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ABSTRACT
Introduction: The objective of the study is to elucidate the effect of Aegle marmelos bark hydroalcoholic extract (AMHE) and the role of its constituents marmelosin, umbelliferone, and Para-coumaric acid in attenuating neuropathic pain.
Methodology: Peripheral neuropathy was induced by vincristine 100 μg/ml. AMHE was administered in three dose levels (100, 200 and 300 mg/kg) for 21 days. Mechanical hyperalgesia and allodynia were assessed by Randall Sellitto and electronic Von-Frey test, respectively. Functional loss and recovery of the nerve were assessed by sciatic functional index test. The nerve conduction velocity and formalin test were done to assess the peripheral and central response of the extract. Inflammatory mediators in both sciatic nerve and brain and neurotransmitters glutamate and aspartate were measured to support the data.
Results and discussion: The inflammatory mediators in both sciatic nerve and brain (TNF-α, IL-1β, and IL-6) were found to be attenuated with AMHE-treated group in comparison to the group treated only with vincristine, which indicates the extract has anti-inflammatory property. AMHE treated rats were found to be active in all the behavioural tests, suggesting its activity could be mediated through a central and peripheral mechanism to attenuate the pain response. The levels of excitatory neurotransmitters were found to be reduced with AMHE treatment.
Conclusion: It could be concluded that AMHE is active in attenuating the neuropathic pain caused by vincristine. The peripheral action would have mediated through lowering the inflammatory mediators as well as the excitotoxicity caused due to peripheral neuropathy and neuroinflammation.
GRAPHICAL ABSTRACT
Acknowledgements
The authors would like to thank PSG Sons and Charities for providing all the facilities to carry out the work and Dr. Sivaram Hariharan (Professor, Department of Pharmaceutical Chemistry, PSG College of Pharmacy) for advising with language help for scientific writing with appropriate grammars in order to communicate the work, Dr. C.R. Ajeeth Kumar (M.B.B.S., M.D., (Pathology)) Pathologist and Mr. Gnanadeepan (MSc., M.Phil (Biochemistry)) Lab Incharge of Origin Laboratory,Varadharajapuram, Coimbatore, Tamil Nadu for assisting the histopathological work with their pathological expertise.
Disclosure statement
No potential conflict of interest was reported by the authors.
Ethical approval
All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted (Reg. No. 158 / PO / ReBi / SL / 99 / CPCSEA). The plants were verified by BSI Tamil Nadu Agriculture University with authentification no. BSI/SRC/5/23/2015/Tech.469.
Additional information
Funding
Notes on contributors
Mrinmoy Gautam
Mrinmoy Gautam is currently working as a Ph.D student under The Tamil Nadu Dr. MGR Medical University, Chennai, Tamil Nadu and pursuing his research work in PSG College of Pharmacy, Coimbatore, Tamil Nadu. He was appointed as a Junior Research Fellow in 2014 June under a DBT (Department of Biotechnology) funded project which continued for one year and then again extended for another 2 years from (2016 March to 2018 March). Both Ph.D. and Project work are based on neuropathic pain under the guidance of Honourable Dr. M. Ramanathan Sir (Corresponding Author). He is a postgraduate in Pharmacy (M.Pharm, Pharmacology) passed in 2013 from Biju Patnaik University of Technology (BPUT), Odisha, and Bachelors in 2010 from Rashtrashant Tukadoji Maharaj Nagpur University, Nagpur. He also did an internship programme in Indian Institute of Integrative Medicine, CSIR lab Jammu for a period of 6 months as a research trainee as a curriculum of the Post graduation from January 2013 to June 2013 on the topic of Toxicology in Pk/Pd division of the institute.
Publications by the author till date:
Gautam M, Ramanathan M. Saponins of Tribulus terrestris attenuated neuropathic pain induced with vincristine through central and peripheral mechanism. Inflammopharmacology. 2018 (Methodologies in the present manuscript are mostly taken from this paper).
Venkatesh Gunasekaran, Merin Maria Mathew, Mrinmoy Gautam, M. Ramanathan. Neuroprotective role of Pterocarpus marsupium Roxb in streptozotocin-induced diabetic neuropathic pain in Type 2 diabetic rats. Journal of Pharmacy Research. 2017
Muthiah Ramanathan
Dr. Muthiah Ramanathan is the Principal of PSG College of Pharmacy since 2010 and Head of the Department of Department of Pharmacology, PSG College of Pharmacy, Coimbatore, Tamil Nadu. He has worked in various research fields till date which include Neuroscience, Cancer, Herbals, chemical analysis, and Pharmaceutical Formulation etc. Sir has worked as Project Investigator in various projects funded by Govt bodies like DBT, DST, ICMR and international funding agencies like CV Raman Scholarship programme etc. He has guided various Postgraduate and Ph.D. students till date and still continuing. He has authored and Co-Authored as a corresponding author in many esteemed national and international indexed journals and book chapters with good impact factor. He passed his graduation in the year 1987 from Annamalai University Chidambaram, Postgraduation (M.Pharm) from Banaras Hindu University in the year 1994 and Ph.D. in 1997 from Banaras Hindu University, Varanasi.
The details of his postdoctoral work is as follows
Dissertation/ Thesis, Postdoctoral (April’ 02–March’ 03), Study of Locus coeruleus cell death and noradrenaline depletion in APP2576 transgenic mice: Role for Alzheimer’s disease.
Supervisor Dr. Michael T. Heneka, Department of Neurology, University Hospital, University of Bonn, Bonn Germany.
Publications by the author till date:
Gautam M, Ramanathan M. Saponins of Tribulus terrestris attenuated neuropathic pain induced with vincristine through central and peripheral mechanism. Inflammopharmacology. 2018 (Methodologies in the present manuscript are mostly taken from this paper).
Venkatesh Gunasekaran, Merin Maria Mathew, Mrinmoy Gautam, M. Ramanathan. Neuroprotective role of Pterocarpus marsupium Roxb in streptozotocin-induced diabetic neuropathic pain in Type 2 diabetic rats. Journal of Pharmacy Research. 2017