The redox system is closely related to changes in cellular metabolism. Regulating immune cell metabolism and preventing abnormal activation by adding antioxidants may become an effective treatment for oxidative stress and inflammation-related diseases. Quercetin is a naturally sourced flavonoid with anti-inflammatory and antioxidant activities. However, whether quercetin can inhibit LPS-induced oxidative stress in inflammatory macrophages by affecting immunometabolism has been rarely reported. Therefore, the present study combined cell biology and molecular biology methods to investigate the antioxidant effect and mechanism of quercetin in LPS-induced inflammatory macrophages at the RNA and protein levels. Firstly, quercetin was found to attenuate the effect of LPS on macrophage proliferation and reduce LPS-induced cell proliferation and pseudopodia formation by inhibiting cell differentiation, as measured by cell activity and proliferation. Subsequently, through the detection of intracellular reactive oxygen species (ROS) levels, mRNA expression of pro-inflammatory factors and antioxidant enzyme activity, it was found that quercetin can improve the antioxidant enzyme activity of inflammatory macrophages and inhibit their ROS production and overexpression of inflammatory factors. In addition, the results of mitochondrial morphology and mitochondrial function assays showed that quercetin could upregulate the mitochondrial membrane potential, ATP production and ATP synthase content decrease induced by LPS, and reverse the mitochondrial morphology damage to a certain extent. Finally, Western blotting analysis demonstrated that quercetin significantly upregulated the protein expressions of SIRT1 and PGC-1α, that were inhibited by LPS. And the inhibitory effects of quercetin on LPS-induced ROS production in macrophages and the protective effects on mitochondrial morphology and membrane potential were significantly decreased by the addition of SIRT1 inhibitors. These results suggested that quercetin reprograms the mitochondria metabolism of macrophages through the SIRT1/PGC-1α signaling pathway, thereby exerting its effect of alleviating LPS-induced oxidative stress damage.

To investigate the effect of polymer blends on the in vitro release/degradation and pharmacokinetics of moxidectin-loaded PLGA microspheres (MOX-MS), four formulations (F1, F2, F3 and F4) were prepared using the O/W emulsion solvent evaporation method by blending high (75/25, 75 kDa) and low (50/50, 23 kDa) molecular weight PLGA with different ratios. The addition of low-molecular-weight PLGA did not change the release mechanism of microspheres, but sped up the drug release of microspheres and drastically shortened the lag phase. The in vitro degradation results show that the release of microspheres consisted of a combination of pore diffusion and erosion, and especially autocatalysis played an important role in this process. Furthermore, an accelerated release method was also developed to reduce the period for drug release testing within one month. The pharmacokinetic results demonstrated that MOX-MS could be released for at least 60 days with only a slight blood drug concentration fluctuation. In particular, F3 displayed the highest AUC and plasma concentration (AUC_0–t = 596.53 ng/mL·d, C_{ave (day 30-day 60)} = 8.84 ng/mL), making it the optimal formulation. Overall, these results indicate that using polymer blends could easily adjust hydrophobic drug release from microspheres and notably reduce the lag phase of microspheres.

Oxidative stress refers to the phenomenon in which the redox balance of the body is disrupted in response to stimuli, leading to an excessive accumulation of reactive oxygen species in vivo, which can lead to a variety of diseases. In contrast to artificial antioxidants, whose safety is controversial, natural antioxidants, which are widely available, pharmacologically active, and have little toxic side effects, are expected to be candidates for the treatment of oxidative stress-related diseases. Polygonum viviparum L. (PV) is a natural herbal medicine with antioxidant properties and is used as a traditional medicine in the Tibetan Plateau region. However, there are few studies that have focused on its antioxidant activity and mechanism of action in vitro and in vivo. Therefore, the present study firstly demonstrated that PV could exert good in vitro antioxidant effects by scavenging DPPH radicals and inhibiting the production of hydroxyl radicals through in vitro experiments. Secondly, PV was proven to attenuate the effects of oxidative stress on body weight gain and thymus development by establishing the Senna leaf-induced diarrhea model in rats, as well as to increase the activity of antioxidant enzymes and the content of non-enzymatic antioxidants in the intestinal tract and to enhance the rats’ own antioxidant defenses, to mitigate the oxidative damage caused by diarrhea. Subsequently, the application of the cellular oxidative stress model evidenced that PV could play a protective role against cellular oxidative stress by inhibiting the overaccumulation of ROS in macrophages. Furthermore, the candidate antioxidant targets of PV were analyzed and screened using a comprehensive network pharmacology method, and their expression were then examined at the mRNA level and protein level. Our results suggest that PV may protect against H₂O₂-induced oxidative damage in macrophages by activating BCL2L1 and inhibiting ESR1, JAK2/STAT3, and MMP2. These findings open new perspectives on the antioxidant mechanism of PV and the prospect of developing it as a novel natural antioxidant drug.

Chronic inflammatory bowel disease, ulcerative colitis (UC), currently lacks specific drugs for clinical treatment, and screening effective therapeutic agents from natural plants represents a critical research strategy. This study aimed to investigate the therapeutic potential of the flavonoid extract of Polygonum viviparum L. (TFPV) against UC. Liquid chromatography-mass spectrometry (LC-MS) was used to identify the chemical components of TFPV, while cell and animal models were employed to evaluate its anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation. The mechanism of anti-inflammatory action was further investigated using a mouse model of UC induced by dextran sulfate sodium (DSS). The results revealed the identification of 32 bioactive components in TFPV, with major compounds such as kaempferol, luteolin, galangin, and quercetin. TFPV effectively mitigated inflammatory damage induced by LPS in IPEC-J2 cells and C57BL/6 mice. In the UC modeled by DSS, TFPV attenuated intestinal inflammation by reducing pro-inflammatory cytokines IL-1β, IL-6, and TNF-α; increasing the anti-inflammatory cytokine IL-10; up-regulating tight junction protein expression such as Claudin-1, Occludin, and ZO-1; and inhibiting the expression of PI3K, AKT, NF-κB, and IL-17 proteins. Analysis of mice fecal samples through 16S rRNA gene sequencing demonstrated that TFPV adjusted the equilibrium of gut microbiota by boosting the abundance of Dubosiella and diminishing that of Enterococcus, Romboutsia, and Enterobacter. Untargeted metabolomics analysis further revealed that TFPV reduced inosine and ADP levels while increasing dGMP levels by the regulation of purine metabolism, ultimately resulting in decreased uric acid levels and thereby alleviating intestinal inflammation. Additionally, TFPV safeguarded the intestinal mucosal barrier by enhancing the expression of tight junctions. In conclusion, TFPV alleviates UC by blocking the PI3K/AKT/NF-κB and IL-17 signaling pathways, lessening intestinal inflammation and injury, safeguarding intestinal barrier integrity, balancing gut microbiota, and lowering uric acid levels, suggesting its promise as a therapeutic agent for UC.

Inflammation is the host response of immune cells during infection and traumatic tissue injury. An uncontrolled inflammatory response leads to inflammatory cascade, which in turn triggers a variety of diseases threatening human and animal health. The use of existing inflammatory therapeutic drugs is constrained by their high cost and susceptibility to systemic side effects, and therefore new therapeutic candidates for inflammatory diseases need to be urgently developed. Natural products are characterized by wide sources and rich pharmacological activities, which are valuable resources for the development of new drugs. This study aimed to uncover the alleviating effect and potential mechanism of natural product Limonium aureum (LAH) on LPS-induced inflammatory responses in macrophages. The experimental results showed that the optimized conditions for LAH ultrasound-assisted extraction via response surface methodology were an ethanol concentration of 72%, a material-to-solvent ratio of 1:37 g/mL, an extraction temperature of 73 °C, and an extraction power of 70 W, and the average extraction rate of LAH total flavonoids was 0.3776%. Then, data of 1666 components in LAH ethanol extracts were obtained through quasi-targeted metabolomics analysis. The ELISA showed that LAH significantly inhibited the production of pro-inflammatory cytokines while promoting the secretion of anti-inflammatory cytokines. Finally, combined with the results of network pharmacology analysis and protein expression validation of hub genes, it was speculated that LAH may alleviate LPS-induced inflammatory responses of macrophages through the AKT1/RELA/PTGS2 signaling pathway and the MAPK3/JUN signaling pathway. This study preliminarily revealed the anti-inflammatory activity of LAH and the molecular mechanism of its anti-inflammatory action, and provided a theoretical basis for the development of LAH as a new natural anti-inflammatory drug.

The prevalence of infections by methicillin-resistant Staphylococcus aureus (MRSA) has led to dramatically increased mortality and threated the public health worldwide. Pleuromutilin compound 14-O-[(4-(pyrrolidine-1-yl)-6-methylpyrimidine-2-yl) thioacetyl] mutilin (PMTM) is a new antibacterial agent with excellent antibacterial efficacy against Gram positive bacteria. For further developing PMTM as a potential drug against MRSA infections, the in vitro antibacterial efficacy and preclinical safety were explored in this study. The results revealed that PMTM presented the higher anti-MRSA activity, increasing post-antibiotic effect (PAE) and limited potential to develop resistance. In safety evaluation, PMTM demonstrated low cytotoxicity, poor hemolytic activity, tolerable oral acute toxic effects in rats, devoid of mutagenic response and weak inhibitory potential on CYP3A4, but displayed moderate potential hERG K⁺ channel inhibition. Furthermore, two salts of PMTM with sulfuric acid and hydrochloric acid were prepared and confirmed. The sulfate salt of PMTM exhibited the highest solubility based on powder dissolution experiments and was chosen to evaluate pharmacokinetics properties, in which it displayed improved mouse pharmacokinetics parameters and oral bioavailability. The present study successfully provides a good foundation of PMTM for new antibacterial drug development.