Prospective single-arm observational study of human chymase inhibitor Polygonum hydropiper L in subjects with hypertension

摘要

Background and Purpose: Human chymase (h-chymase) is a serine protease that forms local angiotensin II and has been proven to be related to onset of hypertension, arteriosclerosis, and post myocardial infarction cardiac remodeling. Since no chymase inhibitor was clinically available, an extensive screening for inhibition of h-chymase in three different extracts (water, hot water,?and ethanol) of approximately 800 food ingredients had been performed and we identified Polygonum hydropiper L (Polygonum). Using a dried and powdered Polygonum, we conducted a prospective, single-arm, pilot study to investigate its safety and antihypertensive effect in subjects with normal high blood pressure to moderate hypertension.Methods: First, a single oral dose of Polygonum powder (4000爉g) was administered to assess acute toxicity. Then, a pilot study was conducted in 11 subjects using the sequence of placebo and Polygonum for 2爓eeks each. The dose of Polygonum was increased sequentially (2002000爉g/day). Home blood pressure and pulse rate were monitored.Results: Oral administration of Polygonum (4000爉g) did not cause any adverse events. In the dose-escalation phase, evening systolic blood pressure was significantly decreased at 800爉g, 2000爉g doses post-treatment (p??.05, and p??.05, respectively). Depressor responders to Polygonum intake had significantly higher salt intake in spot urine (p??.05). No adverse events or reactions occurred.Conclusion: This was the first investigation that an h-chymase inhibitory Polygonum intake for safety and tolerability was proven and, in addition, chymase inhibitory Polygonum appeared to have depressor effect especially in a hypertensive subject with excessive salt intake.