Liu Ye, Zhu Ruizheng, Liu Bei, Wang Wuqing, Yang Ping, Cao Zhonglian, Yang Xiaolei, Du Wandi, Yang Qing, Liang Jingru, Hu Jiarong, Ma Guo
School of Pharmacy, Fudan University, Shanghai, China.
Department of Dermatology, Minhang Hospital, Fudan University, Shanghai, China.
Front Pharmacol. 2022 May 26;13:875014. doi: 10.3389/fphar.2022.875014. eCollection 2022.
This study aimed to disclose the antidiabetic mechanisms of Radix (RR). The antidiabetic effect of RR was studied in Streptozocin (STZ)-induced diabetes mellitus (DM) rats and HepG2 cells with insulin resistance (IR). Antidiabetic targets and signaling pathways of RR were confirmed by the network pharmacology and transcriptome analysis as well as HK2 cells induced by high glucose (HG). After the DM rats were administrated RR extract (RRE) for 4 weeks, their body weight was 10.70 ± 2.00% higher than those in the model group, and the fasting blood glucose (FBG), AUC of the oral glucose tolerance test, and insulin sensitivity test values were 73.23 ± 3.33%, 12.31 ± 2.29%, and 13.61 ± 5.60% lower in the RRE group, respectively. When compared with the model group, an increase of 45.76 ± 3.03% in the glucose uptake of HepG2 cells with IR was seen in the RRE group. The drug (RR)-components-disease (DM)-targets network with 18 components and 58 targets was established. 331 differentially expressed genes (DEGs) were identified. TRPV1 and SCD1 were important DEGs by the intersectional analysis of network pharmacology and renal transcriptome. The overexpression significantly inhibited apoptosis and oxidative stress of the HK2 cells induced by HG, while overexpression induced apoptosis and oxidative stress of the HK2 cells induced by low and high glucose. When compared to the HG group, the mRNA and protein expressions of TRPV1 in the presence of RRE (100 μg/ml) increased by 3.94 ± 0.08 and 2.83 ± 0.40 folds, respectively. In summary, RR displayed an inspiring antidiabetic effect by reducing FBG and IR, upregulating the mRNA and protein expressions of TRPV1, and downregulating mRNA expression of SCD1. Induction of TRPV1 and inhibition of SCD1 by RR was possibly one of its antidiabetic mechanisms.
本研究旨在揭示红芪（RR）的抗糖尿病机制。在链脲佐菌素（STZ）诱导的糖尿病（DM）大鼠和具有胰岛素抵抗（IR）的HepG2细胞中研究了RR的抗糖尿病作用。通过网络药理学和转录组分析以及高糖（HG）诱导的HK2细胞确定了RR的抗糖尿病靶点和信号通路。给DM大鼠灌胃RR提取物（RRE）4周后，其体重比模型组高10.70±2.00%，RRE组的空腹血糖（FBG）、口服葡萄糖耐量试验的AUC和胰岛素敏感性试验值分别低73.23±3.33%、12.31±2.29%和13.61±5.60%。与模型组相比，RRE组中具有IR的HepG2细胞的葡萄糖摄取增加了45.76±3.03%。建立了包含18种成分和58个靶点的药物（RR）-成分-疾病（DM）-靶点网络。鉴定出331个差异表达基因（DEG）。通过网络药理学和肾脏转录组的交叉分析，TRPV1和SCD1是重要的DEG。过表达显著抑制HG诱导的HK2细胞的凋亡和氧化应激，而过表达诱导低糖和高糖诱导的HK2细胞的凋亡和氧化应激。与HG组相比，在RRE（100μg/ml）存在下TRPV1的mRNA和蛋白表达分别增加了3.94±0.08倍和2.83±0.40倍。总之，RR通过降低FBG和IR、上调TRPV1的mRNA和蛋白表达以及下调SCD1的mRNA表达显示出令人鼓舞的抗糖尿病作用。RR诱导TRPV1和抑制SCD1可能是其抗糖尿病机制之一。
