Bicyclol

Bicyclol (BIC), a synthetic hepatoprotective agent widely prescribed in China, lacks comprehensive safety and activity profiles for its degradation products (DPs). Here, we systematically investigated BIC's forced degradation behavior using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). Three hydrolytic degradation products (DP1-DP3) were isolated via HPLC and structurally characterized, revealing methylenedioxy group hydrolysis as the primary degradation pathway. Molecular docking simulations demonstrated enhanced target binding affinities of DPs compared to BIC, supported by absorption, distribution, metabolism, and excretion (ADME) predictions showing improved drug-likeness. In an alcohol-induced fatty liver zebrafish model, both BIC and its DPs attenuated hepatic macrovesicular steatosis and inflammatory responses. Mechanistically, treatment normalized lipid metabolism by downregulating alcohol-induced expression of FASN, SREBP1, PPARα, and PPARγ, while reduced IL-6 and TNF-α levels confirmed anti-inflammatory efficacy. These findings demonstrate that BIC DPs exhibit dual pharmacological activity through lipid homeostasis modulation and inflammation suppression, providing critical insights for quality control and therapeutic applications.

Five previously undescribed spirobenzofuranoid dibenzocyclooctadiene lignans, xuetonlignans L-P (1-5), and three known dibenzocyclooctadiene lignans (6-8) were isolated from the fruits of Kadsura heteroclita. Their structures were elucidated by analysis of HR-ESI-MS, NMR spectroscopy, CD spectra and single-crystal X-ray structure determination. The hepatoprotective activity against H₂O₂-induced toxicity in HepG2 cells and anti-inflammatory activity against NO (nitric oxide) were performed. Compounds 4 and 8 showed potent hepatoprotective activity against H₂O₂-induced toxicity in HepG2 cells compared to the positive control, bicyclol. Furthermore, compound 6 significantly inhibited the NO production in LPS-induced RAW264.7 cells at a concentration of 20 μM.