Abstract
Background
Methods
Results
Conclusion
mSMS exhibits potent antihypertensive effects through the inhibition of the RhoA/Rho-kinase pathway, reduction of vascular remodeling, oxidative stress, and renal protection. These findings support the potential of mSMS as a novel therapeutic agent for hypertension, offering a multi-targeted approach with fewer side effects compared to conventional therapies. Further clinical studies are required to confirm its clinical efficacy.
Introduction
Hypertension, also known as high blood pressure, affects over 1 billion people worldwide. Hypertension is a major risk factor for cardiovascular diseases, stroke, and kidney failure, contributing significantly to morbidity and mortality rates globally1. In the United States, nearly half of adults are affected or treated for hypertension2. Current antihypertensive medications include diuretics, beta-blockers, ACE inhibitors, Angiotensin II receptor blockers (ARBs) and calcium channel inhibitors (CCIs). However, most of these drugs are associated with various side effects and limitations3, 4. Therefore, herbal medicines are gaining attention for their potential antihypertensive properties, due to the fewer side effects and multi-targeted nature5. Emerging research has shown that certain herbal compounds can effectively reduce blood pressure and improve overall cardiovascular health, making them a promising adjunct or alternative to conventional antihypertensive drugs6, 7, 8, 9.
The small guanosine triphosphatase (GTP) binding protein Ras homolog family member A (RhoA) and its downstream effector Rho-kinase play an important role in smooth muscle contraction by agonist-induced Ca2+-sensitization10. Activated RhoA increases the Ca2+ sensitivity of both MLC phosphorylation and contraction in smooth muscle11. Activation of Rho-kinase decreases the activity of myosin light-chain phosphatase (MLCP) through phosphorylation of myosin phosphatase targeting subunit 1 (MYPT1) at Thr855 and protein kinase C (PKC)-potentiated inhibitory protein for heterotrimeric MLCP of 17 kDa (CPI17) at Thr38, enhancing vascular contractility12. Because of this key role in vascular smooth muscle contraction13, RhoA/Rho-kinase pathway is a promising target for novel antihypertensive strategies.
This study focuses on the antihypertensive potential of a modified version of an herbal medicine decoction named Saengmaeksan (mSMS). We conducted a series of experiments including organ bath studies, mouse studies using the NG nitro L-arginine methyl ester (L-NAME) model14, and studies on spontaneously hypertensive rats (SHR)15. Also, organ bath studies were designed to investigate the direct effects of mSMS on vascular smooth muscle tone. We also compared the effect of mSMS with currently prescribed hypertension drugs such as amlodipine and losartan. Our results provide evidence of the efficacy and potential mechanisms of mSMS as a novel antihypertensive agent.
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Young Mi Seok, Hye-Lin Kim, Hyo In Kim, Hobin Moon, Yohan Han, Eun Sang Cho, Hyun Hee Leem, Hyo Jung Kim, Sujin Shin, Se-Jin Kim, Jin Ki Jung, Wei Huang, Kyung Oh Jung, Doo Suk Lee, Sung Giu Jin, Hyunwoo Kim, Changsop Yang, Kyungjin Lee, Jinbong Park, Modified Saengmaeksan, an herbal formula containing six herbs, improves hypertension through RhoA/Rho kinase-mediated vasorelaxation, Integrative Medicine Research, 2025, 101207, ISSN 2213-4220, https://doi.org/10.1016/j.imr.2025.101207.
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