Jinkui Shenqi Pill and Its Active Component Diosgenin Mitigate UUO-Induced Renal Fibrosis Via Targeting the PI3K/AKT Axis

Abstract

Luyao Wu, Xiaoying Xu, Haoxiang Fang, Yingying Dong, Haowen Yang, Siqi Shen, Wenxiu Xu and Yanfei Shao

Background: Chronic kidney disease (CKD) may result in renal fibrosis. It is a huge health crisis all over the world without any cure for it until now. JKSQ is a well-known TCM formula used clinically for CKD. JKSQ is used on the basis of warming the kidney and augmentation of deficiency, but the mechanisms of protection of renal fibrosis remain unknown. This study aims to completely understand the antifibrotic activity of JKSQ, as well as to seek out the active major parts and to learn about the parts and to see how their function plays in the PI3K/AKT signal pathway.

Methods: The chemical profile of JKSQ was characterized using UHPLC-Q-Exactive-Orbitrap-MS. Anti-fibrotic effects were assessed in a unilateral ureteral obstruction (UUO) rat model. Use network pharmacology and molecular docking to forecast active components, goals, and pathways. And the predicted one, the key component DIO, was proved both in vivo and in vitro. Fibrosis markers, inflammatory and oxidative stress indicators, and PI3K/AKT pathway activation were examined via histopathology, qRT-PCR, Western blotting, and ELISA. Pathway specificity was tested using the PI3K agonist 740Y-P.

Results: JKSQ administration significantly alleviated renal pathological damage, collagen deposition, and expression of fibrosis markers in UUO rats, while also reducing inflammation and oxidative stress. Network pharmacology and molecular docking results show that the PI3K/AKT pathway plays an important role, with AKT1, IL-6, TNF, and TP53 as core targets, and DIO exhibiting the strongest binding affinity. Both JKSQ and DIO blocked PI3K/AKT activation in vivo and in vitro, and this was reversed by 740Y-P, confirming pathway dependency.

Conclusions: JKSQ mostly stops kidney fibrosis from growing by messing with the PI3K/AKT signal pathway. The UHPLC-MS shows quite a lot of bioactivity segments were there in JKSQ; one majorly active element found was diosgenin when it was connected to this anti-fibrotic activity. These findings clarify the material basis and mechanism of JKSQ, providing a scientific rationale for its potential use in the clinical management of renal fibrosis.

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