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Ethnopharmacological Relevance: Ajuga iva (L.) Schreb. (Labiatae) (AI) is used in folk medicine for a variety of ailments, including diabetes mellitus and hypertension., Aim of the Study: In this work, we aimed to investigate the antihypertensive and vasorelaxant effects of AI aqueous extract in stroke prone spontaneously hypertensive rats (SHR-SP)., Material and Methods: Male SHR-SP rats were orally force-fed AI aqueous extract (500 mg/kg body weight) daily for one week. Systolic blood pressure and urine output were recorded in vivo by non-invasive methods. AI vasoactive effects on noradrenaline contractile response and acetylcholine-evoked relaxation were assessed ex vivo on aorta rings of treated and untreated SHR-SP rats. AI extract was then subjected to bio-guided fractionation using solvents of increasing polarity. For each fraction, in vitro vasorelaxation assay was performed on noradrenaline-precontracted aorta of Wistar rats, in the absence/presence of N-nitro-L-arginine (L-NNA). HPLC analysis of AI total extract, and the most in vitro active AI residual aqueous extract fraction (A1) was performed using naringin, naringenin, apigenin, apigenin 7-O-glucoside as marker compounds., Results: AI aqueous extract (500 mg/kg) significantly (P < 0.05) decreased systolic blood pressure (SBP) in SHR-SP rats, while not affecting the urine output. In ex vivo experiments, the total extract decreased contractile response to noradrenaline of aortic rings isolated from AI-treated SHR-SP rats with or without addition of N-nitro-L-arginine, but endothelium dependent relaxation evoked by acetylcholine in noradrenaline-contracted aortic rings was not affected by the extract treatment. In vitro experiments on AI aqueous extract fractions showed that its polar fraction was the only one affecting in vitro noradrenaline induced contractions, but only in an endothelium dependent manner. This fraction was shown by HPLC-UV to contain flavonoid glycosides among other polar compounds whose activity and mode of action may be modified in vivo by metabolization., Conclusion: These results support the use of AI as antihypertensive treatment in folk medicine. The systolic blood pressure decrease may be attributed at least in part to vasorelaxant glycosylated/polar phenolic compounds as flavonoids and/or their metabolites., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Ajuga iva (L.,) Schreb (A. iva). is a medicinal plant commonly used in Africa to treat several diseases such as diabetes, rheumatism, allergy, cancer, renal, metabolic disorders, cardiovascular disorders, digestive, and respiratory disorders., Aim of the Review: We highlighted previous reports on A. iva including its ethnopharmacological uses, the chemistry of its secondary metabolites, in vitro and in vivo pharmacological properties, and toxicological evidence., Materials and Methods: The data on A. iva were gathered using scientific research databases such as ScienceDirect, PubMed, SpringerLink, Web of Science, Scopus Wiley Online, and Google Scholar. In this review, studies focused on A. iva and its phytopharmacological activities were explored., Results: A. iva is used by many North African folk medicine practitioners especially against diabetes and immunological diseases. Our analysis of the previous reports confirmed the scientific evidence of A. iva ethnomedicinal uses, especially the antidiabetic and anti-hypercholesterolemia activity. However, there was no clear correlation between previous pharmacological reports on A. iva and its other ethnomedicinal uses in the treatment of rheumatism, allergy, metabolic, digestive, and respiratory disorders. The extracts and isolated compounds from A. iva exhibited numerous in vitro and in vivo pharmacological activities such as antidiabetic, antioxidant, antimicrobial, anti-hypercholesterolemia, insecticide, and litholitic effects. Chemical characterization using GC-MS, HPLC, and NMR revealed the presence of many chemical compounds such as 20-hydroxyecdysone, cyasterone, ajugasterone, apigenin dihexoside, apigenin, carvacrol, ecdysterone, palmitic acid in different parts of A. iva. These compounds belong to different classes of chemical compounds such as steroids, flavonoids, fatty acids, and terpenoids., Conclusions: A. iva extracts especially from the leaves showed significant antidiabetic, antioxidant, anti-hypercholesterolemia, and analgesic effects. Future studies are required to validate the results of clinical trials on A. iva antidiabetic, anti-hypercholesterolemia, antioxidant/anti-inflammatory, antimicrobial, and analgesic properties. Toxicological validation and pharmacokinetics investigation are necessary to validate the efficacy and safety A. iva extracts and its secondary metabolites. An in-depth investigation is needed to reveal the biological activity of A. iva active compounds in preventing the development of cancer and neurodegenerative disorders such as Alzheimer's and Parkinson's diseases., Competing Interests: Declaration of competing interest There was no conflict of interest between authors., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Ajuga bracteosa Wall Ex Benth. (Labiateae) is described in Ayurveda for the treatment of rheumatism, gout, palsy and amenorrhea., Aim of the Study: The aim of present investigation is to study anti-inflammatory activity of Ajuga bracteosa, to understand possible mechanism of action and to identify the constituents responsible for its activity., Materials and Methods: The anti-inflammatory activity of 70% ethanolic extract was evaluated in TPA-induced mouse ear edema assay and in vitro cyclooxygenase (COX)-1 and COX-2 inhibitory activity was determined using EIA kits employing appropriate reference standards. Aajugarin I, lupulin A, withaferin A, reptoside and 6-deoxyharpagide were isolated from the 70% ethanolic extract by silica gel column chromatography., Results: The 70% ethanol extract of whole plants of Ajuga bracteosa showed a significant (p<0.05) and dose-dependent anti-inflammatory activity in an acute inflammation model at the dose of 0.5 and 1.0 mg/ear. The extract also exhibited a strong in vitro COX-1 and COX-2 inhibitory activity at 25 and 50 μg/mL concentration. Among the isolated compounds 6-deoxyharpagide exhibited highest COX-2 inhibition while rest of the compounds exhibited weak to moderate COX-1 and COX-2 inhibition at 30 μM concentration., Conclusions: The results suggest that the 70% ethanol extract of Ajuga bracteosa possesses promising anti-inflammatory activity, which is possibly mediated through inhibition of COX-1 and COX-2 enzymes. The isolated constituents could be responsible in part for its anti-inflammatory and COX inhibitory activity. The study supports traditional use of Ajuga bracteosa for inflammatory diseases., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

The present study was designed to explore the possible antioxidant and hypolipidemic effects of the aqueous extract of Ajuga iva (0.5% in the diet) in rats fed a high-cholesterol (1%) diet (HCD). The results indicated that the HCD-Ai versus HCD treatment led to many changes in biochemical parameters. They showed a decrease of plasma total cholesterol (TC) and VLDL-cholesterol but an increase of HDL(2)-cholesterol. The triacylglycerol contents were reduced in plasma and in VLDL. The lipid peroxidation determined by TBARS was decreased by 75% in plasma. TBARS in liver, heart and kidneys were highly reduced excepted in the adipose tissue. Ajuga iva treatment enhanced superoxide dismutase activity in liver and kidney. Glutathione reductase activity was lowered in adipose tissue but increased in liver and in kidney. A significant increase was noted in glutathione peroxidase activity in liver, heart and kidney but a low value in adipose tissue was observed. In conclusion, the present study demonstrates that in addition to its potent TG and TC-lowering effects, Ajuga iva is effective in improving the antioxidant status by reducing lipid peroxidation in plasma and tissues and enhancing the antioxidant enzymes in rats fed high-cholesterol diet. Furthermore, Ajuga iva may reduce intestinal cholesterol absorption.