Alkaloid derivatives in Qing-Luo-Yin alleviated experimental arthritis in rodents by activating PPARγ.

The herbal formula Qing-Luo-Yin (QLY) shows potential in activating PPARγ. This study investigated how this property contributed to its anti-rheumatic effects. Some mice with antigen-induced arthritis (AA) were orally treated with QLY and/or PPARγ antagonist/agonist (T0070907/rosiglitazone). PPARγ agonists were screened out by molecular docking and validated by experiments in vitro. Rosiglitazone and QLY ameliorated arthritis, inflammation and lipid depletion of AA mice. The effects of QLY were weakened by T0070907. Among the compounds abundant in QLY extract and QLY-treated adjuvant-induced arthritis (AIA) rats' serum, matrine, sophocarpine and sinomenine exhibited high affinities to PPARγ, and elevated its thermal stability and transcriptional activity. They suppressed fat utilisation in AIA serum-incubated HepG2 hepatocytes. Accumulated fatty acids in the medium reduced TNF-ɑ, IL-6 and IL-1β secretion of lipopolysaccharide-stimulated THP-1 monocytes by inhibiting p65 phosphorylation. In short, certain alkaloids in QLY activate PPARγ signalling, which contributes to the improvements of both immune and metabolic environments.