Yam Mun Fei, Tew Wan Yin, Tan Chu Shan, Loh Hui Wei, Qiu Qiyue, Yan Chong Seng, Xu Xiangyang, Ouyang Liyun, Zhou Ruixian, Yap Yau Pin, Xu Wei, Xu Wen, Teh Lai Kuan
College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China.
Department of Chinese Medicine, M. Kandiah Faculty of Medicine & Health Sciences, Universiti Tunku Abdul Rahman, Kajang, Selangor, Malaysia.
Hypertens Res. 2025 Sep 18. doi: 10.1038/s41440-025-02298-6.
Orthosiphon stamineus Benth, commonly used in Southeast Asia for its medicinal properties, is traditionally employed to treat diabetes and hypertension. Scientific research has validated that O. stamineus extract exhibits significant vasodilatory action on rat aorta. This effect is primarily due to the synergistic interaction among key compounds: eupatorin, sinensetin and 3'-hydroxy-5,6,7,4'-tetramethoxyflavone (TMF). Our previous publication identified the optimum formulation, G28, which contains eupatorin, sinensetin and TMF in the ratio of EC:EC:EC. Therefore, the aim of this study was to investigate the antihypertensive effect and mechanism of action of formulation G28. In this study, aortic rings from spontaneously hypertensive rats (SHRs) and Sprague-Dawley (SD) rats were used to examine the vasodilation mechanisms. The antihypertensive effect of G28 was also assessed through repeated-dose administration in SHRs. G28 exhibited stronger vasorelaxant effects in SHR versus SD rat aortic rings, indicating higher potency under hypertensive conditions. The effect was partially endothelium-dependent, as endothelium removal reduced responses in both aortic rings. G28 retained efficacy with Nω-Nitro-1-arginine methyl ester, methylene blue and 1H-[1,2,4]Ox-adiazolol[4,3-α]quinoxaline-1-one, suggesting involvement of the NO/sGC/cGMP pathway. Additionally, G28's effect diminished with glibenclamide, barium chloride, 4-aminopyrine and tetraethylammonium, indicating potassium channel involvements. The vasorelaxant effect was not significantly altered by indomethacin, atropine, or propranolol (in SD rats only), suggesting independence from the cyclooxygenase, beta-adrenergic (in SD rats only) and muscarinic pathways. G28 also reduced intracellular Ca²⁺ in vascular smooth muscle by antagonising voltage-gated calcium channel and Inositol triphosphate receptor. In vivo, G28 significantly reduced blood pressure in SHRs over 21 days of oral administration, underscoring its potential for hypertension control. G28 shows strong antihypertensive effects via NO/sGC/cGMP, potassium and calcium channels. Its sustained blood pressure reduction in SHRs highlights potential as a promising hypertension treatment option.
猫须草（Orthosiphon stamineus Benth）在东南亚因其药用特性而被广泛使用，传统上用于治疗糖尿病和高血压。科学研究证实，猫须草提取物对大鼠主动脉具有显著的血管舒张作用。这种作用主要归因于关键化合物之间的协同相互作用：泽兰黄酮、华良姜素和3'-羟基-5,6,7,4'-四甲氧基黄酮（TMF）。我们之前的出版物确定了最佳配方G28，其含有泽兰黄酮、华良姜素和TMF，比例为EC:EC:EC。因此，本研究的目的是研究配方G28的降压作用及其作用机制。在本研究中，使用自发性高血压大鼠（SHR）和Sprague-Dawley（SD）大鼠的主动脉环来研究血管舒张机制。还通过在SHR中重复给药来评估G28的降压作用。与SD大鼠主动脉环相比，G28在SHR中表现出更强的血管舒张作用，表明在高血压条件下具有更高的效力。这种作用部分依赖于内皮，因为去除内皮会降低两个主动脉环的反应。G28在使用Nω-硝基-1-精氨酸甲酯、亚甲蓝和1H-[1,2,4]恶二唑并[4,3-α]喹喔啉-1-酮时仍保持疗效，表明涉及NO/sGC/cGMP途径。此外，G28的作用在使用格列本脲、氯化钡、4-氨基吡啶和四乙铵时减弱，表明涉及钾通道。吲哚美辛、阿托品或普萘洛尔（仅在SD大鼠中）对血管舒张作用没有显著影响，表明其独立于环氧化酶、β-肾上腺素能（仅在SD大鼠中）和毒蕈碱途径。G28还通过拮抗电压门控钙通道和肌醇三磷酸受体来降低血管平滑肌细胞内的Ca²⁺。在体内，口服G28 21天可显著降低SHR的血压，突出了其控制高血压的潜力。G28通过NO/sGC/cGMP、钾和钙通道显示出强大的降压作用。其在SHR中持续降低血压突出了其作为一种有前景的高血压治疗选择的潜力。
