Trop J Nat Prod Res, May 2024; 8(5):7301-7308 ISSN 2616-0684 (Print) ISSN 2616-0692 (Electronic) 7301 © 2024 the authors. This work is licensed under the Creative Commons Attribution 4.0 International License Tropical Journal of Natural Product Research Available online at https://www.tjnpr.org Original Research Article Anti-apoptotic, Antioxidant, and Anti-Inflammatory Activities of Sida corymbosa Leaf Methanol Extract Ameliorate Lead Acetate-Induced Testicular Functions Alteration in Wistar Rats Wahab A. Oyeyemi 1 *, Adeniran O. Akinola 2 , Oore-oluwapo O. Daramola 3 , Yinusa Raji 4 1 Department of Physiology, Faculty of Basic Medical Sciences, Osun State University, Osogbo, Nigeria. 2 Department of Physiology, Faculty of Basic Medical Sciences, University of Medical Sciences, Ondo-City, Nigeria, 3 Department of Physiology, Faculty of Basic Medical Sciences, Redeemer’s University, Ede, Nigeria 4 Reproductive Physiology and Developmental Programming, Department of Physiology, Faculty of Basic Medical Sciences, University of Ibadan, Ibadan, Nigeria Introduction Growing apprehension exists around the harmful effects of environmental pollution in developing countries. Non-regulation policies of industrial and mining activities in developing countries have contributed immensely to the increase in environmental pollutants. Social habits, lifestyle, living conditions, or occupational hazards are common sources of exposure to these pollutants. Environmental toxicants are well-documented to disrupt testicular functions in human and experimental animals. 1,2 Heavy metals are one of the major environmental toxicants. Thus, it has been reported that cadmium and lead-induced oxidative stress by depleting endogenous antioxidants, disturbance of the hypothalamic-pituitary-testicular axis, inhibition of steroidogenesis, and reduction of steroidogenic enzymes that are involved in androgen synthesis. 3,4 *Corresponding author. E mail: oyeyemiwahab@gmail.com Tel: +2347034891903 Citation: Oyeyemi WA, Akinola AO, Daramola OO, Raji Y. Anti- apoptotic, Antioxidant, and Anti-Inflammatory Activities of Sida corymbosa Leaf Methanol Extract Ameliorate Lead Acetate-Induced Testicular Functions Alteration in Wistar Rats. Trop J Nat Prod Res. 2024; 8(5): 7301-7308. https://doi.org/10.26538/tjnpr/v8i5.36 Official Journal of Natural Product Research Group, Faculty of Pharmacy, University of Benin, Benin City, Nigeria One of the mechanisms of heavy metals in disrupting spermatogenesis and steroidogenesis is through the generation of reactive oxygen species (ROS). 2 ROS is one of the major causes of inflammation. 5,6 Inflammatory response involves the generation/release of hydrogen peroxide and, the metabolism of neutrophil and nicotinamide adenine dinucleotide phosphate oxidase. 6 Release of tumour necrotic factor- alpha (TNF-α) and interleukin-6 (IL-6) that promote inflammation usually further generates more ROS. 7 Increase in ROS may overwhelm total antioxidant capacity and result in peroxidation damage to spermatozoa. 2 Apoptosis plays a substantial role in spermatogenesis in the human testis. 8 The increase in pro-apoptotic cytokines can cause permanent loss of spermatogenesis. 9 Also, inflammatory cytokines, ROS, and nitric oxide can inhibit Leydig cell function. 10,11 Lead was also reported to disrupt the pituitary-testicular axis, inhibit testicular expression, and reduce steroidogenic enzymes such as 17β- hydroxysteroid dehydrogenase. 12 Sida corymbosa (broom-weed) is a shrubby semi-woody perennial weed that belongs to the Malvaceae family. Varied claims have been made in traditional medicine on the plant’s potency in curing such ailments as stomach ulcers, fever, gonorrhea, inflammation, infertility, and wound healing. 13,14 The plant has also been scientifically reported to facilitate uterine contraction and parturition, 15 possess anti- inflammatory activity, 16 and anti-ulcer. 14 Recently, it was reported that methanol extract of Sida corymbosa leaves (SC) contains alkaloids, cardiac glycosides, flavonoids, saponin, sterol, and tannic. Also, some biologically important fatty acids such as hexadecenoic acid methyl ester, hexadecenoic acid, 9-octadecenoic acid methyl ester, 9,12- octadecadienoic acid, and methyl heptadecanoic acid are present in SC. 17 Hexadecenoic acid methyl ester, one of the compounds present in SC have been reported to reduce oxidative stress and inflammatory markers like TNF-α, IL-6, IL-10, nitric oxide, COX-2 and PGE2. 18 It ARTICLE INFO ABSTRACT Article history: Received 25 January 2024 Revised 05 May 2024 Accepted 13 May 2024 Published online 01 June 2024 Lead acetate (Pb) is an environmental toxicant widely reported to distort testicular functions. Methanol extract of Sida corymbosa leaves (SC) possesses antioxidant and anti-inflammatory properties. This study was designed to evaluate the role of SC on lead acetate-induced alteration in testicular functions. Thirty adult male Wistar rats were grouped randomly and equally into six and treated as follows: control, Pb (15 mgkg -1 ), SC (100 mgkg -1 ), SC (200 mgkg -1 ), Pb+SC (100 mgkg -1 ), and Pb+SC (200 mgkg -1 ) respectively. Administrations were orally done for 54 days. Computer-aided sperm analyzer, ELISA, spectrophotometry, immunohistochemistry, and PCR techniques were used. Pb significantly reduced follicle-stimulating hormone, luteinizing hormone, testosterone, androgen receptors expression, 3β- and 17β-hydroxysteroid dehydrogenase, sperm concentration, progressive sperm motility, viability, catalase, superoxide dismutase activities, and BCL-2. Pb significantly increased abnormal sperm morphology, malondialdehyde, 8- hydroxydeoxyguanosine, BAD, TNF-α, and IL-6. The combination of SC and Pb significantly reverses the hormones, steroidogenic enzymes, sperm quality, testicular oxidant, antioxidant enzymes, testicular DNA damage, apoptosis, and inflammation when compared with the Pb group. Anti-apoptosis, antioxidant, and anti-inflammatory activities of Sida corymbosa improve lead acetate-induced testicular functions alteration in Wistar rats. Keywords: Apoptosis, Inflammation, Lead acetate, Sida corymbosa, Steroidogenic enzymes Copyright: © 2024 Oyeyemi et al. This is an open- access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.