Background/Objectives: Ulcerative colitis (UC) is a chronic and easily recurrent inflammatory bowel disease. The gut microbiota and plasma metabolites play pivotal roles in the development and progression of UC. Therefore, therapeutic strategies targeting the intestinal flora or plasma metabolites offer promising avenues for the treatment of UC. Luteolin (Lut), originating from a variety of vegetables and fruits, has attracted attention for its potent anti-inflammatory properties and potential to modulate intestinal flora. Methods: The therapeutic efficacy of Lut was evaluated in an established dextran sodium sulfate (DSS)-induced colitis mice model. The clinical symptoms were analyzed, and biological samples were collected for microscopic examination and the evaluation of the epithelial barrier function, microbiome, and metabolomics. Results: The findings revealed that Lut administration at a dose of 25 mg/kg significantly ameliorated systemic UC symptoms in mice, effectively reduced the systemic inflammatory response, and significantly repaired colonic barrier function. Furthermore, Lut supplementation mitigated gut microbiota dysbiosis in a UC murine model, increasing the abundance of Muribaculaceae, Rikenella, and Prevotellaceae while decreasing Escherichia_Shigella and Bacteroides levels. These alterations in gut microbiota also influenced plasma metabolism, significantly increasing phosphatidylcholine (PC), 6′-Deamino- 6′-hydroxyneomycin C, and gamma-L-glutamyl-butyrosine B levels and decreasing Motapizone and Arachidoyl-Ethanolamide (AEA) levels. Conclusions: This study reveals that Lut supplementation modulates intestinal inflammation by restoring the gut microbiota community structure, thereby altering the synthesis of inflammation-related metabolites. Lut is a potential nutritional supplement with anti-inflammatory properties and offers a novel alternative for UC intervention and mitigation. In addition, further studies are needed to ascertain whether specific microbial communities or metabolites can mediate the recovery from UC.

The demand for economic benefits has led to an increase in the proportion of high-concentrate (HC) feed in the ruminant diet, resulting in an increased incidence of subacute ruminal acidosis (SARA). During SARA, a high concentration of lipopolysaccharide (LPS) translocated in the rumen induces a systemic inflammatory response. Inflammatory diseases, such as endometritis and mastitis, are often associated with SARA; however, in sheep, the mechanism of the effect of SARA on the endometrium has rarely been reported. Therefore, the aim of this study was to investigate, for the first time, the influence of LPS translocation on endometrial tight junctions (TJs) during SARA in sheep. The results showed that LPS and TNFα levels in the ruminal fluid, serum, and endometrial tissue supernatant during SARA increased, transcription levels of TLR4, NFκB, and TNFα in the endometrium increased, the protein expression level of claudin-1 in the endometrium increased, and the protein expression level of occludin decreased. 17β-estradiol (E₂) inhibits claudin-1 protein expression and promotes occludin expression, and progesterone (P₄) promotes claudin-1 protein expression and inhibits occludin protein expression. E₂ and P₄ regulate claudin-1 and occludin protein expression through their receptor pathways. Here, we found that LPS hindered the regulatory effect of E₂ and P₄ on endometrial TJs by inhibiting their receptor expression. The results of this study indicate that HC feeding can cause SARA-induced LPS translocation in sheep, increase susceptibility to systemic inflammation, induce the endometrial inflammatory response, and cause endometrial epithelial TJ damage directly and/or by obstructing E₂ and P₄ function. LPS translocation caused by SARA has also been suggested to induce an endometrial inflammatory response, resulting in endometrial epithelial barrier damage and physiological dysfunction, which seriously affects ruminant production. Therefore, this study provides new evidence that SARA is a potential factor that induces systemic inflammation in ruminants. It provides theoretical support for research on the prevention of endometritis in ruminants.

Progesterone (P4) can participate in the development of female mammalian antral follicles through nuclear receptor (PGR). In this experiment, the differences of P4 synthesis and PGR expression in different developmental stages of sheep antral follicles (large > 5mm, medium 2-5mm, small < 2mm) were detected by enzyme-linked immunosorbent assay, immunohistochemistry, qRT-PCR and Western blotting. Secondly, sheep follicular granulosa cells were cultured in vitro. The effects of different concentrations of FSH and LH on P4 synthesis and PGR expression were studied. The results showed that acute steroid regulatory protein (StAR), cholesterol side chain lyase (P450scc) and 3β Hydroxysteroid dehydrogenase (3β-HSD) and PGR were expressed in antral follicles, and with the development of antral follicles in sheep, StAR, P450scc and the expression of 3β-HSD and PGR increased significantly. In vitro experiments showed that FSH and LH alone or together treatment could regulate P4 secretion and PGR expression in sheep follicular granulosa cells to varying degrees, hint P4 and PGR by FSH and LH, and LH was the main factor. Our results supplement the effects of FSH and LH on the regulation of P4 synthesis during follicular development, which provides new data for further study of steroid synthesis and function in follicular development.

As a critical disease usually infected by Staphylococcus aureus, with a worldwide effect on dairy animals, subclinical mastitis is characterized by persistence and treatment resistance. During mastitis, the blood–milk barrier (BMB)’s integrity is impaired, resulting in pathogen invasion and milk quality decline. In this study, it was found that ginsenoside Rg1 (Rg1), a natural anti-inflammatory and antioxidant compound derived from ginseng, inhibited the onset of tight junction (TJ) dysfunction and ameliorated lipoteichoic acid (LTA)-induced BMB disruption inside and outside the organisms. According to subsequent mechanistic studies, Rg1 inhibited excessive autophagy and inactivated the NLRP3 inflammasome by blockading ROS generation, thereby alleviating TJ dysfunction. Peroxisome proliferator-activated receptor gamma (PPARγ) was identified as a potential target of Rg1 by means of molecular docking plus network pharmacology analysis. Furthermore, it was demonstrated that Rg1 inhibited the oxidative stress levels by activating PPARγ, and regulating the upstream autophagy-related AMPK/mTOR signaling pathway, thus decreasing excessive in vivo and in vitro autophagy. The ROS/autophagy/NLRP3 inflammasome axis was identified as a promising target for treating subclinical bovine mastitis in this study. In conclusion, Rg1 is proven to alleviate BMB disruption by activating PPARγ to inhibit oxidative stress and subsequent excessive autophagy in the case of subclinical bovine mastitis.

Mastitis in dairy cows, typically caused by bacterial infection, is a common inflammatory condition of the mammary tissue that leads to fibrosis, adversely affecting cow health, milk production, and dairy product quality. Astragalus polysaccharide (APS) has shown effectiveness in alleviating inflammation and fibrosis in various organs. The study employed lipopolysaccharide (LPS) to induce fibrotic conditions in two experimental systems: MAC-T bovine mammary epithelial cells and Kunming mouse models. Key parameters, including relative gene mRNA expression, protein levels, and reactive oxygen species (ROS) levels, were assessed using RT-qPCR, Western blotting (WB), and 2’,7’-Dichlorofluorescin diacetate (DCFH-DA) techniques, while histological analysis of mammary tissue was performed using H&E and Masson trichrome staining. Measuring malondialdehyde (MDA) levels, assessing the enzyme activities of catalase (CAT), and superoxide dismutase (SOD) were two methods of assessing oxidative stress. These methods were also tested in mouse mammary glands. APS significantly decreased ROS concentrations (p < 0.01), restored oxidative stress balance in mice (p < 0.05), and reduced fibrosis and inflammation, as demonstrated by histological observations and analysis. It also exerted regulatory effects on fibrosis markers (E-cadherin, N-cadherin, α-SMA) and inflammation markers (NLRP3, ASC, Caspase-1, IL-1β), as demonstrated by changes in their mRNA and protein expression. These findings endorse APS’s viability as an alternative therapeutic agent for mammary fibrosis therapy by demonstrating its ability to inhibit epithelial-mesenchymal transition (EMT) in vitro and mammary fibrosis in vivo, while also mitigating ROS production and reducing inflammation.