Modified Saengmaeksan, an herbal formula containing six herbs, improves hypertension through RhoA/Rho kinase-mediated vasorelaxation

Background: Saengmaeksan is a traditional herbal formula used in Korean medicine. We composed a modified formula based on Saengmaeksan (mSMS) with Puerariae Radix, Platycodonis Radix, Liriopis seu Ophiopogonis Tuber, Schisandrae Fructus, Coicis Semen, and Dioscoreae Rhizoma to investigate its in vivo and ex vivo antihypertensive effects and underlying mechanisms. Methods: The antihypertensive efficacy of mSMS was assessed using L-NAME-induced hypertensive mice and spontaneously hypertensive rats (SHR). The animals were treated with mSMS, and blood pressure was monitored weekly. Vascular effects were evaluated through organ bath studies and aortic histology, while oxidative stress was assessed using DCF-DA staining. Renal protection was examined via H&E and immunofluorescence staining for AT1R expression. The molecular mechanisms were explored through Western blot analysis and GTP-RhoA assays. Results: mSMS significantly reduced systolic and diastolic blood pressure in both hypertensive models, with the ethanol extract demonstrating superior efficacy. mSMS inhibited the RhoA/Rho kinase pathway, leading to reduced phosphorylation of MYPT1 and CPI17, and improved vascular relaxation. Additionally, mSMS attenuated aortic wall thickening, oxidative stress, and renal damage, with a marked decrease in AT1R expression in the kidneys. Conclusions: 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.