Total flavonoids from sea buckthorn ameliorates lipopolysaccharide/cigarette smoke‐induced airway inflammation

Abstract

The total flavonoids from sea buckthorn (TFSB) exhibit a potent anti-inflammatory activity; however, the effect of TFSB on respiratory inflammatory disease is not fully known. The present study evaluated the potential of TFSB to prevent airway inflammation and the underlying mechanism. The results showed that TFSB remarkably inhibited lipopolysaccharide/cigarette smoke extract (LPS/CSE)-induced expression of IL-1β, IL-6, CXCL1, and MUC5AC at both mRNA and protein levels in HBE16 bronchial epithelial cells. TFSB also decreased the production of PGE 2 through inhibition the expression of COX2 in LPS/CSE-stimulated HBE16 cells. Furthermore, bronchoalveolar fluid and histological analyses revealed that LPS/cigarette smoke exposure-induced elevated cell numbers of neutrophils and macrophages in bronchoalveolar fluid, inflammatory cell infiltration, and airway remodeling were remarkably attenuated by TFSB in mice. Immunohistochemical results also confirmed that TFSB decreased the expression of IL-1β, IL-6, COX2, CXCL1, and MUC5AC in LPS/CSexposed mice. Mechanistically, TFSB blocked LPS/CSE-induced activation of ERK, Akt, and PKCα. Molecular docking further confirmed that the main components in TFSB including quercetin and isorhamnetin showed potent binding affinities to MAPK1 and PIK3CG, two upstream kinases of ERK and Akt, respectively. In summary, TFSB exerts a potent protective effect against LPS/CS-induced airway inflammation through inhibition of ERK, PI3K/Akt, and PKCα pathways, suggesting that TFSB may be a novel therapeutic agent for respiratory diseases. KEYWORDS chronic bronchitis, ERK, PI3K/Akt, and PKC pathways, lipopolysaccharide/cigarette smoke, sea buckthorn, total flavonoids

Exposure to environmental black carbon exacerbates nasal epithelial inflammation via the reactive oxygen species (ROS)–nucleotide‐binding, oligomerization domain–like receptor family, pyrin domain containing 3 (NLRP3)–caspase‐1–interleukin 1β (IL‐1β) pathway

“…Nuclear proteins and cytoplasmic proteins obtained from hNECs exposed for 24 hours to 25 µg/mL BC ± 200 µg/mL pollen, with or without inhibitors of ROS, NLRP3, or Caspase‐1 (100µM NAC, 10µM MCC950, or 50µM YVAD, respectively), were purified using a nuclear and cytoplasmic protein extraction kit (Beyotime Biotechnology), according to the manufacturer's instruction. NLRP3 and β‐actin were evaluated by Western blot analysis, as described 28 …”

“…NLRP3 and β-actin were evaluated by Western blot analysis, as described. 28 Anti-NLRP3 primary antibody and Anti-β-actin were purchased from Abcepta (NLRP3 Antibody (N-term); Abcepta, San Diego, CA), and the protein bands were visualized using chemiluminescence reagent (Millipore, Bedford, MA). Scanned images were digitized, and densitometry analysis was performed using ImageJ software (NIH, Bethesda, MD; http://imagej.nih.gov/ij/).…”

WITHDRAWN: LncRNA TUG1 knockdown mitigates inflammatory injury induced by cigarette smoke extract in chronic obstructive pulmonary disease via miR-34c/BRD4 axis

“…The cells were cultivated in RPMI-1640 medium (Gibco; Thermo Fisher Scientific, Rockville, MD, USA) supplemented with 10% fetal bovine serum (FBS, Thermo Fisher Scientific) and 1% penicillin/streptomycin (Invitrogen, Carlsbad, CA, USA) in a 5% CO 2 incubator at 37°C. CSE were prepared as previously reported [20,21]. In brief, the smoke from cigarette was collected using a peristaltic pump apparatus and bubbled into RPMI-1640 medium.…”

Network pharmacology analysis of the therapeutic mechanisms of the traditional Chinese herbal formula Lian Hua Qing Wen in Corona virus disease 2019 (COVID-19), gives fundamental support to the clinical use of LHQW

“…Beta-sitosterol significantly inhibited the TNF alpha-induced expression of VCAM1, which also played a key role in various inflammatory diseases ( Gupta et al., 2010 ). Quercetin showed potent binding affinities to PIK3CG, and exerted a potent protective effect against LPS/CS-induced airway inflammation through inhibition of ERK, PI3K/Akt, and PKCα pathways ( Ren et al., 2019 ). JAK1 is a member of Janus Kinases (JAK) which are intracellular tyrosine kinases linked to intracellular domains of many cytokine receptors.…”