Hericium rajendrae is an emerging species in the genus Hericium with few members. Despite being highly regarded due to its rarity, knowledge about H. rajendrae remains limited. In this study, we sequenced, de novo assembled, and annotated the complete genome of H. rajendrae NPCB A08, isolated from the Qinling Mountains in Shaanxi, China, using the Illumina NovaSeq and Nanopore PromethION technologies. Comparative genomic analysis revealed similarities and differences among the genomes of H. rajendrae, H. erinaceus, and H. coralloides. Phylogenomic analysis revealed the divergence time of the Hericium genus, while transposon analysis revealed evolutionary characteristics of the genus. Gene family variation reflected the expansion and contraction of orthologous genes among Hericium species. Based on genomic bioinformation, we identified the candidate genes associated with the mating system, carbohydrate-active enzymes, and secondary metabolite biosynthesis. Furthermore, metabolite profiling and comparative gene clusters analysis provided strong evidence for the biosynthetic pathway of erinacines in H. rajendrae. This work provides the genome of H. rajendrae for the first time, and enriches the genomic content of the genus Hericium. These findings also facilitate the application of H. rajendrae in complementary drug research and functional food manufacturing, advancing the field of pharmaceutical and functional food production involving H. rajendrae.

Introduction: Cynaroside exhibits various biological properties, including anti-inflammatory, antiviral, antitumor, and cardioprotective effects. However, its involvement in methotrexate (MTX)-induced intestinal inflammation remains inadequately understood. Thus, we investigated the impact of cynaroside on MTX-induced intestinal inflammation and its potential mechanisms.Methods: To assess the protective potential of cynaroside against intestinal inflammation, Sprague-Dawley rats were subjected to a regimen of 7 mg/kg MTX for 3 days, followed by treatment with cynaroside at varying doses (10, 20, or 40 mg/kg). Histopathological evaluations were conducted alongside measurements of inflammatory mediators to elucidate the involvement of the NLRP3 inflammasome in alleviating intestinal inflammation.Results: Administration of 7 mg/kg MTX resulted in decreased daily food intake, increased weight loss, and elevated disease activity index in rats. Conversely, treatment with cynaroside at 20 or 40 mg/kg ameliorated the reductions in body weight and daily food intake and suppressed the MTX-induced elevation in the disease activity index. Notably, cynaroside administration at 20 or 40 mg/kg attenuated inflammatory cell infiltration, augmented goblet cell numbers and lowered serum levels of tumor necrosis factor-α, interleukin (IL)-1β, and IL-18, as well as the CD68-positive cell rate in the intestines of MTX-induced rats. Furthermore, cynaroside downregulated the expression levels of NLRP3, cleaved caspase 1, and cleaved IL-1β in MTX-induced rats.Discussion: Collectively, our findings indicated that cymaroside alleviates intestinal inflammatory injury by inhibiting the activation of NLRP3 inflammasome in MTX-induced rats.

The pathogenesis of acute lung injury (ALI) is complex and it is a common critical illness in clinical practice, seriously threatening the lives of critically ill patients, for which no specific molecular marker exists and there is a lack of effective methods for the treatment of ALI. The present study aimed to investigate the mechanism of action of honeysuckle and forsythia in treatment of acute lung injury (ALI) based on network pharmacology and in vitro modeling. The active ingredients and targets of honeysuckle and forsythia were predicted using traditional Chinese medicine systems pharmacology, PubChem and Swiss Target Prediction databases, and the Cytoscape 3.7.2 software was used to construct a drug‑component‑potential target network. The potential targets were imported into the Search tool for recurring instances of neighboring genes) database to obtain protein‑protein interactions and subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Targets analysis using Database for Annotation, Visualization, and Integrated Discovery. AutoDock Vina 1.1.2 software was used for docking between key active ingredients and the target proteins to analyze the binding ability of the active ingredients to the primary targets in honeysuckle and forsythia. A total of 64 male BALB/c mice were randomly divided into control, model, positive drug (Lianhua‑Qingwen capsule), honeysuckle, forsythia, honeysuckle + forsythia high‑, medium‑ and low‑dose groups. Lipopolysaccharide (LPS) was used to induced an ALI model. The lung tissues of the mice were stained with hematoxylin‑eosin and the serum levels of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH‑Px) were measured 4 h after the LPS administration. Reverse transcription‑quantitative PCR and western blotting were used to detect NF‑κB mRNA and protein expression, respectively. Active ingredients of honeysuckle and forsythia acted on 265 common targets in ALI, which regulated NF‑κB, tumor necrosis factor‑α (TNF‑α) and PI3K‑AKT signaling pathway, HIF‑1 signalling pathway to slow the inflammatory response in treatment of ALI. In the positive drug group, honeysuckle, forsythia group, honeysuckle + forsythia high‑, medium‑ and low‑dose groups, lung tissue damage were significantly decrease compared with the model group, and inflammatory cell infiltration was reduced. Compared with the model group, honeysuckle + forsythia groups experienced decreased damage caused by the LPS and inflammation in the lung tissues and significantly decreased TNF‑α and NF‑κB and MDA concentration and significantly increased the SOD and GSH‑Px activities. The mechanism of the effect of honeysuckle and forsythia on ALI may be mediated by inhibition of TNF‑α and NF‑κB expression and the activation of antioxidant mechanisms to decrease production of pro‑inflammatory cytokines in lung tissue, thus treating ALI.

Objective: Astragali Complanati Semen (ACS) is a traditional Chinese medicinal herb conventionally applied to tonify the liver and kidney. As the primary bioactive ingredients of ACS, Astragalus complanatus flavonoids (ACF) exert hepatoprotective and anti-fibrotic effects. This study aimed to elucidate the antifibrotic mechanisms of ACF through integrated proteomic and metabolomic analyses combined with experimental validation. Methods: A CCl ₄ -induced rat model of LF and TGF-β1-activated hepatic stellate cell (HSC) model were established to evaluate the antifibrotic effects of ACF. Integrated proteomic and metabolomic analyses were performed to identify differentially expressed proteins (DEPs), differentially expressed metabolites (DMs), and associated signaling pathways. Key molecular targets were validated using quantitative real-time PCR and Western blotting, while pharmacological inhibitors were employed to investigate the involvement of the FAK/AKT signaling pathway in ACF-mediated inhibition of HSC activation. Results: Compared with the LF model group, ACF treatment significantly ameliorated liver function indicators, relieved histopathological injury and collagen deposition, decreased serum fibrosis markers, downregulated the protein levels of Col I, Col IV and α-SMA, and reduced oxidative stress and inflammatory response. Proteomic screening uncovered 401 differentially expressed proteins (DEPs), which were primarily enriched in extracellular matrix (ECM)–receptor interaction, focal adhesion and PI3K/AKT signaling pathways. Protein–protein interaction analysis further pinpointed FN1, CD44, ITGAV, FAK and AKT1 as core target proteins. In vitro experiments demonstrated that ACF blocked TGF-β1-triggered HSC activation, lowered the expression of α-SMA and ITGAV, and inhibited the phosphorylation of FAK and AKT. Pharmacological blockade of either FAK with PF-562271 or AKT with MK2206 strengthened the anti fibrogenic activity of ACF, verifying that the FAK/ AKT axis mediates the anti-HSC activation effect of ACF. Metabolomic analysis identified 108 differentially expressed metabolites (DMs), mainly enriched in glutathione metabolism, primary bile acid biosynthesis and carbohydrate metabolism. Integrated multi-omics analysis confirmed close correlations between DEPs and DMs within ECM–receptor interaction, PI3K/AKT signaling and primary bile acid biosynthesis pathways. Specifically, glycochenodeoxycholic acid, dulcitol and chenodeoxycholate showed strong correlations with coretarget proteins. Conclusion: ACF achieves comprehensive anti-LF effects via suppressing FAK/AKT1 signaling to restrain HSC activation, while coordinately modulating pivotal metabolic pathways.