Rotenoids and Other Specialized Metabolites from the Roots of Mirabilis multiflora: Opioid and Cannabinoid Receptor Radioligand Binding Affinities.

Mirabilis multiflora is an acclaimed hallucinogen consumed traditionally by the Hopi Indians to induce diagnostic visions. Its root extract afforded a new (3) and four known (2, 5, 6, and 7) 12a-hydroxyrotenoids, a known rotenoid (4), and two known secondary metabolites (1 and 8). The structures of the compounds were elucidated based on spectroscopic and spectrometric data analysis. Electronic circular dichroism data were used to define the (6aS,12aR) absolute configuration of the 12a-hydroxyrotenoids. Compounds 2-7 were screened for their radioligand binding affinities toward the opioid (δ, κ, and µ) and cannabinoid (CB1 and CB2) receptor subtypes. The 6-methoxy-substituted rotenoids 3, 4, and 7 showed the highest receptor binding affinity with moderate selectivity toward the δ-opioid receptor subtype, with negligible binding affinities for CB1 and CB2. Their binding affinities toward the δ-opioid receptor were 64.5% (4), 58.7% (7), and 55.3% (3) at 10 µM, respectively.

Plant-derived natural therapeutics targeting cannabinoid receptors in metabolic syndrome and its complications: A review.

The endocannabinoid system (ECS) is natural physiological system in the humans. The presence of the ECS system involves different roles in body. The endocannabinoid system involves regulation of most of the centers, which regulates the hunger and leads to changes in the weight. In the present article, we reviewed the role of natural cannabinoid compounds in metabolic disorders and related complications. We studied variety of a plant-derived cannabinoids in treating the metabolic syndrome including stoutness, fatty acid liver diseases, insulin obstruction, dementia, hypertension, lipid abnormalities, non-alcoholic steatohepatitis, endothelial damage, and polycystic ovarian syndrome and so on. The activation of cannabinoid receptors demonstrates a significant number of beneficial approaches concerning metabolic syndrome and reduces the pro-inflammatory cytokines on account of aggravation, decreased oxidative stress and uneasiness, diminishes liver fibrosis, with reduces adiponectin. Pre-clinical investigations of plant-derived cannabinoids resulted in promising outcomes. The different distinctive plant-derived cannabinoids were discovered like cannabidiol (CBD), cannabinol (CBN), cannabichromene (CBC), and cannabidiol (CBG). It has been observed that endogenous cannabinoids and plant-derived cannabinoids have an advantageous impact on limiting the metabolic disorder arising due to lifestyle changes.

GPR18 Inhibiting Amauromine and the Novel Triterpene Glycoside Auxarthonoside from the Sponge-Derived Fungus Auxarthron reticulatum.

The marine sponge-derived fungus Auxarthron reticulatum produces the cannabinoid receptor antagonist amauromine (1). Recultivation of the fungus to obtain further amounts for more detailed pharmacological evaluation of 1 additionally yielded the novel triterpene glycoside auxarthonoside (2), bearing, in nature, a rather rare sugar moiety, i.e., N-acetyl-6-methoxy-glucosamine. Amauromine (1), which inhibited cannabinoid CB1 receptors (Ki 0.178 µM) also showed antagonistic activity at the cannabinoid-like orphan receptor GPR18 (IC50 3.74 µM). The diketopiperazine 1 may thus serve as a lead structure for the development of more potent and selective GPR18 antagonists, which are required to study the orphan receptor's potential as a new drug target. Despite the execution of many biological assays, to date, no bioactivity could be found for auxarthonoside (2).