Eleven metabolites, six echinosporins (1−6), four dibenzoyls (7−10), and an aromatic compound (11), were isolated from the fermentation broth of lichen-associated Amycolatopsis hippodromi. The structures of the new compounds (1−5, 8−11) were elucidated by comprehensive spectroscopic analysis including data from experimental and calculated ECD spectra. Amycolasporins A−C (1−3) demonstrated antibacterial activities against Bacillus subtilis, Staphylococcus aureus, and Escherichia coli with MIC values of 25 or 100 μg/mL. Amycolasporin C (3) and the known dibenzoyl (7) attenuated the production of NO due to the suppression of the expression of nitric oxide synthase (iNOS) in LPS-induced RAW 264.7 cells in a dose-dependent manner.

BackgroundAspergillus infection seriously jeopardize the health and safety of life of immunocompromised patients. The emergences of antifungal resistance highlight a demand to find new effective antifungal drugs. Angelica sinensis is a medicine–food herb and phthalides are its characteristic components. A few of phthalides have been reported to display satisfactory antifungal activities against plant pathogenic fungi. However, the structure activity relationships and antifungal action mechanism of phthalides remain to be further explored and elucidated.ResultsThe antifungal activities of five natural phthalides and four artificial analogues were investigated, and their structure activity relationships were preliminarily elucidated in current study. The benzene ring moiety played an essential role in their antifungal activities; the oxygen‐containing substituents on the benzene ring obviously impact their activities, the free hydroxyl was favorable to the activity. Typical phthalide senkyunolide B (SENB) exhibited broad antifungal activities against human and plant pathogenic fungi, especially, Aspergillus fumigatus. SENB affected the spore germination and hyphae growth of A. fumigatus via downregulating phosphatidylinositol‐PKC‐calcineurin axis and the expression of ENG genes. Moreover, SENB disturbed the oxidation‐reduction process in A. fumigatus to destroy the mature biofilms. In vivo experiments indicated SENB significantly prolonged survival and decreased fungal burden in mouse model of invasive pulmonary aspergillosis.ConclusionsPhthalides could be considered as the valuable leads for the development of antifungal drug to cure plant and human disease.This article is protected by copyright. All rights reserved.

To discover ulcerative colitis (UC) treatment agents, 28 oleanane-type triterpenoid saponins (1–28) including three new saponins, pulsatillosides P-R (1–3), were isolated from Pulsatilla chinensis. The isolated saponins could observably ameliorate UC by improving the intestinal epithelial cell barrier and intestinal flora in vivo. The structure–activity relationship indicated that the oligosaccharide chain at C-28 was essential for their anti-UC activities; the methyl group at the C-23 site of triterpene saponins showed important effects on anti-UC efficacy; the chain length of oligosaccharides at position C-28 had little effect on their anti-UC activities. In vivo investigation of representative saponins 1 and 13 further confirmed that 23-methyl-3,28-bisdesmosidic oleanane-type saponins inhibited the TNFα-NFκB-MLCK axis to improve the intestinal epithelial cell barrier of the colon in UC mice. These findings revealed the potential of 23-methyl-3,28-bisdesmosidic oleanane-type saponins from P. chinensis as promising candidates for the treatment of UC.

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Radix Astragali (RA) is an important Traditional Chinese Medicine widely used in the treatment of various diseases, such as pneumonia, atherosclerosis, diabetes, kidney and liver fibrosis. The role of isoflavonoids from RA in the treatment of liver injury remains unclear. The study aimed to explore hepatoprotective and anti-inflammatory effects of isoflavonoids from Astragalus mongholicus. Network pharmacological analysis showed that RA had a multi-target regulating effect on alleviating liver injury and inhibiting inflammation through its active ingredients, among which isoflavones were closely related to its key molecular targets. The anti-inflammatory and liver protection effects of isoflavonoids of RA were investigated using lipopolysaccharide (LPS)-induced RAW 264.7 cells in vitro and LPS/D-galactosamine (D-gal)-induced acute liver injury mice in vivo. The experimental results showed that methylnissolin (ML) and methylnissolin-3-O-β-D-glucoside (MLG) presented more notable anti-inflammatory effects. Both of them suppressed the release of pro-inflammatory cytokines, such as iNOS, COX-2, IL-1β, IL-6, and TNF-α in LPS-stimulated RAW 264.7 cells. In vivo investigation demonstrated that ML markedly meliorated liver injury in LPS/D-gal-induced mice. Western blot results revealed that ML and MLG down-regulated the expression of proinflammatory cytokines via NF-κB signaling pathway. The isoflavonoids, methylnissolin (ML), and methylnissolin-3-O-β-D-glucoside (MLG), play a vital role in the hepatoprotective and anti-inflammatory effects of RA.