Elucidation of the underlying mechanism of Hua-ban decoction in alleviating acute lung injury by an integrative approach of network pharmacology and experimental verification.

The pathogenic hyper-inflammatory response has been regarded as the major cause of the severity and death related to acute lung injury (ALI). Hua-ban decoction (HBD) is a classical prescription in traditional Chinese medicine (TCM). It has been extensively used to treat inflammatory diseases; however, its bioactive components and therapeutic mechanisms remain unclear. Here, we established a lipopolysaccharide (LPS)-induced ALI model that presents a hyperinflammatory process to explore the pharmaco-dynamic effect and underlying molecular mechanism of HBD on ALI. In vivo, we confirmed that in LPS-induced ALI mice, HBD improved pulmonary injury by via down-regulating the expression of proinflammatory cytokines, including IL-6, TNF-α, and macrophage infiltration, as well as macrophage M1 polarization. Moreover, in vitro experiments in LPS-stimulated macrophages demonstrated that the potential bioactive compounds of HBD inhibited the secretion of IL-6 and TNF-α. Mechanically, the data revealed that HBD treatment of LPS-induced ALI acted via NF-κB pathway, which regulated macrophage M1 polarization. Additionally, two major HBD compounds, i.e., quercetin and kaempferol, showed a high binding affinity with p65 and IkBα. In conclusion, the data obtained in this study demonstrated the therapeutic effects of HBD, which indicates the possibility for the development of HBD as a potential treatment for ALI.

CTLs: Killers of intracellular bacteria.

Many microbial pathogens have evolved a range of capabilities to evade host immune defense mechanisms and to survive and multiply in host cells. The presence of host intracellular bacteria makes it difficult for specific antibodies to function. After the intracellular bacteria escape the attack of the innate immune system, such as phagocytes, they survive in cells, and then adaptive immunity comes into play. Cytotoxic T lymphocytes (CTLs) play an important role in eliminating intracellular bacteria. The regulation of key transcription factors could promote CD4+/CD8+ T cells to acquire cytolytic ability. The TCR-CD3 complex transduces activation signals generated by TCR recognition of antigen and promotes CTLs to generate multiple pathways to kill intracellular bacteria. In this review, the mechanism of CD4/CD8 CTLs differentiation and how CD4/CD8 CTLs kill intracellular bacteria are introduced. In addition, their application and prospects in the treatment of bacterial infections are discussed.