Leydig cells are essential for steroidogenesis and spermatogenesis. An imbalance in the production of reactive oxygen species (ROS) and the cellular antioxidant level brings about oxidative stress. Oxidative stress (OS) results in the dysfunction of Leydig cells, thereby impairing steroidogenesis, spermatogenesis, and ultimately, male infertility. To prevent Leydig cells from oxidative insults, there needs to be a balance between the ROS production and the cellular protective capacity of antioxidants. Evidence indicates that medicinal plants could improve Leydig cell function at specific concentrations under basal or OS conditions. The increased usage of medicinal plants has been considered a possible alternative treatment for male infertility. This review aims to provide an overview of the impact of oxidative stress on Leydig cells as well as the effects of various medicinal plant extracts on TM3 Leydig cells. The medicinal plants of interest include Aspalathus linearis, Camellia sinensis, Moringa oleifera, Morinda officinale, Taraxacum officinale, Trichilia emetica, Terminalia sambesiaca, Peltophorum africanum, Ximenia caffra, Serenoa repens, Zingiber officinale, Eugenia jambolana, and a combination of dandelion and fermented rooibos (CRS-10). According to the findings obtained from studies conducted on the evaluated medicinal plants, it can, therefore, be concluded that the medicinal plants maintain the antioxidant profile of Leydig cells under basal conditions and have protective or restorative effects following exposure to oxidative stress. The available data suggest that the protective role exhibited by the evaluated plants may be attributed to their antioxidant content. Additionally, the use of the optimal dosage or concentration of the extracts in the management of oxidative stress is of the utmost importance, and the measurement of their oxidation reduction potential is recommended.

According to a recent report by the WHO, 50–80 million people suffer with infertility. Amongst these populations, male counterparts account for 20–50% of infertility cases. The aetiology of infertility in men includes many factors such as psychological issues, lifestyle and environmental factors, hormonal disorders and chromosomal abnormalities. The pathophysiology of these aetiologies may be initiated by a local inflammatory reaction increasing reactive oxygen species (ROS) production, which can negatively affect the male reproductive system by altering the hypothalamic–pituitary–gonadotropin axis (HPG axis). Alteration of the HPG axis may affect testicular steroidogenesis, spermatogenesis, the Leydig cells and Sertoli cells, leading to poor semen quality. The prevalence of male infertility underscores the need for a thorough scientific investigation to identify treatable or reversible factors using plant adjuvants with antioxidative properties. Therefore, this review aims to provide an overview of the currently available knowledge on the aetiologies of male reproductive dysfunction, emphasising infertility risk factors, as well as elucidating the possible ways by which readily available alternatives, such as Moringa oleifera leaves, may mitigate male infertility by highlighting its role on the oxidative stress parameters, reproductive hormonal levels, testicular steroidogenesis and spermatogenesis, gene expression, weight and morphology of the testis and sperm parameters.

Introduction: Moringa oleifera ( M. oleifera ) is a medicinal plant rich in dietary antioxidants that may protect reproductive cells from oxidative stress‐induced damage and male fertility problems. This study investigated M. oleifera aqueous leaf extracts (ALE) effects on TM3 Leydig cells exposed to hydrogen peroxide (H ₂ O ₂ ). Methods: M. oleifera ALE and ascorbic acid (10−1000 µg/mL) were assessed for antioxidant activity. TM3 Leydig cells were exposed to various concentrations of M. oleifera ALE (0−1000 µg/mL) or α‐tocopherol (50 µM) for 24 h, alongside 200 µM H ₂ O ₂ , with or without hCG (4 ng/mL). Cell viability, testosterone production, mitochondrial membrane potential (MMP), total protein and oxidative stress parameters (reactive oxygen species [ROS], superoxide dismutase [SOD], reduced glutathione [GSH], total antioxidant capacity [TAC] and lipid peroxidation [MDA]) were assessed. Results: Ascorbic acid demonstrated superior DPPH radical scavenging and FRAP activity compared to M. oleifera ALE at most concentrations ( p < 0.0001). H ₂ O ₂ (200 µM) exposure significantly reduced cell viability, MMP, SOD, GSH and TAC levels, while increasing ROS and MDA levels ( p < 0.05). Treatment with M. oleifera ALE or α‐tocopherol significantly increased cell viability, total protein, SOD activity and GSH levels while reducing ROS and MDA compared to H ₂ O ₂ control ( p < 0.05). However, testosterone levels remained unchanged ( p > 0.05). Conclusions: M. oleifera ALE effectively protects the TM3 Leydig cells from H ₂ O ₂ ‐induced oxidative stress by restoring the redox balance, though unchanged testosterone levels suggest limitations in using TM3 Leydig cells for assessing testosterone synthesis.