Unlocking the anthelmintic potential of Grewia bilamellata Gagnep.: In-vitro and molecular docking studies on adult Indian earthworms

Subject Areas : Pharmacognosy

Poornima  Gurivelli ¹ (Pharmacognosy and Phytochemistry Division, Gitam School of Pharmacy, Gitam University, Visakhapatnam, 530 045, Andhra Pradesh, India)
Sunitha  Katta ² (Pharmacognosy and Phytochemistry Division, Gitam School of Pharmacy, Gitam University, Visakhapatnam, 530 045, Andhra Pradesh, India)

Received: 2023-04-09 Accepted : 2023-06-30 Published : 2023-06-01

Keywords: <i>In silico</i>, <i>Pheretima posthuma</i>, Malvaceae, Molecular docking, <i>Grewia bilamellata</i> Gagnep, HR-LC-MS,

Abstract :

Anthelmintic resistance remains a significant challenge for the treatment of gastrointestinal parasites. The search for novel compounds is costly, but the traditional knowledge of Sashechalam hill practitioners led us to investigate Grewia bilamellata Gagnep. We assessed its anthelmintic activity against Indian earthworms (Pheretima posthuma) using various extract concentrations (10, 20, 50, and 100 mg/mL), with albendazole as the positive control and normal saline as the negative control. The duration of paralysis and death indicated anthelmintic efficacy. G. bilamellata ethanol extract (GBEE) demonstrated a significant concentration-dependent effect. The IC50 values for albendazole, G. bilamellata petroleum ether extract (GBPE), G. bilamellata ethyl acetate extract (GBEA), and GBEE were 181.947, 310.337, 270.488, and 223.468 mg/mL, respectively. GBEE exhibited potent anthelmintic activity comparable to that of albendazole, with the lowest paralysis and death rates in the model. The HR-LC-MS analysis of GBEE identified 38 phytoconstituents, of which 22 compounds obeyed Lipinski&rsquo;s rule. Molecular docking with &beta;-tubulin revealed that 15 compounds exhibited superior binding energy (-8.3 to -6.3 kcal/mol) compared to albendazole (-6.1 kcal/mol). Further investigations are crucial to isolate and evaluate these compounds for the development of new anthelmintic drugs. Our findings support the traditional use of G. bilamellata Gagnep. as an anthelmintic, and highlight its potential for future therapeutic applications.

References:

Abbasi, M., Omrani, M., Raiatparvar Malieki, L., Sonboli, A., Nejad Ebrahimi, S., 2021. Phytochemical studies of Tetrataenium nephrophyllum and anti-acetylcholinesterase activities. Trends Phytochem. Res. 5(4), 210-217.
Anita Margret, A., Maheswari, R., Sherlin Rosita, A., Jesucastin, E., 2022. Discerning the regulated wound healing potential of Ocimum americanum by probing the rosmarinic acid content-a paradigm on zebrafish caudal fin regeneration. Trends Phytochem. Res. 6(2), 106-115. 
Arbonnier, M., 2004. Trees, Shrubs and Lianas of West African Dry Zones. Trees, Shrubs and Lianas of West African Dry Zones, pp. 1-574.
Baell, J.B., Holloway, G.A., 2010. New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays. J. Med. Chem. 53(7), 2719-2740.
Bickerton, G.R., Paolini, G.V., Besnard, J., Muresan, S., Hopkins, A.L., 2012. Quantifying the chemical beauty of drugs. Nat. Chem. 4(2), 90-98.
Borah, S., Mahato, M.K., Kumar, M.M., Das, M.B., Barman, K., Kakoti, B.B., 2022. Lasia spinosa: An Ethnomedicinal Antidiabetic Plant of Assam. Bhumi Publishing, Maharashtra, India.
Das, S.S., Dey, M., Ghosh, A.K., 2011. Determination of anthelmintic activity of the leaf and bark extract of Tamarindus indica linn. Indian J. Pharm. Sci. 73(1), 104-107.
DSNBK, P., Atla, S.R., Atla, R.P., 2021. In-vitro Anthelmintic activity of Aralia racemosa. L (root) and Argyreia pilosa Wight & Arn.(Whole plant) against Pheretima posthuma. Iran. J. Pharm. Sci. 17(3), 23-32.
Ejeh, S., Uzairu, A., Shallangwa, G.A., Abechi, S.E., 2021. In silico design, drug-likeness and ADMET properties estimation of some substituted thienopyrimidines as HCV NS3/4A protease inhibitors. Chem. Africa 4(3), 563-574.
Ferreira, L.L.G., Andricopulo, A.D., 2019. ADMET modeling approaches in drug discovery. Drug Discov. Today 24(5), 1157-1165.
Khandelwal, K.R., 2008. Practical Pharmacognosy. Pragati Books Pvt. Ltd.
Kumar, S., Singh, B., Bajpai, V., 2022. Traditional uses, phytochemistry, quality control and biological activities of genus Grewia. Phytomedicine Plus 2(3), 100290.
Lounkine, E., Keiser, M.J., Whitebread, S., Mikhailov, D., Hamon, J., Jenkins, J.L., Lavan, P., Weber, E., Doak, A.K., Cote, S., Shoichet, B.K., Urban, L., 2012. Large-scale prediction and testing of drug activity on side-effect targets. Nature 486(7403), 361-367.
Ma, C., Zhang, H.J., Tan, G.T., Hung, N.V., Cuong, N.M., Soejarto, D.D., Fong, H.H., 2006a. Antimalarial compounds from Grewia bilamellata. J. Nat. Prod. 69(3), 346-350.
Mohammadhosseini, M., Frezza, C., Venditti, A., Akbarzadeh, A., 2019a. Ethnobotany and phytochemistry of the genus Eremostachys Bunge. Curr. Org. Chem. 23, 1828-1842.
Mohammadhosseini, M., Frezza, C., Venditti, A., Mahdavi, B., 2022. An overview of the genus Aloysia Palau (Verbenaceae): Essential oil composition, ethnobotany and biological activities. Nat. Prod. Res. 36(19), 5091-5107.
Mohammadhosseini, M., Venditti, A., Akbarzadeh, A., 2019b. The genus Perovskia Kar.: Ethnobotany, chemotaxonomy and phytochemistry: A review. Toxin Rev. 40(4), 484-505.
Nayar, M., Sastry, A.R.K., 1987. Red Data Book of Indian Plants.
Norinder, U., Bergstrom, C.A., 2006. Prediction of ADMET properties. ChemMedChem 1(9), 920-937.
Noumi, E., Snoussi, M., Anouar, E.H., Alreshidi, M., Veettil, V.N., Elkahoui, S., Adnan, M., Patel, M., Kadri, A., Aouadi, K., De Feo, V., Badraoui, R., 2020. HR-LC-MS-based metabolite profiling, antioxidant, and anticancer properties of Teucrium polium L. methanolic extract: Computational and in vitro study. Antioxidants (Basel) 9(11), 1089.
Pandiyan, R., Samiappan, S.C., Sugumaran, A., Sivakumar, S., 2022. Stomach-affecting intestinal parasites as a precursor model of Pheretima posthuma treated with anthelmintic drug from Dodonaea viscosa Linn. Green Process. Synth. 11(1), 492-502.
Pillai, L.S., Nair, B.R., 2011. A comparative study of the anthelmintic potential of Cleome viscosa L. and Cleome burmanni W. and A. Indian J. Pharm. Sci. 73(1), 98-100.
Prasanth, D., Panda, S.P., Rao, A.L., Chakravarti, G., Teja, N., Vani, V.B.N., Sandhya, T., 2020a. In-silico strategies of some selected phytoconstituents from zingiber officinale as sars cov-2 main protease (COVID-19) inhibitors. Indian J. Pharm. Educ. Res. 54(3), s552-559.
Prasanth, D.S.N.B.K., Panda, S.P., Rao, A.L., Teja, N., Vani, V.B.N., Sandhya, T., Rao, P.B.B., 2020b. In vitro Anthelmintic impact of various extracts of Pavetta tomentosa root on Pheretima posthuma and in-silico molecular docking evaluation of some isolated phytoconstituents. Indian J. Pharm. Educ. Res. 54(2), S251-S260.
Quattrocchi, U., 2012. CRC World Dictionary of Medicinal and Poisonous Plants: Common Names, Scientific Names, Eponyms, Synonyms, and Etymology (5 Volume Set). CRC press.
Sarkar, S., Hoda, M.U., Das, S., 2023. Anti-melanogenic, antioxidant potentialities and metabolome classification of six Ocimum species: Metabolomics and in-silico approaches. Trends Phytochem. Res. 7(1), 30-50.
Senguttuvan, J., Paulsamy, S., Karthika, K., 2014. Phytochemical analysis and evaluation of leaf and root parts of the medicinal herb, Hypochaeris radicata L. for in vitro antioxidant activities. Asian Pac. J. Trop. Biomed. 4, S359-S367.
Setlur, A.S., Naik, S.Y., Skariyachan, S., 2017. Herbal lead as ideal bioactive compounds against probable drug targets of ebola virus in comparison with known chemical analogue: A computational drug discovery perspective. Interdiscip. Sci. 9(2), 254-277.
Shahriari, M., Nourmandipour, F., Norouzi, S., Nejad Ebrahimi, S., 2021. Investigation of inhibitory properties of triphenyl-LasR enzyme involved in the quorum sensing of Pseudomonas aeruginosa by molecular modeling. Trends Phytochem. Res. 5(3), 126-135.
Sharma, V., Pattanaik, K.K., Jayprakash, V., Basu, A., Mishra, N., 2009. A utility script for automating and integrating AutoDock and other associated programs for virtual screening. Bioinformation 4(2), 84.
Singh, P.K., Singh, J., Medhi, T., Kumar, A., 2022. Phytochemical screening, quantification, FT-IR analysis, and in silico characterization of potential bio-active compounds identified in HR-LC-MS analysis of the polyherbal formulation from Northeast India. ACS Omega 7(37), 33067-33078.
Sreejith, M., Kannappan, N., Santhiagu, A., Mathew, A.P., 2013. Phytochemical, anti-oxidant and anthelmintic activities of various leaf extracts of Flacourtia sepiaria Roxb. Asian Pac. J. Trop. Biomed. 3(12), 947-953.
Ullah, W., Uddin, G., Siddiqui, B.S., 2012. Ethnic uses, pharmacological and phytochemical profile of genus Grewia. J. Asian Nat. Prod. Res. 14(2), 186-195.