Konjac glucomannan-based highly antibacterial active films loaded with thyme essential oil through bacterial cellulose nanofibers/Ag nanoparticles stabilized Pickering emulsions.

The aim of this study was to develop novel konjac glucomannan (KGM)-based highly antibacterial active films, where five types of films were prepared and compared. The microstructure results showed that KGM-based films loaded with thyme essential oil (TEO) through bacterial cellulose nanofibers/Ag nanoparticles (BCNs/Ag nanoparticles) stabilized Pickering emulsions (Type V films) displayed the smoothest surface and the most evenly dispersed TEO droplets as compared with the other four types of films. Moreover, Type V films showed the highest contact angle value (86.28°), the best thermal stability and mechanical properties. Furthermore, Type V films presented the highest total phenol content (13.23 mg gallic acid equivalent/g film) and the best antioxidant activity (33.96 %) as well as the best sustained-release property, thus showing the best antibacterial activity, which was probably due to that BCNs/Ag nanoparticles and TEO displayed a synergistic effect to some extent. Consequently, Type V film-forming solutions were used as coatings for tangerines. The results showed that the tangerines treated with Type V coatings displayed excellent fresh-keeping properties. Therefore, the coatings, KGM-based film-forming solutions loaded with TEO through BCNs/Ag nanoparticles stabilized Pickering emulsions, have great potential for the preservation of fruits and vegetables.

Recent Advances in Current Uptake Situation, Metabolic and Nutritional Characteristics, Health, and Safety of Dietary Tryptophan.

Tryptophan (Trp) is an essential amino acid which is unable to be synthesized in the body. Main sources of Trp are uptake of foods such as oats and bananas. In this review, we describe the status of current dietary consumption, metabolic pathways and nutritional characteristics of Trp, as well as its ingestion and downstream metabolites for maintaining body health and safety. This review also summarizes the recent advances in Trp metabolism, particularly the 5-HT, KYN, and AhR activation pathways, revealing that its endogenous host metabolites are not only differentially affected in the body but also are closely linked to health. More attention should be paid to targeting its specific metabolic pathways and utilizing food molecules and probiotics for manipulating Trp metabolism. However, the complexity of microbiota-host interactions requires further exploration to precisely refine targets for innovating the gut microbiota-targeted diagnostic approaches and informing subsequent studies and targeted treatments of diseases.

Nonextractable Polyphenols from Fu Brick Tea Alleviates Ulcerative Colitis by Controlling Colon Microbiota-Targeted Release to Inhibit Intestinal Inflammation in Mice.

This study was designed to elucidate the colon microbiota-targeted release of nonextractable bound polyphenols (NEPs) derived from Fu brick tea and to further identify the possible anti-inflammatory mechanism in dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice. 1.5% DSS drinking water-induced C57BL/6J mice were fed rodent chow supplemented with or without 8% NEPs or dietary fibers (DFs) for 37 days. The bound p-hydroxybenzoic acid and quercetin in NEPs were liberated up to 590.5 ± 70.6 and 470.5 ± 51.6 mg/g by in vitro human gut microbiota-simulated fermentation, and released into the colon of the mice supplemented with NEPs by 4.4- and 1.5-fold higher than that of the mice supplemented without NEPs, respectively (p < 0.05). Supplementation with NEPs also enhanced the colonic microbiota-dependent production of SCFAs in vitro and in vivo (p < 0.05). Interestingly, Ingestion of NEPs in DSS-induced mice altered the gut microbiota composition, reflected by a dramatic increase in the relative abundance of Dubosiella and Enterorhabdus and a decrease in the relative abundance of Alistipes and Romboutsia (p < 0.05). Consumption of NEPs was demonstrated to be more effective in alleviating colonic inflammation and UC symptoms than DFs alone in DSS-treated mice (p < 0.05), in which the protective effects of NEPs against UC were highly correlated with the reconstruction of the gut microbiome, formation of SCFAs, and release of bound polyphenols. These findings suggest that NEPs as macromolecular carriers exhibit targeted delivery of bound polyphenols into the mouse colon to regulate gut microbiota and alleviate inflammation.

Atypical Plant miRNA cal-miR2911: Robust Stability against Food Digestion and Specific Promoting Effect on Bifidobacterium in Mice.

Previous studies showed that cal-miR2911, featuring an atypical biogenesis, could target genes of virus and in turn inhibit virus replication. Given its especial sequence motif and cross-kingdom potential, the stability of miR2911 under digestive environment and its impact on intestinal microbes in mice were examined. The results showed that miR2911 was of considerable stability during oral, gastric, and intestinal digestion. The coingested food matrix enhanced its stability in the gastric phase, contributing to the existence of miR2911 in mouse intestines. The survival miR2911 promoted the growth of Bifidobacterium in mice and maintained the overall composition and diversity of the gut microbiota. miR2911 specifically entered the cells of Bifidobacterium adolescentis and potentially modulated the gene expression as evidenced by the dual-luciferase assay. The current study provided evidence on the cross-kingdom communication between dietary miRNAs and gut microbes, suggesting that modulating target bacteria using miRNAs for nutritional and therapeutic ends is promising.

Synthesis of bacterial cellulose nanofibers/Ag nanoparticles: Structure, characterization and antibacterial activity.

The aim of this study was to compare the characterization of bacterial cellulose nanofibers/Ag nanoparticles (BCNs/Ag nanoparticles) obtained by three different pretreatment methods of BCNs (no pretreatment, sodium hydroxide activation pretreatment and TEMPO-mediated oxidation pretreatment), which were recoded as N-BCNs/Ag nanoparticles, A-BCNs/Ag nanoparticles and O-BCNs/Ag nanoparticles, respectively. The results of scanning electron microscopy and transmission electron microscopy showed the prepared Ag nanoparticles by three different pretreatment methods were spherical and dispersed on the surface of BCNs, while the Ag nanoparticles in O-BCNs/Ag nanoparticles displayed the smallest diameter with a value of 20.25 nm and showed the most uniform dispersion on the surface of BCNs. The ICP-MS result showed O-BCNs/Ag nanoparticles had the highest content of Ag nanoparticles with a value of 2.98 wt%, followed by A-BCNs/Ag nanoparticles (1.53 wt%) and N-BCNs/Ag nanoparticles (0.84 wt%). The cytotoxicity assessment showed that the prepared BCNs/Ag nanoparticles were relatively safe. Furthermore, the O-BCNs/Ag nanoparticles had the best antioxidant and antibacterial activities as compared with the other two types of BCNs/Ag nanoparticles, where O-BCNs/Ag nanoparticles destroyed the structure of bacterial cell membranes to lead the leakage of intracellular components. This study showed that O-BCNs/Ag nanoparticles as antibacterial agents have great potential in food packaging.

peu-MIR2916-p3-enriched garlic exosomes ameliorate murine colitis by reshaping gut microbiota, especially by boosting the anti-colitic Bacteroides thetaiotaomicron.

Plant-derived exosome-like nanoparticles (ELNs) have drawn considerable attention for oral treatment of colonic diseases. However, the roles of ELNs derived from garlic on colitis remain unclear. Here, we demonstrate that garlic ELNs (GELNs), with desirable particle sizes (79.60 nm) and trafficking large amounts of functional proteins and microRNAs, stably roam in the gut and confer protection against ulcerative colitis (UC). In mice with DSS-induced colitis, orally administered GELNs effectively ameliorated bloody diarrhea, normalized the production of proinflammatory cytokines, and prevented colonic barrier impairment. Mechanistically, GELNs were taken up by gut microbes and reshaped DSS-induced gut microbiota dysbiosis, in which Bacteroides was the dominant respondent genus upon GELNs treatment. Notably, GELNs-enriched peu-MIR2916-p3 specifically promoted the growth of Bacteroides thetaiotaomicron, an intestinal symbiotic bacterium with palliative effects on colitis. Our findings provide new insights into the medicinal application of GELNs and highlight their potential as natural nanotherapeutic agents for preventing and treating UC.

Stability of high internal-phase emulsions prepared from phycocyanin and small-molecule sugars.

BACKGROUND: The use of high internal-phase Pickering emulsions in the food industry is widespread due to their excellent stability and special rheological properties. Proteins are often used as food-grade Pickering stabilizers due to their safety and nutritious properties. Nowadays, the development and efficient utilization of novel proteins as Pickering stabilizers has become a new challenge. RESULTS: Phycocyanin complexes with small-molecule sugars (SMS), formed as a result of non-thermal interactions, can serve as stabilizers for high internal-phase Pickering emulsions. The addition of SMS-enabled gel-like emulsions significantly reduced the amount of emulsifier used. When the SMS was sorbitol, the emulsion had excellent elastic properties and self-supporting ability and was stable during long-term storage, when subjected to centrifugation, and under different temperature conditions. The fluorescent property of phycocyanin was utilized to investigate the formation mechanism of the emulsion. Small-molecule sugars were able to form 'sugar-shell' structures on the surface of proteins to enhance the structural stability of proteins. Phycocyanin-SMS-stabilized emulsions provided superior protection for photosensitive and volatile substances. The retention rates of trans-resveratrol and n-hexane increased by 384.75% and 30.55%, respectively. CONCLUSION: These findings will encourage the development of proteins that stabilize Pickering emulsions. They will also provide new ideas for protecting photosensitive and volatile substances. © 2023 Society of Chemical Industry.

Effects of Fu brick tea polysaccharides on gut microbiota and fecal metabolites of HFD/STZ-induced type 2 diabetes rats.

The prevalence of type 2 diabetes mellitus (T2DM) has dramatically increased globally, and the antidiabetic effects and underlying mechanisms of the polysaccharides extracted from Fu brick tea (FBTP) were investigated in high-fat diet (HFD)/streptozotocin (STZ)-induced T2DM rats. Administration of FBTP at 200 and 400 mg per kg bw significantly relieved dyslipidemia (i.e. TC, TG, LDL-C and HDL-C), insulin resistance (IR) and pancreas oxidative stress (i.e. CAT and GSH-Px) in T2DM rats. Mechanistically, FBTP rescued the HFD/STZ-induced alterations in the abundance of Bacteroidota, Actinobacteriota, Proteobacteria and Firmicutes. At the genus level, FBTP notably increased the abundance of Ruminococcus, Lactobacillus and Lachnospiraece_NK4A136_group, but reduced the population of Prevotella and Faecalibaculum in T2DM rats. FBTP also significantly elevated colonic short-chain fatty acid (SCFAs) levels. Moreover, apparent changes in amino acid absorption and metabolism were observed upon FBTP intervention. These findings suggested that FBTP might alleviate T2DM by reshaping the gut microbiota and regulating intestinal metabolites.

Preparation of acid-driven magnetically imprinted micromotors and selective loading of phycocyanin.

Phycocyanin, a macromolecular protein known for its robust fluorescence, proves to be highly suitable for verifying the successful deposition of imprinted layers. In this study, an acid-propelled magnetic micromotor was successfully fabricated by utilizing surface imprinting and self-propelled nanomotor technology to achieve selective loading and capture of targets such as phycocyanin for future applications in environmental monitoring and precision drug delivery in vivo. This micromotor features a distinct recognition layer achieved through a template electrodeposition method. The outermost imprint layer of the micromotor was meticulously crafted using poly(3,4-ethylenedioxythiophene)/poly(sodium-4-styrenesulfonate) in the presence of a template, while the Pt layer serves as the supportive foundation, the Ni layer acts as the magnetic guidance component, and the innermost layer consists of metal Zn. In acidic environments, the Zn reacts to generate bubbles, which propels the micromotor's motion. The micromotor was comprehensively characterized using techniques such as scanning electron microscopy. Findings highlight the exceptional self-propulsion of the Zn-based micromotor, which is a fusion of molecular imprinting and micromotor technologies. This innovative design achieves an impressive maximum velocity of approximately 100 µm s-1, as well as commendable magnetic steering performance. Furthermore, the micromotor demonstrates the ability to imprint target protein through the imprint layer, enabling selective recognition and capture for transport of specific phycocyanin. In vitro cytotoxicity tests have also demonstrated that the micromotors are non-toxic to cells. This breakthrough concept offers a novel avenue for realizing targeted capture and transport of specific nutrients within the human gastric environment.

Recent research advances on oral colon-specific delivery system of nature bioactive components: A review.

Oral colon-specific delivery system (OCDS) is a targeted approach that aims to directly deliver bioactive compounds directly to the colon following oral administration, thereby enhancing the colonic release of bioactive substances and minimizing adverse reactions. The effectiveness of bioactive substances in the colon hinges on the degree of release, which are affected by various factors including pH, mucosal barrier, delivery time and so on. Therefore, this review provides a comprehensive overview of the key factors affecting oral colon-specific release of bioactive components firstly. Considering the oral safety, this review then mainly focuses on the types of carriers with edible OCDS and preparation strategies for OCDS. Finally, several preparation strategies for loading typical natural bioactive ingredients into oral safe OCDS are reviewed, along with future development prospects.

Eurotium cristatum from Fu Brick Tea Promotes Adipose Thermogenesis by Boosting Colonic Akkermansia muciniphila in High-Fat-Fed Obese Mice.

This study investigated the potential fat-thermogenic effects of Eurotium cristatum, and elucidated the underlying mechanisms. The 12-week administration of E. cristatum in HFD-fed obese mice reduced body weight and improved glucolipid metabolism disorders. The administration of E. cristatum also efficiently promoted thermogenesis by increasing the expression of UCP1 and PRDM16 in both interscapular brown adipose tissue (iBAT) and inguinal white adipose tissue (iWAT) of HFD-fed mice. Furthermore, E. cristatum shaped the gut microbiome by increasing the abundance of Parabacteroides and Akkermansia muciniphila, and also elevated the levels of cecal short-chain fatty acids, particularly propionate and acetate. Of note, A. muciniphila was highly negatively correlated with body weight gain (r = -0.801, p < 0.05) and the iWAT index (r = -0.977, p < 0.01), suggesting that A. muciniphila may play an important role in the thermogenic mobilization induced by E. cristatum. Continuous supplementation with A. muciniphila suppressed adipose accumulation, improved glucolipid metabolism, and enhanced the thermogenic activity of iWAT and iBAT. Collectively, our results propose that boosted A. muciniphila acts as a key microbe in tea-derived probiotic E. cristatum-mediated fat-thermogenic and anti-obesity effects.

The Development of Highly pH-Sensitive Bacterial Cellulose Nanofibers/Gelatin-Based Intelligent Films Loaded with Anthocyanin/Curcumin for the Fresh-Keeping and Freshness Detection of Fresh Pork.

The aim of this study was to develop highly pH-sensitive bacterial cellulose nanofibers/gelatin-based intelligent films, where the intelligent films were loaded with different ratios (10:0, 0:10 2:8, 5:5 and 8:2, w/w) of curcumin:anthocyanin (Cur/ATH), and the characterization of intelligent films was investigated. The results showed that the microstructures of intelligent films were much rougher as the proportion of curcumin increased. FTIR results showed that anthocyanin and curcumin were fixed in gelatin matrix by hydrogen bonds. Moreover, XRD results showed that curcumin had a significant effect on the crystal structure of the films. Interestingly, films loaded with a Cur/ATH ratio of 5:5 had the best mechanical and antioxidant properties and a high pH-sensitivity property. Consequently, the bacterial cellulose nanofibers/gelatin-based intelligent films loaded with a Cur/ATH ratio of 5:5 were used for the packaging of fresh pork, displaying good fresh-keeping and freshness detection effects. Therefore, this study suggested that bacterial cellulose nanofibers/gelatin-based intelligent films have great potential in the fresh-keeping and freshness detection of meat.

Research Advances in the High-Value Utilization of Peanut Meal Resources and Its Hydrolysates: A Review.

Peanut meal (PM) is a by-product of extracting oil from peanut kernels. Although peanut meal contains protein, carbohydrates, minerals, vitamins, and small amounts of polyphenols and fiber, it has long been used as a feed in the poultry and livestock industries due to its coarse texture and unpleasant taste. It is less commonly utilized in the food processing industry. In recent years, there has been an increasing amount of research conducted on the deep processing of by-products from oil crops, resulting in the high-value processing and utilization of by-products from various oil crops. These include peanut meal, which undergoes treatments such as enzymatic hydrolysis in industries like food, chemical, and aquaculture. The proteins, lipids, polyphenols, fibers, and other components present in these by-products and hydrolysates can be incorporated into products for further utilization. This review focuses on the research progress in various fields, such as the food processing, breeding, and industrial fields, regarding the high-value utilization of peanut meal and its hydrolysates. The aim is to provide valuable insights and strategies for maximizing the utilization of peanut meal resources.

Broccoli-Derived Exosome-like Nanoparticles Alleviate Loperamide-Induced Constipation, in Correlation with Regulation on Gut Microbiota and Tryptophan Metabolism.

Constipation, a common gastrointestinal dysfunction, damages patients' life quality and predisposes them to other serious diseases. Current strategies against constipation often cause drug dependency and side effects. Here, we demonstrated that broccoli-derived exosome-like nanoparticles (BENs), a natural product with high gastrointestinal stability, ameliorated LOP-induced constipation in mice. Specifically, orally administered BENs (17.5 mg/kg/d) effectively shortened defecation time, sped up intestinal propulsion rate, and increased feces amount in constipated mice. BENs also raised excitatory neurotransmitters SP and MTL and reduced inhibitory neurotransmitters VIP and ET-1. Mechanistically, BENs were taken up by gut microbes, restored LOP-disordered gut microbiota, and altered microbial metabolism of SCFAs and tryptophan, as evidenced by the results of fluorescence microscopy, 16S rRNA gene sequencing, and nontargeted metabolomics. Thereinto, BEN-enriched SCFA-producing microorganisms are closely associated with the feces amount and SP and VIP levels and BEN-elevated indole-3-pyruvic acid and 3-indoleacetic acid are highly linked to ET-1, SP, and MTL levels. Conclusively, BENs, mitigating constipation by regulating gut microbiota and microbial tryptophan metabolism, showed high potential to be developed as alternative regimens for constipation.

Plant miRNA bol-miR159 Regulates Gut Microbiota Composition in Mice: In Vivo Evidence of the Crosstalk between Plant miRNAs and Intestinal Microbes.

New evidence reveals that bol-miR159, an miRNA rich in fruits and vegetables, cross-kingdomly functions in mammalian bodies. However, whether the miRNA could regulate gut microbiota remains unclear. Here, the effect of miR159 on mouse intestinal microbes was comprehensively examined. The results showed that supplementation of miR159 to the chow diet significantly enhanced the diversity of mouse gut microbiota without causing pathological lesions or inflammatory responses on the intestines. At the phylum level, miR159 increased the abundance of Proteobacteria and decreased the Firmicute-to-Bacteroidetes (F/B) ratio. miR159 had prebiotic-like effects on mouse gut microbiota, as it promoted the growth of the bacteria that is beneficial for maintaining gut health. The miRNA can target bacteria genes and get into the bacteria cells. The data provide direct in vivo evidence on the crosstalk between plant miRNAs and intestinal microbes, highlighting the potential for miRNA-based strategies that modulate gut microbes to improve host health.

Polysaccharide from Ziyang Selenium-Enriched Green Tea Prevents Obesity and Promotes Adipose Thermogenesis via Modulating the Gut Microbiota.

The objective of the current study was to explore the potential mechanism of Ziyang selenium-enriched green tea polysaccharide (Se-GTP) against obesity. The results showed that Se-GTP significantly alleviated obesity and related metabolic disorders caused by high-fat diet (HFD) in mice. 16S rRNA gene sequencing results revealed that Se-GTP improved gut microbiota disturbance of obese mice and facilitated proliferation of probiotics such as Bacteroides, Bifidobacterium, Lactobacillus, and Akkermansia. In addition, the colonic content of succinate, a product of microbial metabolite in connection with adipocyte thermogenesis, was significantly enhanced by Se-GTP treatment. Therefore, Se-GTP facilitated brown adipose tissue (BAT) thermogenesis and inguinal white adipose tissue (iWAT) browning in obese mice, which could be revealed by increased expressions of thermogenic marker proteins UCP1, PGC-1α, and CIDEA in BAT and iWAT. Interestingly, Se-GTP intervention also observably increased the content of M2-like macrophages in iWAT of obese mice. To summarize, the results of this study are the first to show that Se-GTP can stimulate the browning of iWAT and BAT thermogenesis to counteract obesity, which may be pertinent with the alteration of gut microbiota in obese mice.

Bacterial cellulose nanofibers used as nanofillers improved the fresh-keeping performance of gelatin-based edible coating for fresh-cut apples.

In this study, bacterial cellulose nanofibers (BCNs) (0%, 1%, 2%, and 3%) were used as nanofillers to prepare gelatin-based edible films, and their physical properties and fresh-keeping performance were investigated. The microstructure observation showed that the BCNs were well dispersed in the gelatin-based edible films and the surface roughness of the films increased with the increase of BCNs content. X-ray diffraction and thermogravimetric analysis showed that the crystallinity and thermal stability of the film were significantly increased with the increase of BCNs. Fourier-transform infrared spectroscopy analysis suggested that hydrogen bond interactions occurred between BCNs and gelatin polymers, leading to improved mechanical properties with the increase of BCNs content. Furthermore, the barrier performance was also improved with the increase of BCNs content, where gelatin-based edible films with 2% BCNs showed the best mechanical property. Meanwhile, the gelatin-based film-forming solutions (FFSs) containing different BCNs were coated on the fresh-cut apples and the corresponding fresh-keeping performance was investigated. The results showed that the fresh-keeping parameters of fresh-cut apples coated with FFSs containing BCNs were better as compared with those of pure gelatin FFSs. Moreover, the fresh-keeping parameters were improved with the increase of BCNs, especially the FFSs containing 2% BCNs that showed the best fresh-keeping parameters. Therefore, BCNs, used as nanofillers, are an excellent enhancer to improve the fresh-keeping performance of the gelatin-based edible coating, showing a promising potential application in the food preservation field.

Low oil Pickering emulsion gels stabilized by bacterial cellulose nanofiber/soybean protein isolate: An excellent fat replacer for ice cream.

Food-grade Pickering emulsion gels with different oil phase fractions stabilized by Bacterial cellulose nanofibers/Soy protein isolate complex colloidal particles were prepared by one-step method. The properties of Pickering emulsion gels with different oil phase fractions (5 %, 10 %, 20 %, 40 %, 60 %, 75 %, v/v) and their applications in ice cream were investigated in the present study. The microstructural results showed that Pickering emulsion gels with the low oil phase fractions (5 %-20 %) were an emulsion droplet-filled gel, where the oil droplets were embedded in the network structure of cross-linked polymer, while Pickering emulsion gels with higher oil phase fractions (40 %-75 %) were an emulsion droplet-aggregated gel, which formed a network structure by flocculated oil droplets. The rheology result showed that the low oil Pickering emulsion gels had the same excellent performance as the high oil Pickering emulsion gels. Furthermore, the low oil Pickering emulsion gels showed good environmental stability under harsh conditions. Consequently, Pickering emulsion gels with 5 % oil phase fraction were used as fat replacers in ice cream and ice cream with different fat replacement rates (30 %, 60 % and 90 %, w/w) was prepared in this work. The results showed the appearance and texture of the ice cream with low oil Pickering emulsion gels as fat replacers was similar to that of the ice cream with no fat replacers, and the melting rate of the ice cream with low oil Pickering emulsion gels as fat replacers showed the lowest value of 21.08 % during the 45 min of melting experiment, as the fat replacer rate in the ice cream reached to 90 %. Therefore, this study demonstrated that low oil Pickering emulsion gels were excellent fat replacers and had great potential application in low calorie food production.

Lycium ruthenicum Murr. anthocyanins inhibit hyperproliferation of synovial fibroblasts from rheumatoid patients and the mechanism study powered by network pharmacology.

BACKGROUND: Rheumatoid arthritis (RA), is a typical autoimmune disease affecting nearly 1% of the world's population. The dysfunctional hyperproliferation of synovial fibroblast (SF) in articular cartilage of RA patients is considered as the essential etiology. Traditional chemotherapeutic agents for RA treatment are imperfect for their high cost and unpredictable side-effects. L. ruthenicum anthocyanins (LRAC) is a natural product that of potential for therapeutic application against RA. METHODS: LRAC was characterized by UPLC-MS/MS. Bioinformatics analyses based on network pharmacology were applied to predict the potential targets of LRAC, and to select DEGs (differentially expressed genes) caused by RA pathogenesis from GSE77298. Interactions between LRAC and the predicted targets were evaluated by molecular docking. Effects of LRAC on SFs from RA patients were examined by in vitro assays, which were analyzed by flow cytometry and western blotting (WB). RESULTS: LRAC was able to inhibit the abnormal proliferation and aggressive invasion of SFs from RA patients. LRAC was mainly constituted by petunidin (82.7%), with small amount of delphinidin (12.9%) and malvidin (4.4%) in terms of anthocyanidin. Bioinformatics analyses showed that in 3738 RA-related DEGs, 58 of them were collectively targeted by delphinidin, malvidin and delphinidin. AR, CDK2, CHEK1, HIF1A, CXCR4, MMP2 and MMP9, the seven hub genes constructed a central network mediating the signal transduction. Molecular docking confirmed the high affinities between the LRAC ligands and the protein receptors encoded by the hub genes. The in vitro assays validated that LRAC repressed the growth of RASF by cell cycle arresting and cell invasion paralyzing (c-Myc/p21/CDK2), initiating cell apoptosis (HIF-1α/CXCR4/Bax/Bcl-2), and inducing pyroptosis via ROS-dependent pathway (NOX4/ROS/NLRP3/IL-1ß/Caspase-1). CONCLUSION: LRAC can selectively inhibit the proliferation of RASFs, without side-effecting immunosuppression that usually occurred for RA treatment using MTX (methotrexate). These findings demonstrate the potential application of LRAC as a phytomedicine for RA treatment, and provide a valid approach for exploring natural remedies against autoimmune diseases.