Three new lanostane-type triterpenes from the epidermis of Wolfiporia cocos.

Wolfiporia cocos is commonly used as a traditional Chinese medicine for its diuretic, tonifying, and invigorating effects on the spleen. However, the epidermis of W. cocos is discarded as scrap during harvesting because of its low price, resulting in a great waste of resources and environmental pollution. In this work, the epidermis of W. cocos was studied and three new lanostane triterpenoids were isolated. The structures were determined using NMR and HRESIMS, with absolute configurations established by comparison of the calculated and experimental ECD spectra. The three new compounds were evaluated for their antimicrobial activities in vitro against Staphylococcus aureus, Escherichia coli, and Saccharomyces cerevisiae. None of the tested compounds showed inhibition against these three strains of indicator microbes at a concentration of 128 µg/ml. This study provides a reference for further medicinal development and the utilization of the epidermis of W. cocos.

An integrated network pharmacology approach reveals that Darutigenol reduces inflammation and cartilage degradation in a mouse collagen-induced arthritis model by inhibiting the JAK-STAT3 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Darutigenol (DL) is a natural active product derived from the Chinese herbal medicine Sigesbeckia glabrescens (Makino) Makino. It is administered as a traditional Chinese medicine (TCM) to dispel rheumatism, benefit the joints, and detoxify. However, its potential mechanism in the treatment of rheumatoid arthritis (RA) remains unknown. AIMS OF THE STUDY: The objectives of this research were to determine the effects and elucidate the modes of action of DL on RA-related joint inflammation. MATERIALS AND METHODS: Network pharmacology and molecular docking were used to screen and validate candidate DL targets for RA treatment, respectively. A DBA/1 mouse rheumatoid arthritis model was induced with bovine type II collagen. Intragastric DL administration was followed by the calculation of the clinical arthritis index. A section of the ankle joint was excised and stained and the pathological changes in it were observed. Enzyme-linked immunosorbent assays (ELISA) and western blotting (WB) were used to clarify the mechanisms of DL in RA treatment. RESULTS: DL effectively attenuated the inflammation, mitigated the articular cartilage degradation, and bone erosion, and alleviated the inflammatory joints associated with RA. Network pharmacology screened six key targets of DL while molecular docking revealed that it docked well with its protein targets. The DL treatment group presented with significantly less ankle joint redness and swelling, a lower arthritis index scores and serum and bone marrow supernatant IL-6 levels, more complete ankle joint surfaces, and less synovial inflammation, cartilage degradation, and bone erosion than the collagen-induced arthritis (CIA) group. The DL treatment also substantially downregulated the Janus kinase (JAK)1, JAK3, matrix metalloproteinase (MMP)2, MMP9, and phospho-signal transducer and activator of transcription (p-STAT)3 proteins in the joints. CONCLUSIONS: To the best of our knowledge, the present work was the first to demonstrate that DL has significant anti-inflammatory efficacy and reduces cartilage degradation and bone erosion. It also demonstrated that the anti-RA effect of DL may be explained by its ability to inhibit joint inflammation and reduce articular cartilage degradation through the interleukin (IL)-6/JAK1,3/STAT3 axis and downregulate MMP2 and MMP9. Hence, DL might play a therapeutic role in a mouse RA model.

Five previously undescribed compounds from Ajuga lupulina Maxim. and their in vitro activities.

A new biflavone (philonotisflavone-3'''-methyl ether), three diterpenes (lupulin G, lupulin H, lupulin I), a new ecdysteroid (ajugasterone E), and four known compounds were isolated from the whole plant of Ajuga lupulina Maxim. Their structures were determined by spectroscopic analysis, including MS, NMR and ECD spectral data. Compounds 1-3 has DPPH radical scavenging ability, and compound 1 has stronger activity than vitamin C. Compounds 2, 3, 7 and 8 have potential cytotoxic activity against Hela, with IC50 values less than 20.0 µM. Abietane diterpenes 2, 3, 7 and 8 are also found to have NO inhibitory effects with IC50 values less than 40.0 µM.

New Lanostane-Type Triterpenes with Anti-Inflammatory Activity from the Epidermis of Wolfiporia cocos.

A chemical study on the epidermis of cultivated edible mushroom Wolfiporia cocos resulted in the isolation and identification of 46 lanostane triterpenoids, containing 17 new compounds (1-17). An experimental determination of their anti-inflammatory activity showed that poricoic acid GM (39) most strongly inhibited NO production in LPS-induced RAW264.7 murine macrophages with an IC50 value at 9.73 µM. Furthermore, poricoic acid GM induced HO-1 protein expression and inhibited iNOS and COX2 protein expression as well as the release of PGE2, IL-1ß, IL-6, TNF-α, and reactive oxygen species (ROS) in LPS-induced RAW264.7 cells. Mechanistically, poricoic acid GM suppressed the phosphorylation of the IκBα protein, which prevented NF-κB from entering the nucleus to lose transcriptional activity and inhibited the dissociation of Keap1 from Nrf2, thereby activating Nrf2 into the nucleus to regulate antioxidant genes. Furthermore, the MAPK signaling pathway may play a significant role in poricoic acid GM-induced elimination of inflammation. This work further confirms that lanostane triterpenoids are key ingredients responsible for the anti-inflammatory properties of the edible medicinal mushroom W. cocos.