the walls
2. Sarcoma - cancer that begins in bone, cartilage, fat, of nearby lymph vessels or blood vessels. In circulation
muscle, blood vessels, or other connective or supportive cancer cells move through the lymphatic system and the
tissue. bloodstream to other parts of the body [7].
3. Leukemia - cancer that starts in blood-forming tissue
such as the bone marrow and causes large numbers of
abnormal blood cells to be produced and enter the blood.
4. Lymphoma and myeloma - cancers that begin in the
cells of the immune system.
5. Central nervous system cancers - cancers that begin in
the tissues of the brain and spinal cord.

1.2 How Cancer Starts

All cancers begin in cells, the body's basic unit of life. To
understand cancer, it's helpful to know what happens when
normal cells become cancer cells. The body is made up of
many types of cells. These cells grow and divide in a
controlled way to produce more cells as they are needed to
keep the body healthy. When cells become old or damaged,
they die and are replaced with new cells. However, Various kind of drugs play very important role in human life.
sometimes this orderly process goes wrong. The genetic
material (DNA) of a cell can become damaged or changed, Some Chemotherapeutic medicines are used for cancer
producing mutations that affect normal cell growth and treatment [8].
division. When this happens, cells do not die when they
should and new cells form when the body does not need • Taxanes: paclitaxel
them. The extra cells may form a mass of tissue called a • Dacarbazine and temozolomide
tumor. The effect on DNA is called nano effect. • Thiotepa and altretamine
• Cladribine, Clofarabine, Cytarabine
• Pentostatin Thioguanine
• Daunorubicin
• Doxorubicin
• Epirubicin
• Idarubicin etc.

1.4 Impurity how damage the DNA this HIV Drug

Viracept (DNA damage)
11 Sep 2007 Drug Company Pfizer Inc together with the US
Food and Drug Administration (FDA) warned yesterday,
Fig 1: spreading of metastatic cancer cells invade lymph vessels
Monday, that its HIV drug Viracept (nelfinavir mesylate)
and blood vessels
may be contaminated with a potential carcinogen and asked
1.3. Site of Cancer Development in Human body: doctors not to start pregnant women or children on the drug.
The most common sites of cancer metastasis are the lungs, Children who are already on the drug and are stable may
bones, and liver. Although most cancers have the ability to continue to take Viracept, but pregnant women should be
spread to many different parts of the body, they usually switched to an alternative antiretroviral said Pfizer and the
spread to one site more often than others. The following FDA. The drug company issued a Dear Healthcare
table shows, in descending order from left to right, the three Professional letter about the presence of an impurity, ethyl
most common sites of metastasis, excluding lymph nodes, methanesulfonate (EMS), that has entered the Viracept
for several types of cancer:- formula during the manufacturing process. The letter also
gives guidelines on the use of Viracept in pediatric patients
Cancer type Main sites of metastasis and pregnant women. Although no human studies exist,
Breast Lungs, liver, bones
EMS is considered a potential human carcinogen: animal
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studies indicate it to be teratogenic (causing birth defects), malignancy. The process of cancer metastasis is consisting
mutagenic (causing mutation through DNA damage) and of series of sequential interrelated steps, each of which is
carcinogenic (causing cancer). In the meantime the FDA has rate limiting. Plants with chemical contains chemo protective
asked Pfizer to limit the amount of EMS in its US [9]. activities of some of them are undergoing clinical trial.
Inhibition of angiogenesis is a novel process of cancer
1.5 Effect of Chemotherapy on immunity therapy. The selected and careful use of this plant
Chemotherapy can make patient more likely to get combination may definitely in anti-angiogenic therapy and
infections. This happens because most anticancer drugs thus in cancer management. Triphala is commonly used in
affect the bone marrow, making it harder to make white Ayurvedic medicine to treat variety of diseases; however its
blood cells (WBCs), the cells that fight many types of mechanism of action remains unexplored. This study
infections [7]. elucidates the molecular mechanism of Triphala against
human cancer in the cellular and In vivo model.
1.6 Ayurvedic herbal formula Triphala
Cancer is an abnormal malignant growth of body tissue or 1.7 Some anticancer Phytochemicals [10]
cell. A cancerous growth is called a malignant tumor or

Tanic acid

Ellagic Acid Quinic acid

Ethyl galate Shikimic acid

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Galicacid B-Sitosterol

The phytochemicals found in the triphala are of medical turn was associated with generation of ROS. Pretreatment of
importance to cure the diseases. In the modern system of Capan-2 cells with antioxidant NAC blocked ROS
medicine all drugs are synthetic and have lot of side effects generation and completely protected the cells from Triphala-
in the human and animal body. The chemical investigations induced apoptosis. The results also demonstrate that
have found that triphala have a lot of chemical compounds to Triphala treatment caused DNA damage resulting in the
cure the cancer and ulcerous cells in human body. Some of activation of ATM and ERK leading to stabilization.
the phytochemical structures have given above shows Blocking ERK activation by MEK-1/2 inhibitor U0126 or
medicinal properties are as follows- Beta-sitosterol, gallic p53 activation by pifithrin-a completely protected Capan-2
acid, ellagic acid, ethyl gallate, galloyl glucose, chebulagic (wild type p53) cells from Triphala-induced apoptosis.
acid. Gallic acid biological activities of gallic acid include: Similarly, U0126 treatment blocked Triphala-induced
Analgesic, Anti- inflammatory, And Antioxidant, Ellagic apoptosis in BxPC-3 (mutated p53) cells, suggesting ERK as
acid: Ellagic acid is a phenolic compound and known to a molecular target of Triphala in pancreatic cancer cells.
inhibit certain carcinogen-induced cancers and may Further, orally feeding 50 mg/kg or 100 mg/kg Triphala to
have other chemo- preventive properties. The effects of nude mice significantly retarded the growth of Capan-2
ellagic acid on cell cycle events and apoptosis were studied pancreatic tumor xenograft. Tumors from Triphala treated
in cervical carcinoma cells [11]. mice demonstrated increased apoptosis in the tumor cells,
which was due to the activation of ERK and p53. To the best
1.8 Elemental Contents in Triphala of our knowledge, this is the first study to report the
The presence of elemental contents is suggests that triphala molecular mechanism of the chemotherapeutic effects of
as a whole is rich in Mg, K, Ca, Fe, and Zn, though Se Triphala against pancreatic cancer.
(Selenium) is also present in significant amounts. There Reactive oxygen species (ROS) are the known mediators of
appears to be an association between Se deficiency and intracellular signaling cascades. Excessive production of
protein malnutrition disease, multiple sclerosis, cancer and ROS nonetheless leads to oxidative stress, loss of cell
heart disease. It has been suggested that Se (Selenium) as function and apoptosis or necrosis 14-17. Our results reveal
glutathione peroxidase inhibits the replication of tumour that Triphala-induced apoptosis in pancreatic cancer cells is
viruses and prevents the malignant transformation of cells initiated by ROS generation, the effect of which can be
[12]
. The triphala and its three constituents have shown V blocked by antioxidant NAC. Several previous studies
content in the range 1-2 g/g, which has been suggested to including those from our laboratory have implicated ROS as
play vital role in the treatment of cancer and diabetes [13]. a possible mechanism for DNA damage and induction of
apoptosis [15, 17, 18]. DNA damage plays a critical role in
2. Discussion maintaining genomic integrity. Tumor cells exhibit genetic
Triphala is novel dietary or natural chemopreventive instability causing functional inactivation of p53 that plays
formulation. Triphala has been used for centuries in an important role in DNA damage checkpoint pathways. In
Ayurvedic medicine to treat various types of response to DNA damage, p53 is stabilized through
gastrointestinal-related disorders; however, the molecular phosphorylation at Ser 15 by ATM 19-21. The effects of
mechanisms of triphala have not been studied yet. In the Triphala are compatible with this assertion. The results do
present studies, it has demonstrated that aqueous extract of indicate that Triphala treatment causes DNA damage as
triphala is effective in inhibiting the growth of pancreatic depicted by increased phosphorylation of H2A.X at Ser 139,
cancer cells in culture as well as in the In vivo model. The an indicator for the presence of DNA double-strand breaks.
results reveal that Triphala treatment drastically reduces the
survival of Capan-2 and BxPC-3 human pancreatic cancer Pancreatic tumor growth inhibition and induction of
cells in a dose- dependent manner. On the other hand, apoptosis In vivo was observed by the oral administration of
Triphala failed to cause any cytotoxic effects on the growth 50 mg/kg or 100 mg/kg Triphala 5 times a week the results
of HPDE-6 near normal pancreatic epithelial cells. were consistent with previous studies where Triphala was
Suppression of pancreatic cancer cell growth by Triphala in shown to be effective in suppressing the growth of Barc- 95
studied model was due to induction of apoptosis, which in (mouse thymic lymphoma) xenograft in mice22. Although,
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pharmacokinetics of Triphala in humans has not been evoke differential response in intracellular ROS generation.
determined, it has been used safely for centuries in the The differential response of normal and tumor cells to
Ayurvedic medicinal system in India for the treatment of Triphala in vitro and the substantial regression of
various gastrointestinal-related disorders. The effective dose transplanted tumor in mice fed with Triphala points to its
of Triphala in our animal model for suppressing tumor potential use as an anticancer drug for clinical treatment [3].
growth, if extrapolated to humans ranges from 4 to 8 grams
per day for a person weighing 70 kg. These doses of Triphala The presence of elemental contents is suggests that triphala
come within the dose range already being used by humans in as a whole is rich in Mg, K, Ca, Fe, and Zn, though Se
countries such as India. (Selenium) is also present in significant amounts. There
Triphala churna is a powdered preparation of three appears to be an association between Se deficiency and
myrobalan fruits, Emblica officinalis (Amla), Terminalia protein malnutrition disease, multiple sclerosis, cancer and
chebula (Haritaki) and Terminalia belerica (Bibhitaki) in heart disease. It has been suggested that Se (Selenium) as
equal proportions. This fruit formulation has been glutathione peroxidase inhibits the replication of tumour
extensively used in the traditional Indian system of viruses and prevents the malignant transformation of cells
medicine, Ayurveda for the treatment of several disorders of 30. The triphala and its three constituents have shown V
the gastrointestinal and cardiovascular systems [23-26]. In content in the range 1-2 µg/g, which has been suggested to
addition, THL is also consumed by the people of Indian play vital role in the treatment of cancer and diabetes [31].
subcontinent for its high nutritional value [26]. Recently, it
has been demonstrated that THL can inhibit the growth of In the recent past, there has been growing interest in
carcinogen induced stomach cancer, murine thymic exploiting the biological activities of different ayurvedic
lymphoma and human pancreatic cancer in mice. However, medicinal herbs, owing to their natural origin, cost
there is no mention in these reports regarding the effects of effectiveness and lesser side effects [32, 33]. Triphala is one of
THL on tumor angiogenesis [25-28]. the ayurvedic medicinal herbal formulations prescribed by
High performance liquid chromatography (HPLC) has most health care practitioners. It is used as colon tonic,
revealed gallic acid (GA), ellagic acid (EA) and chebulinic laxative, eye rejuvenator, anti-inflammatory, anti-viral etc.
acid (CI) to be the major constituents of THL [24, 26]. The Triphala is gentle for people of all ages, from children to
plasma levels of GA and EA after oral intake of fruits seniors and hence is recommended for everybody [34].
containing these two compounds, and thereby their Triphala has been tested as an antioxidant and also as a
bioavailability has been reported to be poor 29. As THL has radioprotector in mice [25, 35]. In the recent study, it is tested
been shown to inhibit malignant tumor growth in animals25- the in vitro antioxidant activity under y-radiation induced
28, therefore there is a possibility that other bioactive conditions. In order to understand the factors responsible for
compounds present in THL mediate its anti-tumor effects in the antioxidant and radio protection activity, free radical
these animals. reactions and phytochemical analysis of triphala were carried
The cytotoxic effects of aqueous extract of Triphala, an out.
ayurvedic formulation, were investigated on human breast
cancer cell line (MCF-7) and a transplantable mouse thymic 3. Conclusion
lymphoma (barcl-95). The viability of treated cells was The rapid increase in utilization of herbal remedies
found to decrease with the increasing concentrations of worldwide has been inspired by several factors, including the
Triphala. On the other hand, treatment of normal breast concept that herbal products are safe and effective and so
epithelial cells, MCF-10 F, human peripheral blood investigation on medicinal plants is increasing day by day.
mononuclear cells, mouse liver and spleen cells, with similar Triphala is known as the mother of medicine as it has a
concentrations of Triphala did not affect their cytotoxicity biodiversity of both nutritional as well as medicinal
significantly. The drug treatment was found to induce components. It is suggested that any herb or plant
apoptosis in MCF-7 and barcl-95 cells in vitro as determined ingredients taken must be tested before being used as a
by annexin-V fluorescence and proportion of apoptotic cells remedy. Therefore, from this study, it is clear that the
was found dependent on Triphala concentration. MCF-7 medicinal plants play a vital role against various diseases.
cells treated with Triphala when subjected to single cell gel Triphala has an antiulcer, Antipyretic, Anti-diabetic and
electrophoresis, revealed a pattern of DNA damage, Anti-cancerous activity in different animal models. Hence
characteristic of apoptosis. Studies on Triphala treated MCF- the review study is concluded that the triphala possesses
7 and barcl-95 cells showed significant increase in antiulcer, anti-cancerous activity and it has been proved by
intracellular reactive oxygen species (ROS) in a different animal models which give many links to develop
concentration dependent manner. ROS increase was, the future trials. The ill community gets maximum benefits
however, found to be insignificant in MCF-10 F as well as in from traditional system of medicine. Hopefully, this review
murine spleen and liver normal cells. In vivo, direct oral will encourage more awareness towards research and more
feeding of Triphala to mice (40 mg/kg body weight) confidence towards utilization of herbal medicines. It will be
transplanted with barcl-95 produced significant reduction in a link between science and men.
tumor growth as evaluated by tumor volume measurement. It
was also found that apoptosis was significantly higher in the 4. Acknowledgements
excised tumor tissue of Triphala fed mice as compared to the The review article of the investigation triphala was supported
control, suggesting the involvement of apoptosis in tumor by the Shri Sharangi Rishi Trust. Authors wish to thank Shri
growth reduction. These results suggest that Triphala Vinod Kumar, Director, Shri Sharangi Rishi Trust, Karnawal
possessed ability to induce cytotoxicity in tumor cells but for providing assistance and solid proof for Triphala as an
spared the normal cells. The differential effect of Triphala on anticancer medicine.
normal and tumor cells seems to be related to its ability to
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