The discovery of potentially active diterpenoids to inhibit the pyroptosis from Callicarpa arborea.

Pyroptosis is a programmed-inflammatory cell death, which leads to release of inflammatory cellular contents and formation of inflammation. Uncontrollable pyroptosis can result in serious immune diseases, such as cytokine release syndrome (CRS), sepsis, disseminated intravascular coagulation (DIC), and acute organ damage, including acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI). Members of the Callicarpa genus are significant raw materials for traditional Chinese medicine, widely used for analgesia, hemostasis, and anti-inflammation. Previously, we have reported some ent-clerodane diterpenoids from Callicarpa arborea, shown potent inhibitory effects against pyroptosis. In this study, we went on investigating this kind of diterpenoids, and yielded 66 ent-clerodane diterpenoids, including 52 new compounds, from Callicarpa arborea. Their structures featured with a 5/6- (1-25) or a 6/6- (26-66)-fused double-ring scaffolds, were elucidated using spectroscopic data, electrostatic circular dichroism (ECD) and X-ray diffraction analyses. Screening for the inhibitory activity against pyroptosis by detecting of IL-1ß secretion in J771A.1 cells, revealed 28 compounds with an IC50 below 10.5 µM. Compound 1 was the most potent with an IC50 of 0.68 µM and inhibited the J774A.1 macrophage pyroptosis by blocking the NLR pyrin domain containing 3 (NLRP3) inflammasome activation. An in vivo study further revealed that compound 1 decreased infiltration of CD11b + F4/80 + macrophages into lung and attenuated the lipopolysaccharide (LPS)-induced lung injury. Taken together, this study indicated the potential of compound 1 as a candidate for pyroptosis-related inflammation treatment, as well as provided the chemical and pharmacological basis for the further development of Callicarpa genus as a herbal medicine.

Natural NO inhibitors from the leaves of Callicarpa kwangtungensis: Structures, activities, and interactions with iNOS.

A phytochemical investigation to obtain new NO inhibitors resulted in the isolation of a new diterpenoid with a rare 9,10-seco-abietane skeleton (1) and twelve known terpenoids (2-13) from Callicarpa kwangtungensis. Their structures were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analyses, and the absolute configuration of compound 1 was established by comparison of the calculated and experimental electronic circular dichroism (ECD) spectra. The inhibitory activities on lipopolysaccharide-induced NO production in murine microglial BV-2 cells of these terpenoids were evaluated, and all of the compounds showed inhibitory effects. The following molecular docking studies showed interactions of the bioactive compounds with the iNOS protein.

Hepatoprotective triterpenoid saponins from Callicarpa nudiflora.

Four new triterpenoid saponins, 2α,3α,19α,24-tetrahydroxyolean-12-en-28-oic-acid 28-O-ß-D-glucopyranosyl ester (1), 2α,3α,19α,23-tetrahydroxyolean-12-en-28-oic-acid 28-O-ß-D-xylopyranosyl-(1→2)-ß-D-glu-copyranosyl ester (2), 2α,3α,19α-trihydroxyolean-12-en-28-oic-acid 28-O-ß-D-xylopyranosyl-(1→2)-ß-D-glucopyranosyl ester (3), 2α,3α,23,29-tetrahydroxyurs-12,19-dien-28-oic-acid 28-O-ß-D-glucopyranosyl ester (4), together with three known compounds (5-7), were isolated from the leaves of Callicarpa nudiflora HOOK. Their structures were established by means of spectroscopic methods and chemical evidence. Hepatoprotective activities of the isolated compounds against D-galactosamine-induced toxicity have been tested. Among them, compounds 1-3 showed pronounced hepatoprotective activities against D-galactosamine-induced toxicity in WB-F344 rat hepatic epithelial stem-like cells.

A natural plant growth promoter calliterpenone from a plant Callicarpa macrophylla Vahl improves the plant growth promoting effects of plant growth promoting rhizobacteria (PGPRs).

Experiments were conducted to evaluate the efficacy of calliterpenone, a natural plant growth promoter from a shrub Callicarpa macrophylla Vahl., in enhancing the growth and yield promoting effects of plant growth promoting rhizobacteria (PGPRs), in menthol mint (Mentha arvensis L).This study is based on our previous results indicating the microbial growth promotion by calliterpenone and assumption that application of calliterpenone along with PGPRs will improve the population of PGPRs resulting in higher impacts on plant growth and yield. Of the 15 PGPRs (identified as potent ones in our laboratory), 25 µl of 0.01 mM calliterpenone (8.0 µg/100 ml) was found to be useful in improving the population of nine PGPRs in culture media. The five selected strains of PGPRs exhibiting synergy with calliterpenone in enhancing growth of maize compared to PGPR or calliterpenone alone were selected and tested on two cultivars (cvs. Kosi and Kushal) of M. arvensis. Of the five strains, Bacillus subtilis P-20 (16S rDNA sequence homologous to Accession No NR027552) and B. subtilis Daz-26 (16SrDNA sequence homologuos to Accession No GU998816) were found to be highly effective in improving the herb and essential oil yield in the cultivars Kushal and Kosi respectively when co-treated with calliterpenone. The results open up the possibilities of using a natural growth promoter along with PGPRs as a bio-agri input for sustainable and organic agriculture.