Wang Dan-Dan, Song Meng-Ke, Yin Qin, Chen Wen-Gang, Olatunji Opeyemi Joshua, Yang Kui, Zuo Jian
Xin'an Medicine Research Center, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital), Wuhu, 241000, People's Republic of China.
Department of Pharmacy, the Second Affiliated Hospital of Wannan Medical College, Wuhu, 241000, People's Republic of China.
J Inflamm Res. 2024 Sep 24;17:6691-6706. doi: 10.2147/JIR.S474329. eCollection 2024.
Nicotinamide adenine dinucleotide (NAD)-dependent deacetylase SIRT1 regulates both metabolism and immune functions. This study investigated if SIRT1 inhibitory property of herbal formula Qing-Luo-Yin (QLY) contributed to its anti-rheumatic effects.
Adjuvant-induced arthritis (AIA) rats were treated by QLY and nicotinamide mononucleotide (NMN, a biosynthesis precursor of NAD) for 38 days. After sacrifice, blood, paws, liver and white adipose tissues (WAT) were collected. Pre-adipocytes were cultured by the rats' serum. The medium was used for monocytes culture. Some pre-adipocytes were treated by QLY-derived SIRT1 inhibitors. was silenced or overexpressed beforehand. The samples were subjected to kits-based quantification, polymerase-chain reaction, western-blot, immunofluorescence, and histology experiments.
AIA rats experienced significant fat loss in liver and WAT. Expression of many SIRT1-related signals like PPARγ, PGC-1α, HSL, ATGL and CPT-1A were altered. QLY attenuated all these abnormalities and joint injuries. By pan-acetylation up-regulation, visfatin was obviously reduced in QLY-treated AIA rats' blood (from 191.8 to 127.0 pg/mL). NMN sustained SIRT1 activation by replenishing NAD, and weakened these effects. QLY-containing serum and the related compounds showed similar impacts on pre-adipocytes, resembling the changes in QLY-treated AIA rats' WAT. These treatments suppressed AIA serum-induced visfatin secretion (from 49.3 to 36.1 and 30.7 pg/mL). This effect was impaired by overexpression. The medium from the compounds-treated pre-adipocytes impaired NF-κB activation in AIA serum-cultured monocytes.
Besides fat depletion, SIRT1 up-regulation in rheumatic subjects' WAT promotes visfatin production, and exacerbates inflammation. SIRT1 inhibition in WAT is an anti-rheumatic way of QLY independent of immune regulation.
烟酰胺腺嘌呤二核苷酸（NAD）依赖性脱乙酰酶SIRT1调节代谢和免疫功能。本研究调查了中药方剂清络饮（QLY）的SIRT1抑制特性是否有助于其抗风湿作用。
用QLY和烟酰胺单核苷酸（NMN，NAD的生物合成前体）治疗佐剂性关节炎（AIA）大鼠38天。处死后，收集血液、爪子、肝脏和白色脂肪组织（WAT）。用大鼠血清培养前脂肪细胞。该培养基用于单核细胞培养。一些前脂肪细胞用QLY衍生的SIRT1抑制剂处理。事先使沉默或过表达。对样品进行基于试剂盒的定量、聚合酶链反应、蛋白质印迹、免疫荧光和组织学实验。
AIA大鼠肝脏和WAT出现明显脂肪减少。许多与SIRT1相关的信号如PPARγ、PGC-1α、HSL、ATGL和CPT-1A的表达发生改变。QLY减轻了所有这些异常和关节损伤。通过泛乙酰化上调，在QLY治疗的AIA大鼠血液中内脂素明显降低（从191.8降至127.0 pg/mL）。NMN通过补充NAD维持SIRT1激活，并减弱了这些作用。含QLY血清和相关化合物对前脂肪细胞有类似影响，类似于QLY治疗的AIA大鼠WAT中的变化。这些处理抑制了AIA血清诱导的内脂素分泌（从49.3降至36.1和30.7 pg/mL）。这种作用因过表达而受损。化合物处理的前脂肪细胞培养基损害了AIA血清培养的单核细胞中NF-κB的激活。
除脂肪消耗外，风湿患者WAT中SIRT1上调促进内脂素产生并加重炎症。WAT中SIRT1抑制是QLY独立于免疫调节的抗风湿途径。
