Evaluation of anti-nociceptive and anti-inflammatory activities of Piper sylvaticum (Roxb.) stem by experimental and computational approaches
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Piper sylvaticum Roxb., (Family: Piperaceae), commonly known as pahaari peepal, is used in traditional medicine for the treatment of rheumatic pain, headache, asthma, chronic cough, diarrhea, and wounds. To provide scientific proof for its traditional use, the present study was designed to investigate the antinociceptive and anti-inflammatory properties of methanol extract of P. sylvaticum stem (MEPSS) in pain models. Additionally, computational studies viz. molecular docking, ADME and toxicological property predictions were performed to identify the potent phytochemicals of this plant for antinociceptive and anti-inflammatory activities with good oral bioavailability and safety features. Quantitative phytochemical analysis of MEPSS was performed using established protocols. The antinociceptive activity was determined using acetic acid and formalin test in mice at the doses of 200 and 400 mg/kg while paw edema induced by carrageenan used for anti-inflammatory activity. Molecular docking study was performed by Schrödinger Maestro 10.1 whereas the SwissADME and admetSAR were used for ADME and toxicity prediction respectively. The total phenolic and flavonoid contents of MEPSS were 93.39 and 53.74 mg gallic acid and quercetin equivalent/g of extract respectively. The methanol extract exhibited significant and dose-dependent antinociceptive and anti-inflammatory effects in experimental pain models. Also, our docking study showed that piperine, piperlonguminine, and sylvamide have the best binding affinities to cyclooxygenase enzymes with good ADME/T properties. This study confirmed that MEPSS possess significant antinociceptive and anti-inflammatory activities which could be due to the presence of phytochemicals and three bioactive compounds (piperine, piperlonguminine, and sylvamide) were found to be most effective in computational studies.
KeywordsPiper sylvaticum Antinociceptive Anti-inflammatory Molecular docking ADME and toxicity prediction
Methanol extract of Piper sylvaticum stem
Absorption, distribution, metabolism, elimination
Organization for Economic Co-operation and Development
Protein data bank
Optimized potentials for liquid simulations
Statistical package for the social sciences
Standard error of the mean
Analysis of variance
The authors are grateful to the Department of Pharmacy, International Islamic University Chittagong, Bangladesh for providing all the laboratory facilities and support to complete this research work. The authors are also thankful to GUSTO A Research Group for their kind help.
Md. Nazim Uddin Chy, Md. Adnan and Arkajyoti Paul conceived and designed the experiments. Akash Kumar Rauniyar and Md. Moksadul Amin helped to write the original draft and contributed to data analysis. Md. Nazim Uddin Chy, Md. Adnan, Kaniz Farhana, Fayejun Nesa, Muazzem Ahmad Sany, Mohammad Akramul Hoque Tanim, and Tanvir Iqram Siddique carried out experimental works, analyzed and interpreted experimental results and wrote the manuscript. Md. Nazim Uddin Chy, Arkajyoti Paul, and Mohuya Majumder performed the computational study and wrote the relevant potion. This study was carried out in collaboration between all authors. All authors read and approved the final manuscript.
Compliance with ethical standards
This study was carried out in accordance with the internationally accepted principle for proper use of laboratory animals namely National Institutes of Health and the International Council for Laboratory Animal Science. The present study protocol was reviewed and approved by the “P&D committee” of the Department of Pharmacy, International Islamic University Chittagong, Bangladesh with a reference number: Pharm-P&D-61/08’16-125.
Conflicts of interest
Md. Nazim Uddin Chy has no conflict of interest. Md. Adnan has no conflict of interest. Akash Kumar Rauniyar has no conflict of interest. Md. Moksadul Amin has no conflict of interest. Mohuya Majumder has no conflict of interest. Md. Sahidul Islam has no conflict of interest. Shanta Afrin has no conflict of interest. Kaniz Farhana has no conflict of interest. Fayejun Nesa has no conflict of interest. Muazzem Ahmad Sany has no conflict of interest. Mohammad Akramul Hoque Tanim has no conflict of interest. Tanvir Iqram Siddique has no conflict of interest. Arkajyoti Paul has no conflict of interest.
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