Effect Of Herbal Preparation On Chemical Induced Cancer And Fertility Models And Their Anti-Cancer And Anti-Fertility Potential
Wilfred Dias * and Renu Rathore
* Research Scholar, Faculty of Science, B N University, Udaipur, Rajasthan, 313002
Abstract
Cancer is known to be one of the principalcauses of death and day by day the numbers of cases of cancer are also increasing globally. Fertility control is an important issue globally especially in developing and under-developed countries. Over population is the leading cause of poverty and pollution in developing countries as well. Population growth is responsible for many harmful effects on life surviving resources on the earth. Therefore, regulation of fertility is an important concern for the preservation of life supporting resources as well as good reproductive health of both males and females. This article aims to highlight the herbal products which are used as anti-cancer and anti- fertility agents. However, plants and plant derived products have proved to be effective and safe in the treatment and management of various cancer diseases.Several herbal plants and their products hold different types of antifertility potential for both males and females.
Keywords: cancer, tumours, fertility, anti-cancer, anti-fertility, herbal medicine, plant extracts
Introduction Cancer
Cancer is a disease which is the outcome of the cellular changes which results in the uncontrolled growth and division of cells. These cells can form tumors, damage the immune system and can also alter the normal functioning of the body.
Several medicines are present in the market to treat the different types of cancer but no drug among them have been found to be completely potent and safe. The problems associated with chemotherapy of cancer is the toxicity of the conventional drugs. However, plants and plant derived products have proved to be effective and safe in the treatment and management of various cancer diseases. Now a days most of the research work on drugs for cancer is embattled on plants and plants derived natural products and their anti-cancer potential is being identified.(1)
Clinical uses of herbal medicines having anticancer potential
A series of clinical studies have proved that a wide range of anticancer activities from various herbal medicines can be identified. The use of the plants or plant derived natural products are being advantageous to combat cancer.
From ancient time onwards it was known that plants are having various health benefits and can be considered as source of medicine. From various studies conducted so far it was established that about 80- 85% of world’s population are dependent on traditional or herbal medicines for the cure of their primary ailments. These traditional or herbal medicines uses various plant extracts or their active principles. Although a series of investigations have been carried out for treatment and control of cancer but synthetic drugs are having many disadvantages along with various side effects.(2, 3, 4, 5)
Vinca Alkaloids
These alkaloids are the oldest group of the plant alkaloids which are used to treat cancer since ancient times. (6)Vinca alkaloids are obtained from Madagascar periwinkle plant Catharanthus roseus and have shown significant anticancer activities against many cell types.
(7, 8)There are five major vinca alkaloids which are having clinical uses: vincristine, vinblastine, vinorelbine, vindesine and vinflunine, but only vincristine, vinblastine, and vinorelbine have been approved for clinical use in the United States. (9)Vinca alkaloids act by interacting with tubulin and results in disruption of microtubule functioncausing metaphase arrest, which in turn block mitosis by inhibiting the process of cell division.(10)
The vinca alkaloids are generally used in combination chemotherapy in order to minimize the adverse effects associated with them. Vinca alkaloids can be used to treat different kinds of tumors when used in combination with other chemotherapy agents. (11)
Adiantum venustum
Adiantum venustumhave significant anticancer activity and is very useful in treating tumour.
It possesses terpenoids and flavonoids which helps in reducing elevated level of lipid peroxidation. The ethanolic extract of A. venustumexhibited vast anti-cancer and anti-oxidant activity. (12)Suspension of ethanolic extract Adiantum venustum (EEAV), was prepared by mixing the ethanolic extract in a mixture containing propylene glycol and sterile physiological saline comprising Tween 20 in ratio 1:3 to get the desired concentration for the dose of 150 and 250 mg/kg.(13)Terpenoid, phytosterols, flavanoid, and saponin which are supposed to be the chief potential for anticancer activity are present in the ethanolic extract of Adiantum venustum. (14)
Anemopsis californica
Four different parts of the plant Anemopsis californica viz; bracts, leaves, roots and stems were used to evaluatetheirpotential on the growth and migration of human colon cancer cells, HCT-8, and the breast cancer cell lines Hs 578T and MCF-7/AZ.Extract of Anemopsis californicain the mixture of water and ethyl acetateshowed the anticancer properties. The consequence of the plant extracts on cell viability was tested. MTT reagent was used to measure the activity of mitochondrial dehydrogenase. Cells were seeded in appropriate culture media and incubated for about 24 hours. The incubated cells were treated with 10 different concentrations of different crude extracts in range of 20 to 200 μg/ml. From the results obtained it was concluded that the extract of the stems showed growth inhibitory activity on MCF-7/AZ cells, while the growth of HCT-8 colon cancer cells was significantly affected by the EtOH extract of the roots.(15, 16)
Alangiumsalvifolium
The ethanolic extract of Alangiumsalvifolium leaves (EASL) was evaluated in order to determine its anticancer potential.Anticancer potential of the extract was evaluated by EAC in the doses of 100 and 200 mg/kg body weight model in Swiss albino mice. The dose was administered once a day orally for 14 days, after 24 hours of tumor inoculation. Leaves extract of Alangiumsalvifolium exhibited noteworthy decrease in tumor volume and body
weight, and also exhibited increase in total and non-viable cell count, along with raised life span of EAC-bearing mice. The EASL showed potent dose-dependent antitumor activity due to the presence of phenols and flavonoids.(17)
Allium sativum
A. sativum is well known for strengthening the immune system, which is important to combat cancer. The extracts of A. sativum control lymphocyte proliferation which was triggered by T-cells. (18)Garlic bulb possess allicin, which is responsible for the anticancer effect of garlic.
Allicin helps in inhibiting the spread of human mammary (MCF-7), endometrial, and colon(HT-29) cancer cells. (19)
Many studies have suggested that allium vegetables and garlic constituents possess anti- cancer potential. Several compounds are responsible for its anticancer effect. A. sativum contains allyl sulfur and other compounds which help in minimizing or preventing the growth of tumor cells. Allyl sulfur compounds make cells vulnerable to the stress created by products of cell division. Because cancer cells divide very rapidly, they produce more stressors than the normal cells. Thus, cancer cells are damaged by the presence of allyl sulfur compounds to a much greater extent than normal cells.(20, 21)
Emblica officinalis
It is rich in polyphenols and hydrolysable tannin derived compounds that act as antioxidants.
Emblica officinalis extract have been used from generations for the treatment of tumors.(22, 23)
Emblica officinalis extract containing polyphenols or simple aqueous extracts have also shown cytotoxic potential against cervical and ovarian cancer cells.(24)
Apoptosis was induced from aqueous extract of Phyllanthus emblica at concentrations ranging from 50 to 100 micrograms/mL. From these extracts upto 4-fold lower sensitivity was observed in normal fibroblasts. (25)
Anti-fertility
Fertility control is an important issue globally especially in developing and under-developed countries. Over population is the leading cause of poverty and pollution in developing countries as well. Population growth is responsible for many harmful effects on life surviving resources on the earth. Therefore, regulation of fertility is an important concern for the preservation of life supporting resources as well as good reproductive health of both males and females. (26, 27)
Due to the disadvantages associated with population growth, regulation of fertility comprising contraception and management of infertility forms an important component of reproductive health.(28)
Hormonal, chemical and immunological methods are the important methods which are employed for the induction of infertility in an individual. But these approaches are associated with many adverse effects like obesity, GIT trouble and carcinoma of breast and cervix, asthma and thromboembolism which minimizes their popularity and utility among women.
The hormonal contraceptives are also found to be associated with many carcinogenic effects.
Therefore, now a days, herbal products has been used a primary source of naturally occurring fertility regulating agents because of their minimal and no side effects.(29)
Several herbal plants and their products hold different types of antifertility potential for both males and females.(30)
Clinical uses of herbal medicines having antifertility potential in males Gossypium herbaceum
It is a phenolic substance which is isolated from cotton seed oil and is supposed to be used as a male contraceptive. It helps in lowering the levels of serum testosterone and luteinizing hormone in dose and duration dependent manner. Azoospermia or oligospermia is also caused by using Gossypium herbaceum as it directly acts on the testes. It also helps in inhibiting the sperm motility by blocking the process of cAMP formation. It was also found that it acts on pituitary gonadal axis and helps in decreasing the secretory activity of accessory sex glands.(31, 32, 33, 34)
Carica papaya
Methanolic extract of Carica papaya is known to have potent anti-fertility potential, when tested in rats it induced sterility because of complete suppression of sperm motility. Carica papaya also helps in inducing long term but reversible azoospermia. It causes changes in the cauda epididymal microenvironment and diminished its contractile responses. It also caused degeneration of germinal epithelium and germ cells, lowering the number of leydig cells and vacuoles in the tubules.(35, 36, 37)
Azadirachta indica
It causes alterations in the structural and functional activities of testis and spermatozoa. It helps in reducing the serum testosterone level and also causes histopathological and biochemical changes in the caput and cauda. It helps in arresting the spermatogenesis stage (late XII) by introducing mass atrophy in spermatogenic elements. Azadirachta indica also posses the spemicidal property.(38, 39)
Catharanthus roseus
It leads to impairment of epididymal functions because it possesses potential to produce pathological changes in the principle and apical cells of caput and nuclear cells of cauda.
It affected spermatogenic cell lines other than spermatogonia.(40)
Clinical uses of herbal medicines having antifertility potential in females Momordica charantia
It helps in increasing the duration of estrous cycle by exhibiting irregular pattern of estrous cyclicity. The disruption in theestrous cycle was found to be accomplished by disturbance in ovarian function and estrous cyclicity through interaction of ovarian and extraovarian hormones. Momordica charantiamay be inhibiting the estrogen production or competing for its receptor.(41)
Cannabis sativa
It has strong abortifacient activity. Substantial reduction in ovarian and uterine weight and non-significant increase in body weight is observed. Insignificant increment in serum progesterone level and decrement in serum estrogen level was also observed. Cannabis sativa is also known to significantly decrease the level of LH and FSH.(42)
Aspilia Africana
Aspilia Africana helps in prolonging proestrousand reducing diestrous and estrous phase by causing the changes in estrous cycle. It also assists in reducing the number of ova in oviduct.
It also triggers the inflammation of the fallopian tube which results in the degeneration of ovarian cortex in the stroma cells of the ovaries. Disruption in the endometrium of the uterus is also observed after using Aspilia Africana.(43)
Piper betel
Piper betel possess anti-estrogenic activity and helps in reducing the weight of the ovaries.
It also helps in reducing the circulating level of estrogen and hence the fertility. Decline in serum glucose concentration, enzyme activity of acid phosphatise, SGOT and SGPT and increase in the level of cholesterol and ascorbic acid was also observed used by its use.(44)
Coriandrum sativum
It caused significant decrease in progesterone level of serum on day-5 of progesterone indicating abortifacient activity.(45)
Trianthemaportula castrum
It has significant abortifacient activity and produces substantial surge in weight and diameter of the uterus as well as in the thickness of endometrium which specifies its mild anti- estrogenic activity.(46)
CONCLUSION
Traditional medicinal plants have received much attention due to their various beneficial properties like; low cost, ease of access and minimum side effects as compared to other synthetic medicines. This review article summarizes anti-cancer and antifertility potential of various herbal medicinal plants which are being used traditionally. The herbal medicinal plants highlighted in the present work act as anti-cancer and antifertility agents via different mechanisms. Future research is also required to better ascertain the preparation of these herbal plants in scientific manner to make them safe and effective.
Conflicts of Interest
The authors declare no conflict of interest.
Reference:
1. https://www.medicalnewstoday.com/articles/323648
2. Ignacimuthu S, Ayyanar M and Sivaraman S.K., “Ethnobotanical investigations among tribes in Madurai district of Tamil Nadu (India)”, Journal of Ethnobiology and Ethnomedicine, 2. 1. 2006.
3. Elujoba A. A., Odeleye O. M. and Ogunyemi C. M., “Traditional medicine development for medical and dental primary health care delivery system in Africa” African Journal of Traditional, Complementary and Alternative Medicines, 2. 46. 2005.
4. Tomlinson T. R. and Akerele O., “Medicinal plants: their role in health and biodiversity”
University of Pennsylvania Press, Philadelphia, 1998.
5. Gordon M. C. and David J., “Plants as a source of anti-cancer agents” Journal of Ethnopharmacology, 100. 72. 2005.
6. Brogan C. Alkaloids cancer treatments. 2010. Jun 7, [Cited on 2010 Sep 23]. Available from: http://www.Vinca alkaloids\AlkaloidsCancer Treatment Livestrong_com.mh.
7. Kufe DW, Pollock RE, Weichselbaum RR, Bast RC, Gansler TS, Holland JF, et al. 6th ed. Hamilton (ON): BC Decker Inc; 2003. Holland-Frei cancer medicine.
8. Nayak B.S., Anderson M., Pinto Pereira L.M. Evaluation of wound-healing potential of Catharanthus roseus leaf extract in rats. Fitoterapia. 2007;78(7-8):540–544.
9. Moudi M., Go R., Yien C.Y., Nazre M. Vinca Alkaloids. Int. J. Prev.
Med. 2013;4(11):1231–1235.
10. Himes RH. Interactions of the catharanthus (Vinca) alkaloids with tubulin and microtubules. PharmacolTher. 1991;51:257–67.
11. Song W., Tang Z., Li M., Lv S., Sun H., Deng M., Liu H., Chen X. Polypeptide-based combination of paclitaxel and cisplatin for enhanced chemotherapy efficacy and reduced side-effects. Acta Biomater. 2014;10(3):1392–1402.
12. Devmurari VP, Pandey S, Goyani MB, Jivani NP, Marotrao S, Sivakumar P. Evaluation of Anticancer Activity of Adiantum venustum(Don). Int J PharmacogPhy Res.
2010;2(1):5-10.
13. Ng TB, Gao W, Li L, Niu SM, Zhao L, Liu J, et al. Rose (Rosa rugosa) - flower extract increases the activities of antioxidant enzymes and their gene expression and reduce lipid peroxidation. Biochem Cell Biol. 2005;83:78–85.
14. D Viral, P Shivanand, and NP Jivani, Anticancer Evaluation of Adiantum venustum Don, J Young Pharm. 2011; 3(1): 48–54.
15. Romijn JC, Verkoelen CF, Schroeder FH. Application of the MTT-assay to human prostate cancer cell lines in vitro: establishment of test conditions and assessment of hormone-stimulated growth and drug-induced cytostatic and cytotoxic effects. Prostate.
1988;12:99–110.
16. Catherine N. Kaminski, et al., In vitro anticancer activity of Anemopsis californica, Oncol Lett. 2010 Jul; 1(4): 711–715.
17. Prathima C., et al., Evaluation of anticancer potential of ethanolic extract of alangiumsalvifolium leaves in animal models, Asian Journal of Pharmaceutical and Clinical Research, Vol. 12, no. 2, Jan. 2019, pp. 397-00.
18. Colic M, Vucevic D, Kilibarda V, Radicevic N, Savic M. Modulatory effects of garlic extracts on proliferation of T-lymphocytes in vitro stimulated with concanavalin A.
Phytomedicine 2002; 9: 117–24.
19. Hirsch K, Danilenko M, Giat J, Miron T, Rabinkov A, Wilchek M, Mirelman D, Levy J, Sharoni Y. Effect of purified allicin, the major ingredient of freshly crushed garlic, on cancer cell proliferation. Nutr Cancer 2000; 38: 245–54.
20. Hsing AW, Chokkalingam AP, Gao YT, MadiganMP, Deng J, Gridley G, Fraumeni JFJr.Allium vegetablesand risk of prostate cancer: a population-based study. J Natl Cancer Inst 2002; 94: 1648–51.
21. Agarwal KC. Therapeutic actions of garlic constituents. Med Res Rev 1996; 16: 111–24.
22. Yang B., Liu P. Composition and biological activities of hydrolyzable tannins of fruits of phyllanthusemblica. Journal of Agricultural and Food Chemistry. 2014;62(3):529–541.
23. Unander D. W., Webster G. L., Blumberg B. S. Records of usage or assays in Phyllanthus (Euphorbiaceae) I. Subgenera Isocladus, Kirganelia, Cicca and Emblica, Journal of Ethnopharmacology, 1990;30(3):233–264.
24. De A., Papasian C., Hentges S., Banerjee S., Haque I., Banerjee S. K. Emblica officinalis extract induces autophagy and inhibits human ovarian cancer cell proliferation, angiogenesis, growth of mouse xenograft tumors. PLoS ONE. 2013;8(8).
25. Ngamkitidechakul C., Jaijoy K., Hansakul P., Soonthornchareonnon N., Sireeratawong S.
Antitumour effects of Phyllanthus emblica L.: induction of cancer cell apoptosis and inhibition of in vivo tumour promotion and in vitro invasion of human cancer cells. Phytotherapy Research. 2010;24(9):1405–1413.
26. Gupta RS and Sharma R: A review on medicinal plants exhibiting antifertility activity in males. Natural product radiance 2006; 5:389-410.
27. Mamatha A, Elumalai A, Eswaraiah MC, Mathangi N: An updated review on antifertility plants-2012. International Journal of Pharmacotherapy 2012; 2:4-6.
28. Allag IS and Rangari K: Extragenomic action of steroids on spermatozoa: Prospects for regulation of fertility. Health Population 2002; 25:38-44.
29. Bhowmik D, Umadevi M, and Kumar PKS and Duraivel S: Medicinal Plants with Potential Antifertility Activity. Journal of Medicinal Plants Studies 2013; 1:26-33.
30. Saravanan K, Priya G and Renuka C: Medicinal plants with potential antifertility activity- A review of sixteen years of herbal medicine research (1994-2010). International Journal of Pharm Tech Research 2012; 4:481-494.
31. Sultana Arshiya et al; Gossypium herbaceum Linn: An Ethnopharmacological Review, 1 (5), Sept – Oct 2012, 1-5.
32. Hadley MA, Lin YC and Dym M: Effect of gossypol on reproductive system of male rats.
Journal of Andrology 1981; 2:190-199.
33. Taitzoglou IA, Tsantarliotou M, Koretas D and Kokolis NA: Gossypol induced inhibition of plasminogen activator activity in humans and ovine acrosomal extract. Andrologia 1999; 31: 355-359.
34. Zavos PM and Zavos ZPN: The inhibitory effect of gossypol on human sperm motility characterstics: Possisible modes of reversibility of those effects. Tohoku Journal of Experimental Medicine 1996; 179:167-175.
35. Lohiya NK, Manivannan B, Mishra PK, Pathak N, Sriram S, Bhande SS and Panneerdoss S: Chloroform extract of Carica papaya seeds induces long term reversible azoospermia in langur monkey. Asian Journal of Andrology 2002; 4:17-26.
36. Pathak N, Miashra PK, Manivannan B and Lohiya NK: Sterlity due to inhibition of sperm motility by oral administration of benzene chromatographic fraction of the chloroform extract of the seeds of Carica papaya in rats. Phytomedicine 2000; 7:325-333.
37. Udoh P and Kehinde A: Studies on antifertility effect of pawpaw seeds (Carica papaya) on the gonads of male albino rats. Phytotherapeutic Research 1999; 13:226-228.
38. Shaikh PD, Manivannan B, Pathar KM, Kasturi M and Ahmed RN: Antispermatic activity of Azadirachta indica leaves in albino rats. Current Science 1993; 64: 688-689.
39. Kasturi M, Manivannan B, Ahmed RN, Shaikh PD and Pathar KM: Changes in epididymal structure and function of albino rat treated with Azadirachta indica Indian Journal of Experimental Biology 1995; 33:725-729.
40. Averal HI, Stanley A, Murugaian P, Polanisamy A and Akborsha MA: Specific effect of vincristine on epididymis. Indian Journal of Experimental Biology 1996; 34:53-56.
41. Ifeanyi AC, Eboetse YO, Ikechukwu DF, Adewale OA, Carmel NC and Olugbenga OA:
Effect of Momordica charantia on estrous cycle of sprague-dawley rats. Pacific Journal of Medical Sciences 2011; 8: 6.
42. Zade V, Wikhe M, Dabhadkar D, Dawada S and Patil U: Antifertility efficacy of Cannabis sativa leaves on female albino rats. International Journal of Science Inventions Today 2013; 2:107-117.
43. Oyesola TO, Oyesola OA and Okoye CS: Effects of aqueous extract of Aspilia africana on reproductive functions of female Wistar rats. Pakistan Journal of Biological Sciences 2010; 13:126-131.
44. Sharma JD, Sharma L and Yadav P: Antifertility Efficacy of Piper betel (Petiole) on Female Albino Rats. Asian Journal of Experimental Sciences 2007; 21:145-150.
45. Al-Said MS, Al-Khamis KI, Islam MW, Parmar NS, Tariq M and Ageel AM: Post-coital antifertility activity of the seeds of Coriandrum sativum in rats. Journal of Ethnopharmacology 1987; 21:165-173.
46. Pare S, Zade V and Dabhadkar D: Evaluation of potential antifertility activity of plant Trianthemaportula castrum in female albino rat. Int. J.A.PS.BMS. 2013; 2:007-011.
