Neuroprotective Effects of Isolated Mangiferin from Swertia chirayita Leaves Regulating Oxidative Pathway on Streptozotocin-Induced Diabetic
Neuropathy in Experimental Rats

Shivam; Asheesh   Kumar   Gupta

doi:10.2174/0118715249255977231213053039

Abstract

Background: Oxidative stress has an important role in the pathogenesis and development of diabetic peripheral neuropathy (DPN), the most common and debilitating complication of diabetes mellitus. Swertia chirayita is a rich source of phenolic constituents and has hypoglycemic, anti-inflammatory, and antioxidant properties.

Aims: This study was performed to evaluate the neuroprotective effect in diabetes by enhancing antioxidant defense against oxidative stress, which exhibits a neuroprotective effect in streptozotocin- induced diabetic rats.

Objectives: The objective of this study was to elucidate the therapeutic potential of bioactive compounds of Swertia chirayita for diabetic complications.

Methods: The present work focused on isolating the bioactive from the leaves of Swertia absinthe for acute toxicity studies, assessing its protective effects against diabetes and diabetic neuropathy as well as its mode of action in STZ-induced Wistar rats. The local area of Moradabad is the place from where the leaves of Swertia chirayita were gathered. Mangiferin was isolated and identified using spectroscopic techniques, such as UV, HPLC, 1H NMR, C13 NMR, MAS, and FTIR. Mangiferin was administered in doses of 15 and 30 mg/kg to test its effect on experimentally induced diabetes. The sciatic nerves of all groups were examined histopathologically. The protective effect of the drug against diabetes and diabetic neuropathy was demonstrated by measures, such as blood glucose level, body weight, food intake, thermal hyperalgesia, grip strength, spontaneous locomotor test, and lipid profile analysis. Sciatic nerve cells of the treated groups showed less inflammation, degeneration, and necrosis.

Results: The results of this study confirmed that mangiferin alleviated diabetic neuropathic pain, possibly by reducing inflammatory cytokines (TNF-α, TGF-β1, IL-1β, and IL-6), strong antioxidant activity, and NGF in sciatic nerves. It may be a therapeutic agent.

Conclusion: Our results suggested that active phytochemicals of Swertia chirayita showed preventive and curative effects against STZ-induced diabetic neuropathy in rats, which might be due to its antioxidant, anti-inflammatory, and anti-apoptotic properties.

Keywords: Diabetic neuropathy, mangiferin, diabetes, Swertia chirayita, oxidative stress, inflammation, inflammatory cytokines.

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[1]
Upsher, R.; Taylor, A.M.; Reece, I.; Chamley, M.; Ismail, K.; Forbes, A.; Winkley, K. Experiences of attending group education to support insulin initiation in type 2 diabetes: A qualitative study. Diabetes Ther.,  2020, 11(1), 119-132.
 [http://dx.doi.org/10.1007/s13300-019-00727-7] [PMID: 31732858]

[2]
Low, L.L.; Tong, S.F.; Low, W.Y. Social influences of help-seeking behaviour among patients with type 2 diabetes mellitus in Malaysia. Asia Pac. J. Public Health,  2016, 28(S1), 17S-25S.
 [http://dx.doi.org/10.1177/1010539515596807] [PMID: 26219560]

[3]
Gharib, E.; Kouhsari, M.S. Study of the antidiabetic activity of Punica granatum L. fruits aqueous extract on the alloxan-diabetic wistar rats. Iran. J. Pharm. Res.,  2019, 18(1), 358-368.
 [PMID: 31089370]

[4]
Tang, D.; Liu, L.; Ajiakber, D.; Ye, J.; Xu, J.; Xin, X.; Aisa, H.A. Anti-diabetic effect of Punica granatum flower polyphenols extract in type 2 diabetic rats: Activation of Akt/GSK-3β and inhibition of IRE1α-XBP1 pathways. Front. Endocrinol.,  2018, 9, 586.
 [http://dx.doi.org/10.3389/fendo.2018.00586] [PMID: 30374328]

[5]
Qureshi, Z.; Ali, M.N.; Khalid, M. An insight into potential pharmacotherapeutic agents for painful diabetic neuropathy. J. Diabetes Res.,  2022, 2022, 1-19.
 [http://dx.doi.org/10.1155/2022/9989272] [PMID: 35127954]

[6]
Oh, J. Clinical spectrum and diagnosis of diabetic neuropathies. Korean J. Intern. Med.,  2020, 35(5), 1059-1069.
 [http://dx.doi.org/10.3904/kjim.2020.202] [PMID: 32921007]

[7]
Kumar, V.; Van Staden, J. A review of swertia chirayita (Gentianaceae) as a traditional medicinal plant. Front. Pharmacol.,  2016, 6, 308.
 [http://dx.doi.org/10.3389/fphar.2015.00308] [PMID: 26793105]

[8]
Zhou, N.J.; Geng, C.A.; Huang, X.Y.; Ma, Y.B.; Zhang, X.M.; Wang, J.L.; Chen, J.J. Anti-hepatitis B virus active constituents from Swertia chirayita. Fitoterapia,  2015, 100, 27-34.
 [http://dx.doi.org/10.1016/j.fitote.2014.11.011] [PMID: 25447162]

[9]
Leong, X.Y.; Thanikachalam, P.V.; Pandey, M.; Ramamurthy, S. A systematic review of the protective role of swertiamarin in cardiac and metabolic diseases. Biomed. Pharmacother.,  2016, 84, 1051-1060.
 [http://dx.doi.org/10.1016/j.biopha.2016.10.044] [PMID: 27780133]

[10]
Padhan, J.K.; Kumar, V.; Sood, H.; Singh, T.R.; Chauhan, R.S. Contents of therapeutic metabolites in Swertia chirayita correlate with the expression profiles of multiple genes in corresponding biosynthesis pathways. Phytochemistry,  2015, 116, 38-47.
 [http://dx.doi.org/10.1016/j.phytochem.2015.05.007] [PMID: 26028519]

[11]
Imran, M.; Arshad, M.S.; Butt, M.S.; Kwon, J.H.; Arshad, M.U.; Sultan, M.T. Mangiferin: A natural miracle bioactive compound against lifestyle related disorders. Lipids Health Dis.,  2017, 16(1), 84.
 [http://dx.doi.org/10.1186/s12944-017-0449-y] [PMID: 28464819]

[12]
Figueroa, J.D.; Lemus, F.E.; Dorta, E.; Melin, V.; Ríos, C.J.; Faúndez, M.; Contreras, D.; Denicola, A.; Álvarez, B.; Davies, M.J.; Alarcón, L.C. Quantification of carbonate radical formation by the bicarbonate-dependent peroxidase activity of superoxide dismutase 1 using pyrogallol red bleaching. Redox Biol.,  2019, 24, 101207.
 [http://dx.doi.org/10.1016/j.redox.2019.101207] [PMID: 31102971]

[13]
Kumar, P.; Negi, S.; Kumar, M.; Singh, D. Role of ethics in animal experimentation as per CPCSEA guidelines. National Symposium & Annual Convention of LASAI,  28-29 April, p. 20182018.

[14]
Meyers, C. Current protocols in nucleic acid chemistry; Beaucage, S.L., Ed.; Appendix 3, Appendix 3E, 2001. 

[15]
Susan, M.A.B.H.; Ara, G.; Islam, M.M.; Rahman, M.M.; Mollah, M.Y.A. Thin layer chromatography-A tool to investigate kinetics of michael addition reaction. J. Scient. Res.,  2018, 10(3), 323-329.
 [http://dx.doi.org/10.3329/jsr.v10i3.37190]

[16]
Muñoz, M.N.M.; Alvarado, U.G.; Reyes, J.I.L.; Watanabe, K. Acute oral toxicity assessment of ethanolic extracts of Antidesma bunius (L.) Spreng fruits in mice. Toxicol. Rep.,  2021, 8, 1289-1299.
 [http://dx.doi.org/10.1016/j.toxrep.2021.06.010] [PMID: 34221900]

[17]
Jayaprasad, B.; Sharavanan, P.S.; Sivaraj, R. Antidiabetic effect of Chloroxylon swietenia bark extracts on streptozotocin induced diabetic rats. Beni. Suef Univ. J. Basic Appl. Sci.,  2016, 5(1), 61-69.
 [http://dx.doi.org/10.1016/j.bjbas.2016.01.004]

[18]
Panda, S.P.; Haldar, P.K.; Bera, S.; Adhikary, S.; Kandar, C.C. Antidiabetic and antioxidant activity of Swietenia mahagoni in streptozotocin-induced diabetic rats. Pharm. Biol.,  2010, 48(9), 974-979.
 [http://dx.doi.org/10.3109/13880200903390051] [PMID: 20731547]

[19]
Akbarzadeh, A.; Norouzian, D.; Mehrabi, M.R.; Jamshidi, S.; Farhangi, A.; Verdi, A.A.; Mofidian, S.M.A.; Rad, B.L. Induction of diabetes by Streptozotocin in rats. Indian J. Clin. Biochem.,  2007, 22(2), 60-64.
 [http://dx.doi.org/10.1007/BF02913315] [PMID: 23105684]

[20]
Shoaib, A. Badruddeen; Dixit, R.K.; Ganash, M.; Barreto, G.; Ashraf, G.M.; Siddiqui, H.H. Beneficial effects of n-hexane bark extract of Onosma echioides L. on diabetic peripheral neuropathy. J. Cell. Biochem.,  2019, 120(10), 16524-16532.
 [http://dx.doi.org/10.1002/jcb.28912] [PMID: 31099436]

[21]
Tsafack, E.G.; Mbiantcha, M.; Ateufack, G.; Nguemnang, D.D.S.F.; Yousseu, N.W.; Atsamo, A.D.; Marthe Mba, M.V.; Adjouzem, C.F.; Ben Besong, E. Antihypernociceptive and neuroprotective effects of the aqueous and methanol stem-bark extracts of Nauclea pobeguinii (Rubiaceae) on STZ-induced diabetic neuropathic pain. Evid. Based Complement. Alternat. Med.,  2021, 2021, 1-17.
 [http://dx.doi.org/10.1155/2021/6637584] [PMID: 33603820]

[22]
Erbaş, O.; Oltulu, F.; Yılmaz, M.; Yavaşoğlu, A.; Taşkıran, D. Neuroprotective effects of chronic administration of levetiracetam in a rat model of diabetic neuropathy. Diabetes Res. Clin. Pract.,  2016, 114, 106-116.
 [http://dx.doi.org/10.1016/j.diabres.2015.12.016] [PMID: 26795972]

[23]
Koneri, R.; Samaddar, S.; Simi, S.M.; Rao, S. Neuroprotective effect of a triterpenoid saponin isolated from Momordica cymbalaria Fenzl in diabetic peripheral neuropathy. Indian J. Pharmacol.,  2014, 46(1), 76-81.
 [http://dx.doi.org/10.4103/0253-7613.125179] [PMID: 24550589]

[24]
Chen, Y.; Ji, P.; Ma, G.; Song, Z.; Tang, B.Q.; Li, T. Simultaneous determination of cellular adenosine nucleotides, malondialdehyde, and uric acid using HPLC. Biomed. Chromatogr.,  2021, 35(10), e5156.
 [http://dx.doi.org/10.1002/bmc.5156] [PMID: 33955024]

[25]
Akerboom, T.P.M.; Sies, H. Assay of glutathione, glutathione disulfide, and glutathione mixed disulfides in biological samples. Methods Enzymol.,  1981, 77, 373-382.
 [http://dx.doi.org/10.1016/S0076-6879(81)77050-2] [PMID: 7329314]

[26]
Hashemi, S.A.; Bathaie, S.Z.; Mohagheghi, M.A. Interaction of saffron carotenoids with catalase: in vitro, in vivo and molecular docking studies. J. Biomol. Struct. Dyn.,  2020, 38(13), 3916-3926.
 [http://dx.doi.org/10.1080/07391102.2019.1668302] [PMID: 31537178]

[27]
Kakkar, M.; Behl, T.; Cruz, C.V.D.L.; Makeen, H.A.; Albratty, M.; Alhazmi, H.A.; Meraya, A.M.; Albadrani, G.M.; Abdel-Daim, M.M. Tridax procumbens ameliorates streptozotocin-induced diabetic neuropathy in rats via modulating angiogenic, inflammatory, and oxidative pathways. Evid. Based Complement. Alternat. Med.,  2022, 2022, 1-12.
 [http://dx.doi.org/10.1155/2022/1795405] [PMID: 36091594]

[28]
Nadipelly, J.; Sayeli, V.; Kadhirvelu, P.; Shanmugasundaram, J.; Cheriyan, B.V.; Subramanian, V. Effect of certain trimethoxy flavones on paclitaxel - Induced peripheral neuropathy in mice. Integr. Med. Res.,  2018, 7(2), 159-167.
 [http://dx.doi.org/10.1016/j.imr.2018.03.006] [PMID: 29984177]

[29]
Green, L.A.; McGuire, J.; Gabriel, D.A. Effects of the proprioceptive neuromuscular facilitation contraction sequence on motor skill learning-related increases in the maximal rate of wrist flexion torque development. Front. Hum. Neurosci.,  2021, 15, 764660.
 [http://dx.doi.org/10.3389/fnhum.2021.764660] [PMID: 34803640]

[30]
Kanzler, C.M.; Schwarz, A.; Held, J.P.O.; Luft, A.R.; Gassert, R.; Lambercy, O. Technology-aided assessment of functionally relevant sensorimotor impairments in arm and hand of post-stroke individuals. J. Neuroeng. Rehabil.,  2020, 17(1), 128.
 [http://dx.doi.org/10.1186/s12984-020-00748-5] [PMID: 32977810]

[31]
Alam, M.M.; Khan, A.A.; Farooq, M. Effects of vibration therapy on neuromuscular efficiency & features of the EMG signal based on endurance test. J. Bodyw. Mov. Ther.,  2020, 24(4), 325-335.
 [http://dx.doi.org/10.1016/j.jbmt.2020.06.037] [PMID: 33218530]

[32]
Lu, H.J.; Tzeng, T.F.; Liou, S.S.; Da Lin, S.; Wu, M.C.; Liu, I.M. Ruscogenin ameliorates diabetic nephropathy by its anti-inflammatory and anti-fibrotic effects in streptozotocin-induced diabetic rat. BMC Complement. Altern. Med.,  2014, 14(1), 110.
 [http://dx.doi.org/10.1186/1472-6882-14-110] [PMID: 24666993]

[33]
Oyenihi, A.B.; Chegou, N.N.; Oguntibeju, O.O.; Masola, B. Centella asiatica enhances hepatic antioxidant status and regulates hepatic inflammatory cytokines in type 2 diabetic rats. Pharm. Biol.,  2017, 55(1), 1671-1678.
 [http://dx.doi.org/10.1080/13880209.2017.1318293] [PMID: 28447512]

[34]
Nasiry, D.; Ahmadvand, H.; Amiri, T.F.; Akbari, E.J.B.c. Protective effects of methanolic extract of Juglans regia L. leaf on streptozotocin-induced diabetic peripheral neuropathy in rats. BMC Complement. Altern. Med.,  2017, 17(1), 476.

[35]
Saraswat, N.; Sachan, N.; Chandra, P. Anti-diabetic, diabetic neuropathy protective action and mechanism of action involving oxidative pathway of chlorogenic acid isolated from Selinum vaginatum roots in rats. Heliyon,  2020, 6(10), e05137.
 [http://dx.doi.org/10.1016/j.heliyon.2020.e05137] [PMID: 33088940]

[36]
Giacco, F.; Brownlee, M. Oxidative stress and diabetic complications. Circ. Res.,  2010, 107(9), 1058-1070.
 [http://dx.doi.org/10.1161/CIRCRESAHA.110.223545] [PMID: 21030723]

[37]
Schreiber, A.K.; Nones, C.F.; Reis, R.C.; Chichorro, J.G.; Cunha, J.M. Diabetic neuropathic pain: Physiopathology and treatment. World J. Diabetes,  2015, 6(3), 432-444.
 [http://dx.doi.org/10.4239/wjd.v6.i3.432] [PMID: 25897354]

[38]
Themistocleous, A.C.; Ramirez, J.D.; Shillo, P.R.; Lees, J.G.; Selvarajah, D.; Orengo, C.; Tesfaye, S.; Rice, A.S.C.; Bennett, D.L.H. The Pain in Neuropathy Study (PiNS): A cross-sectional observational study determining the somatosensory phenotype of painful and painless diabetic neuropathy. Pain,  2016, 157(5), 1132-1145.
 [http://dx.doi.org/10.1097/j.pain.0000000000000491] [PMID: 27088890]

[39]
Lasyoud, A.; Alsharari, N. Towards an understanding of the dimensions and factors of management accounting change. Asia Pac. Manag. Accounting. J,  2017, 12(1), 105-142.

[40]
Kumar, J.U.S.; Chaitanya, M.J.K.; Semotiuk, A.J. Applications indigenous knowledge on medicinal plants used by ethnic communities of South India. Ethnobot. Res. Applicat.,  2019, 18, 1-112.

[41]
Jensen, T.S.; Finnerup, N.B. Allodynia and hyperalgesia in neuropathic pain: clinical manifestations and mechanisms. Lancet Neurol.,  2014, 13(9), 924-935.
 [http://dx.doi.org/10.1016/S1474-4422(14)70102-4] [PMID: 25142459]

[42]
Basu, P. In vitro and in vivo effects of flavonoids on peripheral neuropathic pain. Molecules,  2020, 25(5), 1171.

[43]
Ayala, A.; Muñoz, M.F.; Argüelles, S. Lipid peroxidation: Production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid. Med. Cell. Longev.,  2014, 2014, 1-31.
 [http://dx.doi.org/10.1155/2014/360438] [PMID: 24999379]

[44]
Matough, F.A.; Budin, S.B.; Hamid, Z.A.; Alwahaibi, N.; Mohamed, J. The role of oxidative stress and antioxidants in diabetic complications. Sultan Qaboos Univ. Med. J.,  2012, 12(1), 5-18.
 [http://dx.doi.org/10.12816/0003082] [PMID: 22375253]

[45]
Tiwari, B.K.; Pandey, K.B.; Abidi, A.B.; Rizvi, S.I. Markers of oxidative stress during diabetes mellitus. J. Biomark.,  2013, 2013, 1-8.
 [http://dx.doi.org/10.1155/2013/378790] [PMID: 26317014]

[46]
Sivakumar, V.; Rajan, D.M.S. Antioxidant effect of Tinospora cordifolia extract in alloxan-induced diabetic rats. Indian J. Pharm. Sci.,  2010, 72(6), 795-798.
 [http://dx.doi.org/10.4103/0250-474X.84600] [PMID: 21969757]

[47]
Feldman, E.L.; Nave, K.A.; Jensen, T.S.; Bennett, D.L.H. New horizons in diabetic neuropathy: Mechanisms, bioenergetics, and pain. Neuron,  2017, 93(6), 1296-1313.
 [http://dx.doi.org/10.1016/j.neuron.2017.02.005] [PMID: 28334605]

[48]
Ayaz, M.; Sadiq, A.; Junaid, M.; Ullah, F.; Subhan, F.; Ahmed, J. Neuroprotective and anti-aging potentials of essential oils from aromatic and medicinal plants. Front. Aging Neurosci.,  2017, 9, 168.
 [http://dx.doi.org/10.3389/fnagi.2017.00168] [PMID: 28611658]

[49]
Ekor, M. The growing use of herbal medicines: Issues relating to adverse reactions and challenges in monitoring safety. Front. Pharmacol.,  2014, 4, 177.
 [http://dx.doi.org/10.3389/fphar.2013.00177] [PMID: 24454289]

[50]
Macedo, A. Response to Yadav et al. J. Pediatr. Urol.,  2012, 2012, 8.

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DOI https://dx.doi.org/10.2174/0118715249255977231213053039	Print ISSN 1871-5249
Publisher Name Bentham Science Publisher	Online ISSN 1875-6166

Central Nervous System Agents in Medicinal Chemistry

Neuroprotective Effects of Isolated Mangiferin from Swertia chirayita Leaves Regulating Oxidative Pathway on Streptozotocin-Induced Diabetic Neuropathy in Experimental Rats

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