Protective effects of the Terminalia bellirica tannin-induced Nrf2/HO-1 signaling pathway in rats with high-altitude pulmonary hypertension.

Abstract

BACKGROUND:

Oxidative stress and endothelial cell dysfunction induced by high-altitude hypoxia have important roles in the pathological process of high-altitude pulmonary hypertension (HAPH). Tannins present in Terminalia bellirica (Gaertn.) Roxb. (TTR) have pharmacological activities that produce oxidation resistance and exert anti-inflammatory effects. Whether TTR exerts a protective effect on HAPH remains unknown.

METHODS:

A rat model of HAPH was established. The mean pulmonary arterial pressure (mPAP) of the animals was measured, the serum levels of SOD, MDA, and GSH-Px were measured using ELISA, and the expression of Bax, Bcl-2, Nrf2, and HO-1 proteins in the lung tissue of each group of rats was measured using Western blotting. Pathological changes in the lung tissue were also observed. A model of damage to H2O2-induced pulmonary artery endothelial cells (PAECs) was generated, and cell proliferation was measured using CCK-8 assays. Flow cytometry was used to measure ROS levels in PAECs. Western blotting was used to detect the expression of Bax, Bcl-2, Nrf2, and HO-1 proteins in PAECs.

RESULTS:

The hemodynamic and pathologic findings showed that the mPAP of HAPH rats increased markedly, and the vascular wall thickness increased (P < 0.05). TTR reduced mPAP, alleviated or slowed pulmonary arterial remodeling, increased GSH-Px and SOD activity, lowered the level of MDA (P < 0.05), and downregulated the expression of Bax in the lung tissues of HAPH rats, while the expression of Bcl-2, Nrf2, and HO-1 was upregulated (P < 0.05). The results of the cell experiments showed that TTR inhibited H2O2-induced PAEC apoptosis and ROS production (P < 0.05), downregulated the expression of Bax in PAECs, and upregulated the expression of Bcl-2, Nrf2, and HO-1 (P < 0.05).

CONCLUSION:

The results suggest that TTR reduces pulmonary arterial pressure, decreases oxidative stress during HAPH, and exerts protective effects in rats with HAPH and that its mechanism of action is related to regulation of the Nrf2/HO-1 signaling pathway.

• Authors: Salamaiti Aimaier, Yang Tao, Fang Lei, Zhang Yupeng, Shi Wenhui, Ainiwaer Aikemu, Dilinuer Maimaitiyiming
• Journal: BMC complementary medicine and therapies (BMC Complement Med Ther) Vol. 23 Issue 1 Pg. 150 (May 06 2023) ISSN: 2662-7671 [Electronic] England
• PMID: 37149589 (Publication Type: Journal Article)
• Copyright: © 2023. The Author(s).

Chemical References

• bcl-2-Associated X Protein
• Hydrogen Peroxide
• NF-E2-Related Factor 2
• Proto-Oncogene Proteins c-bcl-2
• Reactive Oxygen Species
• Superoxide Dismutase
• Tannins

Topics

• Animals
• Rats
• Altitude
• Altitude Sickness
• bcl-2-Associated X Protein
• Endothelial Cells (metabolism)
• Hydrogen Peroxide (adverse effects)
• Hypertension, Pulmonary (drug therapy)
• NF-E2-Related Factor 2 (metabolism)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Reactive Oxygen Species (metabolism)
• Signal Transduction
• Superoxide Dismutase (metabolism)
• Tannins (pharmacology)
• Terminalia