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Protein & Peptide Letters

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ISSN (Online): 1875-5305

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Research Article

Hydroalcoholic Extract of Solanum lycocarpum A. St. Hil. (Solanaceae) Leaves Improves Alloxan-Induced Diabetes Complications in Mice

Author(s): Victor Hugo Dantas Guimarães, Jéssica Nayara Basilio Silva, Daniela Fernanda de Freitas, Otávio Cardoso Filho, Luiz Henrique da Silveira, Barbhara Mota Marinho, Alfredo Maurício Batista de Paula, Geraldo Aclécio Melo and Sérgio Henrique Sousa Santos*

Volume 28, Issue 7, 2021

Published on: 28 January, 2021

Page: [769 - 780] Pages: 12

DOI: 10.2174/0929866528999210128205817

Price: $65

Abstract

Background: Solanum lycocarpum is a medicinal plant used in Brazil with hypoglycemic activity by its fruits use. However, the fruits production is restricted in some periods of the year, differently of leaves.

Objective: To evaluate the effects of hydroalcoholic extracts of S. lycocarpum leaves in alloxan-induced diabetic mice.

Methods: Hydroalcoholic extract of S. lycocarpum was characterized by phytochemical and GCMS analysis. The Antidiabetic activity was assessed following treatment for 22 days with S. lycocarpum extract at 125, 250, and 500 mg/kg. Bodyweight, water, and food intake, glycemia, biochemical parameters, anatomy-histopathology of the pancreas, liver and kidney, and expression of target genes were analyzed. In addition, oral acute toxicity was evaluated.

Results: Animals treated showed a significant reduction (p < 0.05) in glycemia following a dose of 125 mg/kg. Food intake remained similar for all groups. Decreased polydipsia symptoms were observed after treatment with 250 (p < 0.001) and 500 mg/kg (p < 0.01) compared with diabetic control, although normal rates were observed when 125 mg/kg was administered. A protective effect was also observed in the pancreas, liver, and kidneys, through the regeneration of the islets. Hypoglycemic activity can be attributed to myo-inositol, which stimulates insulin secretion, associated with α-tocopherol, which prevents damage from oxidative stress and apoptosis of β-pancreatic cells by an increased Catalase (CAT) and Glutathione peroxidase 4 (GPX4) mRNA expression. The toxicological test demonstrated safe oral use of the extract under the present conditions.

Conclusion: Hydroalcoholic extract of S. lycocarpum promotes the regulation of diabetes in the case of moderate glycemic levels, by decreasing glycemia and exerting protective effects on the islets.

Keywords: Diabetes mellitus, hypoglycemic activity, medicinal plants, folk medicine, Myo-inositol, α-tocopherol, phytochemistry, Lobeira.

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[1]
Guariguata, L. Estimating the worldwide burden of type 1 diabetes. Diabetes Voice, 2011, 56(2), 6-8.
[2]
Federation, I.D. IDF Diabetes Atlas, 9th ed.; Brussels, Belgium: International Diabetes Federation., 2019.
[3]
José, E.; Sérgio, V. Organizadores. Diretrizes da Sociedade Brasileira de Diabetes: 2013-2014/Sociedade Brasileira de Diabetes, São Paulo: AC Farmacêutica, 2014.
[4]
Association, A.D. Diagnosis and classification of diabetes mellitus. Diabetes Care., 2010, 33(Suppl 1), S62-69.
[5]
Tripathi, K. Essentials of Medical Pharmacology; JP Medical Ltd., 2013.
[6]
Stein, S.A.; Lamos, E.M.; Davis, S.N. A review of the efficacy and safety of oral antidiabetic drugs. Expert Opin. Drug Saf., 2013, 12(2), 153-175.
[http://dx.doi.org/10.1517/14740338.2013.752813] [PMID: 23241069]
[7]
Kulkarni, Y.A.; Garud, M.S. Effect of Bauhinia variegata Linn.(Caesalpiniaceae) extract in streptozotocin induced type I diabetic rats. Orient. Pharm. Exp. Med., 2015, 15(3), 191-198.
[http://dx.doi.org/10.1007/s13596-015-0186-6]
[8]
Modak, M.; Dixit, P.; Londhe, J.; Ghaskadbi, S.; Devasagayam, T.P. Indian herbs and herbal drugs used for the treatment of diabetes. J. Clin. Biochem. Nutr., 2007, 40(3), 163-173.
[http://dx.doi.org/10.3164/jcbn.40.163] [PMID: 18398493]
[9]
Farina, F.; Piassi, F.G.; Moysés, M.R.; Bazzolli, D.M.; Bissoli, Nde.S. Glycemic and urinary volume responses in diabetic mellitus rats treated with Solanum lycocarpum. Appl. Physiol. Nutr. Metab., 2010, 35(1), 40-44.
[http://dx.doi.org/10.1139/H09-131] [PMID: 20130665]
[10]
Yoshikawa, M.; Nakamura, S.; Ozaki, K.; Kumahara, A.; Morikawa, T.; Matsuda, H. Structures of steroidal alkaloid oligoglycosides, robeneosides A and B, and antidiabetogenic constituents from the Brazilian medicinal plant Solanum lycocarpum. J. Nat. Prod., 2007, 70(2), 210-214.
[http://dx.doi.org/10.1021/np0680580] [PMID: 17249729]
[11]
Perez, A.C.; Franca, V.; Daldegan, V.M., Jr; Duarte, I.D. Effect of Solanum lycocarpum St. Hill on various haematological parameters in diabetic rats. J. Ethnopharmacol., 2006, 106(3), 442-444.
[http://dx.doi.org/10.1016/j.jep.2006.02.017] [PMID: 16600544]
[12]
da Costa, G.A.; Morais, M.G.; Saldanha, A.A.; Assis Silva, I.C.; Aleixo, Á Antioxidant, antibacterial, cytotoxic, and anti-inflammatory potential of the leaves of Solanum lycocarpum A. St. Hil. (Solanaceae). Evid. Based Complementary Altern. Med., 2015, 2015, 315987.
[13]
Vieira, G., Jr; Ferreira, P.M.; Matos, L.G.; Ferreira, E.C.; Rodovalho, W.; Ferri, P.H.; Ferreira, H.D.; Costa, E.A. Anti-inflammatory effect of Solanum lycocarpum fruits. Phytother. Res., 2003, 17(8), 892-896.
[http://dx.doi.org/10.1002/ptr.1247] [PMID: 13680819]
[14]
Munari, C.C.; de Oliveira, P.F.; Campos, J.C.; Martins, Sde.P.; Da Costa, J.C.; Bastos, J.K.; Tavares, D.C. Antiproliferative activity of Solanum lycocarpum alkaloidic extract and their constituents, solamargine and solasonine, in tumor cell lines. J. Nat. Med., 2014, 68(1), 236-241.
[http://dx.doi.org/10.1007/s11418-013-0757-0] [PMID: 23475509]
[15]
Matias, L.J.; Mercadante-Simões, M.O.; Royo, V.A.; Ribeiro, L.M.; Santos, A.C.; Fonseca, J. Structure and histochemistry of medicinal species of Solanum. Rev. Bras. Farmacogn., 2016, 26(2), 147-160.
[http://dx.doi.org/10.1016/j.bjp.2015.11.002]
[16]
Brasileira, C.P.d.R.d.F. Parte II, III e IV. Rio de Janeiro. Farmacopeia Brasileira., 1988.
[17]
Latha, M.; Pari, L.; Ramkumar, K.M.; Rajaguru, P.; Suresh, T.; Dhanabal, T.; Sitasawad, S.; Bhonde, R. Antidiabetic effects of scoparic acid D isolated from Scoparia dulcis in rats with streptozotocin-induced diabetes. Nat. Prod. Res., 2009, 23(16), 1528-1540.
[http://dx.doi.org/10.1080/14786410902726126] [PMID: 19606382]
[18]
Royo, V.A.; Araújo, B.C.P.; Barros, B.P. Metodos fitoquímicos para identificação de metabolitos secundarios; Novas Edições Academicas, 2015.
[19]
Ou, Y.; Ren, Z.; Wang, J.; Yang, X. Phycocyanin ameliorates alloxan-induced diabetes mellitus in mice: Involved in insulin signaling pathway and GK expression. Chem. Biol. Interact., 2016, 247, 49-54.
[http://dx.doi.org/10.1016/j.cbi.2016.01.018] [PMID: 26827782]
[20]
Baddar, N.W.; Aburjai, T.A.; Taha, M.O.; Disi, A.M. Thujone corrects cholesterol and triglyceride profiles in diabetic rat model. Nat. Prod. Res., 2011, 25(12), 1180-1184.
[http://dx.doi.org/10.1080/14786419.2010.496116] [PMID: 21740283]
[21]
Toma, A.; Makonnen, E.; Debella, A.; Tesfaye, B. Antihyperglycemic effect on chronic administration of butanol fraction of ethanol extract of Moringa stenopetala leaves in alloxan induced diabetic mice. Asian Pac. J. Trop. Biomed., 2012, 2(3), S1606-S1610.
[http://dx.doi.org/10.1016/S2221-1691(12)60461-4]
[22]
Friedewald, W.T.; Levy, R.I.; Fredrickson, D.S. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin. Chem., 1972, 18(6), 499-502.
[http://dx.doi.org/10.1093/clinchem/18.6.499] [PMID: 4337382]
[23]
Walum, E. Acute oral toxicity. Environ. Health Perspect., 1998, 106(Suppl 2), 497-503.
[24]
Li, K.K.; Liu, C.L.; Shiu, H.T.; Wong, H.L.; Siu, W.S.; Zhang, C.; Han, X.Q.; Ye, C.X.; Leung, P.C.; Ko, C.H. Cocoa tea (Camellia ptilophylla) water extract inhibits adipocyte differentiation in mouse 3T3-L1 preadipocytes. Sci. Rep., 2016, 6, 20172.
[http://dx.doi.org/10.1038/srep20172] [PMID: 26833256]
[25]
Livak, K.J.; Schmittgen, T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods, 2001, 25(4), 402-408.
[http://dx.doi.org/10.1006/meth.2001.1262] [PMID: 11846609]
[26]
Shen, X.; Deng, C.; Wang, B.; Dong, L. Quantification of trimethylsilyl derivatives of amino acid disease biomarkers in neonatal blood samples by gas chromatography-mass spectrometry. Anal. Bioanal. Chem., 2006, 384(4), 931-938.
[http://dx.doi.org/10.1007/s00216-005-0241-0] [PMID: 16385411]
[27]
Oplos, C.; Eloh, K.; Spiroudi, U.M.; Pierluigi, C.; Ntalli, N. Nematicidal weeds, Solanum nigrum and Datura stramonium. J. Nematol., 2018, 50(3), 317-328.
[http://dx.doi.org/10.21307/jofnem-2018-017] [PMID: 30451417]
[28]
Guo, J.; Shi, Y.; Xu, C.; Zhong, R.; Zhang, F.; Zhang, T.; Niu, B.; Wang, J. Quantification of plasma myo-inositol using gas chromatography-mass spectrometry. Clin. Chim. Acta, 2016, 460, 88-92.
[http://dx.doi.org/10.1016/j.cca.2016.06.022] [PMID: 27342997]
[29]
Medeiros, P.M.; Simoneit, B.R.T. Analysis of sugars in environmental samples by gas chromatography-mass spectrometry. J. Chromatogr. A, 2007, 1141(2), 271-278.
[http://dx.doi.org/10.1016/j.chroma.2006.12.017] [PMID: 17207493]
[30]
Tang, L.Q.; Wei, W.; Chen, L.M.; Liu, S. Effects of berberine on diabetes induced by alloxan and a high-fat/high-cholesterol diet in rats. J. Ethnopharmacol., 2006, 108(1), 109-115.
[http://dx.doi.org/10.1016/j.jep.2006.04.019] [PMID: 16759828]
[31]
Watson, J.; Baker, T.; Bell, S.; Gann, A.; Levine, M. Molecular Biology of the Gene. Benjamin Cummings: San Francisco, CA, USA, 2003.
[32]
Akah, P.; Okoli, C.; Nwafor, S. Phytotherapy in the management of diabetes mellitus. J. Nat. Rem., 2002, 2(1), 1-10.
[33]
Carvalho-Filho, M.A.; Carvalheira, J.B.C.; Velloso, L.A.; Saad, M.J.A. Insulin and angiotensin II signaling pathways cross-talk: implications with the association between diabetes mellitus, arterial hypertension and cardiovascular disease. Arq. Bras. Endocrinol. Metabol., 2007, 51(2), 195-203.
[http://dx.doi.org/10.1590/S0004-27302007000200008] [PMID: 17505626]
[34]
Jacobson, A.M. The psychological care of patients with insulin-dependent diabetes mellitus. N. Engl. J. Med., 1996, 334(19), 1249-1253.
[http://dx.doi.org/10.1056/NEJM199605093341907] [PMID: 8606721]
[35]
Ferreira, R. Efeito da Infusão dos Frutos de Momordica charantia L. Ratas Diabéticas. Brazil, 76p. Tese (Doutorado em Bioquímica Agrícola)-Universidade Federal de Viçosa, Minas Gerais., 2008.
[36]
Szkudelski, T. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol. Res., 2001, 50(6), 537-546.
[PMID: 11829314]
[37]
Croze, M.L.; Vella, R.E.; Pillon, N.J.; Soula, H.A.; Hadji, L.; Guichardant, M.; Soulage, C.O. Chronic treatment with myo-inositol reduces white adipose tissue accretion and improves insulin sensitivity in female mice. J. Nutr. Biochem., 2013, 24(2), 457-466.
[http://dx.doi.org/10.1016/j.jnutbio.2012.01.008] [PMID: 22658648]
[38]
Croze, M.L.; Soulage, C.O. Potential role and therapeutic interests of myo-inositol in metabolic diseases. Biochimie, 2013, 95(10), 1811-1827.
[http://dx.doi.org/10.1016/j.biochi.2013.05.011] [PMID: 23764390]
[39]
Ortmeyer, H.K. Dietary myoinositol results in lower urine glucose and in lower postprandial plasma glucose in obese insulin resistant rhesus monkeys. Obes. Res., 1996, 4(6), 569-575.
[http://dx.doi.org/10.1002/j.1550-8528.1996.tb00271.x] [PMID: 8946442]
[40]
Takemoto, K.; Doi, W.; Masuoka, N. Protective effect of vitamin E against alloxan-induced mouse hyperglycemia. Biochim. Biophys. Acta, 2016, 1862(4), 647-650.
[http://dx.doi.org/10.1016/j.bbadis.2015.12.022] [PMID: 26723540]
[41]
Garber, A.J. Attenuating CV risk factors in patients with diabetes: clinical evidence to clinical practice. Diabetes Obes. Metab., 2002, 4(Suppl. 1), S5-S12.
[http://dx.doi.org/10.1046/j.1462-8902.2001.00038.x] [PMID: 11843949]
[42]
Woo, M.N.; Bok, S.H.; Lee, M.K.; Kim, H.J.; Jeon, S.M.; Do, G.M.; Shin, S.K.; Ha, T.Y.; Choi, M.S. Anti-obesity and hypolipidemic effects of a proprietary herb and fiber combination (S&S PWH) in rats fed high-fat diets. J. Med. Food, 2008, 11(1), 169-178.
[http://dx.doi.org/10.1089/jmf.2007.082] [PMID: 18361753]
[43]
Farmer, J.A. Diabetic dyslipidemia and atherosclerosis: evidence from clinical trials. Curr. Diab. Rep., 2008, 8(1), 71-77.
[http://dx.doi.org/10.1007/s11892-008-0013-2] [PMID: 18367002]
[44]
Prasath, G.S.; Sundaram, C.S.; Subramanian, S.P. Fisetin averts oxidative stress in pancreatic tissues of streptozotocin-induced diabetic rats. Endocrine, 2013, 44(2), 359-368.
[http://dx.doi.org/10.1007/s12020-012-9866-x] [PMID: 23277230]
[45]
Oloyede, H.O.; Bello, T.O.; Ajiboye, T.O.; Salawu, M.O. Antidiabetic and antidyslipidemic activities of aqueous leaf extract of Dioscoreophyllum cumminsii (Stapf) Diels in alloxan-induced diabetic rats. J. Ethnopharmacol., 2015, 166, 313-322.
[http://dx.doi.org/10.1016/j.jep.2015.02.049] [PMID: 25749145]
[46]
Cotran, R.; Kumar, V.; Robbins, S.; Schoen, F.I. Patologia Estrutural e Funcional, 6° Edição ed.; Rio de Janeiro: Guanabara Koogan., 2000.
[47]
Houssay, B.A.; Mazocco P, B.R. Alloxan and diabetes. Rev. Soc. Argent. Biol., 1946, 22, 195-231.
[48]
Gomori, G.; Goldner, M.G. Production of diabetes mellitus in rats with alloxan. Proc. Soc. Exp. Biol. Med., 1943, 54(3), 287-290.
[http://dx.doi.org/10.3181/00379727-54-14406]
[49]
Abdel-Zaher, A.O.; Salim, S.Y.; Assaf, M.H.; Abdel-Hady, R.H. Antidiabetic activity and toxicity of Zizyphus spina-christi leaves. J. Ethnopharmacol., 2005, 101(1-3), 129-138.
[http://dx.doi.org/10.1016/j.jep.2005.04.007] [PMID: 16009520]
[50]
Paul, B.; Li, Y.; Tollefsbol, T.O. The effects of combinatorial genistein and sulforaphane in breast tumor inhibition: role in epigenetic regulation. Int. J. Mol. Sci., 2018, 19(6), 1754.
[http://dx.doi.org/10.3390/ijms19061754] [PMID: 29899271]
[51]
Morais, M.G.; Saldanha, A.A.; Costa Rodrigues, J.P.; Cotta Mendes, I.; Ferreira, L.M.; Avelar Amado, P.; de Souza Farias, K.; Samúdio Santos Zanuncio, V.; Brentan da Silva, D.; Carmo Horta Pinto, F.; Soares, A.C.; Alves Rodrigues Dos Santos Lima, L. Chemical composition, antioxidant, anti-inflammatory and antinociceptive activities of the ethanol extract of ripe fruits of Solanum lycocarpum St. Hil. (Solanaceae). J. Ethnopharmacol., 2020, 262, 113125.
[http://dx.doi.org/10.1016/j.jep.2020.113125] [PMID: 32736057]
[52]
Zemolin, A.P.P.; Meinerz, D.F.; de Paula, M.T.; Mariano, D.O.C.; Rocha, J.B.T.; Pereira, A.B.; Posser, T.; Franco, J.L. Evidences for a role of glutathione peroxidase 4 (GPx4) in methylmercury induced neurotoxicity in vivo. Toxicology, 2012, 302(1), 60-67.
[http://dx.doi.org/10.1016/j.tox.2012.07.013] [PMID: 22885222]
[53]
Ahmad, B.; Rehman, M.U.; Amin, I.; Mir, M.U.R.; Ahmad, S.B.; Farooq, A.; Muzamil, S.; Hussain, I.; Masoodi, M.; Fatima, B. Zingerone (4-(4-hydroxy-3-methylphenyl) butan-2-one) protects against alloxan-induced diabetes via alleviation of oxidative stress and inflammation: probable role of NF-kB activation. Saudi Pharm. J., 2018, 26(8), 1137-1145.
[http://dx.doi.org/10.1016/j.jsps.2018.07.001] [PMID: 30532634]
[54]
Takemoto, K.; Tanaka, M.; Iwata, H.; Nishihara, R.; Ishihara, K.; Wang, D-H.; Ogino, K.; Taniuchi, K.; Masuoka, N. Low catalase activity in blood is associated with the diabetes caused by alloxan. Clin. Chim. Acta, 2009, 407(1-2), 43-46.
[http://dx.doi.org/10.1016/j.cca.2009.06.028] [PMID: 19563792]
[55]
Ighodaro, O.M.; Adeosun, A.M.; Akinloye, O.A. Alloxan-induced diabetes, a common model for evaluating the glycemic-control potential of therapeutic compounds and plants extracts in experimental studies. Medicina (Kaunas), 2017, 53(6), 365-374.
[http://dx.doi.org/10.1016/j.medici.2018.02.001] [PMID: 29548636]
[56]
Luzi, L.; Pozza, G. Glibenclamide: an old drug with a novel mechanism of action? Acta Diabetol., 1997, 34(4), 239-244.
[http://dx.doi.org/10.1007/s005920050081] [PMID: 9451465]
[57]
Lorenzi, H.M. Plantas medicinais no Brasil, 2 ed.; Nova Odessa, SP: Instituto Plantarum., 2008.

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