A Comprehensive Review on Plant derived Natural products for Diabetes and its complication as nephropathy

  • Pankaj G. Jain R.C. Patel Institute of Pharmaceutical Education and Research, Near Karwand Naka, Shirpur-425 405, Dist- Dhule, Maharashtra, India.
  • Priti G. Nayse R.C. Patel Institute of Pharmaceutical Education and Research, Near Karwand Naka, Shirpur-425 405, Dist- Dhule, Maharashtra, India.
  • Dipali J. Patil R.C. Patel Institute of Pharmaceutical Education and Research, Near Karwand Naka, Shirpur-425 405, Dist- Dhule, Maharashtra, India.
  • Sanjay J. Surana R.C. Patel Institute of Pharmaceutical Education and Research, Near Karwand Naka, Shirpur-425 405, Dist- Dhule, Maharashtra, India.


Diabetic nephropathy is one of the most severe microangiopathies of diabetes taking heavy toll on human lives. Diabetic nephropathy is characterized by the accumulation of extracelluar matrix protein leading to irreversible decline in renal function and end stage renal disease. Incomplete knowledge about molecular mechanism underlying nephropathy limit the use of modern medicines to treat this clinical entity. Moreover, current standard of therapy for diabetic nephropathy mainly focus on reduction in hyperglycemia and hypertension. These therapies have limited effect on delaying nephropathy progression. A pressing need for novel therapies initiated studies targeting various molecular pathways involved in nephropathic changes. Herbal medicines with beneficial phytochemicals are reported to delay the progression of nephropathic changes in diabetes in various experimental studies. This review try to summarize various phytoconstituents proved to be effective in management of diabetic nephropathy. The goal is to identify promising phytoconstituents that can be translated into beneficial therapeutic options.

Keywords: Diabetic complications, Medicinal plants, Phytoconstituents, Oxidative stress.


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Author Biographies

Pankaj G. Jain, R.C. Patel Institute of Pharmaceutical Education and Research, Near Karwand Naka, Shirpur-425 405, Dist- Dhule, Maharashtra, India.

R.C. Patel Institute of Pharmaceutical Education and Research, Near Karwand Naka, Shirpur-425 405, Dist- Dhule, Maharashtra, India.

Priti G. Nayse, R.C. Patel Institute of Pharmaceutical Education and Research, Near Karwand Naka, Shirpur-425 405, Dist- Dhule, Maharashtra, India.

R.C. Patel Institute of Pharmaceutical Education and Research, Near Karwand Naka, Shirpur-425 405, Dist- Dhule, Maharashtra, India.

Dipali J. Patil, R.C. Patel Institute of Pharmaceutical Education and Research, Near Karwand Naka, Shirpur-425 405, Dist- Dhule, Maharashtra, India.

R.C. Patel Institute of Pharmaceutical Education and Research, Near Karwand Naka, Shirpur-425 405, Dist- Dhule, Maharashtra, India.

Sanjay J. Surana, R.C. Patel Institute of Pharmaceutical Education and Research, Near Karwand Naka, Shirpur-425 405, Dist- Dhule, Maharashtra, India.

R.C. Patel Institute of Pharmaceutical Education and Research, Near Karwand Naka, Shirpur-425 405, Dist- Dhule, Maharashtra, India.


1. Unnikrishnan R, Pradeep R, Joshi SR, MohanV. Type 2 diabetes: Demystifying the global epidemic. Diabetes. 2017; 66:1432-1442
2. Al-lawati JA. Diabetes mellitus: a local and global public health emergency! Oman Med J. 2017; 32:177-179.
3. Hu FB. Globalization of diabetes. Diabetes Care. 2011; 34:1249-1257.
4. Ritz E, Zeng X. Diabetic nephropathy-epidemiology in Asian and the current state of treatment. Indian J Nephrol. 2011; 21:75-84.
5. Dodda D, Ciddi V. Plants used in the management of diabetic complications. Indian J Pharm Sci. 2014; 76:97-106.
6. Taylor R. Insulin resistance and type 2 diabetes.Diabetes.2012; 61:778-779.
7. Singh R, Kaur N, Kishore L, Gupta G. Management of diabetic complications: a chemical constituents based approach. J Ethnopharmacol. 2013; 150:51-70.
8. Papatheodorou K, Papanas N, Banach M, Papazoglou D, Edmonds M. Complications of diabetes 2016. J Diabetes Res. 2016; 6989453.
9. Silva EF, Ferreira CM, Pinho LD. Risk factors and complications in type 2 diabetes outpatients. Rev Assoc Med Bras. 2017; 63:621-627.
10. Bennett K, Aditya BS. An overview of diabetic nephropathy : epidemiology, pathophysiology and treatment. J Diabetes Nurs. 2015; 18:61-67.
11. Brosius FC, Khoury CC, Buller CL, Chen S. Abnormalities in signaling pathways in diabetic nephropathy. Expert Rev Endocrinol Metab. 2010; 5:51-64.
12. Alicic RZ, Rooney MT, Tuttle KR. Diabetic kidney disease challenges, progress, and possibilities. Clin J Am Soc Nephrol. 2017; 12:2032-2045.
13. Cao Z, Cooper ME. Pathogenesis of diabetic nephropathy. J Diabetes Invest. 2011;2:243-247.
14. Sharma S, Ali A, Ali J, Sahni JK, Baboota S. Rutin : therapeutic potential and recent advances in drug delivery. Expert Opin Investig Drugs. 2013; 22:1063-1079.
15. Kawanami D, Matoba K., Utsunomiya K. Signaling pathways in diabetic nephropathy. Histol Histopathol. 2016; 31:1059-67.
16. Umanath K, Lewis JB. Update on diabetic nephropathy: core curriculum 2018. Am J Kidney Dis. 2018; 71:884-895.
17. Johson SA, Spurney RF. Twnety years after ACEIs and ARBs : emerging treatment strategies for diabetic nephropathy. Am J Physiol Renal Physiol. 2015; 309:F807-20.
18. Sun GD, Li CY, Cui WP, Guo QY, Dong CQ, Zou HB, Liu SJ, Dong WP, Miao LN. Review of herbal traditional Chinese medicine for the treatment of diabetic nephropathy. J Diabetes Res. 2016; 5749857.
19. Jacob B, Narendhirakannan RT. Role of medicinal plants in the management of diabetes mellitus: a review. 3Biotech. 2019; 9:4.
20. Modak M, Dixit P, Londhe J, Ghaskadbi S, Devasagayam TP. Indian herbs and herbal drugs used for the treatment of diabetes. J Clin Biochem Nutr. 2007; 40:163-173.
21. Kooti W, Farokhipour M, Asadzadeh Z, Ashtary-Larky D, Asadi-Samani M. The role of medicinal plants in the treatment of diabetes: a systematic review. Electron Physician. 2016; 8:1832-1842.
22. Farag M, Ahmed WJ, Foud I, Mohammed MS. The role of medicinal plants in the treatment of type-2 diabetes. Adv J Pharm Life Sci Res. 2014; 4:1-8.
23. Bharti SK, Krishnan S, Kumar A, Kumar A. Antidiabetic phytoconstituents and their mode of action on metabolic pathways. The Adv Endocrinol Metab. 2018; 9:81-100.
24. Ghosh SS, Gehr TW, Ghosh S. Curcumin and chronic kidney disease (CKD) : major mode of action through stimulating endogenous intestinal alkaline phosphatase. Molecules. 2014; 19:20139-20156.
25. Lu M, Yin N, Liu W, Cui X, Chen S, Wang E. Curcumin ameliorates diabetic nephropathy by suppressing NLRP3 inflammasome signaling. Biomed Res Int. 2017; 1516985.
26. Asadi S, Goodarzi MT, Karimi J, Hasheminia M, Khodadadi I. Does curcumin or metformin attenuate oxidative stress and diabetic nephropathy in rats? J Nephropathol. 2019; 8:e08.
27. Mukhopadhyay P, Prajapati AK. Quercetin in antidiabetic research and strategies for improved quercetin bioavailability using polymer-based carriers – a review. RSC Adv. 2015; 5:97547-97562.
28. Mahmoud MF, Hassan NA, ElBassossy HM, Fahmy A. Quercetin protects against diabetes-induced exaggerated vasoconstriction in rats: Effect of low grade inflammation. PLoS One. 2013; 8:e63784.
29. Lai PB, Zhang L, Yang LY. Quercetin ameliorates diabetic nephropathy by reducing the expression of transforming growth factor-1 and connective tissue growth factor in streptozotocin-induced diabetic rats. RenFail. 2012; 34:83-7.
30. Gomes IB, Porto ML, Santos MC, Campagnaro BP, Gava AL, Meyrelles SS., Pereira TM, Vasquez EC. The protective effects of oral low-dose quercetin on diabetic nephropathy in hypercholesterolemic mice. Front. Physiol. 2015; 6:247.
31. Yang H, Song Y, Liang Y, Li R. Quercetin treatment improves renal function and protects the kidney in a rat model of adenine-induced chronic kidney disease. Med Sci Monit. 2018; 24:4760-4766.
32. Imran M, Arshad MS, Butt MS, Kwon JH, Arshad MU, Sultan MT. Mangiferin: a natural miracle bioactive compound against lifestyle related disorders. lipids Health Dis. 2017;16:84.
33. Sekar M. Molecules of interest-Mangiferin-a review. Annu Res Rev Biol. 2015; 5:307-320.
34. Sattanathan K,Dhanapal CK,Umarani R,Manavalan R. Beneficial effects of rutin on nephropathy : a serious complication associated with diabetes. J pharm res. 2011; 4:3826-3828.
35. Wang X, Gao L, Lin H, Song J, Wang J, Yin Y, Zhao J, Xu X, Li Z, Li L. Magniferin prevents diabetic nephropathy progression and protects podocyte function via autophagy in diabetic rat glomeruli.Eur J Pharmacol. 2018; 824:170-178.
36. Li X, Cui X, Sun X, Zhu Q, Li W. Magniferin prevents diabetic nephropathy progression in streptozotocin-induced diabetic rats. Phytother Res. 2010; 24:893-9.
37. Liu YW, Zhu X, Zhang L, Lu Q, Wang Jy, Zhang F, Guo H, Yin JL, Yin XX. Up-regulation of glyoxalase 1 by magniferin prevents diabetic nephropathy progression in streptozotocin-induced diabetic rats. Eur J Pharmacol. 2013; 721:355-364.
38. Wang H, Zhu C, Ying Y, Luo L, Huang D, Luo Z. Metformin and beberine, two versatile drugs in treatment of common metabolic diseases.Oncotarget. 2018; 9:10135-10146.
39. Pang B, Zhao L, Zhou Q, Zhao T, Wang H, Gu C, Tong X. Application of berberine on treating type 2 diabetes mellitus.Int J Endocrinol. 2015; ID905749.
40. Sun SF, Zhao TT, Zhang HJ, Huang XR, Zhang WK, Zhang L,Wang H,Wen YM, Pan XP, Lan HY, Li P. Renoprotective effect of berberine on type 2 diabetic nephropathy in rats. Clin Exp Pharmacol Physiol. 2015; 42:662-70.
41. Zhu L, Han J, Yuan R, Xue L. Berberine ameliorates diabetic nephropathy by inhibiting TLR4/NF-kB pathway. BiolRes. 2018; 51:9.
42. Wu Z, Xie Z,Liu J, Wu Q, Wang X.Renoprotective effect of berberine on streptozotocin-induced diabetic nephropathy rats. Int J Pharmacol. 2017; 13:247-256.
43. Li Z, Zhang W. Protective effect of berberine on renal fibrosis caused by diabetic nephropathy. Mol Med Rep. 2017; 16:1055-1062.
44. Ni WJ, Ding HH, Zhou H, Qiu YY, Tang LQ. Renoprotective effects of berberine through regulation of the MMPs/TIMPs system in streptozocin-induced diabetic nephropathy in rats. Eur J Pharmacol. 2015; 764:448-456.
45. Sharma R, Tiku AB, Giri A. Pharmacological properties of emodin-anthraquinone derivatives. J Nat Prod Resour. 2017; 3:97-101.
46. Dong X, Fu J, Yin X, Cao S, Li X, Lin L, Huyiligeqi, Ni J. Emodin : a review of its pharmacology, toxicity and pharmacokinetics. Phytother Res. 2016; 30:1207-18.
47. Chen T, Zheng LY, Xiao W, Gui D, Wang X, Wang N. Emodin ameliorates high glucose induced-podocyte epithelial-mesenchymal transition in vitro and in-vivo. Cell Physiol Biochem. 2015; 35:1425-1436.
48. Jing D, Bai H, S. Renoprotective effects of emodin against diabetic nephropathy in rat models are mediated via PI3K/Akt/GSK-3 and Bax/caspase-3 signaling pathways. Exp Ther Med. 2017; 14:5163-5169.
49. Tian N, Gao Y, Wang X, Wu X, Zou D, Zhu Z, Han Z, Wang T, Shi Y. Emodin mitigates podocytes apoptosis induced by endoplasmic reticulum stress through the inhibition of the PERK pathway in diabetic nephropathy. Drug Des Devel Ther. 2018; 12:2195-2211.
50. Wang J, Huang H, Liu P, Tang F, Qin J, Huang W, Chen F, Guo F, Liu W, Yang B. Inhibition of phosphorylation of p38 MAPK involved in the protection of nephropathy by emodin in diabetic rats. Eur J Pharmacol. 2006; 553:297-303.
51. Cook MT. Mechanism of metastasis suppression by luteolin in breast cancer. Breast Cancer (Dove Med Press). 2018; 10:89-100.
52. Zang Y, Igarashi K, Li Y. Anti-diabetic effects of luteolin and luteolin-7-0-glucoside on KK-Ay mice. Biosci Biotechnol Biochem. 2016; 80:1580-1586.
53. Lin Y, Shi R, Wang X, Shen HM. Luteolin,a flavonoid with potential for cancer prevention and therapy. Curr Cancer Drug Targets. 2008; 8:634-646.
54. Wang GG, Lu XH, Li W, Zhao X, Zhang C. Protective effects of luteolin on diabetic nephropathy in STZ-induced diabetic rats.Evid Based Complement Alternat Med. 2011; 323171.
55. Chen L, Tian G, Tang W, Luo W, Liu P, Ma Z. Protective effect of luteolin on streptozotocin-induced diabetic renal damage in mice via the regulation of RIP 140/NF-kB pathway and insulin signaling pathway. J Funct Foods. 2016; 22:93-100.
56. Goyal SN, Prajapati CP, Gore PR,Patil CR, Mahajan UB, Sharma C, Talla S, Ojha SK. Therapeutic potential and pharmaceutical development of thymoquinone : a multitargeted molecule of natural origin. FrontPharmacol. 2017; 8:656.
57. Banerjee S, Padhye S, Azmi A, Wang Z, Philip PA, Kucuk O, Sarkar FH, Mohammad RM. Review on molecular and therapeutic potential of thymoquinone in cancer. NutrCancer.2010; 62:938-946.
58. Kanter M. Protective effects of thymoquinone on streptozotocin-induced diabetic nephropathy. J Mol Histol. 2009; 40:107-15.
59. Sayed AA. Thymoquinone and proanthocyanidin attenuation of diabetic nephropathy in rats.Eur Rev Med Pharmacol Sci.2012; 16:808-815.
60. Omran OM. Effects of thymoquinone on STZ-induced diabetic nephropathy : An immunohistochemical study. Ultrastruct Pathol. 2014; 38:26-33.
61. Zhou J, Chan L, Zhou S. Trigonelline : a plant alkaloid with therapeutic potential for diabetes and central nervous system disease.CurrMedChem. 2012; 19:3523-31.
62. Mohamadi N, Sharififar F, Pournamdari M, Ansari M. A review on biosynthesis, analytical techniques, and pharmacological activities of Trigonelline as a plant alkaloid. J Diet Suppl. 2018; 15:207-222.
63. Ghule AE, Jadhav SS, Bodhankar SL. Trigonelline ameliorates diabetic hypertensive nephropathy by suppression of oxidative stress in kidney and reduction in renal cell apoptosis and fibrosis in streptozotocin induced neonatal diabetic (nSTZ) rats.Int Immunopharmacol. 2012; 14:740-8.
64. Kamble HV, Bodhankar SL. Trigonelline and sitagliptin attenuates nicotinamide-streptozotocin induced diabetic nephropathy in wistar rats. Int J Pharm Pharm Sci. 2013; 5:583-589.
65. Alam MA, Subhan N, Rahman MM, Uddin SJ, Reza HM, Sarker SD. Effects of citrus flavonoids, naringin and naringenin, on metabolic syndrome and their mechanism of action. AdvNutr. 2014; 5:404-417.
66. Rao PV, Kiran SD, Rohini P, Bhagyasree P. Flavonoid : a review on naringenin. J Pharmacogn Phytochem. 2017; 6:2778-2783.
67. Yan N, Wen L, Peng R, Li H, Liu H, Peng H, Sun Y, Wu T, Chen L, Duan Q, Sun Y, Zhou Q, Wei L, Zhang Z. Naringenin ameliorated kidney injury through Let-7a/TGFBR1 signaling in diabetic nephropathy. J Diabetes Res. 2016; 8738760.
68. Roy S, Ahmed F, Banerjee S, Saha U. Naringenin ameliorates streptozotocin-induced diabetic rat renal impairment by downregulation of TGF-1 and IL-1 via modulation of oxidative stress correlates with decreased apoptotic events. Pharm Biol. 2016; 54:1616-1627
69. Tsai SJ, Huang CS, Mong MC, Kam WY, Huang HY, Yin MC. Antiinflammatory and antifibrotic effects of naringenin in diabetic mice. J Agric Food Chem. 2012; 60:514-21.
70. Li C, Schluesener H. Health-promoting effects of the citrus flavanone hesperidin. CritRevFoodSciNutr. 2017;57:613-631.
71. Stanisic D, Costa AF, Durán N. Anticancer activities of hesperidin and hisperetin in vivo and their potentiality against bladder cancer. J Nanomed Nanotechnol. 2018; 9:515.
72. Jain DP, Somani RS. Hesperidin ameliorates streptozotocin and high-fat diet induced diabetic nephropathy in rats. J Exp Integr Med. 2014; 4:261-267.
73. Zhang Y, Wang B, Guo F, Li Z, Qin G. Involvement of the TGF1-ILK-Akt signaling pathway in the effects of hesperidin in type 2 diabetic nephropathy.Biomed Pharmacother; 105:766-772.
74. Morishita Y, Kusano E. Direct renin inhibitor : aliskiren in chronic kidney disease. Nephrourol Mon. 2013; 5:668-672.
75. Lukawski K, Gaszczyk IB. Aliskiren-an antihypertensive renin inhibitor in the treatment of patients with chronic kidney disease, J Pre Clin Clin Res. 2017; 11:81-85.
76. Zhang Y, Wang Y, Chen , Deb DK, Sun T, Zhao Q, Li YC. Inhibition of renin activity by aliskiren ameliorates diabetic nephropathy in type 1 diabetes mousel model.Journal of diabetes mellitus. 2012; 3:353-360.
77. Hamed AT, Taha MM, Nasser LM. Renoprotective effect of aliskiren monotherapy and aliskiren-pentoxifylline combination in hypertensive-diabetic type 2 patients with diabetic nephropathy. Bull Fac Pharm Cairo univ. 2013; 51:221-227.
78. Persson F, Lewis JB, Lewis EJ, Rossing P, Hollenberg NK, Parving HH. Aliskiren in combination with losartan reduces albuminuria independent of baseline blood pressure in patients with type 2 diabetes and nephropathy. Clin J Am Soc Nephrol. 2011; 6:1025-1031.
79. Semwal DK,Semwal RB, Combrinck S, Viljoen A. Myricetin : a dietary molecule with diverse biological activities. Nutrients. 2016; 8:90.
80. Li Y, Ding Y. Minireview: Therapeutic potential of myricetin in diabetes mellitus. Food Science and Human Wellness. 2012; 1:19-25.
81. Ozcan F, Ozmen A, Akkaya B, Aliciguzel Y, Aslan M. Beneficial effect of myricetin on renal functions in streptozotocin-induced diabetes. ClinExpMed. 2012; 12:265-72.
82. Kandasamy N, Ashokkumar N. Renoprotective effect of myricetin restrains dyslipidemia and renal mesangial cell proliferation by the suppression of sterol regulatory element binding proteins in an experimental model of diabetic nephropathy. EurJPharmacol. 2014; 15:53-62.
83. Ali F, Rahul, Naz F, Jyoti S, Siddique YH. Health functionality of apigenin : a review. Int J Food Prop. 2016; 20:1197-1238.
84. Shukla S, Gupta S. Apigenin: A promising molecule for cancer prevention.PharmRes. 2010; 27:962-978.
85. Malik S, Suchal K, Khan SI, Bhatia J, Kishore K, Dinda AK, Arya DS. Apigenin ameliorates streptozotocin-induced diabetic nephropathy in rats via MAPK-NF-kB-TNF- and TGF-1-MAPK-fibronectin pathways.Am J Physiol Renal Physiol. 2017; 313:F414-422.
86. Hossain CM, Ghosh MK, Satapathy BS, Dey NS, Mukherjee B. Apigenin causes biochemical modulation, GLUT4 and CD38 alterations to improve diabetes and to protect damages of some vital organs in experimental diabetes.Am J Pharmacol Toxicol. 2014; 9:39-52.
87. Chen H, Dong Y, He X, Li J, Wang J. Paeoniflorin improves cardiac function and decreases adverse postinfarction left ventricular remodeling in a rat model of acute myocardial infarction. Drug Des Devel Ther. 2018; 12:823-836.
88. Manayi A,Omidpanah S,Barreca D,Ficarra S,Daglia M,Nabavi SF,Nabavi SM. Neuroprotective effects of paeoniflorin in neurodegenerative diseases of the central nervous system. Phytochem Rev. 2017; 16:1173-1181.
89. Fu J, Li Y, Wang L, Gao B, Zhang N, Ji Q. Paeoniflorin prevents diabetic nephropathy in rats. CompMed. 2009; 59:557-66.
90. Shao YX, Xu XX, Wang K, Qi XM, Wu YG. Paeoniflorin attenuates incipient diabetic nephropathy in streptozotocin-induced mice by the suppression of the Toll-like receptor-2 signaling pathway. Drug Des Devel Ther. 2017; 11:3221-3222.
91. Zhang T, Zhu Q, Shao Y, Wang K, Wu Y. Paeoniflorin prevents TLR2/4-mediated inflammation in type 2 diabetic nephropathy. BiosciTrends. 2017; 11:308-318.
92. Li X, Wang Y, Wang K, Wu Y. Renal protective effect of paeoniflorin by inhibition of JAK2/STAT3 signaling pathway in diabetic mice.BiosciTrends. 2018; 12:168-176.
93. Al-dhabi NA, Arasu MV, Park CH, Park SU. An up-to-date review of rutin and its biological and pharmacological activities.ExcliJ. 2015; 14:59-63.
94. Ganeshpurkar A, Saluja AK. The pharmacological potential of rutin. Saudi Pharm J. 2017; 25:149-164.
95. Sharma V, Sharma PL. Role of different molecular pathways in the development of diabetes-induced nephropathy. J Diabetes Metab. 2013; S9:004.
96. Hao HH, Shao ZM, Tang DQ, Lu Q, Chen X, Yin XX, Wu J, Chen H. Preventive effects of rutin on the development of experimental diabetic nephropathy in rats. Life Sci. 2012; 91:959-67.
97. Han CS, Liu K, Zhang N, Li SW, Gao HC. Rutin suppresses high glucose-induced ACTA2 and p38 protein expression in diabetic nephropathy. ExpTherMed. 2017; 14:181-186.
98. Bayan L, Koulivand PH, Gorji A. Garlic: a review of potential therapeutic effects. Avicenna J Phytomed. 2014; 4:1-14.
99. Borlinghaus J, Albrecht F, Gruhlke MC, Nwachukwu ID, Slusarenko AJ. Molecules. 2014; 19:12591-618.
100. Huang H, Jiang Y, Mao G, Yuan F, Zheng H, Ruan Y, Wu T. Protective effects of allicin on streptozotocin-induced diabetic nephropathy in rats. J Sci Food Agric. 2017; 97:1359-1366.
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How to Cite
Jain, P. G., Nayse, P. G., Patil, D. J., & Surana, S. J. (2019). A Comprehensive Review on Plant derived Natural products for Diabetes and its complication as nephropathy. Journal of Drug Delivery and Therapeutics, 9(2-s), 625-633. https://doi.org/10.22270/jddt.v9i2-s.2512