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

ABSTRACT

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 mg) was administered to assess acute toxicity. Then, a pilot study was conducted in 11 subjects using the sequence of placebo and Polygonum for 2 weeks each. The dose of Polygonum was increased sequentially (200–2000 mg/day). Home blood pressure and pulse rate were monitored.

Results: Oral administration of Polygonum (4000 mg) did not cause any adverse events. In the dose-escalation phase, evening systolic blood pressure was significantly decreased at 800 mg, 2000 mg doses post-treatment (p < 0.05, and p < 0.05, respectively). Depressor responders to Polygonum intake had significantly higher salt intake in spot urine (p < 0.05). 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.

KEYWORDS:

• Chymase
• polygonum hydropiper L
• angiotensin II
• blood pressure
• hypertension
• serine endopeptidase

Acknowledgments

We thank Mrs. Harumi Arimura, Mrs. Nao Totake, Mrs. Rieko Yoshida, Mrs. Yoko Tagomori and Mrs. Satomi Uchida for their excellent technical assistance.

Disclosure Statement

The authors received financial support from Biotechnology and Food Research Institute Fukuoka Industrial Technology Center and Nutrition for Life Association (120240FR, 130513MJ, 13-P13). The authors are responsible for the content and writing of the paper.

Additional information

Funding

This work was supported by the Nutrition for Life Association [120240FR, 130513MJ, 13-P13];This research was done with support of Nutrition for Life Association.