Traditional Chinese Medicine (Zhong Jing) School, Henan University of Chinese Medicine, Zhengzhou, Henan Province, China.
The Second Affiliated Hospital of Luohe Medical College, Luohe, Henan Province, China.
PLoS One. 2022 Nov 3;17(11):e0277061. doi: 10.1371/journal.pone.0277061. eCollection 2022.
Ursolic acid (UA), a natural pentacyclic triterpenoid obtained from fruit and several traditional Chinese medicinal plants, exhibits anti-inflammatory and hypoglycemic properties. However, its protective effects against type 1 diabetes mellitus (T1DM) have not been explored. In this study, streptozotocin-induced T1DM rat models were established and treated with UA for six weeks. T1DM rats treated with UA were used to observe the effects of UA on body weight and fasting blood glucose (FBG) levels. Pathological changes in the pancreas were observed using immunohistochemical staining. The gut microbiota distribution was measured using 16S rDNA high-throughput sequencing. The proportions of Th17 and Treg cells were examined using flow cytometry. Protein and mRNA expression of molecules involved in Th17/Treg cell differentiation were assessed by quantitative real-time PCR and western blotting. The correlation between gut microbiota and Th17/Treg cell differentiation in T1DM was analyzed using redundancy analysis (RDA) analysis. Compared with the model group, FBG levels declined, and the progressive destruction of pancreatic β cells was alleviated. The diversity and uniformity of gut microbiota in T1DM rats treated with UA increased significantly. Interestingly, the Th17/Treg cell differentiation imbalance was corrected and positively correlated with the expression of Foxp3 and IL-10, and negatively correlated with the expression of RORγt, IL-17A, and TNF-α. These findings suggest that UA can lower FBG levels in T1DM rats, delay the progressive destruction of pancreatic β-cells, and modulate gut microbiota homeostasis and immune function in streptozotocin-induced T1DM rats.
熊果酸（UA）是一种从水果和几种传统中药植物中获得的天然五环三萜，具有抗炎和降血糖作用。然而，其对 1 型糖尿病（T1DM）的保护作用尚未得到探索。在本研究中，建立了链脲佐菌素诱导的 T1DM 大鼠模型，并使用 UA 治疗 6 周。使用 UA 治疗的 T1DM 大鼠用于观察 UA 对体重和空腹血糖（FBG）水平的影响。使用免疫组织化学染色观察胰腺的病理变化。使用 16S rDNA 高通量测序测量肠道微生物群落的分布。使用流式细胞术检查 Th17 和 Treg 细胞的比例。通过定量实时 PCR 和 Western blot 评估参与 Th17/Treg 细胞分化的分子的蛋白和 mRNA 表达。使用冗余分析（RDA）分析 T1DM 中肠道微生物群与 Th17/Treg 细胞分化之间的相关性。与模型组相比，FBG 水平下降，胰腺β细胞的进行性破坏得到缓解。UA 治疗的 T1DM 大鼠肠道微生物群落的多样性和均匀性显著增加。有趣的是，Th17/Treg 细胞分化失衡得到纠正，并与 Foxp3 和 IL-10 的表达呈正相关，与 RORγt、IL-17A 和 TNF-α 的表达呈负相关。这些发现表明，UA 可降低 T1DM 大鼠的 FBG 水平，延缓胰腺β细胞的进行性破坏，并调节链脲佐菌素诱导的 T1DM 大鼠肠道微生物群稳态和免疫功能。
