Research Paper Volume 16, Issue 4 pp 3773—3789
Yangyinghuoxue decoction exerts a treatment effect on hepatic fibrosis by PI3K/AKT pathway in rat model: based on the network pharmacology and molecular docking
- 1 School of Traditional Chinese Medicine, Ningxia Medical University, Yinchuan 750004, China
- 2 Yinchuan Hospital of Traditional Chinese Medicine, Ningxia Medical University, Yinchuan 750001, China
- 3 Ningxia Regional Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of High Incidence, Ningxia Medical University, Yinchuan 750004, China
Received: January 17, 2023 Accepted: December 22, 2023 Published: February 15, 2024
https://doi.org/10.18632/aging.205559How to Cite
Copyright: © 2024 Bai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: Yangyinghuoxue decoction (YYHXD) is a Traditional Chinese medicine (TCM) compound with satisfactory clinical efficacy in the treatment of hepatic fibrosis (HF). However, the pharmacological molecular mechanisms of YYHXD in the treatment of hepatic fibrosis have not yet been clarified.
Objective: To determine the pharmacological mechanisms of YYHXD for the treatment of hepatic fibrosis via network pharmacology analysis combined with experimental verification.
Methods: First, the bioactive ingredients and potential targets of YYHXD and HF-related targets were retrieved from the online databases and literatures. Next, the “herb-ingredient-target-disease” network and PPI network were constructed for topological analyses and key active compounds and targets screening. Enrichment analyses were performed to identify the critical biological processes and signaling pathways. Then, the molecular docking experiment was performed to initially validate the network pharmacology prediction results. Finally, the antifibrotic effect and pharmacological mechanisms of YYHXD were investigated in CCl4 induced liver fibrosis in rats.
Results: In total, 141 active compounds in YYHXD, 637 YYHXD-related targets and 1598 liver fibrosis-related targets were identified. Among them, 69 overlapped targets were finally obtained. Network analysis screened 5 critical bioactive components and 34 key targets. Functional enrichment analysis indicated that YYHXD obviously influenced biological processes such as oxidative stress, cellular inflammation and hepatocyte apoptosis and signaling pathways such as PI3K-Akt, Apoptosis, and JAK-STAT in the treatment of HF. The molecular docking results suggested that the YYHXD may have a direct impact on the PI3K-Akt signaling pathway. Further, in vivo experiment indicated that YYHXD treatment not only reduced liver injury and protected liver function, but also decrease the apoptosis of hepatic parenchyma cells, reducing inflammatory and attenuating oxidative stress. Moreover, YYHXD significantly attenuated the upregulation of target proteins enriched in PI3K signaling pathway, including P-PI3K, P-Akt1, HSP90, MYC, p53.
Conclusions: The mechanisms of YYHXD against liver fibrosis were involved in multiple ingredients, multiple targets and multiple signaling pathways. The PI3K/Akt pathway could be the most important pharmacological mechanism of YYHXD therapy for liver fibrosis.