INTRODUCTION:

Ayurveda is one of the most ancient traditional systems of medicine that has been originated in the age of ascetics. Ayurveda means ‘Knowledge of Life’. It is comprised of two Sanskrit words ‘Ayu’ i.e. life and ‘Veda’ i.e. knowledge of science. The knowledge of ancient traditional medicines was progressed from the saints to their followers and afterwards to the common people by different ways¹. In India, there is a wide variety of traditional systems of medicine, but Ayurveda is the most practiced and used by masses, since several centuries. Some of the other conventional systems of medicine in India are Homeopathy, Unani, Siddha, Naturopathy and Yoga². In the last ten years, Ayurveda has experienced more popularity and increased interest of researchers, towards its applications³.

In the 21st century, due to change in environmental condition and toxins, pollution, unhealthy lifestyle and excess intake of allopathic medicines increases the risk of diseases like diabetes, hypertension, renal diseases and obesity has increases⁴.

Indian society and traditional medicine:

Since thousands of years, plants have been a significant source of medicinal agents and a rich source of unconventional medicinal agents. More than 200,000 varieties of indigenous plants have been investigated methodically for their medicinal purposes in different medicinal systems, and it is found that around 5–15% of these could be a very good source of new biologically active compounds and may be used as pharmacotherapeutic agents⁵. Derivatives of herbal products and medicines made from herbal plants are very effective in the healthcare system because they are cost effective, bio-friendly, relatively safe and easily available mainly in developing countries. Herbal plants are important source of effective medicinal agents, for e.g. reserpine, noscapine, codeine, sennoside, guggul steroids, deserpidine, digitalis cardiac glycosides, vinica alkaloids, morphine, artemisin, guggulsterone and ginkgotoxin, that have been included directly or their synthetic analogues included into different herbal medicines^6-7. India has abundance of herbs and has ability to supply medicinal plants for fulfilling its global requirements⁸. In India, approximately 65% to 70% of contemporary medicines are obtained from herbal sources and plants are served as lead for most of synthetic drugs⁹. It is estimated that only very few (around 6-7%) of plant species of all therapeutically important plants have been analyzed chemically and a very small portion of it have been analyzed pharmacologically.

Herbal medicine and its importance in India:

Around seventy percent of the Indian people utilize herbs or herbal medicines for their wellbeing¹⁰. In different conventional system of medicines, plants/herbs have been important source of drugs for the treatment of different diseases. In the 21st century, people are opting for herbal products and herbal medicines for improving their health. People have been using herbal medicines as therapeutic agents (alone or in combination with other agents). As per World-Health-Organization report, a large population worldwide is using herbal products for their primary healthcare requirements. Herbal medicines are combination of whole herbs, herbal substance (like different parts of plants), and active ingredients of plants origin or processed and finished herbal preparations^11-12.

In India, since Vedic eras, a huge number of plants are being used in different conventional medicinal systems. Around 1200 to 1800 plants are included in Ayurveda, while in other traditional systems like Siddha, 500 to 900 plants are included. In Amchi medicine system, around 300 plants are used while in Unani medicine system around 400 to 700 medicinal plants are used. Almost 8000 medicinal plant species are used by folk medicines and 25,000 plants based effective formulations are used by the ethnic and rural communities of India for the treatment of different diseased conditions^13-14.

Status of renal disease at national level:

Renal failure is now a days, fast growing problem of early adult mortality in India, which is due to the improper treatment of diabetes, mainly in non-rural areas¹⁵. Availability of dialysis and renal transplantation is not proportionate and it is not enough with the huge increasing number of renal patients. Greater concentration should be given to reduce kidney failure as well as to provide cost effective availability of prophylactic and curative measures, in India and other developing countries.

In India, survey has been done to compare data of the years 2001-2003 and 2010-2013 for estimating the number of premature adult deaths from kidney failure, due to hyperglycaemia, hypertension, and heart disease. Diet is also a major contributing factor for the renal failure. Between year 2001 and 2003, in the age group of 15 to 69 years, around 2% of total mortality was due to kidney failure. In India, by 2010 -13, the percentage of deaths due to kidney failure, had risen to around 2.9%. By 2015, these numbers have increased to around 3%, which represents around 136000 Indian adults, who died prematurely. These numbers are around 1.5 times of the numbers observed a decade earlier. These observations show that there is a rapid increase in the number of premature adult deaths and this is much more in comparison to deaths from other communicable diseases in the rural areas and non-infectious diseases in the city and suburban areas.

In modern system of medicine, the conception of nephroprotection is not very old and it was not very common before year 1980. The renal diseases and their development to kidney failure (both acute and chronic) have complex mechanism and its management is also very difficult. Most of the cases of kidney disease still remain undiscovered until they develop to very advanced stages and at that stage conventional medicines are not sufficient to treat these conditions. However, the main difficulty with renal disease is its development to a condition, where the only useful option is the renal replacement therapy (RRT). The main constituents of renal replacement therapy (RRT) are dialysis and kidney replacement. Both of these procedures are highly complex and very costly, so not affordable for ordinary income group. Only a very small high-income group population can afford such type of advanced treatment, subject to its availability in their reach. In the developing countries like India, majority of the renal disease patients are not getting treatment and are left to die due to lack of renal replacement therapy facilities or due to its high cost. So it has forced the researchers and doctors to go for different other means of preserving the kidney function and also slow the progression of renal disease. It will help in protecting the kidney and avoid need of RRT. A drug, which acts as a nephroprotective agent and doesn’t have any major side effect, will be the best option for renal dysfunction patients.

Medicinal herbal plants are a rich source of natural antioxidants and are utilized for the cure of different diseases worldwide¹⁶. Some of these properties are antimicrobial¹⁷, anticancer¹⁸, anti-diabetic¹⁹, anti-atherosclerosis²⁰, immunomodulatory²¹ and even nephroprotective or liver protective. In some of recent-time studies, a huge number of medicines derived from herbal plants, have demonstrated very good nephroprotective action.

Status of renal disease at international level:

In the year 2015, a survey was conducted regarding total mortality due to different diseases. Renal disease was the twelfth most usual cause of premature death, and it was more than one million deaths in the world. In last ten years, overall death rate due to Chronic Kidney Disease (CKD) has increased to more than 30% and has become one of fastest growing causes of mortality. Out of different life-threatening diseases, which are causing huge loss of human life years globally, Chronic Kidney Disease is at 17^th position and has increased by more than 18% since year 2005. Since 2005, Chronic Kidney Disease has seen 3^rd fastest increase in comparison to other major causes of deaths. Number of life year’s loss due to Chronic Kidney Disease is quite high, in comparison to other non-infectious diseases like CVS and COPD, where during the same time-period; global life years’ loss has come down to 10.2% and 3.0% respectively. During years 2005 to 2015, the pervasiveness of renal disease had increased to around 40% worldwide. Mexico is the country, with highest rate of worldwide deaths, due to Chronic Kidney Disease and more than 50% of these are reported due to diabetes. In other developing countries like India, Indonesia and China etc., similar disease patterns have been reported and these patterns are indicating that there is shift in metabolic diseases and other factors associated with heart diseases²². The major consequence of Chronic Kidney Disease, like early cardiovascular death or development to last stage renal disease, are expected to happen in people with Chronic Kidney Disease in India than in the people from North American countries due to lack of proper treatment. In India, patients are treated with drugs having serious side effects e.g. Angiotensin Converting Enzyme inhibitors and/or oral anti-diabetic agents²³.

As per very orthodox estimates, in the last decade, more than 50% patients have died worldwide due to lack of kidney donors and unavailability of dialysis facility. Huge disparities were observed in the access of kidney transplant in African countries (mainly eastern and middle Africa). In these countries, very few patients (< 3%) people have access to kidney transplant²⁴. Huge burden of Chronic Kidney Disease is mainly observed in those countries, which have poor facilities of costly and life-saving treatment of kidney transplant and dialysis. Though good treatment options are available, but due to high treatment cost, majority of Chronic Kidney Disease patients are continuously dying. The high cost of kidney transplant is a major economic reason for making improvements in preventing, detecting and managing the Chronic Kidney Disease in middle-income and low-income countries. In the majority of middle and low-income countries, there is very less public/government funding (~40%) for the management of associated risk factors for prevention of progression of Chronic Kidney Disease and treatment of the associated complications.

Supervision of Chronic-Kidney-Disease by using approximated UAC (urinary albumin creatinine) ratio and GFR (glomerular filtration rate) is available in very less number (< 20%) of low and middle income countries (WHO, 2010). There is a big shortage of nephrologists worldwide, because approximately 35% of lower-income countries lack a nephrology training program²⁵. So it is very necessary to improve the primary care services for proper management of Chronic Kidney Disease. Cuba, Uruguay and Chile are some of the successful countries, which are very well managing screening, detection and treatment of Chronic Kidney Disease²⁶.

Herbal plants’ demand is increasing in developing countries like India. Investigation of herbal plants is an important field of analysis worldwide. There is a requirement to concentrate on the biological safety assessment of medicinal plants^27-28. Renal failure is one of the common diseases in India. Infact, along with nutritional therapy, herbal formulations were used for the treatment of different diseases before the era of modern system of allopathic medicine²⁹. These herbal plants can acclimatize to reduce the dialysis requirement, by curing the causes and alter symptoms of renal failure and also helpful in reducing side effects of dialysis³⁰.

Nephrotoxicity and herbal nephroprotective agents:

Human kidneys are two in number, reddish brown in colour, like bean in shape and lie on either side of vertebral column in lumber region. Kidney is concerned with maintenance of overall chemical composition of intracellular environment by regulating sodium, potassium, chloride, phosphate and water. Kidney is responsible for metabolism of most therapeutic agents such as NSAID’s, aminoglycoside antibiotics (e.g. gentamycin, streptomycin, kanamycin), anticancer agents (e.g. cyclophosphamide, cisplatin). Exposure to few toxic agents such as sodium oxalate and heavy metal elements (e.g. mercury, cadmium, lead, arsenic etc.), ethylene glycol, carbon tetrachloride, also produces nephrotoxicity. Adverse effect of all these agents on kidney causes nephrotoxicity, which may results in acute renal failure (reversible loss of renal function), chronic renal failure (irreversible loss of renal function), chronic renal nephritis and nephritic syndrome etc. Prompt recognition of the disease and discontinuation of responsible drugs are usually the only necessary therapy.

The substances or agents, which possess protective activity against nephrotoxicity, are called as Nephroprotective agents. Medicinal plants have properties to cure diseases, which occur due to the presence of various phytoconstituents. From literature review, it has been proved that medicinal plants have ability to cure nephrotoxicity. For the cure of renal failure, a number of plants are used in different traditional medicinal system worldwide, e.g. Withania somnifera, Tribulus terresteris, Angelica radix, Boerhavia diffusa, Piper cubeba, Picrorhiza kurrooa, Astragalus membranaceus. Some other plants used for nephroprotection are Tinospora cordifolia, Ginko biloba, Glycyrrhizae radix, Zingiber officinale, Salvia miltiorrhiza, Ephedra distachya³¹. Before initiation of allopathic system of medicine, herbal preparations (along with the nutritional supplements) were used for treatment of diseases. In view of this context, it is a valuable thought to assess the native plants which would be useful as adjunct as nephroprotective. This helps to reduce the adverse effects of the nephrotoxic agents like gentamicin, cyclophosphamide, acetaminophen etc.

Here is a list of few selected plants they are used in different Indian traditional medicine for their nephroprotective action. The extract of different parts of selected plants have dose dependent nephroprotection action in drug-induced nephrotoxicity in different animal models.

Medicinal Herbs against Drug Induced Nephrotoxicity:

Medicinal plants are an effective source of both traditional and modern medicines. About 80% of rural population depends on it as primary health care. [WHO, (2005)]. Phytochemicals such as tannins, alkaloids, carbohydrates, terpenoids, steroids and flavonoids are widely used in the human therapy, veterinary, agriculture, scientific research and countless other areas. These phytoconstituents are extracted by using extraction technique like maceration, infusion, percolation, decoction, Soxhlet extraction (Hot continuous extraction) with the solvents like water, alchohol or mixture of both. These extracts are often used as such for nephroprotective activity against drug-induced nephrotoxicity and some of the medicinal plants are given below in Table-1.

Table-1: List of Nephroprotective Plants

S. No.	Name of Plant	Family	Common Name	Part Used	Animal Study	Plant Picture
1.	Croton zambesicus	Euphorbiaceace	Rushfoil	Root	Ethanolic extract of root (27 and 54 mg/kg per day) showed significant protective effect in gentimicin-induced kidney injury and this activity is due to the flavonoids constituent of the root³².
2	Solanum xanthocarpum	Solanaceae	Kateli	Mature fruit	Ethanolic extract of fruit (200-400 mg/kg single dose) showed significant protective effect in gentimicin-induced kidneyinjury in both biochemical and histopathological parameter³³.
3.	Biophytum sensitivum	Oxalidaceae	Little tree plant, Makahia	Whole plant	Aqueous and methanol extracts of whole plant (200 mg/kg per day) showed significant nephroprotective activity in gentamicin induced nephrotoxicity³⁴.
4.	Bauhinia variegata	Caesalpiniaceae	Kanchanar	Leaves	Methanolic leaf extract of the plant (400 mg/kg per day) has significant nephroprotective activity in gentamicin-induced nephrotoxicity³⁵.
5.	Trema guineensis	Ulmaceae	Charcoal tree	Leaves	The aqueous extract and hydroalcholic extract of leaves (200 mg/kg per day) possessed good nephroprotective activity in gentimicin-induced nephrotoxicity³⁶.
6.	Elephantntophus scaber	Asteraceae	Elephant’s foot	Leaves	Ethanolic leaf extract of the plant (200-600 mg/kg per day) has significant nephroprotective activity in gentimicin-induced nephrotoxicity³⁷.
7.	Tinospora cordifolia	Menispermaceae	Giloy	Roots	Hydralcholic extract of roots (250-400 mg/kg per day per oral for) for 10 day in Cisplatin inducedNephrotoxicity model³⁸.
8.	Indigofera tinctoria	Fabaceae	Indigo	Root, leaves	Decoctionofroot andleaves (500 - 1000 mg/kg / day for 14 days) showed profund significant nephroprotection in cisplatin-induced nephrotoxicity³⁹.
9.	Annona reticulata	Annonaceae	Custard apple	Aerial parts	Ethanolic extract of aerial parts (250-500 mg/kg per day per oral for) 24-day and 15-day Gentamicin and Cisplatin-induced Nephrotoxicity model⁴⁰.
10.	Urtica diocia	Urticaceae	Nettle	Whole plant	Ethanolic extract of the whole plant (100 mg/kg per day) for 10 day has significant nephroprotection in gentimicin-induced nephrotoxicity in male rabbit⁴¹.
11.	Murraya Koenigii	Rutaceae	Curry leaves	Leaves	Methanolic and aqueous leaf extract of the plant (100-200 mg/kg per day) has significant nephroprotective activity in cyclophosphamide-induced nephrotoxicity⁴².
12.	Hemidesmus Indicus	Apocynaceae	Anantmul	Root, Bark	Ethanolic extract of roots (250 and 500 mg/kg) have significant nephroprotective activity in Cisplatin induced Nephrotoxicity model⁴³.
13.	Tribulus terrestris	Zygophyllaceae	Hard thorns	Fruit	Ethanolic extract of fruit has significant dose dependant protection against uroliths induced by glass bead implantaion in rats.⁴⁴
14.	Aerva lanata	Amaranthaceae	Mountain knot grass	Whole plant	Ethanolic extract ofWhole plant (200 mg/kg and 400 mg/kg/day per oral) have profound effect on Mercuric chloride induced renal harm in rats⁴⁵.
15.	Vitex negundo	Verbenaceae	Begunia	Root	Methanol and dichloromethane (1:1) extracts of root (200 mg/kg/per oral) for 7 days showed the significant nephroprotection against gentamicin induced nephrotoxicity⁴⁵.
16.	Oroxylum indicum Vent	Bignoniaceae	Tatelo	Whole plant	Methanol and dichloromethane (1:1) extracts of root (200 mg/kg; per oral) for 7 days showed the significant nephroprotection against gentamicin induced nephrotoxicity⁴⁵.
17.	Barringtonia acutangula Linn	Barringtoniaceae	Hinjal	Leaves	Methanol-dichloromethane (1:1) extracts of root (200 mg/kg; per oral) for 7 days showed the significant nephroprotection against gentamicin induced nephrotoxicity⁴⁶.
18.	Moringa oleifera	Moringaceae	Drumstick	Leaves	Aqueous and ethanolic extract of leaves (150 -300mg/kg) showed the significant nephroprotection against gentamicin induced nephrotoxicity in rabbit⁴⁷.
19.	Crataeva nurvala	Capparidaceae	Varuna	Stem bark	Ethanolic extract of leaves (200-600mg/kg) showed the significant nephroprotection against cisplatin induced nephrotoxicity in albino rat⁴⁸.
20.	Aerva javanica	Amaranthaceae	Dessert Cotton	Root	Aqueous extract of roots 400 mg/kg) showed significant nephroprotection in cisplatin induced nephrotoxicity in rats⁴⁹.
21.	Scrophularia hypericifolia	Scrophulariaceae		Aerial parts	Ethanolic extract of aerial parts (250-500 mg/kg) showed the significant nephroprotection against paracetamol induced nephrotoxicity in albino rats⁵⁰.
22.	Pedalium murex	Pedaliaceae	Big Gokhru	Fruit	ethanolic and aqueous extracts of fruits(600 mg/kg/ per oral) showed significant nephroprotection in gentamicin-induced renal toxicity in rats⁵¹.
23.	Ficus religiosa	Moraceae	Peepal	Latex	Methanolic extracts of latex (200 mg/kg of body weight) showed nepheroprotective activity in cisplatin induced acute renal failure in wistar adult male rats⁵².
24.	Coleus aromaticus	Lamiaceae	Indian Mint	Aerial Parts	Aqueous extract of whole plant (500 mg/kg) showed significant effect on Glycerol induced Acute Renal Failure (ARF) in albino rats⁵³.

CONCLUSION:

By observing the effect of various medicinal plants in treatment of drug induced nephropathy in animal models, we can say that herbal plants assume a pronounced role as nephroprotective agents. This nephroprotection may be due to the chemical constituents present in these medicinal herbs. This review article provide support for exploration of these medicinal plants for researchers to develop cost effective competent polyherbal formulation in the future.

CONFLICTS OF INTEREST:

We do not have conflicts of interest with publication of this manuscript.

REFERENCES:

1. Yogini S, Jaiswal L, Williams L. A glimpse of Ayurveda: the forgotten history and principles of Indian traditional medicine. Journal of Traditional Complimentry medicine. 2017; 7: 50-53.

2. Mukherjee P. Evaluation of Indian traditional medicine. Drug Information journal 2001; 2: 623.

3. Sen S and Chakraborty. Towards the integration and advancement of herbal medicine: a focus on Traditional Indian medicine. Biologics: Targets Therapy 2015; 5: 33-44.

4. Saikat S, Chakraborty R. Revival, modernization and integration of Indian traditional herbal medicine in clinical practice, Importance, challenges and future. Journal of Traditional Complimentry medicine 2017; 7: 234-244.

5. Cragg GM, Newman DJ. Biodiversity: A continuing source of novel drug leads, Pure Applied Chemistry 2005; 77: 7-24.

6. Kamboj V. Herbal medicine or modern medicine, Current Science 2000; 78: 35-39.

7. Mukherjee P K, Ponnusankar S and Venkatesh M. Ethno medicine in complementary therapeutics. In: Chattopadhyay D, editor. Ethanomedicine: A Source of Complementary Therapeutics. Trivandrum (India), Research Signpost 2010: 29-52.

8. Verma S and Singh S P: Current and future status of herbal medicines. Veterinary World 2008; 1: 347-50.

9. Sharma A, Shanker C, Tyagi L K, Singh M. and Rao Ch V: Herbal medicine for market potential in India: an overview. Journal of Plant Sciences 2008; 1: 26-36.

10. Vaidya A D B. Devasagayam T P A. Current status of herbal drugs in India: an overview. Journal of Clinical Biochemistry and Nutrition 2007; 4: 1-11.

11. Litscher G. Gao S. Historical perspective of traditional indigenous medical practices: the current renaissance and conservation of herbal resources, Evidence Based Complementary and Alternative Medicine 2014; 1-20. http:// dx.doi.org / 10.1155 / 2014/ 525340.

12. Sen S, Chakraborty R, De B, Ganesh T, Raghavendra H G and Debnath S. Analgesic and inflammatory herbs: a potential source of modern medicine. International Journal of Pharmaceutical Science and Research 2010; 1: 32- 44.

13. Sen S, Chakraborty R, De B and Mazumder J. Plants and phytochemicals for peptic ulcer: an overview. Pharmacognosy Review 2009; 3: 270-279.

14. Debnath P K, Banerjee S, Debnath P, Mitra A and Mukherjee P K. Ayurveda - opportunityfor developing safe and effective treatment choice for the future. In: Mukherjee P K, Evid. Based Validation Herb. Med., Amsterdam, Elsevier Science Publishing Co Inc 2015; 27-454.

15. Yadav S, Arokiasamy P: Understanding epidemiological transition in India. Global Health Action 2014; 7: 232-48.

16. Kopaei M R, Baradaran A Rafieian M. Oxidative stress and the paradoxical effects of antioxidants. Journal of Research in medical Sciences 2013; 18(7): 629.

17. Sharafati-Chaleshtori R, Sharafati-Chaleshtori F. Rafieian M. Biological characterization of Iranian walnut (Juglans regia) leaves. Turkish Journal of Biology 2011; 35: 635-639,

18. Shirzad H, Taji F, Pourgheysari B, Raisi S and Rafieian-Kopaei M. Comparison of antitumour activities of heated and raw garlic extracts on fibro sarcoma in mice. Journal of Babol University of Medical Sciences 2012; 14: 77-83.

19. Kazemi Z, Chang H, Haserodt S, McKen C, Zachara N E. O-linked beta-N-acetylglucosamine (O-GlcNAc) regulates stress-induced heat shock protein expression in a GSK-3beta-dependent manner. Journal of Biolgical Chemistry 2010; 10: 285.

20. Khosravi-Boroujeni H, Mohammadifard N, Sarrafzadegan N, Sajjadi F, Maghroun M, Khosravi A, Alikhasi H, Rafieian M. and Azadbakht L. Potato Consumption and Cardiovascular Disease Risk Factors Among Iranian Population. International Journal of Food Science and Nutrition 2012; 63(8): 913-20.

21. Shirzad M, Karimi A, Armadi S H, Marzban M, Abbasi K, Alinejad B and Moshtaghi N. Effects of body mass index on early outcome of coronary artery bypass surgery. Minerva Chirurgica 2009; 64(1): 17-23. Wang H, Naghavi M and Allen C. GBD 2015 Mortality and Causes of Death Collaborators. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study. The Lancet 2016; 388: 1459-544.

22. Tonelli M, Agarwal S, Cass A, et al. How to advocate for the inclusion of chronic kidney disease in a national non-communicable chronic disease program. Kidney International Journal 2014; 85: 1269-74.

23. Liyanage T, Ninomiya T, Jha V, et al. Worldwide access to treat end-stage kidney disease: a systematic review.The Lancet 2015; 385: 1975-82.

24. Bello A K L A, Tonelli M, Okpechi I G, et al. Global Kidney Health Atlas: A report by the International Society of Nephrology on the current state of organization and structures for kidney care across the globe. Kidney International Supplements 2017; 7 (2): 145-153.

25. Jha V, Garcia-Garcia G, and Iseki K, et al. Chronic kidney disease: global dimension and perspectives. The Lancet 2013; 382: 260-72.

26. Porter G A and Bennett W M. Nephrotoxic Acute Renal Failure Due to Common Drugs. American Journal of Physiology 1981; 241: 252-256.

27. Sundararajan R, Bharampuram A, Koduru R. A Review on Phyto-constituents for Nephroprotective Activity. Pharmacognosy Magzine 2014; 5: 160- 182.

28. Srivastava A K, Kaushik D, Lal V K. Nephroprotective Ethno-medicinal Action of Selected Indian Medicinal Plants. Der Pharmacia Sinica 2017; 8(1):1-24.

29. Talele B D, Mahajan R T, Chopda M Z, Nemade N V. Nephroprotective Plants: A Review. International Journal of Pharmaceutical Science 2012; 4(1): 8-16.

30. Qazi Z A, Nasreen J, Ghufran A, Tajuddin. An Appraisal of Nephroprotection and the Scope of Natural Products in Combating Renal Disorders. Journal of Nephrology Therapeutics 2014; 4(4): 1-6.

31. Okokon J E, Nwafor P A, Noah K. Nephroprotective effect of Croton zambesicus root extract against gentimicin-induced kidney injury, Asian Pacific Jornal of Tropical Medicine 2011; 969-972.

32. Hussain T, Gupta R K, Sweety K, Bavani E, Vijayakumar M, Rao C V. Nephroprotective activity of Solanum xanthocarpumfruit extract against gentamicin-induced nephrotoxicity and renal dysfunction in experimental rodents, Asian Pacific Jornal of Tropical Medicine 2012; 686-691.

33. Chandavarkar S, Desai S N M and Gautam G. Nephroprotective activity of different extracts of Biophytum sensitivum (Linn.) DC. International Journal of Herbal Medicine 2017; 5(1): 31-34.

34. Prusty K B, Harish B, Mamatha C H. Evaluation of Nephroprotective Activity of the Methanolic Extract of Leaves of Bauhinia variegata Linn, (Family-Caesalpiniaceae). Journal Pharmaceutical Science and Technology 2012; 1: 16-19.

35. Droucoula G C, Kouakou S L, Kouakou Y K F, Bamba A, Yapi H F and Okpekon A T: Evaluation of Nephroprotective Activity of Aqueous and Hydroethanolic Extracts of Trema guineensis Leaves (Ulmaceae) against Gentamicin-Induced Nephrotoxicity in Rats. International Journal of Biochemistry Research and Review 2016; 15(2):1-10.

36. Sahoo H B, Swain S R, Nandy S, Sagar R and Bhaiji A, Nephroprotective Activity of ethanolic Extract of Elephantophus scaber Leaves on Albino Rats, International Research Journal of Pharmacy 2012: 246-250.

37. Uppuluri S, Ali S L, Nirmala T, Shanthi M, Sipay B, Uppuluri K B. Nephroprotector activity of hydroalcoholic extract of Tinospora cordifolia roots on cisplatin induced nephrotoxicity in rats. Drug Invention Today 2016; 5:281-287.

38. Priyadarsini G, Kumar A, Anbu J, Ashwini A, Ayyasamy S. Nephroprotective activity of Decoction of Indigofera Tinctoria (Avuri Kudineer) against Cisplatin-Induced Nephropathy in Rats. International Journal of Life Science and Pharma Research 2012; 2(4): 56-61.

39. Aparna R L D M, Deepika M Y, Nagaraju B, Prasad K. Evaluation of Nephroprotective Activity of Ethanolic Extract of Annona reticulata in Gentamicin and Cisplatin Induced Nephrotoxicity in Rats. Journal of Pharmaceutical Science and Research 2016; 8(9): 995-1007.

40. Salih N A. Effect of nettle (Urtica dioica) extract on gentamicin induced nephrotoxicity in male rabbits. Asian Pacific Journal of Tropical Biomedicine 2015; 5(9):756-760.

41. Mahipal P and Pawar R S. Nephroprotective effect of Murraya koenigiion cyclophosphamide induced nephrotoxicity in rats. Asian Pacific Jornal of Tropical Medicine 2017; 10(8): 808-812

42. Kaur A, Singh S, Shirwaikar A and Setty M M: Effect of Ethanolic Extract of Hemidesmus indicus Roots on Cisplatin Induced Nephrotoxicity in Rats. Journal of Pharmacy Research 2011; 4(8): 2523-2525.

43. Wenyi Z, Yijie D, Hong M, Yinmao D, Li L. A review of traditional pharmacological uses, phytochemistry, and pharmacological activities of Tribulus terrestris. Chemistry Central Journal 2017; 1-16.

44. Soumya P, Poornima K, Kumar G R, Kalaiselvi M, Gomathi D, Uma C. Nephroprotective effect of Aerva lanata against Mercuric chloride induced renal injury in rats. Journal of Pharmaceutical Research 2011; 4(1): 2474

45. Mishra S, Pani S R, Saho S. Anti-nephrotoxic activity of some medicinal plants from tribal rich pockets of Odisha. Pharmaceutical Research 2014; 6 (3): 210-217.

46. Ouédraogo M, Lamien S A, Ramdé N, Ouédraogo A S, Ouédraogo M, Zongo S P, et al. Protective effect of Moringa oleifera leaves against gentamicin-induced nephrotoxicity in rabbits. Experimental and Toxicologic Pathology 2013; 65(3): 335-339.

47. Shelkea T T, Bhaskar V H, Adkara P P, Jha U, Oswala R J. Nephroprotective activity of ethanolic extract of stem barks of Crataeva nurvala Buch Ham. International Journal of Pharmaceutical Science and Research 2011; 2(10): 2712-17.

48. MovaliyaaV, Khamarb D, Setty M M. Nephro-protective activity of aqueous extract of Aerva Javanica roots in cisplatin induced renal toxicity in rats. Journal of Pharmacolgy 2011; 1:68-74.

49. Alqasoumi S I. Evaluation of the hepatroprotective and nephroprotective activities of Scrophularia hypericifolia growing in Saudi Arabia. Saudi Pharmaceutical Journal 2013; 1-6.

50. Sreedevi A, LathaY J P and Bharathi K: Protective effect of fruits of Pedalium murex against gentamicin -induced nephrotoxicity in rats. International Journal of Phytopharmacolgy 2011; 2(9): 27-36.

51. Yadav YC, Srivastava D N. Nephroprotective and curative effects of Ficus religiosa latex extracts against cisplatin-induced acute renal failure. Pharmaceutical Biology 2013; 11: 1480-1485.

52. Preeja G, Pillai P, Suresh, Aggarwal G, Doshi G, Bhatia V. Pharmacognostical standardization and toxicity profile of the methanolic leaf extract of Plectranthus amboinicus (Lour) Spreng. Journal of Applied Pharmaceutical Science 2011; 1(1): 75-81.

Received on 24.01.2020 Modified on 21.02.2020

Research J. Pharm. and Tech. 2021; 14(2):1183-1189.

DOI: 10.5958/0974-360X.2021.00211.0