The present study aimed to investigate the protective effects and underlying mechanisms of baicalin on imprinting control region mice infected with influenza A̸FM̸1̸47 (H1N1) virus. Oral administration of baicalin into mice infected with H1N1 prevented death, increased the mean time to death and inhibited lung index and lung consolidation. Subsequently, fluorescence quantitative polymerase chain reaction was used to assess the mRNA expression of toll‑like receptor 7 (TLR7) and myeloid differentiation primary response gene 88 (MYD88), and western blot analysis was used to determine the expression of phosphorylated nuclear factor κB (NF‑κB)‑P65 and c‑jun̸activator protein 1 (AP‑1). An enzyme‑linked immunosorbent assay was applied to test for the inflammatory cytokines, tumor necrosis factor (TNF)‑α and interleukin (IL)‑1β and IL‑6, in the lung tissue. The findings indicated that baicalin downregulated the mRNA expression of TLR7 and MYD88, significantly downregulated the protein expression of NF‑κB‑P65 and AP‑1 and also inhibited the secretion of TNF‑α, IL‑1β and IL‑6. In conclusion, baicalin effectively reduced the pathological damage and inflammation of the lungs by downregulating the TLR7/MYD88‑mediated signaling pathway.

Baicalin is a flavonoid isolated from the root of Scutellaria baicalensis with anti‑inflammatory, antioxidant and antiapoptotic pharmacological properties. however, the therapeutic effect of baicalin on rheumatoid arthritis (RA) is not completely understood. The present study aimed to explore the therapeutic potential and mechanisms underlying baicalin in collagen‑induced arthritis (CIA) model rats. CIA was induced in male SD rats. The hind paw thickness and severity of joint injury were monitored to assess the onset of arthritis. At 28 days after the initial immunization, different doses of baicalin were administered once daily via oral gavage for 40 days. The radiologic and pathological alterations were examined using X‑ray, and hematoxylin and eosin staining, respectively. ELISA was employed to measure the serum levels of proinflammatory cytokines. Reverse transcription‑quantitative PCR and western blotting were conducted to determine the expression of toll‑like receptor (TLR)2, myeloid differentiation factor 88 (MYD88) and NF‑κB p65. Baicalin treatment noticeably alleviated radiographic and histologic abnormalities in the hind paw joints of CIA model rats in a dose‑dependent manner. The serum levels of proinflammatory cytokines were significantly decreased in baicalin‑treated CIA model rats compared with vehicle‑treated CIA model rats. The mRNA expression levels of TLR2 and MYD88, as well as the protein expression levels of TLR2, MYD88 and NF‑κB p65 were significantly decreased by baicalin treatment in the synovial tissue of CIA model rats and human RA fibroblast‑like synoviocytes. The results suggested that baicalin may exert a beneficial effect on CIA, which may be mediated by inhibiting the TLR2/MYD88/NF‑κB signaling pathway.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of synovium, leading to cartilage damage, bone erosion, even joint destruction and deformity. The conventional treatment modalities in RA are associated with side effects, emphasizing the need for alternative therapeutic remedies. Baicalin possesses multiple pharmacological effects and the advantage of low toxicity. This study aimed to reveal the potential gene regulatory mechanisms underlying the alleviating effects of baicalin in joint pathological alterations in Collagen-Induced Arthritis (CIA) rat models. At 28 days after the primary immunization, 60 mg/kg/d of baicalin was administered via intraperitoneal injection once daily for 40 days, and the pathological alterations of hind paw joints were examined with X-ray imaging. Subsequently, the synovial tissue of knee joints was isolated, from which total RNA was extracted, and mRNA and miRNA sequencing libraries were established. Finally, High-throughput transcriptome sequencing(RNA-seq) technology was performed, and the lncRNAs/miRNAs/mRNAs competing endogenous RNA(ceRNA) regulatory network was analyzed. The CIA model was successfully established, and baicalin treatment significantly alleviated the destruction of distal joints of CIA rat models (p < 0.01). We found that 3 potential ceRNA regulatory networks of baicalin were established, including lncRNA ENSRNOT00000076420/miR-144-3p/Fosb, lncRNA MSTRG.1448.13/miR-144-3p/Atp2b2 and lncRNA MSTRG.1448.13/miR-144-3p/Shanks. The validation results from synovial tissue of CIA rats were consistent with the RNA-Seq results. Overall, this study revealed potentially important genes and ceRNA regulatory network that mediate the alleviating effects of baicalin on joint pathological alterations in CIA rats.

This study was conducted to investigate the effects of quercetin on the expression of cyclin‑dependent kinase (CDK4) mRNA and protein in A549 lung epithelial tumor cells infected by H1N1. First, the Thiazolyl Blue Tetrazolium Bromide (MTT) method was used to determine H1N1 virulence, quercetin cytotoxicity and inhibition of the cytopathic effect of H1N1 on A549 cells by quercetin. Subsequently, 100 TCID50 H1N1 was used to infect A549 cells for 2 h prior to culture in maintenance media containing 10 mg̸l quercetin. After 4, 12, 24 and 48 h of culture, the cells were collected and total RNA and protein were extracted. Fluorescent quantitative polymerase chain reaction and western blot analysis were then performed to assess the expression of CDK4 mRNA and protein. The experiment demonstrated that the TCID50 of H1N1 in A549 cells was 10‑4.75, the maximum non‑toxic concentration of quercetin in A549 cells was 30‑60 mg̸l and the minimum effective concentration of quercetin for the inhibition of the H1N1 cytopathic effect on A549 cells was 10 mg/l. The results indicated that quercetin may significantly inhibit CDK4 mRNA and protein overexpression caused by H1N1 within 4‑48 h. In conclusion, quercetin may protect against H1N1 infection by effectively reducing the mRNA and protein expression of CDK4 caused by H1N1 infection.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent synovitis, in which fibroblast-like synoviocytes (FLSs) serve as the primary effector cells that drive the destruction of joints. Baicalin has previously demonstrated efficacy in significantly ameliorating joint symptoms in rats with CIA. As such, this study aims to investigate its underlying molecular mechanisms and impact on the FLSs of rats with CIA through an integrated proteomics and transcriptomics analysis. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was conducted based on two datasets; it revealed that the retrograde endocannabinoid signaling pathway—associated with susceptibility to RA—is the only one involved in both the signaling and metabolic processes modulated by baicalin. Nineteen differentially expressed proteins (DEPs) downregulated by baicalin comprise seventeen subunits of NADH dehydrogenase and two receptors, glutamate receptor 2 (GRIA2) and γ-aminobutyric acid receptor subunit alpha-5 (GABRA5). Three differential metabolites (DMs) were also affected by baicalin: γ-aminobutyric acid (GABA) and phosphatidylcholine (PC) were upregulated and phosphatidylethanolamine (PE) was downregulated. Our findings suggest that the baicalin-mediated alleviation of joint synovitis is closely related to the upregulation of GABA and PC; downregulation of GRIA2, GABRA5, and PE; and preservation of mitochondrial homeostasis within the retrograde endocannabinoid signaling pathway in FLSs.

Ag85B, the primary component of the Ag85 complex and an early secreted protein by Mycobacterium tuberculosis, has shown potential for the treatment of allergic asthma (AA) when used as a Fc-fusion protein. Administered via nasal immunization, Ag85B-Fc fusion protein significantly alleviated airway inflammation and reduced the proportions of some anaphylaxis related cells in lungs, with no significant histopathological injury to major organs in ovalbumin (OVA)-induced AA model mice. To investigate the underlying immune regulatory mechanisms of Ag85B protein, integrated proteomics and transcriptomics analyses were conducted, identifying the complement and coagulation cascades, and phagosomes as the two significantly enriched pathways at both gene and protein levels. Moreover, C3ar1 (C3aR1), Itgam (CD11b), Itgb2 (CD18), fgg (FGG), Cybb (CYBB), and Ncf4 (NCF4) were identified as core target factors that play a central role in allergic and asthmatic responses. Among them, C3aR1 and CR3 consisting of CD11b and CD18, are main complement receptors, indicating that Ag85B alleviated AA by regulating C3aR1- and CR3-mediated signal transduction. The validation results were consistent with the aforementioned findings. Overall, these results provide valuable insight into the application of mucosal immunotherapy in treatment of AA, positioning Ag85B-Fc fusion protein as a safe mucosal immunotherapeutic agent for AA.