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Solasodine Containing Solanum torvum L. Fruit Extract Prevents Chronic Constriction Injury-Induced Neuropathic Pain in Rats: In Silico and In Vivo Evidence of TRPV1 Receptor and Cytokine Inhibition

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Abstract

This study aimed to assess the efficacy of ethanolic extract of Solanum torvum L. fruit (EESTF) containing solasodine in treating chronic constriction injury (CCI)–induced neuropathic pain in rats. Three-dimensional (3D) simulation studies of solasodine binding were conducted on the TRPV1 receptor, IL-6, and TNF-α structures. For in vivo justification, an assessment of behavioral, biochemical, and histological changes was designed after a CCI-induced neuropathic pain model in rats. On days 7, 14, and 21, CCI significantly increased mechanical, thermal, and cold allodynia while producing a functional deficit. IL-6, TNF-α, TBARS, and MPO levels also increased. SOD levels of catalase and reduced glutathione levels also decreased. Administration of pregabalin (30 mg/kg, oral), solasodine (25 mg/kg, oral), and EESTF (100 and 300 mg/kg, oral) significantly reduced CCI-induced behavioral and biochemical changes (P < 0.05). The protective nature of EESTF was also confirmed by histological analysis. Capsaicin, a TRPV1 receptor agonist, abolished the antinociceptive effects of EESTF when used previously. From the observations of the docking studies, solasodine acted as an antagonist at TRPV1, whereas the docking scores of solasodine against TNF-α and IL-6 were reported to be −11.2 and −6.04 kcal/mol, respectively. The attenuating effect of EESTF might be related to its antagonistic effects on TRPV1, suppression of cytokines, and anti-inflammatory and antioxidant properties.

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Acknowledgements

The authors are grateful to UGC, India, for their funding support as a minor research project grant (letter no.—F. No. 41-1371/2012(SR)). The authors are also thankful to Banasthali Vidyapith for providing basic facilities for the research work.

Funding

This work was supported by UGC, India (grant numbers: F.No. 41-1371/2012(SR)).

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Authors and Affiliations

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

    Vivek Jain, Saurabh K. Sinha, Kajol Rustage & Mukesh K. Meena

  2. Department of Pharmacy, Banasthali Vidyapith, Banasthali, Rajasthan, India

    Vivek Jain, Ashutosh Pareek, Aaushi Pareek & Yashumati Ratan

  3. Department of Chemistry, Banasthali Vidyapith, Banasthali, Rajasthan, India

    Manish Srivastava

  4. Department of Pharmaceutical Science, Dibrugarh University, Dibrugarh, Assam, India

    Anshul Shakya

  5. School of Pharmacy, Faculty of Medical Sciences, The University of the West Indies, St Augustine, Trinidad and Tobago

    Madan Mohan Gupta

  6. Department of Biotechnology, Mohanlal Sukhadia University, Udaipur, Rajasthan, India

    Nitish Rai

  7. Department of Biomedical Engineering, Chung Yuan Christian University, Taoyuan City, Taiwan

    Min Hua Chen

  8. Department of Pharmaceutical Sciences, RTM Nagpur University, Nagpur, India

    Satyendra Kumar Prasad

  9. Department of Medical Laboratory Science, College of Health Sciences and Sharjah Institute for Medical Research, University of Sharjah, Sharjah, 27272, United Arab Emirates

    Ghulam Md Ashraf

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  1. Vivek Jain
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Contributions

All authors contributed to the study’s conception and design. Material preparation, data collection, and analysis were performed by Saurabh K. Sinha, Kajol Rustage, Ashutosh Pareek, Manish Srivastava, Mukesh K. Meena, Anshul Shakya, Nitish Rai, Aaushi Pareek, Yashumati Ratan, Min Hua Chen, Satyendra Kumar Prasad, and Ghulam Md Ashraf. The first draft of the manuscript was written by Vivek Jain, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Vivek Jain, Ashutosh Pareek or Ghulam Md Ashraf.

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All the animal experiments (Ref. no.-BU/BT/397/13-14) were preapproved by the Institutional Animal Ethical Committee of Banasthali Vidyapith, and animal experiments were performed according to CPCSEA guidelines.

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Jain, V., Sinha, S.K., Rustage, K. et al. Solasodine Containing Solanum torvum L. Fruit Extract Prevents Chronic Constriction Injury-Induced Neuropathic Pain in Rats: In Silico and In Vivo Evidence of TRPV1 Receptor and Cytokine Inhibition. Mol Neurobiol 60, 5378–5394 (2023). https://doi.org/10.1007/s12035-023-03412-w

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