Acute Toxicological and Histopathological Elucidation of Rheum emodi Rhizome Extract to Demonstrate Antidiabetic Activity in Alloxan-induced Diabetic Rats

Author(s): Ravindran Radhika, Dinesha Ramadas, Baliah Ragavan, Dorairaj Sudarsanam, Vivek H. Kameshwar*

Journal Name: Current Bioactive Compounds

Volume 17 , Issue 2 , 2021


Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

Background: Rheum emodi has been used traditionally to treat diabetes in India. The study was designed to elucidate the effect of 75% ethanolic extract of R. emodi (rhizome) (EE-ReR) and its isolated compounds like emodin and chrysophanol on alloxan-induced diabetic rats, and to check its antidiabetic efficacy. Acute toxicological and histopathological studies were also assessed.

Methods: Experimental rats were divided into six groups, with each group consisting of 6 rats. EEReR and its compounds emodin and chrysophanol were given orally for 30 days.

Results: The experimental rats were sacrificed after 30 days by cervical dislocation. The renal profile and lipid parameters were determined. Histopathological changes in liver, kidney and pancreas were examined in EE-ReR treated group. EE-ReR was fed orally to diabetic rats, which resulted in a decline in the fasting blood glucose, total cholesterol, free fatty acids, creatinine, urea levels, and a rise in the insulin levels was observed almost in the normal range, in the rats which were fed with the extract. Histopathological studies of pancreas, kidney, and liver in diabetic rats revealed that the treated group of rats showed normal regeneration of islets cells. Acute toxicological studies revealed that the extract is safe up to 2000 mg/kg body weight of extract fed orally.

Conclusion: These findings suggested a possible protective method to prevent damage of the internal organs by the R. emodi and its compounds like emodin and chrysophanol, and elevate insulin production during high blood glucose levels without any acute toxicological effect.

Keywords: Cholesterol, emodin, chrysophanol histopathology, kidney function, liver function, urbanization.

[1]
Aswath, M.; Madhusoodan, R. Diabetes mellitus and anxiety-Are they correlated? Int. J. Pharma Bio Sci., 2018, 9(2), 263-265.
[http://dx.doi.org/10.22376/ijpbs.2018.9.2.b263-265]
[2]
Gale, R.; Scanlon, P.H.; Evans, M.; Ghanchi, F.; Yang, Y.; Silvestri, G.; Freeman, M.; Maisey, A.; Napier, J. Action on diabetic macular oedema: Achieving optimal patient management in treating visual impairment due to diabetic eye disease. Eye (Lond.), 2017, 31(S1), S1-S20.
[http://dx.doi.org/10.1038/eye.2017.53] [PMID: 28490797]
[3]
Wild, S.; Roglic, G.; Green, A.; Sicree, R.; King, H. Global prevalence of diabetes: Estimates for the year 2000 and projections for 2030. Diabetes Care, 2004, 27(5), 1047-1053.
[http://dx.doi.org/10.2337/diacare.27.5.1047] [PMID: 15111519]
[4]
Omar, E.A.; Kam, A.; Alqahtani, A.; Li, K.M.; Razmovski-Naumovski, V.; Nammi, S.; Chan, K.; Roufogalis, B.D.; Li, G.Q. Herbal medicines and nutraceuticals for diabetic vascular complications: Mechanisms of action and bioactive phytochemicals. Curr. Pharm. Des., 2010, 16(34), 3776-3807.
[http://dx.doi.org/10.2174/138161210794455076] [PMID: 21128894]
[5]
Chaudhury, A.; Duvoor, C.; Reddy Dendi, V.S.; Kraleti, S.; Chada, A.; Ravilla, R.; Marco, A.; Shekhawat, N.S.; Montales, M.T.; Kuriakose, K.; Sasapu, A.; Beebe, A.; Patil, N.; Musham, C.K.; Lohani, G.P.; Mirza, W. Clinical review of antidiabetic drugs: Implications for type 2 diabetes mellitus management. Front. Endocrinol. (Lausanne), 2017, 8(6), 6.
[http://dx.doi.org/10.3389/fendo.2017.00006] [PMID: 28167928]
[6]
Radhika, R. Krishnakumari., Sudarsanam D. Antidiabetic activity of Rheum emodi in Alloxan induced diabetic rats. Int. J. Pharm. Sci. Res., 2010, 1(8), 296-300.
[7]
Anigboro, A.A.; Avwioroko, O.J.; Ohwokevwo, O.A.; Nzor, J.N. Phytochemical constituents, antidiabetic and ameliorative effects of Polyalthia longifiola leaf extract in alloxan-induced diabetic rats. J. Appl. Sci. Environ. Manag., 2018, 22(6), 993.
[http://dx.doi.org/10.4314/jasem.v22i6.25]
[8]
Ibrahim, M.; Khaja, M.N.; Aara, A.; Khan, A.A.; Habeeb, M.A.; Devi, Y.P.; Narasu, M.L.; Habibullah, C.M. Hepatoprotective activity of Sapindus mukorossi and Rheum emodi extracts: In vitro and in vivo studies. World J. Gastroenterol., 2008, 14(16), 2566-2571.
[http://dx.doi.org/10.3748/wjg.14.2566] [PMID: 18442207]
[9]
Arvindekar, A.; More, T.; Payghan, P.V.; Laddha, K.; Ghoshal, N.; Arvindekar, A. Evaluation of anti-diabetic and alpha glucosidase inhibitory action of anthraquinones from Rheum emodi. Food Funct., 2015, 6(8), 2693-2700.
[http://dx.doi.org/10.1039/C5FO00519A] [PMID: 26145710]
[10]
Singh, P.P.; Ambika, ; Chauhan, S.M. Activity-guided isolation of antioxidants from the roots of Rheum emodi. Nat. Prod. Res., 2013, 27(10), 946-949.
[http://dx.doi.org/10.1080/14786419.2012.682994] [PMID: 22568567]
[11]
Rajkumar, V.; Guha, G.; Ashok Kumar, R. Antioxidant and anti-cancer potentials of Rheum emodi rhizome extracts. Evid. Based Complement. Alternat. Med., 2011, 2011, 697986.
[http://dx.doi.org/10.1093/ecam/neq048] [PMID: 21792364]
[12]
Shah, C.S.; Qadry, J.S.; Bhatt, J.G. Qualitative and quantitative evaluation of anthraquinone derivatives in Indian rhubarb. Planta Med., 1972, 22(1), 103-108.
[http://dx.doi.org/10.1055/s-0028-1099590] [PMID: 5083242]
[13]
Sasaki, T.; Matsui, S. Effect of acetic acid concentration on the color reaction in the o-toluidine-boric acid method for blood glucose estimation. Japanese J. Clin. Chem., 1972, 1(3), 346-353.
[14]
Kameshwar, V.H.; R, K.J.; Priya, B.S.; Swamy, S.N. Synthesis, characterization and bioactivity studies of novel 1,3,4-oxadiazole small molecule that targets basic phospholipase A2 from Vipera russelli. Mol. Cell. Biochem., 2017, 426(1-2), 161-175.
[http://dx.doi.org/10.1007/s11010-016-2888-6] [PMID: 27928710]
[15]
Barrière, D.A.; Noll, C.; Roussy, G.; Lizotte, F.; Kessai, A.; Kirby, K.; Belleville, K.; Beaudet, N.; Longpré, J.M.; Carpentier, A.C.; Geraldes, P.; Sarret, P. Combination of high-fat/high-fructose diet and low-dose streptozotocin to model long-term type-2 diabetes complications. Sci. Rep., 2018, 8(1), 424.
[http://dx.doi.org/10.1038/s41598-017-18896-5] [PMID: 29323186]
[16]
Roy, A.; Jauhari, N.; Bharadvaja, N. Medicinal plants as a potential source of chemopreventive agents. Anticancer Plants: Natural Products and Biotechnological Implements: Springer Singapore, 2018, pp. 109-139.
[http://dx.doi.org/10.1007/978-981-10-8064-7_6]
[17]
Singh, S.; Gupta, S.K.; Sabir, G.; Gupta, M.K.; Seth, P.K. A database for anti-diabetic plants with clinical / experimental trials. Bioinformation, 2009, 4(6), 263-268.
[http://dx.doi.org/10.6026/97320630004263] [PMID: 20975921]
[18]
Divya, K. H K, Vivek., B S, Priya., S N, Swamy. Management of type 2 diabetes mellitus by DPP-IV inhibition-A review. Int. J. Pharm. Phytopharmacol. Res., 2014, 4(2), 138-143.
[19]
Michel, C.G.; Nesseem, D.I.; Ismail, M.F. Anti-diabetic activity and stability study of the formulated leaf extract of Zizyphus spina-christi (L.) Willd with the influence of seasonal variation. J. Ethnopharmacol., 2011, 133(1), 53-62.
[http://dx.doi.org/10.1016/j.jep.2010.09.001] [PMID: 20833236]
[20]
Kondeti, V.K.; Badri, K.R.; Maddirala, D.R.; Thur, S.K.; Fatima, S.S.; Kasetti, R.B.; Rao, C.A. Effect of Pterocarpus santalinus bark, on blood glucose, serum lipids, plasma insulin and hepatic carbohydrate metabolic enzymes in streptozotocin-induced diabetic rats. Food Chem. Toxicol., 2010, 48(5), 1281-1287.
[http://dx.doi.org/10.1016/j.fct.2010.02.023] [PMID: 20178824]
[21]
Bhandari, U.; Ansari, M.N. Antihyperglycaemic activity of aqueous extract of Embelia ribes Burm in streptozotocin-induced diabetic rats. Indian J. Exp. Biol., 2008, 46(8), 607-613.
[PMID: 18814490]
[22]
Lapshina, E.A.; Sudnikovich, E.J.; Maksimchik, J.Z.; Zabrodskaya, S.V.; Zavodnik, L.B.; Kubyshin, V.L.; Nocun, M.; Kazmierczak, P.; Dobaczewski, M.; Watala, C.; Zavodnik, I.B. Antioxidative enzyme and glutathione S-transferase activities in diabetic rats exposed to long-term ASA treatment. Life Sci., 2006, 79(19), 1804-1811.
[http://dx.doi.org/10.1016/j.lfs.2006.06.008] [PMID: 16815474]
[23]
Abro, M.U.R.; Butt, A.; Baqa, K.; Waris, N.; Khalid, M.; Fawwad, A. Association of serum liver enzyme Alanine Aminotransferase (ALT) in patients with type 2 diabetes. Pak. J. Med. Sci., 2018, 34(4), 839-843.
[http://dx.doi.org/10.12669/pjms.344.15206] [PMID: 30190738]
[24]
Judi, L.; Toukan, A.; Khader, Y.; Ajlouni, K.; Khatib, M.A. Prevalence of elevated hepatic transaminases among Jordanian patients with type 2 diabetes mellitus. Ann. Saudi Med., 2010, 30(1), 25-32.
[http://dx.doi.org/10.5144/0256-4947.59369] [PMID: 20103955]
[25]
Rao, BK; Rao, CH Hypoglycemic and antihyperglycemic activity of Syzygium alternifolium (Wt.) Walp. seed extracts in normal and diabetic rats. Phytomedicine: international journal of phytotherapy and phytopharmacology, 2001, 8(2), 88-93.
[26]
Gupta, S.; Kataria, M.; Gupta, P.K.; Murganandan, S.; Yashroy, R.C. Protective role of extracts of neem seeds in diabetes caused by streptozotocin in rats. J. Ethnopharmacol., 2004, 90(2-3), 185-189.
[http://dx.doi.org/10.1016/j.jep.2003.09.024] [PMID: 15013179]
[27]
Shinde, U.A.; Goyal, R.K. Effect of chromium picolinate on histopathological alterations in STZ and neonatal STZ diabetic rats. J. Cell. Mol. Med., 2003, 7(3), 322-329.
[http://dx.doi.org/10.1111/j.1582-4934.2003.tb00233.x] [PMID: 14594557]
[28]
Tabish, S.A. Is diabetes becoming the biggest epidemic of the twenty-first century? Int. J. Health Sci. (Qassim), 2007, 1(2), V-VIII.
[PMID: 21475425]
[29]
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(1), 1832-1842.
[http://dx.doi.org/10.19082/1832] [PMID: 26955456]
[30]
Surya, S.; Salam, A.D.; Tomy, D.V.; Carla, B.; Kumar, R.A.; Sunil, C. Diabetes mellitus and medicinal plants-a review. Asian Pac. J. Trop. Dis., 2014, 4(5), 337-347.
[http://dx.doi.org/10.1016/S2222-1808(14)60585-5]
[31]
Stephen, A.O.; Olugbemiga, O.S.; Grace, O.D.; Adeola, T.A.; Ibibia, E-I.T.; Akhere, O.J.; Adeiza, O.D.; Oluchi, A.Y.; Obiora, N.C. Antidiabetic and antidyslipidemic effect of ethanolic extract of alternanathera pungens on alloxan-induced diabetic rats. Asian Journal of Biochemistry, 2016, 11(2), 82-89.
[http://dx.doi.org/10.3923/ajb.2016.82.89]
[32]
Dra, L.A.; Sellami, S.; Rais, H.; Aziz, F.; Aghraz, A.; Bekkouche, K.; Markouk, M.; Larhsini, M. Antidiabetic potential of Caralluma europaea against alloxan-induced diabetes in mice. Saudi J. Biol. Sci., 2019, 26(6), 1171-1178.
[http://dx.doi.org/10.1016/j.sjbs.2018.05.028] [PMID: 31516346]
[33]
Meenakshi, P.; Bhuvaneshwari, R.; Rathi, M.A.; Thirumoorthi, L.; Guravaiah, D.C.; Jiji, M.J.; Gopalakrishnan, V.K. Antidiabetic activity of ethanolic extract of Zaleya decandra in alloxan-induced diabetic rats. Appl. Biochem. Biotechnol., 2010, 162(4), 1153-1159.
[http://dx.doi.org/10.1007/s12010-009-8871-x] [PMID: 19957208]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 17
ISSUE: 2
Year: 2021
Published on: 29 March, 2020
Page: [174 - 186]
Pages: 13
DOI: 10.2174/1573407216666200330114306
Price: $65

Article Metrics

PDF: 12