Skin damage and premature aging are predominantly driven by UV radiation through several mechanisms. The most common of these are by reactive oxygen species (ROS) generation, upregulation of matrix metalloproteinases (MMPs), and weakened antioxidant defenses. Moringa oleifera is a nutritionally valuable plant with diverse biological activities. This study optimized ethanol concentrations coupled with ultrasonic-assisted extraction to maximize the yield and efficacy of M. oleifera leaf extract (MOLE). We also elucidated the underlying mechanisms of MOLE in protecting against photooxidative damage and skin aging from UVB exposure in HaCaT keratinocytes. Extraction with 50% ethanol produced the highest total phenolic and flavonoid contents, aligning with the greatest antioxidant activity by ABTS and FRAP assays. MOLE showed no significant cytotoxicity up to 1000 µg/mL in the MTT assay. MOLE protected cells from detrimental UVB radiation by scavenging ROS; reducing cell damage and death; enhancing gene expression of superoxide dismutase (SOD-1), glutathione peroxidase (GPx), and catalase (CAT); and improving SOD activity. UVB exposure elevated MMP-1, MMP-3, and MMP-9 expression and decreased collagen type I (col-1) and elastin (ELN) expression, while these effects were ameliorated by MOLE. Our findings suggest that MOLE protected against UVB-induced photooxidative damage and premature aging in the HaCaT keratinocytes.

Diabetes-related osteoporosis has been known to be a consequence of oxidative stress caused by excessive reactive oxygen species (ROS) production in the tissues. Despite the increase in the number of individuals with diabetes-related osteoporosis year on year, there is still no effective drug that does not induce adverse side effects. Glabridin, which exerts hypoglycemic effects and possesses antioxidant properties, may have beneficial effects in the treatment of diabetes-related osteoporosis. In this study, we aimed to investigate the preventive effects of glabridin in counteracting oxidative stress-induced bone loss and its underlying mechanisms. A diabetic rat model was established by a single intraperitoneal injection of streptozotocin into male Wistar rats. The diabetic rats were orally gavaged daily with glabridin or glyburide for 8 weeks. The presence of diabetes significantly decreased the rats’ tibia length, bone thickness, epiphyseal plate length, and collagen deposition compared to the control rats; in comparison, treatment with glabridin for 8 weeks significantly reversed these effects. In our in vitro study, the treatment of MC3T3-E1 preosteoblasts with glabridin up to 7.5 µM for 48 h showed no cytotoxic effect. However, pretreatment with glabridin significantly prevented oxidative stress-induced inhibition of cell proliferation. In addition, glabridin significantly diminished ROS production, restored antioxidant enzyme activity, and mitigated cellular apoptosis. These effects occurred by stimulating the phosphorylation of Akt, GSK-3β, and P65 NF-ĸB proteins. The above results show that glabridin alleviated oxidative stress-induced bone loss and osteoblast cell apoptosis by modulating the expression of the Akt/NF-ĸB and Akt/GSK-3β pathways.

Obesity is a global health concern driven by excessive lipid accumulation and adipocyte dysfunction, requires therapeutic strategies that both inhibit fat formation and promote lipid degradation. This study investigated the dual anti-adipogenic and pro-lipolytic effects of Pseuderanthemum palatiferum leaf extract (PPE) in 3T3-L1 adipocytes. The phytochemical analysis of PPE performed by using gas chromatography-mass spectrometry (GC-MS) and Liquid chromatography-mass spectrometry (LC-MS). The findings revealed that GC-MS analysis of PPE identified 35 volatile compounds, with benzofuran (29.94%) as the major constituent. LC-MS detected 27 non-volatiles phytochemicals, including chlorogenic acid and p-coumaric acid. PPE exhibited no significant cytotoxic effects on 3T3-L1 preadipocytes at doses ranging from 50 - 150 μg/mL. At 150 μg/mL, PPE reduced lipid accumulation by 37.84% and increased glycerol release by 60.46%, indicating both an anti-adipogenic and a lipolytic properties. Gene expression analysis revealed that pre-treatment with 150 μg/mL of PPE promoted the upregulation of early adipogenic markers (C/EBPα, ACC1, FAS, and GLUT4) while downregulating markers associated with mature adipocytes (Adiponectin, AP2, and CD36), indicating interference with adipocyte differentiation and lipid synthesis. Additionally, PPE lowered intracellular reactive oxygen species, suggesting an antioxidative contribution to its anti-obesity action. Collectively, this study provides the first evidence that P. palatiferum exerts complementary regulation of adipogenesis and lipolysis in 3T3-L1 cells, offering new insight into its multi-target mechanisms and potential as a natural therapeutic candidate for obesity management. HIGHLIGHTS Abnormal lipid metabolism contributes to obesity, accompanied by oxidative stress and inflammation. PPE modulates key pathways regulating fat storage and breakdown, leading to reduced lipid accumulation. PPE may influence adipose cells to reduce the release of inflammatory factors and subsequently to diminish oxidative stress. PPE may serve as a natural candidate for dietary or therapeutic strategies targeting obesity. GRAPHICAL ABSTRACT