Atractylodin targets GLA to regulate D-mannose metabolism to inhibit osteogenic differentiation of human valve interstitial cells and ameliorate aortic valve calcification.

Atractylodin (ATL) has been reported to exert anti-inflammatory effects. Osteogenic changes induced by inflammation in valve interstitial cells (VICs) play a key role in the development of calcified aortic valve disease (CAVD). This study aimed to investigate the anti-calcification effects of ATL on aortic valves. Human VICs (hVICs) were exposed to osteogenic induction medium (OM) containing ATL to investigate cell viability, osteogenic gene and protein expression, and anti-calcification effects. Gas chromatography-mass spectroscopy (GC-MS) metabolomics analysis was used to detect changes in the metabolites of hVICs stimulated with OM before and after ATL administration. The compound-reaction-enzyme-gene network was used to identify drug targets. Gene interference was used to verify the targets. ApoE-/- mice fed a high-fat (HF) diet were used to evaluate the inhibition of aortic valve calcification by ATL. Treatment with 20 µM ATL in OM prevented calcified nodule accumulation and decreases in the gene and protein expression levels of ALP, RUNX2, and IL-1ß. Differential metabolite analysis showed that D-mannose was highly associated with the anti-calcification effect of ATL. The addition of D-mannose prevented calcified nodule accumulation and inhibited succinate-mediated HIF-1α activation and IL-1ß production. The target of ATL was identified as GLA. Silencing of the GLA gene (si-GLA) reversed the anti-osteogenic differentiation of ATL. In vivo, ATL ameliorated aortic valve calcification by preventing decreases in GLA expression and the up-regulation of IL-1ß expression synchronously. In conclusion, ATL is a potential drug for the treatment of CAVD by targeting GLA to regulate D-mannose metabolism, thereby inhibiting succinate-mediated HIF-1α activation and IL-1ß production.

Different processing methods and pharmacological effects of Atractylodis Rhizoma.

Atractylodis Rhizoma, a traditional Chinese medicine with an extensive history of treating gastrointestinal disorders and other diseases, undergoes various processing methods in China to enhance its therapeutic efficacy for specific conditions. However, a comprehensive report detailing the changes in chemical composition and pharmacological effects due to these processing methods is currently lacking. This article provides a systematic review of the commonly employed processing techniques for Atractylodis Rhizoma, including raw Atractylodis Rhizoma (SCZ), bran-fried Atractylodis Rhizoma (FCZ), deep-fried Atractylodis Rhizoma (JCZ), and rice water-processed Atractylodis Rhizoma (MCZ). It examines the alterations in chemical constituents and pharmacological activities resulting from these processes and elucidates the mechanisms of action of the primary components in the various processed forms of Atractylodis Rhizoma in the treatment of gastrointestinal diseases.