Ethnomedicinal use, phytochemistry, pharmacology, and toxicology of Ajuga iva (L.,) schreb.

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.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.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.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.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.