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Effect of asiatic acid on the Ang II-AT1R-NADPH oxidase-NF-κB pathway in renovascular hypertensive rats

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Abstract

Asiatic acid, a triterpenoid compound derived from Centella asiatica, has been demonstrated to have antioxidant and anti-inflammatory effects. The present study evaluated the effects of asiatic acid on hemodynamic alterations, renin-angiotensin system (RAS), oxidative stress, and inflammation in 2K-1C hypertensive rats. Renovascular hypertension was induced in male Sprague-Dawley rats and treated with vehicle, asiatic acid (30 mg/kg/day), or captopril (5 mg/kg/day) for 4 weeks. We observed that 2K-1C hypertensive rats exhibited hemodynamic alterations such as high blood pressure, heart rate, hindlimb vascular resistance, and low hindlimb blood flow. Signs of RAS activation, such as increased plasma angiotensin II and serum angiotensin-converting enzyme activity, enhanced AT1R protein expression, and suppressed AT2R expression was observed in 2K-1C hypertensive rats. Overproduction of vascular superoxide, high levels of plasma MDA, low levels of plasma nitric oxide metabolites (NOx), and upregulation of gp91phox protein expression were observed in hypertensive rats. Furthermore, inflammation was observed in hypertensive rats, as evidenced by increased plasma TNF-α, NF-κB, and phospho-NF-κB protein expression. Asiatic acid or captopril alleviated hemodynamic alterations, RAS activation, oxidative stress, and inflammation in 2K-1C hypertensive rats. These findings indicate that asiatic acid is an antihypertensive agent that ameliorates hemodynamic alterations in 2K-1C hypertensive rats. This effect may involve one or both of the following mechanisms: the direct effect of asiatic acid on RAS activation, oxidative stress and inflammation, and/or asiatic acid acting as an ACE inhibitor agent to inhibit the Ang II-AT1R-NADPH oxidase-NF-κB pathway.

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Acknowledgments

This study was funded by grants from the Invitation Research Fund (IN58342, IN59145), Faculty of Medicine, Khon Kaen University and from Khon Kaen University (590050), Thailand and the Thailand Research Fund (RSA6080005). Putcharawipa Maneesai is financially supported by the Cardiovascular Research Group, Khon Kaen University, Thailand. We would like to acknowledge Dr. Justin Thomas Reese for editing this manuscript via the Publication Clinic, KKU, Thailand.

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Authors and Affiliations

  1. Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand

    Putcharawipa Maneesai, Upa Kukongviriyapan & Poungrat Pakdeechote

  2. Cardiovascular Research Group, Khon Kaen University, Khon Kaen, 40002, Thailand

    Putcharawipa Maneesai, Upa Kukongviriyapan, Parichat Prachaney & Poungrat Pakdeechote

  3. Faculty of Medicine, Mahasarakham University, Maha Sarakham, 44000, Thailand

    Sarawoot Bunbupha

  4. Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand

    Laddawan Senggunprai & Veerapol Kukongviriyapan

  5. Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand

    Parichat Prachaney

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  1. Putcharawipa Maneesai
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Maneesai, P., Bunbupha, S., Kukongviriyapan, U. et al. Effect of asiatic acid on the Ang II-AT1R-NADPH oxidase-NF-κB pathway in renovascular hypertensive rats. Naunyn-Schmiedeberg's Arch Pharmacol 390, 1073–1083 (2017). https://doi.org/10.1007/s00210-017-1408-x

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