Evaluation of pancreatic regeneration activity of Tephrosia purpurea leaves in rats with streptozotocin-induced diabetes

10.1016/j.jtcme.2021.03.001

Sumit K. Arora；Prashant R. Verma；Prakash R. Itankar；Satyendra K. Prasad；Kartik T. Nakhate

Pancreatic β-cell ； Diabetes mellitus ； Plant extracts ； Polyphenol ； Antioxidant activity ； Biochemical estimation

Journal of Traditional and Complementary Medicine

11卷5期（2021 / 09 / 01）

435 - 445

英文

Background and aim: Flavonoid rich plant Tephrosia purpurea (T. purpurea), commonly known as Sarpunkha has been used in traditional systems of medicine to treat diabetes mellitus. However, its effectiveness in promoting regeneration of pancreas in diabetes has not been investigated. Therefore, the present study was undertaken to evaluate pancreatic β-cells regeneration, antioxidant and antihyperlipidemic potentials of T. purpurea leaves extract, its fractions and main constituent Rutin in diabetic rats. Experimental procedure: The leaves extract and its fractions were first screened for acute and sub-chronic antidiabetic activity in a dose range of 250-500 mg/kg orally. Further, fractions with potent antidiabetic activity were screened for pancreatic β-cells regeneration activity using histopathological studies and morphometric analysis, which was followed by estimation of biochemical parameters. Results and conclusion: The most significant antidiabetic, pancreatic regeneration and antihyperlipidemic activity was exhibited by n-butanol soluble fraction of ethanol extract at the dose level of 500 mg/kg. Histopathology revealed that treatment with this fraction improved the β-cell granulation of islets and prevented the β-cells damage which was further confirmed by morphometric analysis. Thus, the present study validated the traditional use of T. purpurea plant in the treatment of diabetes, which might be attributed to pancreatic β-cells regeneration potential of its active constituent Rutin. Taxonomy (classification by EVISE): Traditional Medicine; Metabolic Disorder; Experimental Design; Cell Regeneration and Histopathology.

1. Choudhury, H,Pandey, M,Hua, CK(2018).An update on natural compounds in the remedy of diabetes mellitus: a systematic review.J Tradit Complement Med,8(3),361-376.
   連結：
2. Jani, DK,Goswami, S(2020).Antidiabetic activity of Cassia angustifolia Vahl. and Raphanus sativus Linn. leaf extracts.J Tradit Complement Med,10(2),124-131.
   連結：
3. Lartey, NL,Asare-Anane, H,Ofori, EK(2020).Antidiabetic activity of aqueous stem bark extract of Annickia polycarpa in alloxan-induced diabetic mice.J Tradit Complement Med
   連結：
4. Adeyemi, DO,Komolafe, OA,Adewole, OS,Obuotor, EM,Abiodun, AA,Adenowo, TK(2010).Histomorphological and morphometric studies of the pancreatic islet cells of diabetic rats treated with extracts of Annona muricata.Folia Morphol,69(2),92-100.
5. Alberti, KGZP(1998).Definition, diagnosis and classification of diabetes mellitus and its complications : report of a WHO consultation. Part 1, Diagnosis and classification of diabetes mellitus.Diabet Med,15(7),539-553.
6. AlDrak, N,Abudawood, M,Hamed, SS,Ansar, S(2018).Effect of rutin on proinflammatory cytokines and oxidative stress in toxin-mediated hepato-toxicity.Toxin Rev,37(3),223-230.
7. Ansarullah,Bharucha, B,Umarani, M(2012).Oreocnide integrifolia flavonoids augment reprogramming for islet neogenesis and β-cell regeneration in pancreatectomized BALB/c mice.Evid Based Complement Alternat Med,2012,260467.
8. Arulselvan, P,Subramanian, SP(2007).Beneficial effects of Murraya koenigii leaves on antioxidant defense system and ultra structural changes of pancreatic β-cells in experimental diabetes in rats.Chem Biol Interact,165,155-164.
9. Attanayake, AP,Jayatilaka, KAPW,Pathirana, LKBM,Pathirana, C(2019).β-Cell regenerative potential of selected herbal extracts in alloxan induced diabetic rats.Curr Drug Discov Technol,16(3),278-284.
10. Belayneh, YM,Birhanu, Z,Birru, EM,Getenet, G(2019).Evaluation of in vivo antidiabetic, antidyslipidemic, and in vitro antioxidant activities of hydromethanolic root extract of datura stramonium L. (Solanaceae).J Exp Pharmacol,11,29-38.
11. Bolkent, Ş,Yanardağ, R,Tabakoǧlu-Oǧuz, A,Özsoy-Saçan, Ö(2000).Effects of chard (Beta vulgaris L. var. cicla) extract on pancreatic B cells in streptozotocin-diabetic rats: a morphological and biochemical study.J Ethnopharmacol,73(1-2),251-259.
12. Cao, G,Booth, SL,Sadowski, JA,Prior, RL(1998).Increases in human plasma antioxidant capacity after consumption of controlled diets high in fruit and vegetables.Am J Clin Nutr,68(5),1081-1087.
13. Chakravarthy, B,Saroj, G,Gambhir, S,Gode, K(1980).Pancreatic beta-cell regeneration -a novel antidiabetic mechanism of Pterocarpus marsupium, Roxb.Indian J Pharmacol,12,123-127.
14. Chakravarthy, BK,Gupta, S,Gode, KD(1982).Functional beta cell regeneration in the islets of pancreas in alloxan induced diabetic rats by (-)-epicatechin.Life Sci,31(24),2693-2697.
15. Chang, CC,Yang, MH,Wen, HM,Chern, JC(2002).Estimation of total flavonoid content in propolis by two complementary colometric methods.J Food Drug Anal,10,178-182.
16. Chang, LC,Gerhäuser, C,Song, L,Farnsworth, NR,Pezzuto, JM,Kinghorn, AD(1997).Activity-guided isolation of constituents of Tephrosia purpurea with the potential to induce the phase II enzyme, quinone reductase.J Nat Prod,60(9),869-873.
17. Chinniah, A,Mohapatra, S,Goswami, S(2009).On the potential of Tephrosia purpurea as anti-Helicobacter pylori agent.J Ethnopharmacol,124,642-645.
18. Damre, AS,Gokhale, AB,Phadke, AS,Kulkarni, KR,Saraf, MN(2003).Studies on the immunomodulatory activity of flavonoidal fraction of Tephrosia purpurea.Fitoterapia,74,257-261.
19. Ghorbani, A.(2017).Mechanisms of antidiabetic effects of flavonoid rutin.Biomed Pharmacother,96,305-312.
20. Ghorbani, A,Rashidi, R,Shafiee-Nick, R(2019).Flavonoids for preserving pancreatic beta cell survival and function: a mechanistic review.Biomed Pharmacother,111,947-957.
21. Gokhale, AB,Saraf, MN(2000).Tephrosia Purpurea: a review of contemporary literature and medicinal properties.Indian Drugs,37,553-560.
22. Goyal, SN,Reddy, NM,Patil, KR(2016).Challenges and issues with streptozotocin-induced diabetes - a clinically relevant animal model to understand the diabetes pathogenesis and evaluate therapeutics.Chem Biol Interact,244,49-63.
23. Gulecha, V,Sivakuma, T(2011).Anticancer activity of Tephrosia purpurea and Ficus religiosa using MCF 7 cell lines.Asian Pac J Trop Med,4(7),526-529.
24. Gupta, AK,Tandon, N,Sharma, M(2006).Quality Standards of Medicinal Plants.New Delhi:ICMR.
25. Halliwell, B,Gutteridge, JMC(1995).The definition and measurement of antioxidants in biological systems.Free Radic Biol Med,18(1),125-126.
26. Itankar, PR,Lokhande, SJ,Verma, PR,Arora, SK,Sahu, RA,Patil, AT(2011).Antidiabetic potential of unripe Carissa carandas Linn. fruit extract.J Ethnopharmacol,135(2),430-433.
27. Jamall, IS,Crispin Smith, J(1985).Effects of cadmium on glutathione peroxidase, superoxide dismutase, and lipid peroxidation in the rat heart: a possible mechanism of cadmium cardiotoxicity.Toxicol Appl Pharmacol,80,33-42.
28. Johansen, JS,Harris, AK,Rychly, DJ,Ergul, A(2005).Oxidative stress and the use of antioxidants in diabetes: linking basic science to clinical practice.Cardiovasc Diabetol,4,5.
29. Kamalakkannan, N,Prince, PSM(2006).The influence of rutin on the extracellular matrix in streptozotocin-induced diabetic rat kidney.J Pharm Pharmacol,58(8),1091-1098.
30. Khatri, A,Garg, A,Agrawal, SS(2009).Evaluation of hepatoprotective activity of aerial parts of Tephrosia purpurea L. and stem bark of Tecomella undulata.J Ethnopharmacol,122(1),1-5.
31. Kirtikar, KR,Basu, BD(1984).Indian Medicinal Plants.Dehradun:Lalit Mohan publication.
32. Kumar, S,Pandey, AK(2013).Chemistry and biological activities of flavonoids: an overview.Sci World J.,162750.
33. Kumarappan, CT,Thilagam, E,Mandal, SC(2012).Antioxidant activity of polyphenolic extracts of Ichnocarpus frutescens.Saudi J Biol Sci.,19(3),349-355.
34. Lodhi, S,Pawar, RS,Jain, AP,Singhai, AK(2006).Wound healing potential of Tephrosia purpurea (Linn.) Pers. in rats.J Ethnopharmacol,108,204-210.
35. Marston, A,Hostettmann, K(2006).Separation and quantification of flavonoids.Flavonoids: Chemistry, Biochemistry and Applications,Boca Raton:
36. Moutinho, MSS,Aragão, S,Carmo, D(2018).Curcumin and rutin down-regulate cyclooxygenase-2 and reduce tumor-associated inflammation in HPV16-transgenic mice.Anticancer Res,38(3),1461-1466.
37. Movassat, J,Saulnier, C,Portha, BBT-D(1997).Insulin administration enhances growth of the beta-cell mass in streptozotocin-treated newborn rats.Diabetes,46(9),1445-1452.
38. Muller, PH,Schmulling, RM,Liebih, HM,Eggstein, M(1977).A fully enzymatic triglyceride determination.J Clin Chem Clin Biochem,15,457-464.
39. Nagy, M,Grančai, D(1996).Colorimetric determination of flavanones in propolis.Pharmazie,51(2),100-101.
40. Niture, NT,Ansari, AA,Naik, SR(2014).Anti-hyperglycemic activity of Rutin in streptozotocin-induced diabetic rats: an effect mediated through cytokines, antioxidants and lipid biomarkers.Indian J Exp Biol,52(7),720-727.
41. Noor, A,Gunasekaran, S,Vijayalakshmi, MA(2017).Improvement of insulin secretion and pancreatic β-cell function in streptozotocin-induced diabetic rats treated with Aloe vera extract.Pharmacogn Res.,9(Suppl 1),S99-S104.
42. Oecd. OECD environment health and safety publications series on testing and assessment. Assessment. 2004;(46):20-21. https://doi.org/10.1787/9789264079151-en
43. Pandey, KB,Rizvi, SI(2009).Plant polyphenols as dietary antioxidants in human health and disease.Oxid Med Cell Longev,2(5),270-278.
44. Park, YC,Rimbach, G,Saliou, C,Valacchi, G,Packer, L(2000).Activity of monomeric, dimeric, and trimeric flavonoids on NO production, TNF-α secretion, and NF-κB-dependent gene expression in RAW 264.7 macrophages.FEBS Lett,465(2),93-97.
45. Prince, P,Kamalakkannan, N.(2006).Rutin improves glucose homeostasis in streptozotocin diabetic tissues by altering glycolytic and gluconeogenic enzymes.J Biochem Mol Toxicol,20,96-102.
46. Ramadan, BK,Schaalan, MF,Tolba, AM(2017).Hypoglycemic and pancreatic protective effects of Portulaca oleracea extract in alloxan induced diabetic rats.BMC Compl Alternative Med,17(1),37.
47. Reddy, SV,Tiwari, AK,Kumar, US,Rao, RJ,Rao, JM(2005).Free radical scavenging, enzyme inhibitory constituents from antidiabetic ayurvedic medicinal plant Hydnocarpus wightiana blume.Phyther Res,19(4),277-281.
48. Robertson, R,Harmon, J(2006).Diabetes, glucose toxicity, and oxidative stress: a case of double jeopardy for the pancreatic islet beta cell.Free Radic Biol Med,41,177-184.
49. Rösen, P,Nawroth, PP,King, G,Möller, W,Tritschler, H-J,Packer, L(2001).The role of oxidative stress in the onset and progression of diabetes and its complications: asummary of a Congress Series sponsored byUNESCO-MCBN, the American Diabetes Association and the German Diabetes Society.Diabet Metab Res Rev.,17(3),189-212.
50. S, babu Pandurangan,Ignacimuthu, S,Agastian, P,Varghese, B(2009).Partial regeneration of β-cells in the islets of Langerhans by Nymphayol a sterol isolated from Nymphaea stellata (Willd.) flowers.Bioorg Med Chem,17,2864-2870.
51. Salahuddin, M,Jalalpure, SS(2010).Antidiabetic activity of aqueous fruit extract of Cucumis trigonus Roxb. in streptozotocin-induced-diabetic rats.J Ethnopharmacol,127,565-567.
52. Sattanathan, K,Dhanapal, CK,Umarani, R,Manavalan, R(2011).Beneficial health effects of rutin supplementation in patients with diabetes mellitus.J Appl Pharmaceut Sci,1(8),227-231.
53. Sharma, OP,Bhat, TK(2009).DPPH antioxidant assay revisited.Food Chem,113,1202-1205.
54. Shenoy, S,Shwetha, K,Prabhu, K,Maradi, R,Bairy, KL,Shanbhag, T(2010).Evaluation of antiinflammatory activity of Tephrosia purpurea in rats.Asian Pac J Trop Med,3,193-195.
55. Shirwaikar, A,Rajendran, K,Punitha, ISR(2005).Antidiabetic activity of alcoholic stem extract of Coscinium fenestratum in streptozotocin-nicotinamide induced type 2 diabetic rats.J Ethnopharmacol,97,369-374.
56. Singleton, VL,Orthofer, R,Lamuela-Raventós, RM(1999).Analysis of total phenols and other oxidation substrates and antioxidants by means of folin-ciocalteu reagent.Methods Enzymol,299,152-178.
57. Skyler, JS,Bakris, GL,Bonifacio, E(2017).Differentiation of diabetes by pathophysiology, natural history, and prognosis.Diabetes,66(2),241-255.
58. Souza, JNS,Silva, EM,Loir, A,Rees, JF,Rogez, H,Larondelle, Y(2008).Antioxidant capacity of four polyphenol-rich Amazonian plant extracts: a correlation study using chemical and biological in vitro assays.Food Chem.,106(1),331-339.
59. Stanojević, L,Stanković, M,Nikolic, V(2009).Antioxidant activity and total phenolic and flavonoid contents of Hieracium pilosella L. extracts.Sensors,9(7),5702-5714.
60. Su, S,Li, X,Li, S(2019).Rutin protects against lipopolysaccharide-induced mastitis by inhibiting the activation of the NF-κB signaling pathway and attenuating endoplasmic reticulum stress.Inflammopharmacology,27(1),77-88.
61. Tschöpe, D,Hanefeld, M,Meier, JJ(2013).The role of co-morbidity in the selection of antidiabetic pharmacotherapy in type-2 diabetes.Cardiovasc Diabetol,12,62.
62. Tsikas, D(2007).Analysis of nitrite and nitrate in biological fluids by assays based on the Griess reaction: appraisal of the Griess reaction in the l-arginine/nitric oxide area of research.J Chromatogr B.,851(1),51-70.
63. Upendra, Rao, M,Sreenivasulu, M,Chengaiah, B,Jaganmohan Reddy, K,Madhusudhana Chetty, C(2010).Herbal medicines for diabetes mellitus: a review.Int J PharmTech Res,2(3),1883-1892.
64. Varas-Lorenzo, C,Margulis, AV,Pladevall, M(2014).The risk of heart failure associated with the use of noninsulin blood glucose-lowering drugs: systematic review and meta-analysis of published observational studies.BMC Cardiovasc Disord,14,129.
65. Verma, PR,Itankar, PR,Arora, SK(2013).Evaluation of antidiabetic antihyperlipidemic and pancreatic regeneration, potential of aerial parts of Clitoria ternatea.Rev Bras Farmacogn,23(5),819-829.
66. Vinayagam, R,Xu, B(2015).Antidiabetic properties of dietary flavonoids: a cellular mechanism review.Nutr Metab,12(1),60.
67. World Health Organisation(1980).WHO expert committee on diabetes mellitus: second report.
68. Yousef, N,Yousef, F,Mansour, O,Herbali, J(2017).Metformin: a unique herbal origin medication.Global J Med Res.,17,2249-4618.

1. Zanariah Hashim,Tet Soon Wong,Parsaoran Siahaan,Nor Hafizah Zakaria,Fatahiya Mohamed Tap,Fadzilah Adibah Abdul Majid,Abeer Mogadem(2023).Dual actions of gallic acid and andrographolide trigger AdipoR1 to stimulate insulin secretion in a streptozotocin-induced diabetes rat model.Journal of Traditional and Complementary Medicine,13(1),11-19.