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

Abstract

BackgroundM. 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).MethodsA 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.ResultsAfter 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).ConclusionThe 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.

Effect of Melilotus suaveolens extract on pulmonary microvascular permeability by downregulating vascular endothelial growth factor expression in rats with sepsis

“…Therapeutic targeting of capillary leakage in sepsis and systemic inflammation is therefore considered a highly relevant clinical approach. The pharmacological effects of M. suaveolens ( 8 , 29 – 34 ) indicate that one of the active components, coumarin, is able to reduce capillary permeability and vascular resistance ( 8 , 29 ), increase vein tension and improve circulation ( 30 , 31 ), so that the open arteriovenous anastomosis tubes are closed to reduce local congestion, therefore reducing soft tissue bleeding. Coumarin may also inhibit the release of a variety of vascular active substances ( 32 ), suppressing adenosine diphosphate and collagen-induced platelet aggregation as well as the release of 5-hydroxytryptamine, platelet factor 4, thromboxane A2 and platelet-derived growth factor from the platelet ( 33 , 34 ).…”

“…Melilotus suaveolens Ledeb (M. suaveolens) , a Traditional Tibetan Medicine also known as Melilotus suavcolen or wild alfalfa, is a bitter, ‘cold-tasting’ herb which has proven to be effective in fever reduction, detoxification, anti-inflammatory and drying limbs ichor ( 7 ). It is therefore traditionally applied to treat a range of illnesses, including spleen disease, twisted intestinal fever, diphtheria and tonsillitis ( 8 ). Currently, there are few published studies on the effects of M. suaveolens .…”

Small Molecules from Nature Targeting G-Protein Coupled Cannabinoid Receptors: Potential Leads for Drug Discovery and Development

“…It has been found effective in inflammation, pain, and antimicrobial activity. The cannabinoid mediated anti-inflammatory activity of M. suaveolens has been demonstrated in a rat cecal ligation and puncture- (CLP-) induced animal model of acute lung injury representing sepsis in human [ 121 ]. It has shown to upregulate the CB 2 expression in peripheral blood mononuclear cells, reduce the number of neutrophils, lymphocytes, and total cells, and inhibit the induction of proinflammatory cytokines and transcription factors, NF- κβ 65.…”

Anti-Inflammatory Effects of Deuterium-Depleted Water plus Rosa damascene Mill. Essential Oil via Cyclooxygenase-2 Pathway in Rats

“…18,19 The cecal ligation and puncture (CLP) model as a stable, repetitive, and applicable model leads to the pollution of the abdominal cavity by bacteria-carrying intestinal contents and induces a wide range of systemic inflammatory responses leading to sepsis. 20,21 In the CLP model, bacteria spreading from infection sites and entering the bloodstream are rapidly trapped in the many organs such as liver, kidney, lung, and spleen and bound to the surface of specific target cells and macrophages in the target organ and subsequently killed by infiltrated neutroph. 22,23 The organs are damaged in mice with lethal sepsis induced by CLP and also in humans with sepsis.…”