Qi-dan-dihuang decoction ameliorates renal fibrosis in diabetic rats via p38MAPK/AKT/mTOR signaling pathway.

CONTEXT: Qi-dan-dihuang decoction (QDD) has been used to treat diabetic kidney disease (DKD), but the underlying mechanisms are poorly understood. OBJECTIVE: This study reveals the mechanism by which QDD ameliorates DKD. MATERIALS AND METHODS: The compounds in QDD were identified by high-performance liquid chromatography and quadrupole-time-of-flight tandem mass spectrometry (HPLC-Q-TOF-MS). Key targets and signaling pathways were screened through bioinformatics. Nondiabetic Lepr db/m mice were used as control group, while Lepr db/db mice were divided into model group, dapagliflozin group, 1% QDD-low (QDD-L), and 2% QDD-high (QDD-H) group. After 12 weeks of administration, 24 h urinary protein, serum creatinine, and blood urea nitrogen levels were detected. Kidney tissues damage and fibrosis were evaluated by pathological staining. In addition, 30 mmol/L glucose-treated HK-2 and NRK-52E cells to induce DKD model. Cell activity and migration capacity as well as protein expression levels were evaluated. RESULTS: A total of 46 key target genes were identified. Functional enrichment analyses showed that key target genes were significantly enriched in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and mitogen-activated protein kinase (MAPK) signaling pathways. In addition, in vivo and in vitro experiments confirmed that QDD ameliorated renal fibrosis in diabetic mice by resolving inflammation and inhibiting the epithelial-mesenchymal transition (EMT) via the p38MAPK and AKT-mammalian target of rapamycin (mTOR) pathways. DISCUSSION AND CONCLUSION: QDD inhibits EMT and the inflammatory response through the p38MAPK and AKT/mTOR signaling pathways, thereby playing a protective role in renal fibrosis in DKD.

Qi-Deficiency Related Increases in Disease Susceptibility Are Potentially Mediated by the Intestinal Microbiota.

Qi-deficiency (QX) is thought to promote the body's susceptibility to disease, but the underlying mechanism through which this occurs is not clear. We surveyed the traditional Chinese medicine constitution (TCMC) of healthy college students to identify those that were PH (balanced TCMC constitution) and QX (unbalanced TCMC constitution). We then used high-throughput sequencing of the 16SrRNA V3-4 region in fecal microbiota samples to identify differences between those obtained from PH and QX individuals. Our results demonstrated that the alpha diversity of QX samples was significantly lower than that of PH samples (p < 0.05) and that beta diversity was remarkably different in QX and PH samples. Four and 122 bacterial taxa were significantly overrepresented in QX and PH groups, respectively. The genera Sphingobium, Clostridium, and Comamonas were enriched in the QX group and had a certain pathogenic role. The QX group also showed a statistically significant lack of probiotics and anti-inflammatory bacteria such as Bifidobacterium and Bdellovibrio. The functional potential of QX bacterial taxa was reduced in fatty acid metabolism and butanoate metabolism. We contend that the imbalanced intestinal microbiota in QX and the following functional changes in metabolism influence immunity and energy metabolism, which could increase susceptibility to disease.