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Evolvulus alsinoides L. (Sankhaholi) has been traditionally used in Unani (Greco-Arabic) medicine to treat diverse cardiovascular disorders. Notably, preclinical and clinical investigations have substantiated its remarkable potential as an antihypertensive agent. The aim of this study was to compare the efficacy of hydroalcoholic extract of Evolvulus alsinoides L. and ramipril in treating hypertension using a higher dose of the test drug within the recommended limit. In this open-label randomized controlled trial, 57 participants (29 in the test group, 28 in the control group) completed the 42-day study. The test group received 630 mg of dried hydro-alcoholic extract of Evolvulus alsinoides L. in capsule form orally once daily, while the control group received 5 mg of Ramipril orally once daily. Participants in both groups were advised to adhere to the Dietary Approaches to Stop Hypertension (DASH) eating plan in terms of diet and lifestyle adjustments recommended by JNC-8. The primary outcome measures were changes in systolic and diastolic blood pressure as well as changes in plasma levels of hsCRP and IL6. Secondary outcome measures included changes in symptoms such as palpitations, giddiness, headaches, fatigue and shortness of breath. Headaches, palpitations, and giddiness were assessed using a customized Visual Analog Scale (VAS) graded as "none," "mild," "moderate," and "severe". Fatigue was assessed on a binary scale as either absent or present, and dyspnea was assessed using the modified Medical Research Council (mMRC) scale for breathlessness. Both primary and secondary outcomes were assessed at baseline and each follow-up visit (2nd week, 4th week, and 6th week) until the completion of the trial. At the end of the trial, the mean differences for the primary outcomes were as follows:SBP: − 1.88 95 % C I : − 4.82 , 1.05 , p = 0.203 , d = 0.33 , DBP: − 2.83 95 % C I : − 4.67 , − 0.10 , p = 0.003 , d = 0.8 , hsCRP: − 1.40 95 % C I : − 2.80 , − 0.003 , p = 0.49 , d = 0.53 , and IL6: − 88.67 95 % C I : − 148.90 , − 28.43 , p = 0.005 , d = 0.78 . No statistically significant differences were observed between the two groups for any of the secondary outcomes. Based on the preliminary results, it can be inferred that the hydro-alcoholic extract of Evolvulus alsinoides L. exhibits significant antihypertensive potential, comparable to that of ramipril. Furthermore, it appears that Evolvulus alsinoides L. may be more effective than ramipril in reducing the biochemical markers of inflammation associated with primary hypertension. However, additional research is required to validate these findings. [Display omitted] • Evolvulus alsinoides L. (Sankhaholi) is used in Unani medicine for treating various cardiovascular conditions. • The study evaluates Evolvulus alsinoides L. extract for primary hypertension, using a higher dose within recommended limits. • Test group received 630 mg of E. alsinoides extract, while control group took 5 mg of Ramipril, both once daily for 42 days. • Study concludes hydroalcoholic extract of E. alsinoides has significant antihypertensive potential, comparable to Ramipril. [ABSTRACT FROM AUTHOR]