RESUMEN
Male sexual dysfunctions such as infertility and impotence are recognized as the consequences of diabetes. Salazinic acid (Sa) is a depsidone found in lichen genera of Lobaria, Parmelia, and Usnea, which has prominent free radical and α-glucosidase inhibitory actions. The present study establishes the beneficial role of salazinic acid (Sa) to combat the deleterious effects of streptozotocin-induced diabetes on the male reproductive system of rats. In a dose-dependent manner, Sa significantly restored the reproductive organs weight, sperm characteristics, and testicular histoarchitecture in diabetic rats. Further, a significant recovery of insulin, follicle-stimulating hormone, luteinizing hormone and testosterone levels in serum was recorded in Sa-treated diabetic rats. The malondialdehyde levels were significantly lowered, and the activities of glutathione, superoxide dismutase, glutathione peroxidase and catalase, markedly elevated in the blood serum, as well as testicular tissue after Sa-supplementation. Sa also suppressed the protein expression levels of tumor necrosis factor-α in serum. The high dose of Sa showed significant improvement in glycemia and testicular protection, similar to sildenafil citrate. Moreover, the docking results showed that both Sa and sildenafil have a high affinity toward the target protein, PDE5 with binding affinity values found to be -9.5 and -9.2 kcal mol-1, respectively. Molecularly, both Sa and sildenafil share similar hydrogen bonding patterns with PDE5. Hence, our study clearly showed the protective role of Sa against diabetic-induced spermatogenic dysfunction in rats, possibly by competing with cGMP to bind to the catalytic domain of PDE5 and thereby controlling the oxidative impairment of testes.
RESUMEN
Diterpenes are secondary metabolites that have attracted much attention due to their potential biological activities including anti-cancer potential. The aim of the current study is to assess the anticancer potential of the six known clerodane diterpenes (1-6) isolated from Polyalthia longifolia seeds and their underlying molecular mechanisms. These compounds were evaluated for their cytotoxicity in vitro by using MTT assays. The "two-phase model" with NDEA and PB ad libitum was used for induction of HCC and sorafenib was used as the standard drug. Prophylactic studies were carried out for compounds 4/6 at both low (5 mg/kg b.w) and high (10 mg/kg b.w) doses. Based on the MTT assay results, the two best compounds, 4 and 6, were selected for in vivo studies. The results showed that treatment with compound 4/6 significantly restored the changes in biochemical parameters and liver morphology observed in (NDEA + PB)-induced HCC rats. Additionally, the docking studies showed that compound 4/6 interacted with several key proteins such as MDM2, TNF-α, FAK, thereby inhibiting these proteins and reversing the negative impacts of NDEA. In conclusion, our results suggested that compounds 4 and 6 are potential therapeutic agents for HCC, mostly due to their ability to control typical cancer pathways.