Protective effects of polydatin on lipopolysaccharide-induced acute lung injury through TLR4-MyD88-NF-κB pathway
Introduction
Acute lung injury is characteristic by hypoxemia, alveolar-capillary barrier damage, cells recruitment and a cascade of inflammatory process. Literatures have revealed that inflammatory cytokines such as IL-6, IL-1β and TNF-α are highly associated with ALI [1]. Despite the high morbidity and mortality, there has been few effective drug to treat ALI [2]. Recently, large quantities of investigations have proved that Toll like receptors (TLRs) play an essential role in innate immune system which is responsible for the inflammatory process in ALI. TLR family is composed of 10 members (TLR1-TLR10) [3], among which TLR4 can be engaged by LPS which is recognized as the component of outer membrane of Gram negative bacteria. TLR4 initiates a cascade of response including neutrophils infiltration and the accumulation of cytokines [4]. Classically, intratracheal administration of LPS is widely used as an inducer of lung injury in scientific studies.
It is well established that inflammatory process evoked by LPS is mediated by the transmembrane receptor toll-like receptor 4 (TLR4) [5]. After the recognition of LPS by TLR4, a serious of cascades including myeloid differentiating factor 88 (MyD88) are initiated following the activation of IRAKs. Subsequently, the recruitment of IRAK4 and IRAK1 to the MyD88-signaling complex leads to the activation of IKK-α and IKK-β, followed by the phosphorylated degradation of IκB-α and NF-κB initiation [6]. NF-κB, a regulator of inflammatory disorder, is required for the transcription of sufficient cytokines including IL-6, IL-1β, TNF-α [7]. In particular, the activation of NF-κB is attributed to TLR4 and is pivotal to the pathogenesis in various pulmonary diseases, such as ALI [8].
Traditional Chinese medicine has been used for centuries around the world and is still acknowledged as a major source of medicine [9], [10]. Resveratrol (3, 4′, 5-trihydroxy-trans-stilbene) is a non-flavonoid polyphenol and exerts anti-inflammatory and cardioprotective effects on human trials [11], [12]. Evidence emerged indicating that Resveratrol inhibited monocrotaline-induced pulmonary hypertension in rats [13]. Polydatin (PD), a crystal compound extracted from the root of Polygonum cuspidatum, is a glucoside of resveratrol in which the glucoside group bonded in position C-3 substitutes a hydroxyl group. The substitution contributes to the conformational changes of the molecule, which makes PD a potent molecule endowed with greater bioavailability respect to resveratrol [14]. PD is traditionally used for the treatment of chronic bronchitis, hepatitis, and shock [15]. Indraccolo et al. proved that PD showed anti-inflammatory properties during the inflammatory process of chronic pelvic pain in patients [16]. Whereas the pharmacological effects of PD on LPS-induced ALI in mice have not been elucidated. The purpose of this study was to assure the therapeutic efficacy of PD on ALI in mice with LPS challenge.
Section snippets
Reagents
Polydatin was provided by National Institutes for Food and Drug Control (purity more than 99.5%, Beijing, China) (Fig. 1) and dissolved in DMSO at a concentration of 200 mM. The final concentration of DMSO was less than 0.1% [v/v] in all experiments. Dexamethasone (DEX) was supplied by the National Institutes for Food and Drug Control (Beijing, China). LPS (E. coli 055:B5)) was purchased from Beyotime Institute of Biotechnology (Nanjing, China). Mouse IL-6, IL-1β, TNF-α enzyme-linked
Effects of PD on lung W/D ratio in LPS-induced ALI mice
The lung W/D (wet to dry) ratio was determined to reflect the pulmonary edema. As revealed in Fig. 1A, administration of LPS increased the level of lung W/D ratio. Notably, pretreatment with PD (80 mg/kg) significantly declined the magnitude of pulmonary edema, which was slightly less potent than those of pretreatment with dexamethasone. The experimental data suggested that PD could affect the water content of lung tissues in mice (Fig. 2A).
Effects of PD on MPO activity of the lung tissues in LPS-induced ALI mice
As an important measurement of neutrophils
Discussion
Polydatin (PD), isolated from P. cuspidatum, possesses multiple pharmacological actions. It has been reported to exhibit therapeutic effects in LPS-stimulated ALI in rats [17] and exert anti-inflammatory effects via NF-κB in RAW 264.7 cells [18]. However, few research had focused on the pharmacological effects of PD on ALI in LPS-induced mice and the explanation of its potential mechanism as yet.
LPS, the important constituent of the Gram-negative bacteria, is a major component of pathogens for
Conflict of interest
The authors have no conflict of interest.
References (38)
- et al.
Anti-inflammatory effects of water extract of Taraxacum mongolicum hand.-Mazz on lipopolysaccharide-induced inflammation in acute lung injury by suppressing PI3K/Akt/mTOR signaling pathway
J. Ethnopharmacol.
(2015) - et al.
Zingerone attenuates lipopolysaccharide-induced acute lung injury in mice
Int. Immunopharmacol.
(2014) - et al.
Protective effect of apigenin on Freund's complete adjuvant-induced arthritis in rats via inhibiting P2X7/NF-kappaB pathway
Chem. Biol. Interact.
(2015) - et al.
Prime-O-glucosylcimifugin attenuates lipopolysaccharide-induced acute lung injury in mice
Int. Immunopharmacol.
(2013) - et al.
Protective effect of platycodin D on liver injury in alloxan-induced diabetic mice via regulation of Treg/Th17 balance
Int. Immunopharmacol.
(2015) - et al.
One-year supplementation with a grape extract containing resveratrol modulates inflammatory-related microRNAs and cytokines expression in peripheral blood mononuclear cells of type 2 diabetes and hypertensive patients with coronary artery disease
Pharmacol. Res.
(2013) - et al.
One-year consumption of a grape nutraceutical containing resveratrol improves the inflammatory and fibrinolytic status of patients in primary prevention of cardiovascular disease
Am. J. Cardiol.
(2012) - et al.
Effect of palmitoylethanolamide-polydatin combination on chronic pelvic pain associated with endometriosis: preliminary observations
Eur. J. Obstet. Gynecol. Reprod. Biol.
(2010) - et al.
Platycodin D attenuates acute lung injury by suppressing apoptosis and inflammation in vivo and in vitro
Int. Immunopharmacol.
(2015) - et al.
Effects of acteoside on lipopolysaccharide-induced inflammation in acute lung injury via regulation of NF-kappaB pathway in vivo and in vitro
Toxicol. Appl. Pharmacol.
(2015)
The protective effect of CDDO-Me on lipopolysaccharide-induced acute lung injury in mice
Int. Immunopharmacol.
Anti-inflammatory effects of eugenol on lipopolysaccharide-induced inflammatory reaction in acute lung injury via regulating inflammation and redox status
Int. Immunopharmacol.
Quercetin disrupts tyrosine-phosphorylated phosphatidylinositol 3-kinase and myeloid differentiation factor-88 association, and inhibits MAPK/AP-1 and IKK/NF-kappaB-induced inflammatory mediators production in RAW 264.7 cells
Immunobiology
Salidroside ameliorates cognitive impairment in a d-galactose-induced rat model of Alzheimer's disease
Behav. Brain Res.
Protective activity of salidroside against ethanol-induced gastric ulcer via the MAPK/NF-kappaB pathway in vivo and in vitro
Int. Immunopharmacol.
Bradykinin- and lipopolysaccharide-induced bradykinin B2 receptor expression, interleukin 8 release and “nitrosative stress” in bronchial epithelial cells BEAS-2B: role for neutrophils
Eur. J. Pharmacol.
Hypoxia preconditioning increases survival and decreases expression of Toll-like receptor 4 in pulmonary artery endothelial cells exposed to lipopolysaccharide
Pulm Circ
Anti-inflammatory effects of apigenin in lipopolysaccharide-induced inflammatory in acute lung injury by suppressing COX-2 and NF-kB pathway
Inflammation
Esculin inhibits the inflammation of LPS-induced acute lung injury in mice via regulation of TLR/NF-kappaB pathways
Inflammation
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These authors contributed equally and should be considered co-first-authors.