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 <i>in vitro</i>. 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.