Abstract
Mucuna pruriens (L.) DC., Fabaceae, an herbal phytomedicine used in Indian traditional Ayurvedic medicinal concoctions, is known to mediate neurodegeneration. Hydroalcoholic-soluble extracts from seeds were studied to determine their protective potential against ochratoxin A–promoted neurodegeneration. The seed extract was subjected to liquid chromatography coupled to tandem mass spectrometry analysis to identify its bioactive compounds. Ochratoxin A, a widely known mycotoxin food contaminant and identified as being a potent neurotoxin even at low doses, was examined for its neurodegenerative influence. The seed extract and its major bioactive constituent L-dopa were further studied to understand their neuroprotective potential against ochratoxin A–induced oxidative stress via reactive oxygen species generation, mitochondrial membrane potential disruption, nuclear damage and neuronal stress in Neuro-2a cells. The locomotive dysfunction caused by ochratoxin A exposure was studied by examining a battery of behavioural abnormality tests, imbalance in neurotransmitter levels, brain antioxidant status and oxidative stress indices. It was evidenced in the current study that seed extract and L-dopa have the potential to ameliorate neuronal apoptosis by regulating the PI3K/Akt signalling pathway and its consequence on the molecular targets forkhead box transcription factor and glycogen synthase kinase 3β, in addition to deflecting neurodegenerative diseases like Parkinson’s caused by induced neurotoxicity.
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Alburges ME, Narang N, Wamsley JK (1993) A sensitive and rapid HPLC-ECD method for the simultaneous analysis of norepinephrine, dopamine, serotonin and their primary metabolites in brain tissue. Biomed Chromatogr 7:306–310. https://doi.org/10.1002/bmc.1130070605
Benzie IF, Strain JJ (1996) The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Anal Biochem 239:70–76. https://doi.org/10.1006/abio.1996.0292
Bhat PV, Anand T, Mohan Manu T, Khanum F (2018) Restorative effect of L-dopa treatment against Ochratoxin A induced neurotoxicity. Neurochem Int 118:252–263. https://doi.org/10.1016/j.neuint.2018.04.003
Bhat PV, Pandareesh KF, Tamatam A (2016) Cytotoxic effects of ochratoxin A in Neuro-2a cells: role of oxidative stress evidenced by N-acetylcysteine. Front Microbiol 7:1142. https://doi.org/10.3389/fmicb.2016.01142
Cakatay U, Telci A, Kayalì R, Tekeli F, Akçay T, Sivas A (2001) Relation of oxidative protein damage and nitrotyrosine levels in the aging rat brain. Exp Gerontol 36:221–229. https://doi.org/10.1016/s0531-5565(00)00197-2
Cannon JR, Greenamyre JT (2011) The role of environmental exposures in neurodegeneration and neurodegenerative diseases. Toxicol Sci 124:225–250. https://doi.org/10.1093/toxsci/kfr239
Charles M, McEwen J, Tabor CW (1977) Methods in enzymology, XVIIB
Eberhardt MV, Lee CY, Liu RH (2000) Antioxidant activity of fresh apples. Nature 405:903–904. https://doi.org/10.1038/35016151
Ellman GL, Courtney KD, Andres V, Feather-Stone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95. https://doi.org/10.1016/0006-2952(61)90145-9
Elsas SM, Rossi DJ, Raber J, White G, Seeley CA, Gregory WL, Mohr C, Pfankuch T, Soumyanath A (2010) Passiflora incarnata L. (Passionflower) extracts elicit GABA currents in hippocampal neurons in vitro, and show anxiogenic and anticonvulsant effects in vivo, varying with extraction method. Phytomedicine 17:940–949. https://doi.org/10.1016/j.phymed.2010.03.002
Griess P (1879) Bemerkungen zu der Abhandlung der HH. Weselsky und Benedikt “Ueber einige Azoverbindungen”. Berichte der Dtsch Chem Gesellschaft 12:426–428. https://doi.org/10.1002/cber.187901201117
Klockgether T (2004) Parkinson’s disease: clinical aspects. Cell Tissue Res 318:115–120. https://doi.org/10.1007/s00441-004-0975-6
Lampariello LR, Cortelazzo A, Guerranti R, Sticozzi C, Valacchi G (2012) The magic velvet bean of Mucuna pruriens. J Tradit Complement Med 2:331–339. https://doi.org/10.1016/s2225-4110(16)30119-5
Lautert C, Ferreiro L, Wolkmer P, Paim FC, da Silva CB, Jaques JA, Lopes ST, Santurio JM (2014) Individual in vitro effects of ochratoxin A, deoxynivalenol and zearalenone on oxidative stress and acetylcholinesterase in lymphocytes of broiler chickens. Springerplus 3:506. https://doi.org/10.1186/2193-1801-3-506
Liu F, Yu G, Wang G, Liu H, Wu X, Wang Q, Liu M, Liao K, Wu M, Cheng X, Hao H (2012) An NQO1-initiated and p53-independent apoptotic pathway determines the anti-tumor effect of tanshinone IIA against non-small cell lung cancer. PLoS One 7:e42138. https://doi.org/10.1371/journal.pone.0042138
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275
Misra L, Wagner H (2004) Alkaloidal constituents of Mucuna pruriens seeds. Phytochemistry 65:2565–2567. https://doi.org/10.1016/j.phytochem.2004.08.045
Monaci L, Palmisano F (2004) Determination of ochratoxin A in foods: state-of-the-art and analytical challenges. Anal Bioanal Chem 378:96–103. https://doi.org/10.1007/s00216-003-2364-5
Nelson SK, Bose SK, McCord JM (1994) The toxicity of high-dose superoxide dismutase suggests that superoxide can both initiate and terminate lipid peroxidation in the reperfused heart. Free Radic Biol Med 16:195–200. https://doi.org/10.1016/0891-5849(94)90143-0
Ngatchic JTM, Sokeng SD, Njintang NY, Maoundombaye T, Oben J, Mbofung CMF (2013) Evaluation of some selected blood parameters and histopathology of liver and kidney of rats fed protein-substituted mucuna flour and derived protein rich product. Food Chem Toxicol 57:46–53. https://doi.org/10.1016/j.fct.2013.02.045
Rai SN, Birla H, Singh SS, Zahra W, Patil RR, Jadhav JP, Gedda MR, Singh SP (2017) Mucuna pruriens protects against MPTP intoxicated neuroinflammation in Parkinson’s disease through NF-κB/pAKT signaling pathways. Front Aging Neurosci 9:421. https://doi.org/10.3389/fnagi.2017.00421
Raina AP, Khatri R (2011) Quantitative determination of L-dopa in seeds of Mucuna pruriens germplasm by high performance thin layer chromatography. Indian J Pharm Sci 73:459–462. https://doi.org/10.4103/0250-474X.95651
Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C (1999) Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic Biol Med 26:1231–1237. https://doi.org/10.1016/s0891-5849(98)00315-3
Reznick AZ, Packer L (1994) Oxidative damage to proteins: spectrophotometric method for carbonyl assay. Methods Enzymol 233:357–363. https://doi.org/10.1016/s0076-6879(94)33041-7
Rommelfanger KS, Edwards GL, Freeman KG, Liles LC, Miller GW, Weinshenker D (2007) Norepinephrine loss produces more profound motor deficits than MPTP treatment in mice. Proc Natl Acad Sci USA 104:13804–13809. https://doi.org/10.1073/pnas.0702753104
Sakanaka S, Tachibana Y, Okada Y (2005) Preparation and antioxidant properties of extracts of Japanese persimmon leaf tea (kakinoha-cha). Food Chem 89:569–575. https://doi.org/10.1016/j.foodchem.2004.03.013
Sava V, Reunova O, Velasquez A, Harbison R, Sánchez-Ramos J (2006) Acute neurotoxic effects of the fungal metabolite ochratoxin-A. Neurotoxicology 27:82–92. https://doi.org/10.1016/j.neuro.2005.07.004
Sava V, Reunova O, Velasquez A, Sanchez-Ramos J (2006) Can low level exposure to ochratoxin-A cause parkinsonism? J Neurol Sci 249:68–75. https://doi.org/10.1016/j.jns.2006.06.006
Sava V, Velasquez A, Song S, Sanchez-Ramos J (2007) Adult hippocampal neural stem/progenitor cells in vitro are vulnerable to the mycotoxin ochratoxin-A. Toxicol Sci 98:187–197. https://doi.org/10.1093/toxsci/kfm093
Sedlak J, Lindsay RH (1968) Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem 25:192–205. https://doi.org/10.1016/0003-2697(68)90092-4
Shimoji M, Zhang L, Mandir AS, Dawson VL, Dawson TM (2005) Absence of inclusion body formation in the MPTP mouse model of Parkinson’s disease. Brain Res Mol Brain Res 134:103–108. https://doi.org/10.1016/j.molbrainres.2005.01.012
Singh MP, Patel S, Dikshit M, Gupta YK (2006) Contribution of genomics and proteomics in understanding the role of modifying factors in Parkinson’s disease. Indian J Biochem Biophys 43:69–81
Singleton VL, Rossi JA (1965) Colorimetry of total phenolics with phosphomolybdic-phosphotungstic acid reagents. Am J Enol Vitic 16:144–158
Stachurska A, Ciesla M, Kozakowska M, Wolffram S, Boesch-Saadatmandi C, Rimbach G, Jozkowicz A, Dulak J, Loboda A (2013) Cross-talk between microRNAs, nuclear factor E2-related factor 2, and heme oxygenase-1 in ochratoxin A-induced toxic effects in renal proximal tubular epithelial cells. Mol Nutr Food Res 57:504–515. https://doi.org/10.1002/mnfr.201200456
Yadav SK, Rai SN, Singh SP (2017) Mucuna pruriens reduces inducible nitric oxide synthase expression in Parkinsonian mice model. J Chem Neuroanat 80:1–10. https://doi.org/10.1016/j.jchemneu.2016.11.009
Youdim MB, Wadia A, Tatton W, Weinstock M (2001) The anti-Parkinson drug rasagiline and its cholinesterase inhibitor derivatives exert neuroprotection unrelated to MAO inhibition in cell culture and in vivo. Ann N Y Acad Sci 939:450–458. https://doi.org/10.1111/j.1749-6632.2001.tb03656.x
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The authors are grateful to the director, DFRL, Mysuru, for providing the necessary facilities to conduct the study.
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AT: supervision; PVB: conceptualisation and realisation of the work; PVB and AT: drafting, editing and critical revision of the manuscript; PVB, MMT, MP and SBGR: acquisition, analysis and interpretation of the data. All authors have read the final manuscript and approved the final submission.
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The authors declare that no experiments were performed on humans, while conducting the animal experiments, approved regulations by the institute’s animal ethical committee and the Committee for the Control and Supervision of Experiments on Animals (CPCSEA-DFRL/IAEC/01/2015) and OECD guidelines 401 were followed.
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Bhat, P.V., Tamatam, A., T, M.M. et al. Mucuna pruriens Seed Extract: a Possible Protective Agent Against Ochratoxin A Neurodegeneration. Rev. Bras. Farmacogn. 32, 395–409 (2022). https://doi.org/10.1007/s43450-022-00255-9
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DOI: https://doi.org/10.1007/s43450-022-00255-9