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Effect of ethanolic extract of Solanum virginianum Linn. on neuropathic pain using chronic constriction injury rat model and molecular docking studies

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Abstract

The present research work was designed to examine the neuroprotective effect of ethanolic extract of Solanum virginianum Linn. (SV) in chronic construction injury (CCI) of sciatic nerve–induced neuropathic pain in rats. The extract was initially standardized by high-performance thin-layer chromatography using solasodine as a biomarker and was then subjected to assess the degree of mechanical allodynia, thermal allodynia, mechanical hyperalgesia, thermal hyperalgesia and biochemical evaluations. Administration of SV (100 and 200 mg/kg; p.o.) and pregabalin (10 mg/kg; p.o.) as a reference standard significantly debilitated hyperalgesia and allodynia and notably restored the altered antioxidant level and pro-inflammatory cytokine (IL-1β and TNF-α) expression in a dose-dependent manner. Further, to appraise the mechanistic approach of solasodine, docking simulation studies were done on the 3D structure of the voltage-gated N-type calcium channel (Cav 2.2), R-type calcium channel (Cav 2.3) and sodium channel (Nav 1.7), and the results revealed that solasodine properly positioned into Phe 19, Leu 32, Met 51 and Met 71 (FLMM pocket) of Cav 2.2 and Cav 2.3 and being a competitor of Ca2+/N-lobe it may inactivate these calcium channels but did not bind into the desired binding pocket of Nav 1.7. Thus, the study confirmed the role of solasodine as a major biomarker for the observed neuroprotective nature of Solanum virginianum.

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References

  • Amin B, Hosseinzadeh H (2012) Evaluation of aqueous and ethanolic extracts of saffron, Crocus sativus L., and its constituents, safranal and crocin in allodynia and hyperalgesia induced by chronic constriction injury model of neuropathic pain in rats. Fitoterapia 83:888–895

    Article  CAS  PubMed  Google Scholar 

  • Anwikar S, Bhitre M (2010) Study of the synergistic anti-inflammatory activity of Solanum xanthocarpum Schrad and Wendl and Cassia fistula Linn. Int J Ayurveda Res 1:167–171

    Article  PubMed  PubMed Central  Google Scholar 

  • Areti A, Yerra VG, Naidu V, Kumar A (2014) Oxidative stress and nerve damage: role in chemotherapy induced peripheral neuropathy. Redox Biol 2:289–295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Attal N, Cruccu G, Baron R, Haanpaa M, Hansson P, Jensen TS, Nurmikko T (2010) EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. Eur J Neurol 17:1113–e1188

    Article  CAS  PubMed  Google Scholar 

  • Austin PJ, Wu A, Moalem-Taylor G (2012) Chronic constriction of the sciatic nerve and pain hypersensitivity testing in rats. J Vis Exp 13:1–6

    Google Scholar 

  • Bennett GJ, Xie YK (1988) A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 33:87–107

    Article  CAS  PubMed  Google Scholar 

  • Boadas-Vaello P, Vela JM, Verdu E (2017) New pharmacological approaches using polyphenols on the physiopathology of neuropathic pain. Curr Drug Targets 18:160–173

    Article  CAS  PubMed  Google Scholar 

  • Bouhassira D (2019) Neuropathic pain: definition, assessment and epidemiology. Revui Neurologique (Paris) 175(1–2):16–25

    Article  CAS  Google Scholar 

  • Chauhan K, Sheth N, Ranpariya V, Parmar S (2011) Anticonvulsant activity of solasodine isolated from Solanum sisymbriifolium fruits in rodents. Pharm Biol 49:194–199

    Article  CAS  PubMed  Google Scholar 

  • Claiborne A (1985) Catalase activity. CRC handbook of methods for oxygen radical research. 1:283–284

    Google Scholar 

  • Chen QY, Tan CY, Wang Y, Ma KT, Li L, Si JQ (2019) Mechanism of persistent hyperalgesia in neuropathic pain caused by chronic constriction injury. Neural Regen Res 14:1091–1098

    Article  PubMed  PubMed Central  Google Scholar 

  • Duraku LS, Niehof SP, Misirli Y, Everaers M, Hoendervangers S, Holstege J, Boele HJ et al (2014) Rotterdam Advanced Multiple Plate: a novel method to measure cold hyperalgesia and allodynia in freely behaving rodents. J Neurosci Methods 224:1–12

    Article  PubMed  Google Scholar 

  • Dworkin RH (2002) An overview of neuropathic pain: syndromes, symptoms, signs, and several mechanisms. Clin J Pain 18:343–349

    Article  PubMed  Google Scholar 

  • Garrido-Suarez BB, Garrido G, Delgado R, Bosch F, Del CRM (2010) A Mangifera indica L. extract could be used to treat neuropathic pain and implication of mangiferin. Molecules 15:9035–9045

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gazaliev AM, Fazylov SD, Balitskii SN, Kasenov RZ (1992) Synthesis of organophosphorus derivatives of lupinine and solasodine and investigation of their cholinergic activities. Chem Nat Compds 28:472–473

    Article  Google Scholar 

  • Gostine M, Pawl L (2009) Relief of symptoms associated with peripheral neuropathy. Pract Pain Manag 9:1–5

    Google Scholar 

  • Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR (1982) Analysis of nitrate, nitrite, and [15N] nitrate in biological fluids. Anal Biochem 126:131–138

    Article  CAS  PubMed  Google Scholar 

  • Gupta AK, Ganguly P, Majumder UK, Ghosal S (2009) Hepatoprotective and antioxidant effects of total extracts and stereoidal saponins of Solanum xanthocarpum and Solanum nigrumin paracetamol induced hepatotoxicity in rats. Pharmacologyonline 1:757–768

    Google Scholar 

  • Harvey AL (2008) Natural products in drug discovery. Drug Discov Today 13:894–901

    Article  CAS  PubMed  Google Scholar 

  • Jaggi AS, Jain V, Singh N (2011) Animal models of neuropathic pain. Fundam Clin Pharmacol 25:1–28

    Article  CAS  PubMed  Google Scholar 

  • Janzadeh A, Nasirinezhad F, Masoumipoor M, Jameie SB, Hayat P (2016) Photobiomodulation therapy reduces apoptotic factors and increases glutathione levels in a neuropathic pain model. Lasers Med Sci 31:1863–1869

    Article  PubMed  Google Scholar 

  • Jollow DJ, Mitchell JR, Zampaglione N, Gillette JR (1974) Bromobenzene induced liver necrosis. Protective role of glutathione and evidence for 3,4-bromobenzene oxide as the hepatotoxic metabolite. Pharmacology 11:151–169

    Article  CAS  PubMed  Google Scholar 

  • Jones B, Roberts D (1968) The quantitative measurement of motor in co-ordination in naive mice using an accelerating rotarod. J Pharm Pharmacol 20:302–304

    Article  CAS  PubMed  Google Scholar 

  • Kakkar P, Das B, Viswanathan PN (1984) A modified spectrophotometric assay of superoxide dismutase. Indian J Biochem Biophys 21:130–132

    CAS  PubMed  Google Scholar 

  • Kanaan SA, Saade NE, Haddad JJ, Abdelnoor AM, Atweh SF, Jabbur SJ, Garabelian BS (1996) Endotoxin induced local inflammation and hyperalgesia in rats and mice, a new model for inflammatory pain. Pain 66:373–379

    Article  CAS  PubMed  Google Scholar 

  • Kawaguchi M, Satoh Y, Otsubo Y, Kazama T (2014) Molecular hydrogen attenuates neuropathic pain in mice. PLoS One 9:e100352

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kim EY, Rumpf CH, Fujiwara Y, Cooley ES, van Petegem F, Minor DL Jr (2008) Structures of CaV2 Ca2+/CaM-IQ domain complexes reveal binding modes that underlie calcium-dependent inactivation and facilitation. Structure 16:1455–1467

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim HK, Park SK, Zhou JL, Taglialatela G, Chung K, Coggeshall RE, Chung JM (2004) Reactive oxygen species (ROS) play an important role in a rat model of neuropathic pain. Pain 111:116–124

    Article  CAS  PubMed  Google Scholar 

  • Kishore L, Singh R (2017) Effects of different homeopathic potencies of Cephalendra indica in treatment of neuropathic pain in streptozotocin induced diabetes. Bull Fac Pharm, Cairo Univ 55:273–280

    Google Scholar 

  • Kwan KY, Allchorne AJ, Vollrath MA, Christensen AP, Zhang DS, Woolf CJ, Corey DP (2006) TRPA1 contributes to cold, mechanical, and chemical nociception but is not essential for hair-cell transduction. Neuron 50:277–289

    Article  CAS  PubMed  Google Scholar 

  • Laloo D, Prasad SK, Sairam K, Hemalatha S (2013) Gastroprotective activity of ethanolic root extract of Potentilla fulgens Wall. ex Hook. J Ethnopharmacol 148:505–514

    Article  Google Scholar 

  • Lecanu L, Hashim AI, McCourty A, Giscos-Douriez I, Dinca I, Yao W, Vicini S, Szabo G, Erdélyi F, Greeson J, Papadopoulos V (2011) The naturally occurring steroid solasodine induces neurogenesis in vitro and in vivo. Neuroscience 183:251–264

    Article  CAS  PubMed  Google Scholar 

  • Lee S (2013) Pharmacological inhibition of voltage-gated Ca2+ channels for chronic pain relief. Curr Neuropharmacol 11:606–620

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Levy D, Zochodne DW (2004) NO pain: potential roles of nitric oxide in neuropathic pain. Pain Pract 4:11–18

    Article  PubMed  Google Scholar 

  • Lin Y, Chen Z, Tang J, Cao P, Shi R (2018) Acrolein contributes to the neuropathic pain and neuron damage after ischemic–reperfusion spinal cord injury. Neuroscience 384:120–130

    Article  CAS  PubMed  Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    Article  CAS  PubMed  Google Scholar 

  • Morani AS, Bodhankar SL, Mohan V, Thakurdesai PA (2012) Ameliorative effects of standardized extract from Trigonella foenum-graecum L. seeds on painful peripheral neuropathy in rats. Asian Pac J Trop Med 5:385–390

    Article  PubMed  Google Scholar 

  • Muthuraman A, Singh JAS (2011) Effect of hydroalcoholic extract of Acorus calamus on tibial and sural nerve transection-induced painful neuropathy in rats. J Nat Med 65:282–292

  • Muthuraman A, Diwan V, Jaggi AS, Singh N, Singh D (2008) Ameliorative effects of Ocimum sanctum in sciatic nerve transection-induced neuropathy in rats. J Ethnopharmacol 120:56–62

    Article  CAS  PubMed  Google Scholar 

  • Negi G, Kumar A, Sharma SS (2010) Concurrent targeting of nitrosative stress-PARP pathway corrects functional, behavioral and biochemical deficits in experimental diabetic neuropathy. Biochem Biophys Res Commun 391:102–106

    Article  CAS  PubMed  Google Scholar 

  • Oka T, Aou S, Hori T (1993) Intra cerebro ventricular injection of interleukin-1 beta induces hyperalgesia in rats. Brain Res 624:61–68

    Article  CAS  PubMed  Google Scholar 

  • Pandurangan A, Khosa RL, Hemalatha S (2010) Antinociceptive activity of steroid alkaloids isolated from Solanum trilobatum Linn. J Asian Nat Prod Res 12:691–695

    Article  CAS  PubMed  Google Scholar 

  • Park HJ, Lee HG, Kim YS, Lee JY, Jeon JP, Park C, Moon DE (2012) Ginkgo biloba extract attenuates hyperalgesia in a rat model of vincristine-induced peripheral neuropathy. Anesth Analg 115:1228–1233

    Article  CAS  PubMed  Google Scholar 

  • Parmar KM, Itankar PR, Joshi A, Prasad SK (2017) Anti-psoriatic potential of Solanum xanthocarpum stem in Imiquimod-induced psoriatic mice model. J Ethnopharmacol 198:158–166

    Article  PubMed  Google Scholar 

  • Parmar S, Gangwal A, Sheth N (2010) Evaluation of antiasthmatic activity of a polyherbal formulation containing four plant extracts. J Curr Pharm Res 2:40–44

    Google Scholar 

  • Pradeepa R, Rema M, Vignesh J, Deepa M, Deepa R, Mohan V (2008) Prevalence and risk factors for diabetic neuropathy in an urban south Indian population: the Chennai Urban Rural Epidemiology Study (CURES-55). Diabet Med 4:407–412

    Article  Google Scholar 

  • Rahman M, Ahmed M, Alimuzzaman M, Shilpi J (2003) Antinociceptive activity of the aerial parts of Solanum xanthocarpum. Fitoterapia 74:119–121

    Article  CAS  PubMed  Google Scholar 

  • Riffel AP, de Souza JA, Santos MC, Horst A, Scheid T, Kolberg C, Belló-Klein A, Partata WA (2016) Systemic administration of vitamins C and E attenuates nociception induced by chronic constriction injury of the sciatic nerve in rats. Brain Res Bull 121:169–177

    Article  CAS  PubMed  Google Scholar 

  • Scholz J, Finnerup NB, Attal N, Aziz Q, Baron R, Bennett MI, Benoliel R, Cohen M, Cruccu G, Davis KD, Evers S, First M, Giamberardino MA, Hansson P, Kaasa S, Korwisi B, Kosek E, Lavandʼhomme P, Nicholas M, Nurmikko T, Perrot S, Raja SN, Rice ASC, Rowbotham MC, Schug S, Simpson DM, Smith BH, Svensson P, Vlaeyen JWS, Wang SJ, Barke A, Rief W, Treede RD, Classification Committee of the Neuropathic Pain Special Interest Group (NeuPSIG) (2019) The IASP classification of chronic pain for ICD-11: chronic neuropathic pain. Pain 160:53–59

    Article  PubMed  PubMed Central  Google Scholar 

  • Shan Z, Cai S, Yu J, Zhang Z, Vallecillo TGM, Serafini MJ, Thomas AM et al (2019) Reversal of peripheral neuropathic pain by the small-molecule natural product physalin F via block of CaV2.3 (R-type) and CaV2.2 (N-type) voltage-gated calcium channels. ACS Chem Neurosci 10:2939–2955

    Article  CAS  PubMed  Google Scholar 

  • Sharma T, Airao V, Panara N, Vaishnav D, Ranpariya V, Sheth N, Parmar S (2014) Solasodine protects rat brain against ischemia/reperfusion injury through its antioxidant activity. Eur J Pharmacol 725:40–46

    Article  CAS  PubMed  Google Scholar 

  • Shen H, Liu D, Wu K, Lei J, Yan N (2019) Structures of human Nav1.7 channel in complex with auxiliary subunits and animal toxins. Science 363:1303–1308

    Article  CAS  PubMed  Google Scholar 

  • Sommer C, Petrausch S, Lindenlaub T, Toyka KV (1999) Neutralizing antibodies to interleukin-1 receptor reduce pain associated behavior in mice with experimental neuropathy. Neurosci Lett 270:25–28

    Article  CAS  PubMed  Google Scholar 

  • Thiagarajan VR, Shanmugam P, Krishnan UM, Muthuraman A (2014) Ameliorative effect of Vernonia cinerea in vincristine induced painful neuropathy in rats. Toxicol Ind Health 30:794–805

    Article  PubMed  CAS  Google Scholar 

  • Thiagarajan VR, Shanmugam P, Krishnan UM, Muthuraman A, Singh N (2013) Antinociceptive effect of Butea monosperma on vincristine induced neuropathic pain model in rats. Toxicol Ind Health 29:3–13

    Article  PubMed  Google Scholar 

  • Trease GE, Evans WC (2002) Pharmacognosy, 15th edn. W.B. Saunders Company Ltd., London

    Google Scholar 

  • Uceyler N, Sommer C (2008) Cytokine regulation in animal models of neuropathic pain and human diseases. Neurosci Lett 437:194–198

    Article  PubMed  CAS  Google Scholar 

  • VanDenKerkhof EG, Mann EG, Torrance N, Smith BH, Johnson A, Gilron I (2016) An epidemiological study of neuropathic pain symptoms in Canadian adults. Pain Res Manag 2016:1–13. https://doi.org/10.1155/2016/9815750

    Article  Google Scholar 

  • Vanitha S, Thiagarajan VR, Muthuraman A, Krishnan S, Aruna A, Tharabai R (2015) Pharmacological evaluation of methanolic leaf extract of Swietenia mahagoni on acrylamide-induced neuropathic pain in rats. Toxicol Ind Health 31:1185–1194

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Shen W, Yang L, Zhao H, Gu W, Yuan Y (2013) The protective effects of Achyranthes bidentata polypeptides on rat sciatic nerve crush injury causes modulation of neurotrophic factors. Neurochem Res 38:538–546

    Article  PubMed  CAS  Google Scholar 

  • Wills ED (1965) Mechanisms of lipid peroxide formation in tissues. Role of metals and haematin proteins in the catalysis of the oxidation unsaturated fatty acids. Biochim Biophys Acta 98:238–251

    Article  CAS  PubMed  Google Scholar 

  • Yang RY, Tsou S, Lee TC et al (2006) Distribution of 127 edible plant species for antioxidant activities by two assays. J Sci Food Agric 86:2395–2403

    Article  CAS  Google Scholar 

  • Zhang Y, Brewer AL, Nelson JT, Smith PT, Shirachi DY, Quock RM (2019) Hyperbaric oxygen produces a nitric oxide synthase-regulated anti-allodynic effect in rats with paclitaxel-induced neuropathic pain. Brain Res 1711:41–47

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors would like to acknowledge the valuable contribution of the University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh 160 014, India, for providing the lab facility for conducting the experimental work.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Mohanlal Sukhadia University, Udaipur, Rajasthan, 313001, India

    Sonia Verma & Saurabh K. Sinha

  2. Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh, 160 014, India

    Anurag Kuhad & Ranjana Bhandari

  3. Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur, Maharashtra, 440033, India

    Satyendra K. Prasad & Rupali S. Prasad

  4. Department of Pharmaceutical Sciences, Faculty of Science and Engineering, Dibrugarh University, Dibrugarh, Assam, 786004, India

    Anshul Shakya

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  1. Sonia Verma
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Contributions

SKS, AK and SKP designed the framework of the study, while RSP and SKP performed the phytochemical evaluations and standardization of extracts. SV, AK and RB were involved in the initial behavioural evaluation of the pharmacological studies. SV, AS and RSP were involved in performing the biochemical evaluations and cytokine estimations, while SKS and SKP performed the molecular docking studies and its interpretation. SV, AS, RB and RSP contributed significantly in compilation of results and interpretation of data. SV, SKS, SKP and AK contributed in initial drafting of the manuscript, which was further finalized by SKS and SKP. All the authors have read and approved the manuscript before its submission.

Corresponding author

Correspondence to Saurabh K. Sinha.

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The experimental protocol was approved by Institutional Animal Ethics Committee of the university (LRIP/IAEC/2019/PH-03) and was carried out in accordance with the guidelines of Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), Government of India, and Indian National Science Academy Guidelines for the use and care of experimental animals (Publication No. 85–23, revised 1985)

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Verma, S., Kuhad, A., Bhandari, R. et al. Effect of ethanolic extract of Solanum virginianum Linn. on neuropathic pain using chronic constriction injury rat model and molecular docking studies. Naunyn-Schmiedeberg's Arch Pharmacol 393, 1715–1728 (2020). https://doi.org/10.1007/s00210-020-01872-8

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