Synthesis of genipin derivatives and study of their anti-inflammatory activity

This study aimed to evaluate the anti‑inflammatory properties of genipin derivatives. Based on preliminary findings, a series of genipin derivatives were synthesised using either BF₃·Et₂O:H₂O = 1:50 (v:v) or p‑toluenesulfonic acid as catalysts, and their structures were characterised by ¹H‑NMR,¹³C‑NMR, and HRMS. The BV2 microglial cell line was used as the experimental model; cytotoxicity and nitric oxide (NO) levels were assessed via CCK‑8 and Griess assays, respectively, and the therapeutic index (IC₅₀/EC₅₀) was calculated for preliminary screening. All eighteen synthesised derivatives significantly inhibited NO release. Based on the therapeutic index, derivative 1b (1 R‑O‑ethyl genipin) was identified as having superior anti‑inflammatory activity. Further examination in cellular inflammation models using qRT‑PCR, ELISA, and Western blotting revealed that both genipin and derivative 1b dose‑dependently reduced the expression of pro‑inflammatory mediators (TNF‑α, IL‑6, and iNOS) while upregulating anti‑inflammatory markers (IL‑10 and Arg‑1) compared with the model group. Collectively, 1 R‑O‑ethyl genipin exhibits favourable anti‑inflammatory activity, offering new possibilities for the treatment of neuroinflammation and related disorders.