Medicinal Importance of Ajuga Species in Iran: Ethnobotanical and Traditional Applications, Phytochemical, and Pharmacological Studies

Context: Five species of the genus Ajuga (Lamiaceae) having the common name of "bugle" are found in Iran. In Persian medicine (PM), the genus Ajuga (Kamaphytus) is used for treating jaundice, joint pain, gout, amenorrhea, sciatica, and wound healing. This study aimed to review the ethnobotanical, phytochemical, and biological activities of Ajuga species that grow in Iran to determine their therapeutic potentials and suggest further studies on the healing properties of this genus in Iran. Evidence Acquisition: Electronic databases such as PubMed, Scopus, and Google Scholar were comprehensively searched for studies on Ajuga species in Iran, including "Ajuga austro-iranica," "Ajuga chamaecistus," "Ajuga comata" (Syn.: "Ajuga Chia," "Ajuga chamaepitys subsp. Chia"), "Ajuga orientalis," and "Ajuga reptans." The search period was from 1966 to February 2021. The related articles were selected according to the inclusion and exclusion criteria of the current study. Results: Several ethnobotanical and pharmacologic reports have verified the traditional uses of the genus Ajuga for anti-inflammatory, hypoglycemic, hypolipidemic, analgesic, anabolic, anti-arthritis, antipyretic, and hepatoprotective activities. Numerous phytochemicals have been identified from Ajuga species involving phytoecdysteroids, neo-clerodane-diterpenes, iridoids, flavonoids, withanolides, phenylethyl glycoside, and essential oils. Conclusions: Due to the beneficial therapeutic effects of Ajuga genus, it can be considered in future clinical studies as a source of natural antioxidants, dietary supplements in the pharmaceutical industry, and stabilizing food against oxidative deterioration.

In Silico Studies of Lamiaceae Diterpenes with Bioinsecticide Potential against Aphis gossypii and Drosophila melanogaster

Background: The growing demand for agricultural products has led to the misuse/overuse of insecticides; resulting in the use of higher concentrations and the need for ever more toxic products. Ecologically, bioinsecticides are considered better and safer than synthetic insecticides; they must be toxic to the target organism, yet with low or no toxicity to non-target organisms. Many plant extracts have seen their high insecticide potential confirmed under laboratory conditions, and in the search for plant compounds with bioinsecticidal activity, the Lamiaceae family has yielded satisfactory results. Objective: The aim of our study was to develop computer-assisted predictions for compounds with known insecticidal activity against Aphis gossypii and Drosophila melanogaster. Results and conclusion: Structure analysis revealed ent-kaurane, kaurene, and clerodane diterpenes as the most active, showing excellent results. We also found that the interactions formed by these compounds were more stable, or presented similar stability to the commercialized insecticides tested. Overall, we concluded that the compounds bistenuifolin L (1836) and bistenuifolin K (1931), were potentially active against A. gossypii enzymes; and salvisplendin C (1086) and salvixalapadiene (1195), are potentially active against D. melanogaster. We observed and highlight that the diterpenes bistenuifolin L (1836), bistenuifolin K (1931), salvisplendin C (1086), and salvixalapadiene (1195), present a high probability of activity and low toxicity against the species studied.

Dual COX and 5-LOX inhibition by clerodane diterpenes from seeds of Polyalthia longifolia (Sonn.) Thwaites

Natural metabolites with their specific bioactivities are being considered as a potential source of materials for pharmacological studies. In this study, we successfully isolated and identified five known clerodane diterpenes, namely 16-oxo-cleroda-3,13(14)E-dien-15-oic acid (1), 16-hydroxy-cleroda-3,13-dien-15-oic acid (2), 16-hydroxy-cleroda-4(18),13-dien-16,15-olide (3), 3α,16α-dihydroxy-cleroda-4(18),13(14)Z-dien-15,16-olide (4), and 16α-hydroxy-cleroda-3,13(14)Z-dien-15,16-olide (5) from the methanolic extract of seeds of Polyalthia longifolia. Initially, all the isolated metabolites were investigated for COX-1, COX-2, and 5-LOX inhibitory activities using the standard inhibitory kits. Of which, compounds 3, 4, and 5 exhibited to be potent COX-1, COX-2, and 5-LOX inhibitors with the IC50 values similar or lower to those of the reference drugs. To understand the underlying mechanism, these compounds were subjected to molecular docking on COX-1, COX-2, and 5-LOX proteins. Interestingly, the in silico study results were in high accordance with in vitro studies where compounds 3, 4, and 5 hits assumed interactions and binding pattern comparable to that of reference drugs (indomethacin and diclofenac), as a co-crystallized ligand explaining their remarkable dual (COX/LOX) inhibitor actions. Taken together, our findings demonstrated that compounds 3, 4, and 5 functioned as dual inhibitors of COX/5-LOX and can contribute to the development of novel, more effective anti-inflammatory drugs with minimal side-effects.