The flavonoids of Sophora flavescens exerts anti-inflammatory activity via promoting autophagy of Bacillus Calmette-Guérin-stimulated macrophages

Abstract

Tuberculosis (TB), a highly infectious airborne disease, has remained a global health problem. Conventional treatment and preventions such as antibiotics and Bacilli Calmette-Guerin (BCG) vaccine can be unreliable. In view of the increasing prevalence of anti-TB drug resistance, adjunctive therapy may be necessary to shorten the recovery time. We have previously shown that flavonoids in the medicinal herb Sophora flavescens exhibit anti-inflammatory and bactericidal activities. The aim of this study was to investigate the molecular and cellular characteristics of flavonoids of S. flavescens (FSF) in BCG-stimulated macrophages for assessing their roles in antiinflammation and autophagy. Mouse alveolar macrophage (MH-S) cell line and primary mouse peritoneal macrophages were stimulated in vitro with heat-inactivated BCG and treated with FSF, with or without autophagy inhibitor Bafilomycin A1 (BafA1). Gene expression was analyzed using quantitative PCR, and cytokine/chemokine release was analyzed by Milliplex assay and ELISA. Autophagy-related proteins were quantified by Western blot and flow cytometry, and autophagolysosomes were detected using fluorescence microscopy. In both MH-S cell line and mouse peritoneal macrophages stimulated by heat-inactivated BCG, FSF was found to upregulate autophagy-related proteins microtubule-associated protein 1A/1B-light chain 3 (LC3) and protein 62 (p62), and suppress the induced proinflammatory cytokine TNF-, CCL5, and IL-6. FSF actively modulates immune processes through suppressing BCG-mediated inflammation by promoting autophagy in MH-S cells and mouse peritoneal macrophages. We suggest that FSF may be useful as an adjunctive therapeutic agent for TB infection by modulating cell survival through autophagy and reducing inflammation.

Roles of autophagy in killing of mycobacterial pathogens by host macrophages – Effects of some medicinal plants

“…It was reported that the flavonoids of S. flavescens suppressed the formation of granuloma in the lungs of mice injected with trehalose dimycolate, one of the major pathogenic components of the cell wall of MTB [ 62 ]. Flavonoids of S. flavescens suppressed the production of proinflammatory cytokines (TNF-α and IL-6) and chemokines (CCL5) by M. bovis BCG-stimulated alveolar macrophages and peritoneal macrophages, and this effect was associated with the activation of cellular autophagy by these flavonoids through a signaling pathway consisting of the autophagic proteins LC3 and P62 [ 63 ]. S. flavescens flavonoid-induced autophagy may be dependent on lysosomal degradation.…”

“…S. flavescens flavonoid-induced autophagy may be dependent on lysosomal degradation. In addition, flavonoids were shown to serve as a mediator for autophagy-related gene transcription and autophagy-related protein synthesis in M. bovis BCG-stimulated macrophages [ 63 ]. Larrea tridentata …”

In vivo antibacterial activity of medicinal plant Sophora flavescens against Streptococcus agalactiae infection

“…Xanthohumol also has powerful physiological activities, including antimicrobial, antioxidant and anti‐inflammatory (Luo et al, 2023). Besides, the alkaloids and flavonoids of SF can exert anti‐inflammatory activity via promoting autophagy (Hou et al, 2020; Kan et al, 2020; Wang et al, 2019) and increase the expression of c‐type lysozyme in fish (Li et al, 2019; Zhou et al, 2016). These components might play key roles in inhibiting GBS infection in tilapia.…”

Antibacterial Modes of Herbal Flavonoids Combat Resistant Bacteria

“…As shown in Table 1 and Figure 4C , the flavonoids of Sophora flavescens are potential agents in Tuberculosis (TB) infection therapy by enhancing macrophage autophagy to promote cellular survival and then reducing inflammation. ( Kan et al, 2020 ). The Baicalein-7-O-β-D-glucuronide of Scutellariae Radi and Luteolin-7-O-β-D-glucuronide of Impatiens balsamina target MAPKs or Wnt/β-catenin pathway to inhibit the inflammation from bacterial LPS ( Li et al, 2009 ; Kawai, 2018; Liu F. et al, 2020 ; Pereira et al, 2020 ).…”