RESUMEN
Steatohepatitis is a significant risk factor for end-stage liver disease. In this study, the therapeutic potential of Glabridin (GBD), an isoflavan derived from Glycyrrhiza glabra, is investigated in in-vitro and in-vivo models against palmitic acid (PA) or fast food (FF) diet + alcohol (EtOH). Mouse hepatocytes (AML-12 cells) were treated with PA; 250 µM + EtOH; 250 µM ± GBD (10 µM and 25 µM) for 24 h. C57BL/6J mice fed with standard chow (SC) diet, fast food (FF) diet + intermittent oral ingestion of EtOH (10-50%v/v) ± GBD (20 mg/kg and 40 mg/kg) for eight (8) weeks, were analyzed for histological features of steatohepatitis and fibrosis, biochemical indexes, and protein and gene expression studies related to oxidative stress, inflammation, lipogenesis, fibrosis, and apoptosis. GBD therapy considerably reduced intracellular events in AML-12 cells exposed to PA + EtOH. GBD treatments significantly improved body metrics, biochemical indexes, and histological features in C57BL/6J mice compared to FF + EtOH. Moreover, protein and gene expression investigations revealed a strong therapeutic effects on oxidative stress, inflammation, steatosis, fibrosis, and apoptosis -related molecular signaling cascades. In conclusion, these findings suggest that GBD has a strong therapeutic potential to be developed as anti-steatohepatitis/fibrosis medicine.
RESUMEN
Melanoma, the most serious yet uncommon type of cancer, originates in melanocytes. Risk factors include UV radiation, genetic factors, tanning lamps and beds. Here, we described the synthesis and selective anti melanoma activity of [3,2-b]indole fused 18ß-glycyrrhetinic acid, a derivative of 18ß-glycyrrhetinic acid in murine B16F10 and A375 human melanoma cell lines. Among the 14 molecules, GPD-12 showed significant selective cytotoxic activity against A375 and B16F10 cell lines with IC50 of 13.38 µM and 15.20 µM respectively. GPD 12 induced the formation of reactive oxygen species in A375 cells that could trigger oxidative stress mediated cell death as is evident from the increased expression of apoptosis related proteins such as caspase-9 and caspase-3 and the increased ratio of Bax to Bcl2. The results showed that GPD 12 can be used as an effective therapeutic agent against melanoma.
RESUMEN
Ultraviolet radiation (UVR) is the major exogenous agent that disturbs tissue homeostasis and hastens the onset of age-related phenotypes (photoaging). Exposure to UV-B radiation promotes apoptosis in human skin cells via induction of Reactive Oxygen Species (ROS)-mediated Endoplasmic Reticulum (ER) stress by activating the PERK-eIF2α-CHOP pathway, which plays a major role in exacerbating skin photoaging. Alleviating the production of ROS and boosting the antioxidant capacity of cells is the foremost therapeutic strategy to avert the repercussions of ultraviolet radiation exposure. In this study, we investigated the role of 3-(1'-methyltetrahydropyridinyl)-2,4-6-trihydroxy acetophenone (IIIM-8) in thwarting the UV-B-induced photoaging. We observed that IIIM-8 ameliorates UV-B-induced oxidative stress, ER stress, Loss of Mitochondrial membrane potential, MAPK activation and Inflammation in irradiated skin cells. Ultraviolet radiation-related damage to fibroblasts within the dermis leads to collagen degradation-the hallmark of photoaging. IIIM-8 substantially restored the synthesis of collagen and prevented its degradation via the downregulation of matrix metalloproteinases. Topical application of IIIM-8 prevented BALB/c mice skin from UV-B-induced leukocyte infiltration, epidermal thickening and disruption of Extracellular matrix components. Implying that IIIM-8 has a strong photoprotective property and has potential to be developed as a topical therapeutic/cosmeceutical agent against UV-B-induced photoaging.
