Shenyang Pharmaceutical University, Shenyang 110016, China.
Chinese Medicine Gene Expression Regulation Laboratory, State Administration of Traditional Chinese Medicine, and Basic Laboratory of Integrated Traditional Chinese and Western Medicine, Shanxi University of Chinese Medicine, Taiyuan 030000, China.
Food Funct. 2022 Nov 14;13(22):11825-11839. doi: 10.1039/d2fo01983c.
The imbalance of intestinal flora would induce immune inflammation. Cedrol (CE), found from ginger by our group earlier, has been proven to play an excellent role in ameliorating rheumatoid arthritis (RA) acting on JAK3, MAPK, and NF-κB. However, there have been no studies on CE ameliorating RA through the regulation of the micro-environment. In this study, the adjuvant arthritis model (AIA) is established to evaluate the weight, arthritis score, paw swelling, bone destruction, immune organ index, inflammatory cell infiltration, cartilage erosion, and metabolic enzymes of kidneys in AIA rats after CE intervention. The results indicated CE could alleviate paw swelling, reduce arthritis score, decrease the secretion of TNF-, IL-6, and IL-1 in serum in a dose-dependent manner, and inhibit the immune organ index of the spleen while having no significant effect on metabolic enzymes of the kidney. In addition, pathological sections of ankle and knee joints suggested CE might significantly prevent inflammatory cell infiltration, synovial hyperplasia, and joint degeneration and protect articular cartilage. Then, for the first time, 16S rRNA gene was applied to analyze the regulatory effect of CE on intestinal flora. CE could effectively improve the uniformity, diversity, and richness of intestinal flora, reduce the number of pathogenic bacteria, and increase the proportion of beneficial bacteria, and it significantly inhibited the abundance of in RA rats, which was 12.43 times smaller than that in methotrexate. The distribution and excretion of CE were detected by GC-MS. It was found that CE would massively accumulate in the gastrointestinal tract after oral administration, which is then mainly excreted through feces. Interestingly, the research suggested that CE, which plays a role in the dynamic regulation of the intestinal micro-environment, could be used as a potential component to prevent RA.
肠道菌群失衡会引发免疫炎症。我们小组之前从生姜中发现的桉油精（CE）已被证明在改善类风湿关节炎（RA）方面发挥了出色的作用，其作用靶点为 JAK3、MAPK 和 NF-κB。然而，目前还没有关于 CE 通过调节微环境来改善 RA 的研究。在本研究中，建立了佐剂关节炎模型（AIA），以评估 CE 干预后 AIA 大鼠的体重、关节炎评分、爪肿胀、骨破坏、免疫器官指数、炎性细胞浸润、软骨侵蚀和肾脏代谢酶的变化。结果表明，CE 可缓解爪肿胀，降低关节炎评分，且呈剂量依赖性降低血清中 TNF-α、IL-6 和 IL-1 的分泌，抑制脾脏免疫器官指数，但对肾脏代谢酶无显著影响。此外，踝关节和膝关节的病理切片表明，CE 可能显著预防炎性细胞浸润、滑膜增生和关节退变，保护关节软骨。然后，首次应用 16S rRNA 基因分析了 CE 对肠道菌群的调节作用。CE 可有效改善肠道菌群的均匀度、多样性和丰富度，减少致病菌数量，增加有益菌比例，显著抑制 RA 大鼠中的丰度，比甲氨蝶呤组低 12.43 倍。通过 GC-MS 检测 CE 的分布和排泄。结果发现，CE 经口服给药后会在胃肠道内大量积聚，然后主要通过粪便排出。有趣的是，研究表明，CE 可在肠道微环境的动态调节中发挥作用，可作为预防 RA 的潜在成分。
