This study aimed to evaluate the pharmacokinetics of acipimox in rats under simulated high altitude hypoxia conditions. A sensitive and reliable LC–MS/MS method has been established for the quantitation of acipimox in rat plasma and tissue homogenate and validated according to the guidelines of the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). Western blotting and enzyme linked immunosorbent assay (ELISA) were used to investigate the expression of lipid metabolism-related proteins and free fatty acid (FFA) levels, respectively. Cell viability was detected using a Cell Counting kit-8 assay (CCK-8). The method was then successfully applied in a pharmacokinetic comparison between normoxic and hypoxic rats. The results indicated that there were significant differences in the main pharmacokinetics parameters of acipimox between normoxic and hypoxic rats. HCAR2 expression in the hypoxia group was upregulated compared to that in the normoxia group and the levels of FFA decreased more in the hypoxia group. Under the hypoxia condition, the proliferation of HK2 cells was inhibited with increasing concentrations of acipimox. The results provide important and valuable information for the safety and efficacy of acipimox, which indicated that the dosage of acipimox might be adjusted appropriately during clinical medication in hypoxia.

Celastrol, an active triterpenoid extracted from one of the most famous traditional Chinese medicines (TCMs), Tripterygium wilfordii Hook.f., is a novel anti-cancer drug with significant anti-angiogenesis activity. However, the exact molecular mechanisms underlying its anti-tumor angiogenesis effect remain unclear. The process of angiogenesis needs lots of energy supply, which mostly derives from mitochondria, the “energy factory” in our body. This study shows that celastrol exerts visible suppression on tumor growth and angiogenesis in a cell-derived xenograft (CDX). Likewise, it reduced the tube formation and migration of human umbilical vein endothelial cells (HUVECs), suppressed the energy metabolism of mitochondria in the Seahorse XF Mito Stress Test, and triggered mitochondrial fragmentation and NF-κB activation. Mechanically, celastrol downregulated the expression of mitochondrial-sharping protein optic atrophy protein 1 (OPA1), which was further estimated by the OPA1 knockdown model of HUVECs. Specifically, celastrol directly suppressed OPA1 at the mRNA level by inhibiting the phosphorylation of STAT3, and stattic (STAT3 inhibitor) showed the same effects on OPA1 suppression and anti-angiogenesis activity. Overall, this study indicates that celastrol inhibits tumor angiogenesis by suppressing mitochondrial function and morphology via the STAT3/OPA1/P65 pathway and provides new insight for mitochondrion-targeted cancer therapy.

UVB radiation penetrates the epidermis and upper dermis, compromising skin barrier function. This activates pro-inflammatory cells, releasing mediators (e.g., histamine, interleukins) that induce edema. UVB also generates excessive reactive oxygen species (ROS), causing oxidative stress in skin cells. Although the mechanisms of UV-induced skin damage have been extensively studied, the development of effective UV-protective drugs remains a significant challenge. Scutellarin, a flavonoid glycoside predominantly isolated from Erigeron breviscapus, has demonstrated diverse bioactivities including anti-inflammatory, antioxidant, and anti-tumor effects. However, its role in UVB-induced skin damage has not been fully explored. Therefore, we established a UVB-induced skin damage model in mice by irradiating the dorsal skin with a dose of 300 mJ/cm² UVB. Through measurements of transepidermal water loss, detection of barrier-related proteins, assessment of inflammatory factors, and evaluation of oxidative stress indicators, we found that scutellarin can maintain barrier integrity, reduce skin edema, suppress inflammatory responses, and decrease oxidative stress. Moreover, RNA sequencing of mice skin revealed that scutellarin can modulate inflammatory responses and maintain extracellular matrix homeostasis to alleviate skin damage. These findings suggest that scutellarin is a natural compound with potential for UV-protective effects on the skin.