Emodin relieves morphine-stimulated BV2 microglial activation and inflammation through the TLR4/NF-κB/NLRP3 pathway.

The objective of this study is to disclose the role of emodin, a natural anthraquinone derivative that has been proposed to suppress microglial activation and inflammation, in morphine tolerance. Here, cell counting kit-8 method assayed the viability of BV2 microglial cells treated by ascending concentrations of emodin. In emodin-pretreated BV2 microglial cells challenged with morphine with or without transfection of toll-like receptor 4 (TLR4) overexpression plasmids, transwell assay measured cell migration. Immunofluorescence staining and western blot detected the expression of microglial markers. Inflammatory levels were subjected to ELISA and western blot. BODIPY 581/591 C11 assay estimated lipid reactive oxygen species activity. Iron assay kit examined total iron content. Western blot tested the expression of ferroptosis- and TLR4/nuclear factor-kappaB (NF-κB)/NOD-like receptor 3 (NLRP3) pathway-associated proteins. Molecular docking predicted the binding affinity of emodin to TLR4. Emodin was noted to obstruct the migration, activation, inflammatory response, and ferroptosis of BV2 microglial cells induced by morphine. In addition, emodin had a high binding affinity with TLR4 and inactivated TLR4/NF-κB/NLRP3 pathway in morphine-challenged BV2 microglial cells. Upregulation of TLR4 partially countervailed the protective role of emodin against morphine-elicited BV2 microglial cell migration, activation, inflammation, and ferroptosis. Accordingly, emodin might target TLR4 and act as an inactivator of TLR4/NF-κB/NLRP3 pathway, thus inhibiting BV2 microglial activation and inflammation to mitigate morphine tolerance.

The Traditional Uses, Phytochemistry, Pharmacology, Toxicology, and Clinical Uses of Metagentiana Rhodantha (Franch.) T.N.Ho and S.W.Liu, an Ethnomedicine in Southwest China.

Background: Metagentiana rhodantha (Franch.) T.N.Ho and S.W.Liu (MR) belongs to Gentianales, and it is often called Hong-hua-long-dan in Chinese. Traditionally, it has been used to cure acute icteric hepatitis, sore throat, dysentery, acute gastritis, carbuncle, and furuncle based on traditional Chinese medicine (TCM) concepts. Aim of Study: This review manages to provide a critical and comprehensive analysis on the traditional uses, phytochemistry, pharmacology, toxicology, and clinical uses of MR and to evaluate the therapeutic potential of this plant. Methods: Relevant data mainly literatures on MR were selected from available database. All the papers reviewed provided evidence that the source herbs were reliably identified. Results: The heat-clearing and removing the phlegm, and purging fire and removing toxicity of MR contribute to its dispelling jaundice, and clearing lung heat and cough. The compounds isolated from this plant include iridoids and secoiridoids, phenolic acids, ketones, triterpenoids, flavonoids, benzophenone glycosides, and others. Mangiferin (MAF) is a characteristic substance from this plant. The pharmacological studies show that some extracts and compounds from MR exhibit anti-inflammatory, antinociceptive, antibacterial, hepatoprotective, cardioprotective, and other effects which are associated with the traditional uses of this plant. The toxicological studies suggest that MAF is less toxic in mice and dogs. Nowadays, Chinese patent drugs such as Feilike Jiaonang and Kangfuling Jiaonang containing MR have been used to cure cough, asthma, chronic bronchitis, dysmenorrhea, and appendagitis. Conclusion: Although the current studies provide related research information of MR, it is still necessary to systemically evaluate the chemistry, pharmacology, toxicity, and safety of the extracts or compounds from this plant before clinical trials in the future. In addition, except for lung infection-related diseases, analgesia, anti-tumor, and hypertriglycemia may be new and prior therapeutic scopes of this ethnomedicine in the future.