Monoterpenoid indole alkaloids from Melodinus axillaris W.T.Wang exhibit anti-inflammatory activities by inhibiting the NF-κB signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Melodinus axillaris W.T.Wang has been widely used as an important medicine in China. In the folk of China, its whole plant has been used for fractures, rheumatic heart disease, testitis, hernia, abdominal pain, and dyspepsia, etc. Despite its extensive use, there is a shortage of literature investigating the specific bioactive compounds and underlying mechanisms responsible for their anti-inflammatory effects. This knowledge gap serves as the primary impetus for conducting this study, which aims to shed light on the previously unexplored therapeutic potential of M. axillaris. AIM OF THE STUDY: This study aims to investigate the material basis and potential mechanism of anti-inflammatory activity of M. axillaris. MATERIALS AND METHODS: Compounds were isolated from the 95% ethanol extract of M. axillaris using a systematic phytochemical method. The structures were established by extensive spectroscopic analysis, including 1D and 2D NMR, HR-ESI-MS, ECD calculation, and DP4+ analysis. The anti-inflammatory activities of ethanol extract and compounds from M. axillaris were tested by an inflammation model of LPS-stimulated RAW264.7 cells in vitro. Western blot analysis was employed to evaluate the expressions of COX-2, iNOS, and NF-κB signaling pathways, aiming to elucidate the underlying mechanisms. RESULTS: Eleven undescribed monoterpenoid indole alkaloids (MIAs), axillines A-K (1-11), along with thirteen known analogs were isolated from M. axillaris. Compound 1 was the first representative of vincadine alkaloid with unprecedented 6/5/9/6/6 skeletons. Compounds 1-11 and ethanol extract showed significant anti-inflammatory effects in vitro. Among them, compound 2 had the best activity of inhibiting NO release (IC50 = 3.7 ± 0.9 µM). Additionally, subsequent Western blot analysis revealed that 2 could significantly inhibit the up-regulation of NF-κB signaling pathways, iNOS, and COX-2 in LPS-stimulated RAW264.7 cells, thereby demonstrating its anti-inflammatory activity. CONCLUSION: This study provides support for the traditional use of M. axillaris in terms of its anti-inflammatory properties and highlights the potential of MIAs as promising candidates for further development as anti-inflammatory drugs.

Clinopodium chinense Kuntze ameliorates dextran sulfate sodium-induced ulcerative colitis in mice by reducing systematic inflammation and regulating metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Clinopodium chinense Kuntze (CC), traditional Chinese medicine with anti-inflammatory, anti-diarrheal, and hemostatic activities, has been used to treat dysentery and bleeding diseases for thousands of years, which are similar to the symptoms of ulcerative colitis (UC). AIM OF THE STUDY: To obtain a novel treatment for UC, an integrated strategy was developed in this study to investigate the effect and mechanism of CC against UC. MATERIALS AND METHODS: The chemical characterization of CC was scanned by UPLC-MS/MS. Network pharmacology analysis was performed to predict the active ingredients and pharmacological mechanisms of CC against UC. Further, the results of network pharmacology were validated using LPS-induced RAW 264.7 cells and DSS-induced UC mice. The production of pro-inflammatory mediators and biochemical parameters was tested using the ELISA kits. The expression of NF-κB, COX-2, and iNOS proteins was evaluated using Western blot analysis. Body weight, disease activity index, colon length, histopathological examination, and metabolomics analysis in colon tissues were carried out to confirm the effect and mechanism of CC. RESULTS: Based on the chemical characterization and literature collection, a rich database of ingredients in CC was constructed. Network pharmacology analysis provided five core components as well as revealed that the mechanism of CC against UC was highly related to inflammation, especially the NF-κB signaling pathway. In vitro experiments showed CC could inhibit inflammation by LPS-TLR4-NF-κB-iNOS/COX-2 signaling pathway in RAW264.7 cells. Meanwhile, in vivo experimental results proved that CC significantly alleviated pathological features with increased body weight and colonic length, decreased DAI and oxidative damage, as well as mediated inflammatory factors like NO, PGE2, IL-6, IL-10, and TNF-ɑ. In addition, colon metabolomics analysis revealed CC could restore the abnormal endogenous metabolite levels in UC. 18 screened biomarkers were further enriched in four pathways including Arachidonic acid metabolism, Histidine metabolism, Alanine, aspartate and glutamate metabolism as well as the Pentose phosphate pathway. CONCLUSION: This study demonstrates that CC could alleviate UC by reducing systematic inflammation and regulating metabolism, which is beneficial for providing scientific data for the development of UC treatment.

Hepatoprotective Effect Associated with Alkaloids from Corydalis tomentella Franch. based on Network Pharmacology, Molecular Docking and in Vitro Experiment.

Liver is an important metabolic organ with numerous functions in human body. Hepatitis is defined as the inflammation of the liver tissue, which could lead to acute liver failure, liver fibrosis, liver cirrhosis and hepatocellular carcinoma. Corydalis tomentella Franch., a precious herb in China, is often used in the treatment of hepatitis, liver cirrhosis and liver cancer. In this study, 41 isoquinoline alkaloids and derivatives isolated by our lab from C. tomentella and 61 related targets were analyzed by network pharmacology. Their activities were further verified by cell assay evaluated for antitumor activity against HepG2 cells and molecular docking. The results confirmed that the alkaloids from C.tomentella had extensive hepatoprotective effects, and TNF-α was the key target of hendersinate B methyl ester against acute liver damage by viral hepatitis and HCC, which provided a foundation for further in vivo studies.

Isoquinoline alkaloids from the Corydalis tomentella with potential anti-hepatoma and antibacterial activities.

Six undescribed isoquinolines, including one rarely reported N-benzyl isoquinoline together with sixteen known ones were isolated from C. tomentella. Their planar structures and absolute configurations were elucidated by extensive analyses of UV, IR, NMR, HRESIMS, DP4+ probability analysis as well as ECD calculations. Biological evaluations revealed that 3,4-2H-tomentelline C (6) showed significant cytotoxicity (IC50 = 7.42 µM) against the HepG2 cell line while (1'R, 2'S)-coptichine B (3) exhibited stronger antibacterial activities.