Celastrol attenuates impairments associated with lipopolysaccharide-induced acute respiratory distress syndrome (ARDS) in rats

Abstract

Celastrol, a constituent from a traditional Chinese medicinal herb belonging to the family Celastraceae, has been shown to impart anti-inflammatory properties, in part, by inhibiting NF-κB activity and related induction of pro-inflammatory cytokine formation/release. The present study investigated the effects of celastrol in an animal model of acute respiratory distress syndrome (ARDS) induced by intratracheal administration of lipopolysaccharides (LPSs). Celastrol pre-treatment groups received celastrol by intraperitoneal injection on seven consecutive days before LPS treatment. In rats evaluated 24 h after LPS administration, oxygenation indices and lung injury were measured, as were levels of inflammatory cells and cytokines in isolated bronchoalveolar lavage fluid (BALF). Lung tissue expression of proteins involved in NF-κB and ERK/MAPK pathways were measured by Western blot analyses. Celastrol pre-treatments appeared to attenuate LPS-induced lung injury and inflammatory responses in the rats, including decreases in inducible aggregation\infiltration of inflammatory cells and production/release of pro-inflammatory cytokines into the lung airways. Celastrol appeared to also inhibit NF-κB activation, but had no effect on ERK/MAPK pathways in the LPS-induced ARDS. The results here thus indicated that celastrol pre-treatment could impart protective effects against LPS-induced ARDS, and that these effects may be occurring through an inhibition of induction of NF-κB signaling pathways.

Key Aspects in Nutritional Management of COVID-19 Patients

“…In the study reported by Shi et al (2018), this compound improved chronic obstructive pulmonary disease by decreasing interleukin-8 (IL-8), TNF-α, and monocyte chemoattractant protein-1 (MCP1) levels, as well as by increasing enzymatic antioxidant defenses in mice [ 54 ]. These results are in good accordance with those previously reported by Wei and Wang (2017), who observed that celastrol reduced these pro-inflammatory cytokines and NF-kB activation in rats, showing lipopolysaccharide (LPS)-induced acute respiratory distress syndrome [ 55 ]. More recently, Iwata-Yoshikawa et al (2019) showed that NF-kB pathway was regulated by TMPRSS2 protein in the airway of a TMPRSS2 knockout murine model, after coronavirus infection [ 56 ].…”

Should we try the antiinflammatory natural product, celastrol, for COVID‐19?

“…In this case, it could reduce the levels of inflammatory cytokines such as interleukin-8 (IL-8), tumour necrosis factor-α (TNF-α), and monocyte chemoattractant protein-1 while enhancing antioxidant defences (superoxide dismutase and catalase). In rats subjected to lipopolysaccharide (LPS)-induced acute respiratory distress syndrome, celastrol could also ameliorate the inflammation-mediated injury as well as the expression levels of pro-inflammatory cytokines (TNF-α, IL-1, IL-6, and IL-8) and NF-κB (Wei & Wang, 2017). Under asthmatic condition or increased airway hyperresponsiveness, a positive outcome for orally administered celastrol both in the disease level and Th17 inhibition was observed in mice (Zeng, Lin, Zheng, Zhang, & Zhang, 2018).…”

Smoking Attenuates Efficacy of Penehyclidine Hydrochloride in Acute Respiratory Distress Syndrome Induced by Lipopolysaccharide in Rats

“…(3) In the ARDS subgroup (n=16), only penehyclidine hydrochloride (LPS) (3 mg/kg) was injected into the trachea to induce ARDS. The ARDS model was constructed as described in Lang et al [25] and Wei et al [26]. Briefly, rats were anesthetized by 2% pentobarbital (40 mg/kg) through intraperitoneal injection.…”