Mechanism of Bazi Bushen Capsule in Delaying the Senescence of Mesenchymal Stem Cells Based on Network Pharmacology and Experimental Validation

Overview

Journal Heliyon

Specialty Social Sciences

Date 2024 Mar 21

PMID 38509951

Authors

Yaping Zhang

Tongxing Wang

Yanfei Song

Meng Chen

Bin Hou

Bing Yao

Kun Ma

Yahui Song

Siwei Wang

Dan Zhang

Junqing Liang

Cong Wei

Affiliations

Soon will be listed here.

Abstract

Aims: To investigate the effects of Bazi Bushen capsule (BZBS) on the senescence of mesenchymal stem cells (MSCs) and explore its mechanism of action.

Methods: Network pharmacology was used to predict the targets of BZBS in delaying senescence in MSCs. For studies, MSCs were treated with D-gal, BZBS, and NMN, and cell viability, cell senescence, stemness-related genes, and cell cycle were studied using cell counting kit-8 (CCK-8) assay, SA-β-galactosidase (SA-β-gal) staining, Quantitative Real-Time PCR (qPCR) and flow cytometry (FCM), respectively. Alkaline phosphatase (ALP), alizarin red, and oil red staining were used to determine the osteogenic and lipid differentiation abilities of MSCs. Finally, the expression of senescence-related genes and cyclin-related factors was detected by qPCR and western blotting.

Results: Network pharmacological analysis suggested that BZBS delayed cell senescence by interfering in the cell cycle. Our studies suggested that BZBS could significantly increase cell viability (P < 0.01), decrease the quantity of β-galactosidase cells (P < 0.01), downregulate p16 and p21 (P < 0.05, P < 0.01), improve adipogenic and osteogenic differentiation, and upregulate , and genes (P < 0.05, P < 0.01) in senescent MSCs. Moreover, BZBS significantly reduced the proportion of senescent MSCs in the G/G phase (P < 0.01) and enhanced the expression of CDK4, Cyclin D1, and E2F1 (P < 0.05, P < 0.01, respectively). Upon treatment with HY-50767A, a CDK4 inhibitor, the upregulation of E2F1 was no longer observed in the BZBS group.

Conclusions: BZBS can protect MSCs against D-gal-induced senescence, which may be associated with cell cycle regulation via the Cyclin D1/CDK4/E2F1 signalling pathway.

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