Ajuga bracteosa Exerts Antihypertensive Activity in l-NAME-Induced Hypertension Possibly through Modulation of Oxidative Stress, Proinflammatory Cytokines, and the Nitric Oxide/Cyclic Guanosine Monophosphate Pathway

Abstract

Ajuga bracteosa has been used in traditional medicine to treat hypertension and other ailments. The present study has been designed to investigate the beneficial effects of A. bracteosa in l -nitro arginine methyl ester ( l -NAME)-induced hypertensive rats. Hypertension was induced by intraperitoneal injection of l -NAME (185 μmol kg –1 i.p.). The aqueous methanol extract of A. bracteosa (AMEAB, 250 and 500 mg kg –1 ) and coumarin (30 and 70 mg kg –1 ) were administered orally from day 8 to day 35 of the study. In vivo antihypertensive activity was assessed by measuring the blood pressure using a PowerLab data system. The effects of the AMEAB and coumarin on nitric oxide (NO), cyclic guanosine monophosphate (cGMP), interleukin-6 (IL-6), the tumor necrosis factor (TNF-α), and oxidative stress markers were also assessed using kit methods. Phytochemical profiling of the AMEAB was carried out through high-performance liquid chromatography (HPLC) where quercetin, gallic acid, caffeic acid, vanillic acid, benzoic acid, syringic acid, p -coumaric acid, and ferulic acid were labeled as plant constituents including coumarin. The AMEAB and coumarin significantly reduced blood pressure at the tested doses of 500 and 70 mg kg –1 , respectively. Serum levels of NO and cGMP were found to be significantly increased in AMEAB- and coumarin-treated groups when compared with only l -NAME-challenged rats. In addition, a marked decrease was noticed in the serum concentrations of proinflammatory cytokines (IL-6 and TNF-α) in AMEAB- and coumarin-treated rats. Moreover, in AMEAB- and coumarin-treated animals, a noticeable improvement was observed in the levels of antioxidant enzymes including catalase, superoxide dismutase, and malonaldehyde, and the total oxidant status when compared with those of only l -NAME-challenged rats. The data of real-time polymerase chain reaction (RT-PCR) experiments supported that the antihypertensive and anti-inflammatory activities of the AMEAB and coumarin are possibly mediated through modulation of endothelial nitric oxide synthase (eNOS), angiotensin-converting enzyme (ACE), nuclear factor (NF)-kB, and COX-2 gene expressions. This study concludes that A. bracteosa possesses an antihypertensive effect mediated through the modulation of the antioxidant, anti-inflammatory, and NO/cGMP pathways, thus providing a rationale to the antihypertensive use of A. bracteosa in traditional medicine.

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“…Several studies have validated the fact that L-NAME, when chronically administered to rats, induces arterial hypertension which is related with nitric oxide (NO) insufficiency [22] , [53] , [58] , [59] . This was corroborated by our results which show increases in the arterial blood pressure of the experimental rats after L-NAME administration.…”

High-fat, high-carbohydrate diet-induced prediabetes preconception in Sprague–Dawley rats as a risk factor for the development of preeclampsia: assessing changes in placental metabolic insults

“…As expected, at the end of the experimental period, NO concentration in PE animals was lower than in the NPD animals. This is due to the reduction of eNOS activity by L-NAME, thus reducing NO production and bioavailability and promoting and maintaining vasoconstriction ( 49 ). At the end of the experimental period, NO concentration in PE animals was lower than in the PD animals, suggesting that the intermediate hyperglycemia may have not exhausted the eNOS enzymes, thus stimulating the production of NO.…”

The efficacy of natural products for the treatment of nasopharyngeal carcinoma

“…Ajuga bracteosa , belonging to the family Lamiaceae/Labiatae, is distributed in subtropical regions. A. bracteosa has diverse health benefits in malaria, rheumatism, amenorrhea, and gout (Shaukat et al., 2022). Exposure to aqueous extract of A .…”