Folium Microcos (FM), the leaves of Microcos paniculata L., shows various biological functions including antioxidant activity and α‐glucosidase inhibitory effect. However, its therapeutic potential in acute liver injury is still unknown. This study investigated the hepatoprotective effect and underlying mechanisms of the polyphenol‐enriched fraction (FMF) from Folium Microcos. FMF exhibited strong free radical scavenging activities and prevented HepG2/Hepa1–6 cells from hydrogen peroxide‐ (H₂O₂‐) induced ROS production and apoptosis in vitro. Antioxidant activity and cytoprotective effects were further verified by alleviating APAP‐induced hepatotoxicity in mice. Western blot analysis revealed that FMF pretreatment significantly abrogated APAP‐mediated phosphorylation of MAPKs, activation of proapoptotic protein caspase‐3/9 and Bax, and restored expression of antiapoptotic protein Bcl2. APAP‐intoxicated mice pretreated with FMF showed increased nuclear accumulation of nuclear factor erythroid 2‐related factor (Nrf2) and elevated hepatic expression of its target genes, NAD(P)H:quinine oxidoreductase 1 (NQO1) and hemeoxygenase‐1(HO‐1). HPLC analysis revealed the four predominantly phenolic compounds present in FMF: narcissin, isorhamnetin‐3‐O‐β‐D‐glucoside, isovitexin, and vitexin. Consequently, these findings indicate that FMF possesses a hepatoprotective effect against APAP‐induced hepatotoxicity mainly through dual modification of ROS/MAPKs/apoptosis axis and Nrf2‐mediated antioxidant response, which may be attributed to the strong antioxidant activity of phenolic components.

A polyphenol‐enriched fraction (PEF) from Acalypha wilkesiana, whose leaves have been traditionally utilized for the treatment of diverse medical ailments, was investigated for the anti‐inflammatory effect and molecular mechanisms by using lipopolysaccharide‐ (LPS‐) stimulated RAW 264.7 macrophages and acetaminophen‐ (APAP‐) induced liver injury mouse model. Results showed that PEF significantly attenuated LPS‐induced nitric oxide (NO) and prostaglandin E₂ (PGE₂) production and suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX‐2) in RAW 264.7 macrophages. PEF also reduced the secretion of proinflammatory cytokines including tumor necrosis factor‐α (TNF‐α), interleukin‐ (IL‐) 1β, and IL‐6 in LPS‐stimulated RAW 264.7 macrophages. Moreover, PEF potently inhibited LPS‐induced phosphorylation of mitogen‐activated protein kinases (MAPKs) as well as the activation of nuclear factor‐κB (NF‐κB) by preventing the degradation of inhibitor κB‐α (IκB‐α). In vivo, PEF pretreatment ameliorated APAP‐induced liver injury and hepatic inflammation, as presented by decreased hepatic damage indicators and proinflammatory factors at both plasma and gene levels. Additionally, PEF pretreatment remarkably diminished Toll‐like receptor 3 (TLR3) and TLR4 expression and the subsequent MAPKs and NF‐κB activation. HPLC analysis revealed that two predominantly polyphenolic compounds present in PEF were geraniin and corilagin. These results indicated that PEF has an anti‐inflammatory effect, and its molecular mechanisms may be involved in the inactivation of the TLR/MAPK/NF‐κB signaling pathway, suggesting the therapeutic potential of PEF for inflammatory diseases.

Five new oxygenated sesquiterpenes, molestins A–D (1, 3–5) and epi-gibberodione (2), three new cyclopentenone derivatives, ent-sinulolides C, D, and F ((+)-9–(+)-11), one new butenolide derivative, ent-sinulolide H ((+)-13), and one new cembranolide, molestin E (14), together with 14 known related metabolites (6–8, (–)-9–(–)-11, (±)-12, (–)-13, 15–19) were isolated from the Paracel Islands soft coral Sinularia cf. molesta. The structures and absolute configurations were elucidated based on comprehensive spectroscopic analyses, quantum chemical calculations, and comparison with the literature data. Compound 5 is the first example of a norsesquiterpene with a de-isopropyl guaiane skeleton isolated from the genus Sinularia. Molestin E (14) exhibited cytotoxicities against HeLa and HCT-116 cell lines with IC₅₀ values of 5.26 and 8.37 μM, respectively. Compounds 4, 5, and 8 showed significant inhibitory activities against protein tyrosine phosphatase 1B (PTP1B) with IC₅₀ values of 218, 344, and 1.24 μM, respectively.

A new piperidine alkaloid, microcosamine C (1), and one known compound, microcosamine A (2) were isolated from the leaves of Microcos paniculata. Structure elucidation was carried out using HR-ESI-MS, 1D and 2D NMR spectroscopic methods and by comparison with data reported in the literature. The absolute configuration at the C-3 hydroxy group of 1 was established by a Mosher esterification procedure. Both the isolates (1–2) were evaluated for cytotoxicity against four selected tumour cell lines and showed only weak activity against RAW 264.7 cell line.

The marine Streptomyces harbor numerous biosynthetic gene clusters (BGCs) with exploitable potential. However, many secondary metabolites cannot be produced under laboratory conditions. Co-culture strategies of marine microorganisms have yielded novel natural products with diverse biological activities. In this study, we explored the metabolic profiles of co-cultures involving Streptomyces sp. 2-85 and Cladosporium sp. 3-22—derived from marine sponges. Combining Global Natural Products Social (GNPS) Molecular Networking analysis with natural product database mining, 35 potential antimicrobial metabolites annotated were detected, 19 of which were exclusive to the co-culture, with a significant increase in production. Notably, the Streptomyces-Fungus interaction led to the increased production of borrelidin and the discovery of several analogs via molecular networking. In this study, borrelidin was first applied to combat Saprolegnia parasitica, which caused saprolegniosis in aquaculture. We noted its superior inhibitory effects on mycelial growth with an EC₅₀ of 0.004 mg/mL and on spore germination with an EC₅₀ of 0.005 mg/mL compared to the commercial fungicide, preliminarily identifying threonyl-tRNA synthetase as its target. Further analysis of the associated gene clusters revealed an incomplete synthesis pathway with missing malonyl-CoA units for condensation within this strain, hinting at the presence of potential compensatory pathways. In conclusion, our findings shed light on the metabolic changes of marine Streptomyces and fungi in co-culture, propose the potential of borrelidin in the control of aquatic diseases, and present new prospects for antifungal applications.

Six new citreoviridins (citreoviridins J–O, 1–6) and twenty-two known compounds (7–28) were isolated from the deep-sea-derived Penicillium citreonigrum MCCC 3A00169. The structures of the new compounds were determined by spectroscopic methods, including the HRESIMS, NMR, ECD calculations, and dimolybdenum tetraacetate-induced CD (ICD) experiments. Citreoviridins J−O (1–6) are diastereomers of 6,7-epoxycitreoviridin with different chiral centers at C-2–C-7. Pyrenocine A (7), terrein (14), and citreoviridin (20) significantly induced apoptosis for HeLa cells with IC₅₀ values of 5.4 μM, 11.3 μM, and 0.7 μM, respectively. To be specific, pyrenocine A could induce S phase arrest, while terrein and citreoviridin could obviously induce G0-G1 phase arrest. Citreoviridin could inhibit mTOR activity in HeLa cells.