Complementary Antihypertensive Mechanisms of the Tianma-Gouteng Herb Pair Targeting the Endothelium and Smooth Muscle: Emphasizing Endothelial Protection by Tianma Involving the PGR-Associated PI3K/Akt/eNOS Pathway.

Authors

Di Liu, Yuzhuo Wu, Yu Zhang, Yan Chen, Yan Wang, Yanling Qiao, Yuhang Sun, Xiaokui Huo, Xiaochi Ma, Xin Zhao

Published in

Journal of ethnopharmacology. Pages 122483. Oct 05, 2026. Epub Oct 05, 2026.

Abstract

The herb pair Tianma (Gastrodia elata Blume, TM) and Gouteng (Uncaria rhynchophylla (Miq.) Miq., GT) has long been used in traditional Chinese medicine to treat hypertension. However, their combined antihypertensive (anti-HTN) mechanisms remain unclear.
To elucidate the complementary anti-HTN mechanisms of TM-GT, with a particular focus on the endothelial protective effects of TM.
The anti-HTN and vascular protective effects of TM-GT were evaluated in L-NAME-induced hypertensive mice, H₂O₂-injured EA.hy926 endothelial cells, and Ang II-stimulated primary vascular smooth muscle cells (VSMC). Vascular remodeling, endothelial integrity, smooth muscle phenotype, NO/redox balance, mitochondrial function, transcriptomic profiling, PI3K inhibition, and PGR knockdown were used to investigate the underlying mechanisms. The core chemical compounds of TM-GT were characterized using UHPLC-Q-TOF-MS/MS.
TM-GT reduced blood pressure, improved circulating NO-related bioavailability and SOD levels, and decreased Ang II and ET-1, accompanied by attenuated medial thickening. Furthermore, TM preferentially restored endothelial coverage and function, whereas GT preserved medial α-SMA and mitigated VSMC phenotypic switching, suggesting compartment-specific actions. Transcriptomic analysis implicated a PGR-associated PI3K/Akt/eNOS pathway in TM-mediated endothelial protection. Both PI3K inhibition and PGR knockdown significantly attenuated TM-induced improvements in endothelial viability, NO production, migration, mitochondrial integrity, and eNOS phosphorylation. Parishin A was identified as a candidate TM-derived constituent linked to this axis.
TM preferentially protects the endothelial compartment, at least partly in association with the PGR-associated PI3K/Akt/eNOS signaling axis. In contrast, GT stabilizes contractile vascular smooth muscle cells (VSMC) and mitigates medial remodeling. These effects support the traditional use of this herbal pair in treating hypertension-related vascular disorders.

PMID:
42833368
Bibliographic data and abstract were imported from PubMed on 06 Oct 2026.

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