Deregulation of the normal cellular apoptotic function is a fundamental element in the etiology of most cancers and the anti-apoptotic B cell lymphoma 2 (BCL‑2) protein family is known to play crucial role in the regulation of this function. Overexpression of this protein family has been implicated in some cancers, such that agents that could inhibit their over-activity are now being explored for anticancer drug development. A number of studies have revealed the anticancer potential of Morinda lucida-derived extracts and compounds. In search of more inhibitors of this anti-apoptotic protein family from plant resources, 47 compounds, identified in Morinda lucida Benth (Rubiaceae) were screened for their inhibitory activities against BCL-XL, BCL-2, and MCL-1 by molecular docking using BINDSURF, while binding interactions of the top compounds were viewed with PyMOL. Druglikeness and Absorption–Distribution–Metabolism–Excretion (ADME) parameters of the top 6 compounds from docking study were evaluated using SuperPred webserver. Results revealed that out of the 47 compounds, 2 triterpenes (ursolic acid and oleanolic acid) and 4 phytosterols (cycloartenol, campesterol, stigmasterol, and β-sitosterol) have higher binding affinities for the selected BCL-2 proteins, compared to known standard inhibitors; these compounds also fulfill oral drugability of Lipinski rule of five. Therefore, since these Morinda lucida-derived phytosterols and triterpenes show high binding affinity toward the selected anti-apoptotic proteins and exhibited good drugability characteristics, they qualify for further study on drug development against cancers characterized by overexpression of this family of protein.

Finasteride used for treating benign prostatic hyperplasia is associated with undesirable side effects via oxidative stress related mechanisms. This study employed in vivo and in silico methods to investigate the protective role of hesperidin against testicular toxicity induced by finasteride and the possible molecular mechanisms involved. Male Wistar rats were randomized into four groups of six animals each. Group I (control) were administered distilled water, group II received finasteride (3.1 mg/kg bw), group III received hesperidin (100 mg/kg bw), while group IV were co-administered finasteride and hesperidin. Administration was by gavage for 14 days. The binding propensities of finasteride and hesperidin for 5α-reductase were assessed using in silico docking approach. Finasteride administration caused significant reductions of sperm motility, volume, count, and live/dead ratio, with significant increase in numbers of abnormal sperms. Finasteride treatment also resulted in diminished activities of superoxide dismutase, catalase and glutathione-S-transferase, significant reduction in the concentration of reduced glutathione and ascorbic acid, and increased testicular malondialdehyde level relative to control. Moreover, significant increase in the activities of testicular lactate dehydrogenase and γ-glutamyl transferase was observed, with significant decrease in the activities of acid phosphatase and alkaline phosphatase relative to finasteride-treated rats. Furthermore, hesperidin exhibited favorable binding affinity for 5α –reductase (5AR) in silico compared to finasteride. Co-administration with hesperidin ameliorated finasteride-induced testicular damage by suppressing oxidative stress indices, enhancing antioxidant status, improving sperm parameters and alterations in the activities of marker enzymes, as well as possibly inhibiting the binding of finasteride to 5AR.