Harnessing natural product polysaccharides against lung cancer and revisit its novel mechanism.

The incidence and mortality of lung cancer are on the rise worldwide. However, the benefit of clinical treatment in lung cancer is limited. Owning to important sources of drug development, natural products have received constant attention around the world. Main ingredient polysaccharides in natural products have been found to have various activities in pharmacological research. In recent years, more and more scientists are looking for the effects and mechanisms of different natural product polysaccharides on lung cancer. In this review, we focus on the following aspects: First, natural product polysaccharides have been discovered to directly suppress the growth of lung cancer cells, which can be effective in limiting tumor progression. Additionally, polysaccharides have been considered to enhance immune function, which can play a pivotal role in fighting lung cancer. Lastly, polysaccharides can improve the efficacy of drugs in lung cancer treatment by regulating the gut microbiota. Overall, the research of natural product polysaccharides in the treatment of lung cancer is a promising area that has the potential to lead to new clinical treatments. With better understanding, natural product polysaccharides have the potential to become important components of future lung cancer treatments.

3D-QSAR, Scaffold Hopping, Virtual Screening, and Molecular Dynamics Simulations of Pyridin-2-one as mIDH1 Inhibitors.

Isocitrate dehydrogenase 1 (IDH1) is a necessary enzyme for cellular respiration in the tricarboxylic acid cycle. Mutant isocitrate dehydrogenase 1 (mIDH1) has been detected overexpressed in a variety of cancers. mIDH1 inhibitor ivosidenib (AG-120) was only approved by the Food and Drug Administration (FDA) for marketing, nevertheless, a range of resistance has been frequently reported. In this study, several mIDH1 inhibitors with the common backbone pyridin-2-one were explored using the three-dimensional structure-activity relationship (3D-QSAR), scaffold hopping, absorption, distribution, metabolism, excretion (ADME) prediction, and molecular dynamics (MD) simulations. Comparative molecular field analysis (CoMFA, R2 = 0.980, Q2 = 0.765) and comparative molecular similarity index analysis (CoMSIA, R2 = 0.997, Q2 = 0.770) were used to build 3D-QSAR models, which yielded notably decent predictive ability. A series of novel structures was designed through scaffold hopping. The predicted pIC50 values of C3, C6, and C9 were higher in the model of 3D-QSAR. Additionally, MD simulations culminated in the identification of potent mIDH1 inhibitors, exhibiting strong binding interactions, while the analyzed parameters were free energy landscape (FEL), radius of gyration (Rg), solvent accessible surface area (SASA), and polar surface area (PSA). Binding free energy demonstrated that C2 exhibited the highest binding free energy with IDH1, which was -93.25 ± 5.20 kcal/mol. This research offers theoretical guidance for the rational design of novel mIDH1 inhibitors.

Design, synthesis, AML activity and molecular modeling of novel IDH2 inhibitors.

Enasidenib (AG-221) is the only approved IDH2 inhibitor, clinical study found Enasidenib have some side-effects. In this work, we synthesized series of novel s-triazine derivatives, and the in vitro and in vivo activity of anti-AML has been studied using AM7577 model. The cell activity found Ta and Th showed excellent inhibition to AM7577. We further used the HuKemia Acute Leukemia xenograft model to investigate the in vivo efficacy of compounds Ta and Th, compared with AG-221, although Ta and Th can't reduce the 2-HG level obviously, those two compounds can prolong the survival of rats. The research can expand the structure of novel IDH2 inhibitors and provide useful information for further research of novel AML drugs.

Recent advances and potentiality of postbiotics in the food industry: Composition, inactivation methods, current applications in metabolic syndrome, and future trends.

Postbiotics are defined as "preparation of inanimate microorganisms and/or their components that confers a health benefit on the host". Postbiotics have unique advantages over probiotics, such as stability, safety, and wide application. Although postbiotics are research hotspots, the research on them is still very limited. This review provides comprehensive information on the scope of postbiotics, the preparation methods of inanimate microorganisms, and the application and mechanisms of postbiotics in metabolic syndrome (MetS). Furthermore, the application trends of postbiotics in the food industry are reviewed. It was found that postbiotics mainly include inactivated microorganisms, microbial lysates, cell components, and metabolites. Thermal treatments are the main methods to prepare inanimate microorganisms as postbiotics, while non-thermal treatments, such as ionizing radiation, ultraviolet light, ultrasound, and supercritical CO2, show great potential in postbiotic preparation. Postbiotics could ameliorate MetS through multiple pathways including the modulation of gut microbiota, the enhancement of intestinal barrier, the regulation of inflammation and immunity, and the modulation of hormone homeostasis. Additionally, postbiotics have great potential in the food industry as functional food supplements, food quality improvers, and food preservatives. In addition, the SWOT analyses showed that the development of postbiotics in the food industry exists both opportunities and challenges.

Evodiamine and Rutaecarpine as Potential Anticancer Compounds: A Combined Computational Study.

Evodiamine (EVO) and rutaecarpine (RUT) are the main active compounds of the traditional Chinese medicinal herb Evodia rutaecarpa. Here, we fully optimized the molecular geometries of EVO and RUT at the B3LYP/6-311++G (d, p) level of density functional theory. The natural population analysis (NPA) charges, frontier molecular orbitals, molecular electrostatic potentials, and the chemical reactivity descriptors for EVO and RUT were also investigated. Furthermore, molecular docking, molecular dynamics simulations, and the analysis of the binding free energies of EVO and RUT were carried out against the anticancer target topoisomerase 1 (TOP1) to clarify their anticancer mechanisms. The docking results indicated that they could inhibit TOP1 by intercalating into the cleaved DNA-binding site to form a TOP1−DNA−ligand ternary complex, suggesting that they may be potential TOP1 inhibitors. Molecular dynamics (MD) simulations evaluated the binding stability of the TOP1−DNA−ligand ternary complex. The calculation of binding free energy showed that the binding ability of EVO with TOP1 was stronger than that of RUT. These results elucidated the structure−activity relationship and the antitumor mechanism of EVO and RUT at the molecular level. It is suggested that EVO and RUT may be potential compounds for the development of new anticancer drugs.

Psychometric Properties and Factor Structures of the CERQ, DERS, and RESE Measures: A Bifactor Approach.

This study aims to simultaneously compare the psychometric properties and examine the factor structures of 3 emotion regulation (ER) strategy scales using a bifactor approach. Due to good reliability and validity, extensive use, and the same scoring method, the Cognitive Emotion Regulation Questionnaire, Difficulties in Emotion Regulation Scale, and Regulatory Emotional Self-Efficacy Scale were used to assess ER strategies in 1,036 Chinese respondents. A bifactor confirmatory factor analysis was designed to address the multidimensionality of the factor structure, and the corresponding bifactor structures were then applied in a subsequent bifactor multidimensional item response theory (MIRT) analysis. Finally, bifactor MIRT was used to compare the psychometric properties of the 3 measures. The results indicated that bifactor structures were appropriate for the 3 ER strategy measures, which performed well overall. Different measures provide the highest accuracy for specific groups and designs. Some strengths and limitations of this article are discussed.

[Utilization strategies of Chinese medicinal solid waste by pyrolysis and gasification technology].

With the advantages of extensive sources, easy collection, renewability, high yield, carbon circulation, low pollution, and so on, Chinese medicinal solid waste can be converted into clean gas by pyrolysis and gasification, which is then able to serve for industrial production. This is of great practical significance in the context of energy shortage and for solid waste recycling in China. This paper reviews the research progress on biomass gasification principle, gasification medium, and reactor in gasification technology of Chinese medicinal solid waste in recent years. Meanwhile, based on the summary of related research, the defects and improvement measures regarding raw materials, gasification agents, by-products, and reactors were discussed, which provides direction for further development in the gasification technology of Chinese medicinal solid waste in the future.

Sensitive electrochemical sensing platform for selective determination of dopamine based on amorphous cobalt hydroxide/polyaniline nanofibers composites.

In this study, amorphous cobalt hydroxide/polyaniline nanofibers (Co(OH)2/PANINF) composites were successfully prepared. The formation of amorphous Co(OH)2 with irregular surface structure was confirmed by x-ray diffraction, scanning electron microscopy, and selected-area electron diffraction. The non-enzymatic electrochemical sensor for the selective and sensitive determination of dopamine (DA) has been constructed by using Co(OH)2/PANINF composites modified glassy carbon electrode (Co(OH)2/PANINF/GCE), which exhibited excellent electrocatalytic activity toward DA, in a large part owing to the advantages of large surface area of amorphous Co(OH)2 and the synergetic effect between Co(OH)2 and PANINF. The electrochemical kinetics reveal that the DA oxidation involves two electrons and two protons in a quasi-reversible electrode reaction. Differential pulse voltammetry (DPV) studies show remarkable sensing performance for the determination of DA, with a low detection limit of 0.03 µM, and a wide linear range from 0.1 to 200 µM. From a broader perspective, the present study demonstrates that Co(OH)2/PANINF composites would be promising supporting materials for novel sensing platforms.

Facile preparation of novel Pd nanowire networks on a polyaniline hydrogel for sensitive determination of glucose.

In this study, novel Pd nanowire networks (PdNW) grown on three-dimensional polyaniline hydrogel (3D-PANI) were prepared via a facile one-step electrodeposition approach at a constant potential of - 0.2 V and further utilized as an electrochemical sensing material for sensitive determination of glucose in alkaline medium. Compared with the sensor based on Pd nanofilm (PdNF)/3D-PANI prepared by electrodeposition at - 0.9 V, the sensor based on PdNW/3D-PANI presented substantially enhanced electrocatalytic activity towards glucose oxidation, with an excellent sensitivity of 146.6 µA mM-1 cm-2, a linear range from 5.0 to 9800 µM, and a low detection limit of 0.7 µM and was, therefore, demonstrated to be available for the determination of glucose in human serum. These findings are likely attributed to the combination of advantages of both PdNW and 3D-PANI, which outperformed most other Pd-based non-enzymatic glucose sensors reported earlier. Moreover, this non-enzymatic electrochemical sensor based on PdNW/3D-PANI may serve as an alternative tool for the assay of glucose and possibly other biomolecules. Graphical abstract.

Design, synthesis, antitumor activity and theoretical calculation of novel PI3Ka inhibitors.

PI3Kα has been identified as an ideal target to treat with PIK3CA gene mutation disease, including drugs such as Alpelisib and Copanlisib. Five purine analogues and four thiazole analogues were designed and synthesized. Their enzymaticactivity against PI3Ka/ß/γ/δ were tested, respectively. All compounds showed excellent selectivity in modulating PI3Ka activity, and parts of the compounds showed good inhibition. Meanwhile, we used Autodock 4.2 to explore the binding mode of the most potential compound Tg with the target protein. In addition, DFT was used to calculate the HOMO-LUMO maps of the compounds Tf, Tg and positive control. This paper will provide some useful information for further drug design of PI3Kα inhibitors.

A Ferulic Acid Derivative FXS-3 Inhibits Proliferation and Metastasis of Human Lung Cancer A549 Cells via Positive JNK Signaling Pathway and Negative ERK/p38, AKT/mTOR and MEK/ERK Signaling Pathways.

Lung cancer is one of the most common malignancies and is an increasing cause of cancer-related deaths. In our previous study, a series of ferulic acid (FA) derivatives were designed and synthesized; they exhibited positive anti-cancer activities, especially for a compound labelled FXS-3. In this study, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed, wherein it revealed the inhibitory effect of FXS-3 on the proliferation and metastasis of human lung cancer A549 cells. The further flow cytometry assay showed that FXS-3 induced apoptosis of A549 cells induced cell cycle arrest at the G0/G1 phase. The trans-well migration and Matrigel invasion assays revealed that FXS-3 inhibited the migration and invasion of A549 cells. By the western blotting analysis, FXS-3 increased the expression of B-cell lymphoma-2 (Bcl-2) associated X protein (Bax)/Bcl-2 ratio, inhibited matrix metalloproteinase (MMP)-2 and MMP-9, and regulated the extracellular signal-regulated kinase (ERK)/p38, c-Jun N-terminal kinase (JNK), protein kinase B (AKT)/mechanistic target of rapamycin (mTOR), as well as mitogen-activated protein kinase (MEK)/ERK signaling pathways. The subsequent A549 xenograft-bearing mouse model and tail vein injection of A549 cells induced pulmonary tumor metastasis model showed that FXS-3 significantly restrained the tumor growth and metastasis. In conclusion, FXS-3 might inhibit proliferation and metastasis of human lung cancer A549 cells by positively regulating JNK signaling pathway and negativly regulating ERK/p38, AKT/mTOR, and MEK/ERK signaling pathways, which provides important scientific basis for the development of anti-cancer drugs about FA derivatives.

Design, synthesis, biological activities and DFT calculation of novel 1,2,4-triazole Schiff base derivatives.

Series of 1,2,4-triazole Schiff bases (2a-2d, 2f-2h and 3a-3h) have been designed and synthesized. The structure of title compounds was confirmed on the basis of their spectral data and elemental analysis. All the target compounds were screened for their in vitro antifungal activity and antibacterial activity. Two of the tested compounds (2a and 2b) exhibited significant antifungal activity against most fungi, especially compound 2a showed better antifungal activity than triadimefon. Meanwhile, the antibacterial activity assay also indicated compound 2a exhibited excellent antibacterial activities comparable to chloramphenicol. The SAR manifested no substitution at position 5 of the triazole ring caused an increase in activity, and 3-phenoxy phenyl group introduced in 1,2,4-triazole scaffold can enhance the antibacterial activity. The DFT calculation indicated triazole ring, S atom and benzene ring in both of the 2a and 3a make a major contribution to the activity.

Design, Synthesis, and Antifungal Activities of Novel 1,2,4-Triazole Schiff Base Derivatives.

With the aim to find new compounds with high antifungal activity, 21 4-amino-5-substituted-1,2,4-triazole Schiff bases (2a - 2g, 3a - 3g, and 4a - 4g) were designed and synthesized. Their antifungal activities against Pythium solani, Gibberlla nicotiancola, Fusarium oxysporium f. sp. niveum, Gibberlla saubinetii, Alternaria iycopersici, Phytophthora capsici, Physalospora piricola, Cercospora arachidicola hori, and Fusarium oxysporium f. sp. cucumber were tested, parts of the compounds exhibited excellent antifungal activity. This research provides useful information for further study of antifungal agents.

Synthesis, insecticidal activities and structure-activity relationship study of dual chiral sulfilimines.

To investigate the "methyl" impact on bioactivity of sulfiliminyl dicarboxamides, a total of 16 novel N-cyano and N-trifluoroacetyl sulfiliminyl dicarboxamides containing m-heptafluoroisopropylated aromatic amino moiety were studied. Two series of sulfiliminyl substituents were designed, synthesized and evaluated against oriental armyworm (Pseudaletia separata Walker) for their insecticidal activities. Their chemical structures were established by corresponding [Formula: see text] NMR, HRMS and optical polarimetry. Bioassay results revealed that some of the title compounds showed potent insecticidal activities against oriental armyworm. Notably, compounds IIa, IIIa, IVa exhibited 100% activity at [Formula: see text], in particular, IIa showed a comparable control efficacy to that of the commercial product flubendiamide. The SAR of these N-cyano sulfiliminyl isomers can be summarized as follows (Sc, Ss) [Formula: see text] (Sc, Rs), while the N-trifluoroacetyl sulfiliminyl isomers is (Sc, Rs) [Formula: see text] (Sc, Ss). Comparative molecular field analysis indicated that an electropositive substituent, [Formula: see text] group in the benzene ring was very important for the improvement in biological activity. These results could hold promise for novel chiral sulfiliminyl RyR regulators.

Identification of mIDH1 R132C/S280F Inhibitors from Natural Products by Integrated Molecular Docking, Pharmacophore Modeling and Molecular Dynamics Simulations.

Mutant isocitrate dehydrogenase 1 (mIDH1) is a common driving factor in acute myeloid leukemia (AML), with the R132 mutation accounting for a high proportion. The U.S. Food and Drug Administration (FDA) approved Ivosidenib, a molecular entity that targets IDH1 with R132 mutations, as a promising therapeutic option for AML with mIDH1 in 2018. It was of concern that the occurrence of disease resistance or recurrence, attributed to the IDH1 R132C/S280F second site mutation, was observed in certain patients treated with Ivosidenib within the same year. Furthermore, it should be noted that most mIDH1 inhibitors demonstrated limited efficacy against mutations at this specific site. Therefore, there is an urgent need to investigate novel inhibitors targeting mIDH1 for combating resistance caused by IDH1 R132C/S280F mutations in AML. This study aimed to identify novel mIDH1 R132C/S280F inhibitors through an integrated strategy of combining virtual screening and dynamics simulations. First, 2000 hits were obtained through structure-based virtual screening of the COCONUT database, and hits with better scores than -10.67 kcal/mol were obtained through molecular docking. A total of 12 potential small molecule inhibitors were identified through pharmacophore modeling screening and Prime MM-GBSA. Dynamics simulations were used to study the binding modes between the positive drug and the first three hits and IDH1 carrying the R132C/S280F mutation. RMSD showed that the four dynamics simulation systems remained stable, and RMSF and Rg showed that the screened molecules have similar local flexibility and tightness to the positive drug. Finally, the lowest energy conformation, hydrogen bond analysis, and free energy decomposition results indicate that in the entire system the key residues LEU120, TRP124, TRP267, and VAL281 mainly contribute van der Waals forces to the interaction, while the key residues VAL276 and CYS379 mainly contribute electrostatic forces.

Discovery of a Novel Benzothiadiazine-Based Selective Aldose Reductase Inhibitor as Potential Therapy for Diabetic Peripheral Neuropathy.

Aldose reductase 2 (ALR2), an activated enzyme in the polyol pathway by hyperglycemia, has long been recognized as one of the most promising targets for complications of diabetes, especially in diabetic peripheral neuropathy (DPN). However, many of the ALR2 inhibitors have shown serious side effects due to poor selectivity over aldehyde reductase (ALR1). Herein, we describe the discovery of a series of benzothiadiazine acetic acid derivatives as potent and selective inhibitors against ALR2 and evaluation of their anti-DPN activities in vivo. Compound 15c, carrying a carbonyl group at the 3-position of the thiadiazine ring, showed high potent inhibition against ALR2 (IC50 = 33.19 nmol/L) and ∼16,109-fold selectivity for ALR2 over ALR1. Cytotoxicity assays ensured the primary biosafety of 15c. Further pharmacokinetic assay in rats indicated that 15c had a good pharmacokinetic feature (t1/2 = 5.60 h, area under the plasma concentration time curve [AUC(0-t)] = 598.57 ± 216.5 µg/mL * h), which was superior to epalrestat (t1/2 = 2.23 h, AUC[0-t] = 20.43 ± 3.7 µg/mL * h). Finally, in a streptozotocin-induced diabetic rat model, 15c significantly increased the nerve conduction velocities of impaired sensory and motor nerves, achieved potent inhibition of d-sorbitol production in the sciatic nerves, and significantly increased the paw withdrawal mechanical threshold. By combining the above investigations, we propose that 15c might represent a promising lead compound for the discovery of an antidiabetic peripheral neuropathy drug.

Diosgenin Targets CaMKK2 to Alleviate Type II Diabetic Nephropathy through Improving Autophagy, Mitophagy and Mitochondrial Dynamics.

Diabetic nephropathy (DN) is a worldwide health problem with increasing incidence. Diosgenin (DIO) is a natural active ingredient extracted from Chinese yams (Rhizoma dioscoreae) with potential antioxidant, anti-inflammatory, and antidiabetic effects. However, the protective effect of DIO on DN is still unclear. The present study explored the mitigating effects and underlying mechanisms of DIO on DN in vivo and in vitro. In the current study, the DN rats were induced by a high-fat diet and streptozotocin and then treated with DIO and metformin (Mef, a positive control) for 8 weeks. The high-glucose (HG)-induced HK-2 cells were treated with DIO for 24 h. The results showed that DIO decreased blood glucose, biomarkers of renal damage, and renal pathological changes with an effect comparable to that of Mef, indicating that DIO is potential active substance to relieve DN. Thus, the protective mechanism of DIO on DN was further explored. Mechanistically, DIO improved autophagy and mitophagy via the regulation of the AMPK-mTOR and PINK1-MFN2-Parkin pathways, respectively. Knockdown of CaMKK2 abolished AMPK-mTOR and PINK1-MFN2-Parkin pathways-mediated autophagy and mitophagy. Mitophagy and mitochondrial dynamics are closely linked physiological processes. DIO also improved mitochondrial dynamics through inhibiting fission-associated proteins (DRP1 and p-DRP1) and increasing fusion proteins (MFN1/2 and OPA1). The effects were abolished by CaMKK2 and PINK1 knockdown. In conclusion, DIO ameliorated DN by enhancing autophagy and mitophagy and by improving mitochondrial dynamics in a CaMKK2-dependent manner. PINK1 and MFN2 are proteins that concurrently regulated mitophagy and mitochondrial dynamics.

Diosgenin Inhibits ROS Generation by Modulating NOX4 and Mitochondrial Respiratory Chain and Suppresses Apoptosis in Diabetic Nephropathy.

Diosgenin (DIO) is a dietary steroid sapogenin possessing multiple biological functions, such as the amelioration of diabetes. However, the remission effect of DIO on diabetic nephropathy (DN) underlying oxidative stress and cell apoptosis remains unclear. Here, the effect of DIO on ROS generation and its induced cell apoptosis was studied in vitro and in vivo. Renal proximal tubular epithelial (HK-2) cells were treated with DIO (1, 2, 4 µM) under high glucose (HG, 30 mM) conditions. DN rats were induced by a high-fat diet combined with streptozotocin, followed by administration of DIO for 8 weeks. Our data suggested that DIO relieved the decline of HK-2 cell viability and renal pathological damage in DN rats. DIO also relieved ROS (O2- and H2O2) production. Mechanistically, DIO inhibited the expression of NOX4 and restored mitochondrial respiratory chain (MRC) complex I-V expressions. Further, DIO inhibited mitochondrial apoptosis by ameliorating mitochondrial membrane potential (MtMP) and down-regulating the expressions of CytC, Apaf-1, caspase 3, and caspase 9, while up-regulating Bcl2 expression. Moreover, the ER stress and its associated cell apoptosis were inhibited through decreasing PERK, p-PERK, ATF4, IRE1, p-CHOP, and caspase 12 expressions. Collectively, DIO inhibited ROS production by modulating NOX4 and MRC complexes, which then suppressed apoptosis regulated by mitochondria and ER stress, thereby attenuating DN.

Study on the Mechanism of Jiaotai Pill Intervention on Insomnia Animal Model Based on Gut Microbiome and Metabolomics.

Background: With the continuous advancement of clinical application and experimental research of JTP, the application prospect of JTP in nervous system diseases and metabolic diseases is becoming increasingly clear. Jiaotai Pill (JTP) is a traditional Chinese medicine formula for insomnia, consisting of Coptidis rhizoma and Cinnamomi cortex, which dates back to Han Shi Yi Tong in the Ming Dynasty of China. Objective: Based on the brain-gut axis theory, this paper aims to explore the potential mechanism of JTP in the intervention of insomnia by using intestinal microbiome and metabolomics technology, taking the animal model of insomnia as the research object, so as to provide experimental basis for its further application and research. Methods: The insomnia mouse model was induced by intraperitoneal injection of para-chlorophenylalanine (PCPA). The clinical equivalent dose of JTP was administered by gavage for one week. The efficacy of JTP was evaluated by behavioral tests, serum biochemical detection, and brain histomorphological observation. The contents of cecum were analyzed by microbiomics and metabolomics. Results: The results show that insomnia caused by PCPA led to daytime dysfunction, higher HPA axis hormone levels, and morphologically impaired hippocampus. JTP reversed these anomalies. Omics research indicates that JTP significantly reduced gut α diversity; at the phylum level, JTP reduced the relative abundance of Firmicutes, Deferribacterota, Cyanobacteria, and Actinobacteriota and increased the relative abundance of Verrucomicrobiota, Proteobacteria, and Desulfobacterota. At the genus level, JTP reduced the relative abundance of Muribaculaceae, Lachnospiraceae_NK4A136_group, Alistipes, Colidextribacter, Muribaculum, and Mucispirillum and increased the relative abundance of Bacteroides and Akkermansia. JTP also reversed the activation of the linoleic acid metabolism pathway induced by insomnia. The combined analysis of omics suggests that JTP may play a role by regulating the inflammatory state of the body. Further gene expression analysis of brain tissue confirmed this. Conclusions: We hypothesize that JTP may achieve insomnia relief by eliminating inflammation-causing bacteria in the gut and reducing inflammation levels through the brain-gut axis, pointing to potential targets and pathways for future research on JTP.

Linarin ameliorates dextran sulfate sodium-induced colitis in C57BL/6J mice via the improvement of intestinal barrier, suppression of inflammatory responses and modulation of gut microbiota.

Linarin is a natural flavonoid compound found in Chrysanthemum indicum, Mentha species and other plants with various biological activities. The study aimed to investigate the protective effect of linarin supplementation on dextran sulfate sodium (DSS)-induced colitis in C57BL/6J mice and its potential mechanisms. The results showed that doses of linarin at 25 and 50 mg kg-1 day-1 alleviated the DSS-induced histopathological damage, and improved the mucosal layer and intestinal barrier function. Importantly, Linarin significantly suppressed the levels of myeloperoxidase activity and pro-inflammatory cytokines (IL-6, TNF-α, IFN-γ and IL-1ß) in the colon, and enhanced the mRNA level of anti-inflammatory cytokine (IL-10). Moreover, 50 mg kg-1 day-1 linarin reversed the gut microbiota damaged by DSS, including Alistipes, Rikenella and Clostridia UCG-014_norank. Linarin also partly increased the relative abundance of short-chain fatty acids (SCFAs)-producing bacteria, including Lactobacillus, Roseburia, Parabacteroides and Blautia, and elevated the contents of SCFAs. Collectively, linarin attenuates DSS-induced colitis in mice, suggesting that linarin may be a promising nutritional strategy for reducing inflammatory bowel disease.