Qing-Luo-Yin-induced SIRT1 inhibition contributes to the immune improvement of adjuvant-induced arthritis rats

Abstract

The herbal formula Qing-Luo-Yin (QLY) was proved containing SIRT1 inhibitors. Whether they contribute to the anti-rheumatic effects is to be confirmed. Adjuvant-induced arthritis (AIA) rats were treated by QLY or/and nicotinamide mononucleotide (NMN) for 38 days. After sacrifice, main tissues were collected for histological and western-blot experiments. Levels of rheumatoid arthritis (RA)-related indictors in blood or tissue homogenates were detected by commercial kits. Normal pre-adipocytes were cultured by the relevant rat serums, and the medium was collected for monocytes culture. In replicate experiments, some pre-adipocytes received additional compounds or SIRT1 silencing/overexpression treatments. Due to spontaneous remission of inflammation, QLY didnt further improve immune milieu in AIA rats, but greatly eased paw edema and joint injuries. Besides, it reversed triglyceride/glucose depletion in liver and adipose tissues, and inhibited the expression and function of SIRT1, causing concomitant changes of related signals and adipkines production. All the effects were weakened by NMN, which activated SIRT1 by increasing NAD production. The serum from QLY-treated rats improved AIA rat serum-induced metabolism and secretion changes of pre-adipocytes, and reduced the secretion of IL-1{beta}, IL-6 and TNF- in the monocytes cultured with the corresponding medium. A mixture of matrine, sinomenine, sophocarpine, dioscin, berberine showed the similar effects on pre-adipocytes to QLY-containing serum. eNAMPT decrease was especially notable, which was obviously weakened by SIRT1 overexpression but overshadowed SIRT1-silencing. SIRT1 inhibitors in QLY reshaped metabolism and secretion profiles of adipose tissues. It consequently mitigated eNAMPT-mediated inflammation and eased AIA in rats.