Isolation of dihydroagarofuran sesquiterpene from the fruits of Tripterygium hypoglaucum and evaluation of their anti-inflammatory activity

Twelve previously undescribed dihydroagarofuran sesquiterpenes, hypogricins I-XII (1-12), were isolated from the fruits of Tripterygium hypoglaucum, along with 14 known dihydro-beta-agarofuran-type sesquiterpenoids. structural elucidation of these previously undescribed compounds was achieved through using comprehensive spectroscopic analysis, single-crystal X-ray diffraction studies, and electronic circular dichroism (ECD) calculations. All the compounds were evaluated for their effects on HaCaT cell viability and their potential to inhibit tumor necrosis factor alpha (TNF-alpha)- and interleukin 17A (IL-17A)-induced inflammation. Biological assays revealed that compounds 2, 7, 8, 9, 10, 12, 13 and 26 at a concentration of 25 mu M downregulated the expression of relevant inflammatory factors S100 calcium-binding protein A8 (S100A8), defensin beta 4 (DEFB4A), and motif chemokine ligand 2 (CCL-2) induced by TNF-alpha and IL-17A in HaCaT cells to varying extents. Furthermore, this work presents initial findings indicating that petroleum ether extracts from fruits exhibit low toxicity significant anti-inflammatory activity. This study also includes the first evaluation of the cytotoxicity and antiinflammatory effects of sesquiterpenoids on keratinocytes, thereby providing a scientific basis for the treatment of skin inflammation.