ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Anjiang Formula Inhibits PVN Microglial Activation and Lowers Blood Pressure by Targeting RhoA/ROCK2 Pathway: A Retrospective Clinical and Experimental Study
Xuanjing Chen 1
Jun Chen 1
Zhenglin Chen 2
Dwei Lian 2
Jing Wang 1
Jin Luo 2
Meizu Wu 2
Aling Shen 3
Lianfa Chen 3
1. Traditional Chinese Hospital of Xiamen, Xiamen, China
2. Fujian University of Traditional Chinese Medicine, Fuzhou, China
3. Department of Hepatopathy, Xiamen Tong'an Hospital of Traditional Chinese Medicine, Xiamen, China
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Abstract
Background: Neuroinflammation in the hypothalamic paraventricular nucleus (PVN) drives sympathetic overactivity in hypertension. The Anjiang Formula (AJ) shows clinical antihypertensive potential; however, the precise molecular targets mediating its central neuroprotective effects remain undefined. Methods: In this translational study, we investigated the clinical efficacy of AJ and tested the hypothesis that it directly inhibits the central RhoA/ROCK2 signaling axis. We integrated a retrospective cohort analysis with mechanistic validation. Clinically, 85 elderly patients with Grade 1 essential hypertension were treated with AJ (n=43) or lifestyle control (n=42) for 8 weeks. Target engagement was verified using surface plasmon resonance (SPR), microscale thermophoresis (MST), and cellular thermal shift assays (CETSA). Mechanisms were validated in Spontaneously Hypertensive Rats (SHRs) and Angiotensin II-stimulated microglia. Results: Clinically, AJ reduced systolic blood pressure (SBP) by a mean difference of 10.2 mm Hg compared to controls (p<0.001), with a 93% responder rate. This was accompanied by improved flow-mediated dilation (+1.3%) and reduced serum IL-6. Biophysical assays identified Shinflavanone as a direct ROCK2 ligand (KD=20.0 nM; CETSA ΔTm=+5.2 °C). In SHRs, AJ lowered blood pressure and suppressed PVN microglial activation. In vitro, AJ inhibited the RhoA/ROCK2 cascade, downregulated JUN, and upregulated CREB1/NQO1, thereby reducing oxidative stress. These effects were abolished by the ROCK2 agonist lysophosphatidic acid. Conclusion: AJ provides antihypertensive efficacy in elderly patients. These benefits are mechanistically driven by Shinflavanone-mediated inhibition of ROCK2, which attenuates central neuroinflammation and restores redox homeostasis in the PVN.
Summary
Keywords
microglial activation, Neuroinflammation, Oxidative Stress, paraventricular nucleus, ROCK2 signaling, translational medicine, vascular remodeling
Received
24 January 2026
Accepted
10 February 2026
Copyright
© 2026 Chen, Chen, Chen, Lian, Wang, Luo, Wu, Shen and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Aling Shen; Lianfa Chen
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