Indian Pennywort's Anticancer Properties

By Chetana Krishnan

Introduction

Centella asiatica (Linneaus) is commonly known as Indian pennywort. It is also known as Hydrocotyle asiatica L. Indian pennywort has been used as a medicinal herb for thousands of years in India, China, Sri Lanka, Nepal, and Madagascar. Indian pennywort is one of the main herbs in treating skin problems, healing wounds, and revitalizing the nerves and brain cells. It is primarily known as a "brain food" in India.

Centella asiatica belongs to the family Apiaceae, previously known as Umbelliferae. It is an important plant in the international market of medicinal plants. Indian pennywort can be found throughout tropical regions and also sub-tropical regions of India up to an altitude of 600 meters. In some places, it can be found at high altitudes. In Sikkim, it is found at 1550 meters, and in Mount Abu of Rajasthan, it is found at 1200 meters. The plant is spread throughout Southeast Asia, India, Sri Lanka, parts of China, the Western South Sea Islands, Madagascar, South Africa, Southeast USA, Mexico, Venezuela, Columbia, and Eastern South America. Indian pennywort grows in shady, marshy, and damp places, and is a faintly aromatic, stoloniferous, perennial, and creeper herb. It grows up to 15 centimeters in height and the stem looks glabrous (smooth) and striated.

Table 1 Given below are the vernacular names for Centella asiatica in various regions of India.

Chemical Constituents

Claims of the Indian systems of medicines and a variety of scientific studies have proved that biochemical components such as secondary metabolites have been found in Centella asiatica. Therefore, it is medicinally important in the modern medicine system. Centella asiatica is known to have following the types of chemical compounds done by the study:

Triterpenoids: Many acids like asiaticoside, centelloside, madecassoside, isothankunic acid, centellose, asiatic, centellic and madecassic acid, brahmoside, brahminoside, and brahmic acid fall under this category. Their structure is based on brahmic acid, which has melting point of 293 degrees. It has been established as a 6-hydroxy, 23-hydroxy-methyl ursolic acid. Asiaticoside and madecassoside are predominant in the leaves of Indian pennywort with less in roots.

Madecassic acid

Asiaticoside

Alkaloids: Hydrocotylin (C22 H33 NO8) is an alkaloid that has been isolated from the dried plants.

Volatile and Fatty acids: The fatty oils present are glycerides of palmitic, stearic, lignoceric, oleic, linoleic, and linolenic acids.

Glycosides: Asiaticoside, madecassoside, and centelloside are found in various parts of the plant. When hydrolyzed, these glycosides yield the triterpene acids, which are asiatic acid, madegascaric acid, and centellic acid. Except cantellic acid, all the above are present in free form in the plant.

Flavonoids: The flavonoids 3-glucosyl quercetin, 3- glucosyl kaempferol and 7-glucosyl kaempferol have also been isolated from the leaves.

Tannins, sugars, inorganic acids, resins, and amino acids, namely aspartic acid, glycine, glutamic acid, α-alanine and phenylalanine, are observed in the plant.

It also contains chloride, sulfate, phosphate, iron, calcium, magnesium, sodium and potassium. The leaves have rich vitamins such as vitamin B, vitamin C, and vitamin B2.

Pharmacological Uses

Various pharmacological uses of the plant have been studied. They are as follows:

Wound Healing

An extract of this plant named Madecassol contains madecassic acid, asiatic acid and Asiaticoside accelerates cicatrisation and grafting of wounds. Asiaticoside promotes fibroblasts proliferation and also extracellular matrix synthesis in wound healing.

Cytotoxic and Antitumor

When the crude extract of C. asiatica and its halfly purified fractions orally administered induces apoptosis in solid and Ehrlich Ascites tumour and increased the life span of these tumours bearing mice. Asiatic acid shows anticancer effect on skin cancer.

Memory Enhancing

Centella asiatica contains brahmic acid, isobrahmic acid, brahminoside and brahmoside which has psychotropic, sedative and anticonvulsant properties. It is also useful in dementia, mental disorders and anxiety.

Cardioprotective

The alcoholic extract of the whole plant has a strong cardioprotective activity in limiting ischemia-reperfusion induced myocardial infraction in rats.

Radioprotective

Centella asiatica can prevent radiation induced behavioral changes during clinical radiotherapy.

Antidepressant

The total triterpenes acts a antidepressant activity and causes significant reduction of the corticosterone level in serum.

Slimming

C. asiatica extracts can have dramatic increase in the cyclic adenosine monophosphate content with a subsequent rise in the nonesterified fatty acids content in human adipocytes.

Immunomodulating

C. asiatica has immunostimulating activities and preliminary immunomodulatory effect.

Antiprotozoal

Alcoholic extract of the entire plant has antiprotozoal activity against Entamoeba histolytica.

Treatment for Mental Retardation

Centella asiatica tablets has significant increase in general ability and behaviour patterns in mentally retarded persons.

Antitubercular and Antileprotic

Asiaticoside is useful in the treatment of leprosy and certain types of tuberculosis.

Anticancer Activity

C. asiatica shows anticancer activity on MCF-7 cells by inhibiting its growth and other way of apoptosis. Growth inhibitory effects of MECA/asiatic acid on MCF-7 cells:

In a concentration dependent manner, MECA and asiatic acid inhibits the proliferation of human breast cancer cell line MCF-7. MECA possess only moderate cytotoxicity compared to the higher cytotoxicity of asiatic acid, one of its active components.

Asiatic acid has been known for its anticancer effects which have been studied in vitro and in vivo by many researchers in different types of cancer. The interactions of asiatic acid with molecular targets such as nuclear factor erythroid-derived 2-like 2 (Nrf2), nuclear factor kappa B (NF-κB), protein kinase C (PKC), free radicals scavenging, and the cell longevity pathway (CLP) lead to anticancer, cytoprotective, chemosensitizer, and chemopreventive effects. Asiatic acid acts by inhibiting the proliferation of cancer cells and inducing apoptosis. Studies have reported that Asiatic acid could induce apoptotic cell death by modulating the protein expression of several apoptosis regulators, such as caspases, B-cell CLL/lymphoma 2 (BCL-2) family members, and glioblastoma multiforme (GBM) cells. BCL-2 and BCL-XL proteins were decreased by asiatic acid treatment.

References

1. The Wealth of India: A Dictionary of Indian Raw Materials and Industrial Products – Raw Materials Series, Vol. 3, (Publications and Information Directorate, CSIR, New Delhi), Rev Ser, (Ca-Ci), 1992, 428-430.

2. Pandey NK, Tewari KC, Tewari RN, Joshi GC, Pande VN and Pandey G., Medicinal plants of Kumaon Himalaya, strategies for conservation, In: Dhar U (ed) Himalaya Biodiversity Conservation Strategies, Himavikas Publication, Nanital, No 3, 1993, 293-302. 3. Singh HG., Himalayan herbs and drugs, importance and extinction threat, J. Sci Res. Plants Med, 10 (1989) 47-52.

4. Sharma BL and Kumar A., Biodiversity of medicinal plants of Triyugi Narain (Garhwal Himalaya) and their conservation, National conference on recent trends in spices and medicinal plant research, A-78 (2-4 April). Calcutta, WB. India, (1998).

5. Anonymous, Wealth of India, Raw Materials, Vol 2, (CSIR, New Delhi), 1992, 48. 6. Devkota Anjana and Jha Kumar Pramod, Variation in growth of Centella asiatica along different soil composition, Botany Research International, 2(1) (2009) 55-60.

7. Subban Ravi, Veerakumar A., Manimaran R., Hashim K.M., Balachandra Indira, Two new flavonoids from Centella asiatica (Linn.), J Nat Med.,62(2008)369-373.8. Sahu N.P., Roy S.K. and Mahato S.B., Spectroscopic determination of structures of triterpenoid trisaccharides from Centella asiatica, Phytochem, 28 (1989) 2852-2854.

9. Babu TD, Kuttan G and Padikkala J., Cytotoxic and anti-tumour properties of certain taxa of Umbelliferae with special reference to Centella asiatica (L.) Urban, J Ethnopharmacol, 48 (1) (1995) 53-57.

10. Suguna L., Sivakumar P. and Chandrakasan G., Effect of Centella asiatica extract on dermal wound healing in rats, Indian J. Exp. Biol., 34 (1996) 1208-1211.

11. Zainol M.K., Abd-Hamid A., Yusof S. and Muse R., Anti-oxidant activity and total phenolic compounds of leaf, root and petiole of four accessions of Centella asiatica (L.) Urban, Food Chem., 81(2003) 575-581.

12. Kumar M.H.V and Gupta Y.K., Effect of different extracts of Centella asiatica on cognition and markers of oxidative stress in rats, J. Ethnopharmacol, 79 (2002) 253-260.

13. Kakkar KK., Mandukaparni- medicinal uses and therapeutic efficacy, Indian Drugs, 26 (1988) 92-97.

14. Sidhu Kiranjot, Kaur Ramthirath and Pannu Kunwarjeet, For managing editor indigenous way to maternal health care within the social system, J. Soc. Sci., 13(1) (2006) 79-81.

15. Das Sandipan, Khan ML, Rabha Abhijit and Bhattacharjya DK., Ethnomedicinal plants of Manas National Park, Assam, Northeast India, Indian Journal of Traditional Knowledge, 8(4) (2009) 514-517.

16. Narayanan Ratheesh MK and Kumar Anil N., Gendered knowledge and changing trends in utilization of wild edible greens in Western Ghats, India, Indian Journal of Traditional Knowledge, 6(1) (2007) 204-216.

17. Rajendran K., Balaji P and Basu Jothi M., Medicinal plants and their utilization by villagers in southern districts of Tamil Nadu, Indian Journal of Traditional Knowledge, 7(3) (2008) 417-420.

18. Leyel, C.F., Elixiris of Life. Samuel Weiser, Inc., New York, (1970).

19. William A. Emboden., The ethnopharmacology of Centella asiatica (L.) Urban (Apiaceae), J. thnobiol., 5(2) (1985) 101-107.

20. Leonard Bruce David, L.Ac., Medicine at your feet: Healing plants of the Hawaiian kingdom Centella asiatica (Pohe kula), (1998).

21. Mahato R.B. and Chaudhary R.P., Ethnomedicinal study and antibacterial activities of selected plants of Palpa District, Nepal, Scientific World, 3 (2005) 3.

22. Joshi Ananda Raj and Joshi Kunjani, Ethnomedicinal plants used against skin diseases in some villages of Kali Gandaki, Bagmati and Tadi Likhu watersheds of Nepal, Ethnobotanical Leaflets, 11(2007) 235-246.

23. Ahmad B. Fasihuddin and Ismail Ghazally, Medicinal plants used by Kadazandusun communities around Crocker Range, ASEAN Review of Biodiversity and Environmental Conservation (ARBEC) (2003).

24. Rahmatullah Mohammad, Ferdausi Dilara, Mollik Haque Ariful Md., Jahan Rownak, Chowdhury H. Majeedul, Haque Mozammel Wahid, A survey of medicinal plants used by Kavirajes of Chalna Area, Khulna District, Bangladesh, Afr. J. Trad. 7(2) (2010) 91-97.

25. Bontemps J., Gazette Medicale Madagascariensis, Vol 5 (1942) 29.

26. Boiteau P., Dureuil M. and Ratsimamanga R.R., Contribution a l’etude eles properties antituberculeuses de l’oxyasiaticoside de Centella asiatica, Comptes Rendus de l’Academie des Science, Paris, Serie D., 228 (1949) 1165-1167.

27. Prakasha HM and Krishnappa M., People’s knowledge on medicinal plants in Sringeri taluk, Karnataka, Indian Journal of Traditional Knowledge, 5(3) (2006) 353-357.

28. Dutta T and Basu U.P., Isothankunic acid- a new triterpene acid from Centella asiatica (URB), Bull. Nat. Inst. Sci. India, 37 (1968) 178-184.

29. Singh B and Rastogi R.P., A reinvestigation of the triterpenes of Centella asiatica III, Phytochemistry, 8 (1969) 917-921.

30. Aziz Z.A., Davey M.R., Power J.B., Anthony P., Smith R.M. and Lowe K.C., Biologia Plantarum, 51(1) (2007) 34-42.

31. Chopra RN, Nayar SL and Chopra IC., Glossary of Indian Medicinal Plants, (Council for Scientific and Industrial Research, New Delhi), 1956 pp. 58.

32. Schaneberg BT, Mikell JR, Bedir E and Khan IA., An improved HPLC method for quantitative determination of six triterpenes in Centella asiatica extracts and commercial products, Pharmazie, 58(6) (2003) 381-384.

33. Rastogi RP and Mehrotra BN., Compedium of Indian Medicinal Plants, Vol. 1 (Central Drug Institute Lucknow and Publication and Information Directorate, CSIR, New Delhi), 1960-1969 pp. 96.

34. Chopra RN, Chopra IC and Varma BS., Supplement to Glossary of Indian Medicinal Plants, (CSIR, New Delhi, India), 1992 pp. 14.

35. Kapoor LD., CRC Handbook of Ayurvedic Medicinal Plants, (CRC Press LLC, Florida), 2005, 208-209.

36. Malhotra CL, Das PK, Sastry MS and Dhalla NS., Chemical and pharmacological studies on Hydrocotyle asiatica Linn., Indian J Pharm., 23 (1961)

37. Tiwari Nath Kavindra, Sharma Chandra Nilesh, Tiwari Vaibhav and Singh Deo Brahma, Micropropagation of Centella asiatica (L.), a valuable medicinal herb, Plant Cell, Tissue and Organ Culture 63 (2000) 179-185.

38. Srivastava R, Shukla YN and Kumar S., Chemistry and pharmacology of Centella asiatica: a review, J. Medi. Arom. Plant Sci., 19 (1997) 1049-1056.

39. Babu TD and Paddikkala J., DNA fragmentation in Ehrlich Ascites tumour cells by extract of herbal plant Centella asiatica (L.), Amala Res Bull., 14 (1994) 52-56.

40. Park BC, Bosire KO, Lee ES, Lee YS and Kim JA., Asiatic acid induces apoptosis in SK-MEL-2 human melanoma cells, Cancer Lett., 218(1) (2005) 81-90.

41. Nalini K, Aroor AR, Karanth Ks and Rao A., Effect of Centella asiatica fresh leaf aqueous extract on learning and memory and biogenic amine turnover in albino rats, Fitoterapia, 63 (1992) 232-237.

42. Upadhyay S.K., Saha Abhijeet, Bhatia B.D., and Kulkarni Kala Suhas, Evaluation of the efficacy of mentat in children with learning disability Placebo-Controlled Double-Blind clinical trial, Neurosciences Today, (VI), 3 (2002) 184-188.

43. Pragada RR, Veeravalli KK, Chowdary KP and Routhn KP., Cardioprotective activity of Hydrocotyle asiatica L. in ischemia-reperfusion induced myocardial infraction in rats, J Ethnopharmacol, 93 (1) (2004) 105-108.

44. Shobi V and Goel HC., Protection against radiation-induced conditioned taste aversion by Centella asiatica, Physiol Behav., 73(1-2) (2001) 19-23.

45. Chen Y, Han T, Qin L, Rui Y and Zheng H., Effect of total triterpenes from Centella asiatica on the depression behaviour and concentration of amino acid in forced swimming mice, Zhong Yao Cai., 26 (12) (2003) 870-873.

46. Chen Y, Han T, Rui Y, Yin M, Qin L and Zheng H., Effects of total triterpenes of Centella asiatica on the corticosterone levels in serum and contents of monoamine in depression rat brain, Zhong Yao Cai.,28 (6) (2005) 492-496.

47. Tholon L, Neliat G, Chesne C, Saboureau D, Perrier E and Branka JE., An in vitro, ex vivo and in vivo demonstration of the lipolytic effect of slimming liposomes: An unexpected α (2) - adrenergic antagonism, J. Cosmet Sci., 53(4) (2002) 209-218.

48. Young GL and Jewell D., Creams for preventing stretch marks in pregnancy, Cochrane Database Syst Rev., (2) (2000) CD000066.

49. Wang Xs, Dong Q, Zuo JP and Frong JN., Structures and potential immunological activity of a pectin from Centella asiatica (L.) Urban, Carbohydr Res., 338 (22) (2003) 2393-2402.

50. Plohmann B, Bader G, Streich S, Hiller K and Franz G., Immunomodulatory effects of triterpenoid saponins, European J Pharmaceut Sci., 21(1994) 120.

51. Jayathirtha MG and Mishra SH., Preliminary immunomodulatory activities of methanol extracts of Eclipta alba and Centella asiatica, Phytomedicine, 11(4) (2004) 361-365.

52. Dhar ML, Dhar MM, Dhawan BN, Mehrotra BN and Ray C., Screening of plants for biological activity I, Indian J Exp Biol., 6 (1968) 232.

53. Rao Appa MVR, Srinivasan K and Rao KT., Effect of mandookaparni (Centella asiatica) on the mentally retarded children, J Res Indian Med., 8 (1973) 9.

54. (Late) Rao Appa M.V.R., Kanchana Srinivasan, T. Koteswara Rao, The effect of Centella asiatica on the general mental ability of mentally retarded children, Indian J. Psychiat., 19(4) (1977) 54-59.

55. The Useful Plants of India, (Publications and Information Directorate, Council of Scientific & Industrial Research, New Delhi), 1986, pp. 115.

56. Rao Appa MVR, Usha SP, Rajagopalan SS and Sarangan R., Six months result of double blind trial to study the effect of Mandookaparni and Punarnava on normal adults, J Res Indian Med., 2 (1967) 79.

57. Rao Appa MVR, Rajagopalan SS, Srinivasan VR and Sarangan R., Study of Mandookaparni and Punarnava for their Rasayana effects on normal healthy adults, Nagarjun, 12 (1969) 33.

58. Ahmad RU., Medicinal Plants used in ISM- Their procurement, cultivation, regeneration and import/export aspects: a review, In: Medicinal Plants, New Vistas of Research, Part 1, edited by Govil JN, Singh VK and Hashmi S, 1993 221-258.

59. Naidu Bangaru T., Rao Nageswara S., Mani Sarada N., Mohan Jagan Y.S.Y.V. and Pola Sudhakar, Conservation of an endangered medicinal plant Centella asiatica through plant tissue culture, Drug Invention Today, 2(1) (2010) 17-21.