Xiangli Tong1,
Lu Zhang2,
Jie Zhu2,
Zegeng Li1,3 
1Respiratory Medicine, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, China;
2Anhui University of Traditional Chinese Medicine, Hefei, China;
3Institute of Traditional Chinese Medicine (TCM) Respiratory Disease Prevention and Treatment, Anhui Academy of TCM, Hefei, China.
For correspondence:- Zegeng Li
Email: Li6609@126.com Tel:+8655162850171
Accepted: 28 July 2023
Published: 31 August 2023
Citation:
Tong X, Zhang L, Zhu J, Li Z.
Qibai Pingfei capsule induces apoptosis of pulmonary artery smooth muscle cells in hypoxic rats by regulating PI3K/AKT/mitochondrial signaling pathway. Trop J Pharm Res 2023; 22(8):1587-1595
doi:
10.4314/tjpr.v22i8.9
© 2023 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..
Abstract
Purpose: To investigate the effect of Qibai Pingfei capsules (QBPF) medicated serum on the apoptosis of rat pulmonary artery smooth muscle cells (PASMC) in hypoxic rats, and to determine the relationship between that effect and PI3K/Akt/mitochondrial apoptosis pathway.
Methods: Rat PASMCs were isolated, cultured, and the optimal hypoxic time and concentration of QBPF were determined by CCK-8 method. Hypoxic rats were treated with QBPF, QBPF + LY294002, or QBPF + SC79. Apoptosis and mitochondrial membrane potential were assessed using Annexin V-FITC/PI, Hoechst 33258, and Rho123 staining. The protein expression levels of AKT, P-AKT, and apoptosis-related proteins were evaluated via western blot.
Results: CCK-8 studies showed that the optimal hypoxic time was 24 h, while the optimal concentration of QBPF was 20 %. Annexin V-FITC/PI double staining and Hoechst 33258 assay revealed that QBPF significantly promoted the apoptosis of PASMCs in hypoxic rats (p < 0.05). Rho123 test results showed that QBPF inhibited mitochondrial membrane potential level in hypoxic rats' PASMCs, which was enhanced by PI3K inhibitor LY29002 and inhibited by AKT agonist SC79 (p < 0.05). Western blot showed that QBPF reduced the protein level of P-AKT and Bcl-2, and raised the protein levels of Bad, Bax, CytC, casepase-9 and casepase-3, which was enhanced by LY29002 and blocked by SC79 (p < 0.05). No major changes in AKT protein expression were seen between the groups.
Conclusion: In hypoxic rats, QBPF blocks PI3K/AKT signaling pathway and regulates the activation of downstream Bcl-2 family members, thus activating mitochondrial apoptosis pathway and triggering PASMC death.
Keywords: Qibai Pingfei capsule, PI3K/AKT, Pulmonary artery smooth muscle cells (PASMC), Apoptosis
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