Effect of melilotus extract on lung injury by upregulating the expression of cannabinoid CB2 receptors in septic rats

BACKGROUND M. Suaveolens Ledeb has long been used in China to treat inflammatory infectious diseases. Melilotus is extracted from Melilotus Suaveolens Ledeb and its therapeutic potential is associated with its anti-inflammatory activity. However, the precise mechanisms underlying its effects are unknown. This study was conducted to evaluate the protective effects of melilotus extract in a rat cecal ligation and puncture (CLP)-induced animal model of acute lung injury (ALI). METHODS A sepsis model was induced by CLP-like lung inflammation. Two hours prior to CLP administration, the treatment group was administered melilotus extract via oral injection. RT-PCR and Western blotting were used to test the expression of cannabinoid receptor (CB)2, NF-κβ and IκB from single peripheral blood mononuclear cells and lung tissues respectively. Enzyme linked immune sorbent assay was used to detect serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and IL-12. The numbers of neutrophils, lymphocytes, macrophages and total cells in the bronchoalveolar lavage (BAL) fluid were counted. For histologic analysis, hematoxylin and eosin (H&E) stains were evaluated. RESULTS After inducing ALI by CLP for 24 hours, melilotus extract up-regulated peripheral blood mononuclear cell CB2 expression, blocked the activity of NF-κβ65, and the number of neutrophils, lymphocytes and total cells were significantly lower in the melilotus extract group than the control group. In addition, TNF-α and IL-6 levels were significantly decreased in the melilotus extract group. Histological results demonstrated the attenuation effect of melilotus extract on CLP-induced lung inflammation. CB2 was negatively correlated to NF-κβ mRNA and proteins, respectively (r = -0.377, P < 0.05; r = -0.441, P < 0.05). CONCLUSION The results of this study indicated melilotus extract significantly reduced CLP-induced lung inflammation by up-regulating CB2 expression. The remarkable protective effects of melilotus extract suggest its therapeutic potential in CLP induced-acute lung injury treatment.