Klebsiella pneumoniae (Kpn) is an important pathogen of hospital-acquired pneumonia, which can lead to sepsis and death in severe cases. In this study, we simulated pneumonia induced by Kpn infection in mice to investigate the therapeutic effect of naringin (NAR) on bacterial-induced lung inflammation. Mice infected with Kpn exhibited increases in white blood cells (WBC) and neutrophils in the peripheral blood and pathological severe injury of the lungs. This injury was manifested by increased expression of the inflammatory cytokines interleukin (IL)- 18, IL-1β, tumor necrosis factor-α (TNF-α) and IL-6, and elevated the expression of NLRP3 protein. NAR treatment could decrease the protein expression of NLRP3, alleviate lung inflammation, and reduce lung injury in mice caused by Kpn. Meanwhile, molecular docking results suggest NAR could bind to NLRP3 and Surface Plasmon Resonance (SPR) analyses also confirm this result. In vitro trials, we found that pretreated with NAR not only inhibited nuclear translocation of nuclear factor (NF)-κB protein P65 but also attenuated the protein interaction of NLRP3, caspase-1 and ASC and inhibited the assembly of NLRP3 inflammasome in mice AMs. Additionally, NAR could reduce intracellular potassium (K⁺) efflux, inhibiting NLRP3 inflammasome activation. These results indicated that NAR could protect against Kpn-induced pneumonia by inhibiting the overactivation of the NLRP3 inflammasome signaling pathway. The results of this study confirm the efficacy of NAR in treating bacterial pneumonia, refine the mechanism of action of NAR, and provide a theoretical basis for the research and development of NAR as an anti-inflammatory adjuvant.

Critically ill patients with Corona Virus Disease 2019 (COVID-19) often develop secondary bacterial infections that pose a significant threat to patient life safety, making the development of drugs to prevent bacterial infections in the lungs critical to clinical care. Naringin (NAR) is one of the significant natural flavonoids rich in Pummelo Peel (Hua Ju Hong), with anti-inflammatory, antimicrobial, and antioxidant activities, and is commonly used in treating respiratory tract infectious diseases. In this study, the in vitro and in vivo findings revealed that, after Klebsiella pneumoniae (Kpn) infection, NAR inhibited overactivation of the nuclear factor kappa-B(NF-κB) signaling pathway in alveolar macrophages of mice, reduced neutrophil (NEs) recruitment, and lowered the induced production of proinflammatory markers, such as Interleukin-6(IL-6) and tumor necrosis factor α(TNF-α). Thus, it suppressed excessive immune responses in the lungs, as well as attenuated the induced pulmonary fibrosis and inflammatory infiltrates. These results suggest that NAR has a preventive effect against Kpn in mice. In addition, the study evaluated NAR’s potential toxicity, demonstrating that NAR is safe at effective doses. These results suggested that NAR effectively reduces excessive inflammatory damage in the lungs induced by Kpn and enhances the body’s ability to clear bacteria. Therefore, NAR may be an effective and safe healthcare drug for preventing and caring for bacterial pneumonia.

Actinobacillus pleuropneumoniae (APP) causes porcine pleuropneumonia (PCP), which is clinically characterized by acute hemorrhagic, necrotizing pneumonia, and chronic fibrinous pneumonia. Although many measures have been taken to prevent the disease, prevention and control of the disease are becoming increasingly difficult due to the abundance of APP sera, weak vaccine cross-protection, and increasing antibiotic resistance in APP. Therefore, there is an urgent need to develop novel drugs against APP infection to prevent the spread of APP. Naringin (NAR) has been reported to have an excellent therapeutic effect on pulmonary diseases, but its therapeutic effect on lung injury caused by APP is not apparent. Our research has shown that NAR was able to alleviate APP-induced weight loss and quantity of food taken and reduce the number of WBCs and NEs in peripheral blood in mice; pathological tissue sections showed that NAR was able to prevent and control APP-induced pathological lung injury effectively; based on the establishment of an in vivo/in vitro model of APP inflammation, it was found that NAR was able to play an anti-inflammatory role through inhibiting the MAPK/NF-κB signaling pathway and exerting anti-inflammatory effects; additionally, NAR activating the Nrf2 signalling pathway, increasing the secretion of antioxidant enzymes Nqo1, CAT, and SOD1, inhibiting the secretion of oxidative damage factors NOS2 and COX2, and enhancing the antioxidant stress ability, thus playing an antioxidant role. In summary, NAR can relieve severe lung injury caused by APP by reducing excessive inflammatory response and improving antioxidant capacity.

Salmonella typhimurium (S.T) induces damage to the central nervous system; however, the role of Asiatic acid (AA) in this is still unknown. Microglia play a role as macrophages to recognize the invaded pathogenic microbes in the brain. The aim of this study was to investigate the protective effect and mechanism of AA on the central nervous system through an in vitro model of S.T infection in microglia. We pre-treated microglia with AA before S.T infection and explored the anti-infection mechanism of AA by sequencing, quantitative reverse transcription PCR (RT-qPCR), and Western blotting. Long non-coding RNA (lncRNA) sequencing demonstrated that inflammation is a major factor in S.T infection of microglia. RT-qPCR data demonstrated that AA inhibited S.T-induced increases in the mRNA levels of the pro-inflammatory factors interleukin (IL)-1β, IL-6, and IL-18. Western blotting demonstrated that AA inhibited S.T-induced activation of the nuclear factor (NF)-κB pathway and activation of the NLR family, pyrin domain-containing 3 (NLRP3) inflammasome. Expression of the lncRNA TVX1 in microglia was decreased by S.T infection and increased by pretreatment with AA. Inhibition of TVX1 expression reversed the anti-inflammatory effect of AA, and overexpression of TVX1 in microglia suppressed S.T-induced inflammation. In conclusion, AA attenuated S.T-induced microglial inflammation by upregulating the expression of the lncRNA TVX1.

Actinobacillus pleuropneumoniae (APP) is responsible for causing Porcine pleuropneumonia (PCP) in pigs. However, using vaccines and antibiotics to prevent and control this disease has become more difficult due to increased bacterial resistance and weak cross-immunity between different APP types. Naringin (NAR), a dihydroflavonoid found in citrus fruit peels, has been recognized as having significant therapeutic effects on inflammatory diseases of the respiratory system. In this study, we investigated the effects of NAR on the inflammatory response caused by APP through both in vivo and in vitro models. The results showed that NAR reduced the number of neutrophils (NEs) in the bronchoalveolar lavage fluid (BALF), and decreased lung injury and the expression of proteins related to the NLRP3 inflammasome after exposure to APP. In addition, NAR inhibited the nuclear translocation of nuclear factor kappa-B (NF-κB) P65 in porcine alveolar macrophage (PAMs), reduced protein expression of NLRP3 and Caspase-1, and reduced the secretion of pro-inflammatory cytokines induced by APP. Furthermore, NAR prevented the assembly of the NLRP3 inflammasome complex by reducing protein interaction between NLRP3, Caspase-1, and ASC. NAR also inhibited the potassium (K⁺) efflux induced by APP. Overall, these findings suggest that NAR can effectively reduce the lung inflammation caused by APP by inhibiting the over-activated NF-κB/NLRP3 signalling pathway, providing a basis for further exploration of NAR as a potential natural product for preventing and treating APP.