Codonopsis polysaccharide protected LPS-induced acute lung injury by inhibiting MAPK/NF-κB signaling pathway in mice / 实用医学杂志

Objective To observe the protective effects of codonopsis pilosulae polysaccharide on lung tissues in mice with acute lung injury(ALI)induced by lipopolysaccharide(LPS)and its mechanism.Methods Fifty male Kunming mice were randomly divided into control group,model group,dexamethasone group,codonopsis polysaccharide high-dose group(300 mg/kg)and codonopsis polysaccharide low-dose group(150 mg/kg).The ALI model was established by intraperitoneal injection of LPS.All mice were given gavage administration according to the grouping except for the control group.0.3 s force expiratory volume(FEV 0.3)and force spirometry(FVC)and their ratios were measured using multiparametric lung function test system.The histopathology change of mouse lung was detected by hematoxylin-eosin(HE)staining,and the classification and count of inflammatory cells in alveolar lavage fluid(BALF)was detected by Richter-Giemsa staining.Levels of IL-1β,IL-6,MPO and TNF-α were measured by ELISA in BALF,and Western blot was used to detect the protein expression level of p-p38,p-IκB-α and p-p65.Results Compared with those in the control group,lung histopathological damage was more pronounced in the model mice,with significantly lower FEV 0.3,FVC,FEV0.3/FVC assay value,but signifi-cantly higher lung tissue wet mass/dry mass(W/D),neutrophils,lymphocytes,IL-1β,IL-6,MPO,TNF-α,p-p38 MAPK,p-IκB-α,and p-p65(P<0.05);while codonopsis pilosulae polysaccharide could significantly reverse these effects.Conclusion Codonopsis pilosulae polysaccharide plays a protective role against LPS-induced ALI via inhibiting MAPK/NF-κB pathway to reduce the pathological damage of lung tissue,and the level of inflammatory factors,thus to improve lung function in ALI model mice.

Mechanism of crocin alleviating monocrotaline-induced right ventricular injury in rats with pulmonary arterial hypertension / 中国病理生理杂志

AIM:To investigate whether crocin alleviates right ventricular injury induced by monocrotaline(MCT)in rats with pulmonary arterial hypertension(PAH),and to explore the underlying mechanisms.METHODS:Forty male SD rats were randomly divided into 4 groups:normal group,PAH group,crocin group and sildenafil group,with 10 rats in each group.The rats in PAH,crocin and sildenafil groups received subcutaneous injection of MCT(50 mg/kg)to establish the PAH model.Starting from the day of MCT injection,the rats in crocin group received crocin(200 mg/kg),the rats in sildenafil group received sildenafil(30 mg/kg),and those in PAH and normal groups were orally gavaged with an equal volume of saline once daily.After 4 weeks,measurements of right ventricular systolic pressure(RVSP),mean pulmonary artery pressure(mPAP),right ventricular hypertrophy index(RVHI)and right ventricular mass index(RVMI)were taken for the rats in each group.Tissue staining was conducted to observe pathological changes in the right ventricle,and the expression levels of inflammatory factors(IL-1β,IL-6 and TNF-α),the p38 MAPK/NF-κB inflammato-ry pathway,CCL2,CCR2,and the macrophage marker CD68 were assessed.RESULTS:Compared with PAH group,the rats in crocin and sildenafil groups exhibited significant reductions in RVSP,mPAP,RVHI and RVMI(P＜0.05).Right ventricular tissue displayed no evident infiltration of inflammatory cells or proliferation of collagen fibers.The down-regulation of the p38 MAPK/NF-κB pathway and inflammatory factors(IL-1β,IL-6 and TNF-α)was significant(P＜0.05).Additionally,the CCL2/CCR2 pathway and the infiltration of CD68+ macrophages were markedly decreased(P＜0.05).CONCLUSION:Crocin effectively mitigates right ventricular damage in MCT-induced PAH rats,with its effica-cy comparable to that of sildenafil at the dosage utilized in this experiment.Some protective mechanisms of crocin may be attributed to its regulatory effects on inflammation.

Chaihu Longgu Mulitang Relieves Generalized Anxiety Disorder in Rats via p38 MAPK/NF-κB Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo study whether Chaihu Longgu Mulitang can inhibit hypothalamic inflammation， mitigate anxiety-like behavior， and alleviate anxiety symptoms by regulating the p38 mitogen-activated protein kinase/nuclear factor-κB （p38 MAPK/NF-κB） signaling pathway in the rat model of generalized anxiety disorder （GAD）. MethodTwelve out of 74 Wistar rats were randomly selected as the blank group， and the remaining rats were subjected to chronic restraint stress for the modeling of GAD. The open field test （OFT） and elevated Porteus maze test （PMT） were conducted 14 days after modeling to detect the anxiety-like behaviors. Sixty successfully modeled rats were selected and randomized into model， low-， medium-， and high-dose （6， 12， and 24 g·kg-1， respectively） Chaihu Longgu Mulitang， and diazepam （1 mg·kg-1） groups （n=12） and administrated with corresponding drugs for 14 consecutive days. OFT and PMT were then carried out to examine the anxiety-like behaviors of the rats. The levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β） in the hypothalamus and serum of rats were determined by the enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）was conducted to determine the mRNA levels of p38 MAPK， NF-κB p65， nuclear factor κB inhibitor α （IκBα）， and ionized calcium binding adaptor molecule 1 （Iba-1）. The protein levels of p38 MAPK， phosphorylated （p）-p38 MAPK， NF-κB p65， p-NF-κB p65， and IκBα in the hypothalamus of rats were determined by Western blot. The expression of Iba-1 in the hypothalamic microglia was detected by immunofluorescence assay. ResultCompared with the blank group， the model group had decreased body weight， scattered dark yellow fur， increased irritability， and preference to hibernation in the corner. In addition， the modeled rats showed increased edge movement distance and time in OFT （P<0.01） and decreased movement distance and time and the number of entries in the open arm in PMT （P<0.01）. The modeling increased the fluorescence intensity of Iba-1 in paraventricular nucleus of hypothalamus （P<0.01）， elevated the levels of IL-1β， IL-6， and TNF-α in the serum and hypothalamus （P<0.01）， up-regulated the protein and mRNA levels of p38 MAPK， NF-κB p65， p-p38 MAPK， p-NF-κB p65， and Iba-1 （P<0.05， P<0.01）， and down-regulated the protein and mRNA levels of IκBα （P<0.01） in the hypothalamus. Compared with the model group， medium- and high-dose Chaihu Longgu Mulitang and diazepam increased the body weight， improved the fur and behaviors， decreased the edge movement distance and time in OFT （P<0.05， P<0.01）， and increased the movement distance and time in the open arm in PMT （P<0.05， P<0.01）. Furthermore， they decreased the fluorescence intensity of Iba-1 in hypothalamic microglia （P<0.05， P<0.01）， lowered the levels of IL-1β， IL-6， and TNF-α in the serum and hypothalamic tissue （P<0.05， P<0.01）， down-regulated the mRNA and protein levels of p38 MAPK， NF-κB p65， p-p38 MAPK， p-NF-κB p65， and Iba-1 （P<0.05， P<0.01）， and up-regulated the mRNA and protein levels of IκBα （P<0.05， P<0.01） in the hypothalamus. ConclusionChaihu Longgu Mulitang can mitigate anxiety-like behaviors and relieve anxiety in GAD rats by inhibiting the p38 MAPK/NF-κB signaling pathway and reducing the activation of microglia and the levels of pro-inflammatory cytokines in the hypothalamus.

Effect and Mechanism of Action of Epimedii Folium Polysaccharides on Mice with Exercise-induced Fatigue Based on p38 MAPK/NF-κB Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo study the effects of Epimedii Folium polysaccharides on mice with exercise-induced fatigue and explore its possible mechanism of action. MethodICR male mice screened by swimming training were randomly divided into a control group， model group， vitamin C group， and low， medium， and high dose groups of Epimedii Folium polysaccharides， with eight mice in each group. The exercise-induced fatigue model was established by weight-bearing swimming training in each group except for the control group. After two weeks of weight-bearing swimming， the Epimedii Folium polysaccharide groups were given 100， 200， 400 mg∙kg-1 of Epimedii Folium polysaccharides by gavage， and the vitamin C group was given 200 mg∙kg-1 of vitamin C by gavage. The control group and the model group were given equal amounts of saline for 14 d. At the end of the experimental period， the body mass of the mice in each group and the time of last swimming due to exhaustion were recorded. Serum urea nitrogen （BUN）， lactic acid （LA）， lactate dehydrogenase （LDH）， malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione peroxidation （GSH-Px）， myoglycogen （MG） in skeletal muscle， hepatic glycogen （HG） in the liver were detected by kits. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in muscle tissue. Western blot was used to detect the protein expression of p38 mitogen-activated protein kinase （p38 MAPK）， phosphorylation （p）-p38 MAPK， extracellular signal-regulated kinase1/2 （ERK1/2）， nuclear factor-κB （NF-κB）， p-NF-κB， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in muscle tissue. The immunofluorescence （IF） method was used to detect the expression of tumor necrosis factor-α （TNF-α） in skeletal muscle tissue of mice in each group. ResultCompared with the control group， the body mass of mice in the model group decreased， and the time of last swimming due to exhaustion decreased （P<0.01）. In addition， there were significantly higher serum levels of the fatigue metabolites LA， LDH， BUN， and lipid peroxidation product MDA （P<0.01） and decreased levels of MG， HG， SOD， and GSH-Px （P<0.01）. The protein expressions of p-p38 MAPK， ERK1/2， p-NF-κB， IL-1β， IL-6， and TNF-α in skeletal muscle tissue were significantly higher than those of the control group （P<0.01）. Compared with the model group， the body mass and time of last swimming due to exhaustion of the mice in the low， medium， and high dose groups of Epimedii Folium polysaccharides and the vitamin C group were increased （P<0.05， P<0.01）， and the contents of LA， LDH， BUN， and MDA were significantly decreased （P<0.05， P<0.01）. The levels of MG， HG， SOD， and GSH-Px increased （P<0.05， P<0.01）， and the protein expression levels of p-p38 MAPK， ERK， p-NF-κB， IL-1β， IL-6， and TNF-α in skeletal muscle tissue decreased （P<0.05， P<0.01）. ConclusionEpimedii Folium polysaccharides can play a role in alleviating exercise-induced fatigue by inhibiting the p38 MARK/NF-κB signaling pathway， thereby reducing the accumulation of metabolites， improving the activity of antioxidant enzymes， increasing the glycogen content of the body， and reducing inflammation in skeletal muscle.

Effect of baicalin modulation of TLR4/MAPK/NF-ΚB signaling pathway on renal fibrosis in rats with diabetic nephropathy / 中国药理学通报

Aim To investigate the protective effect of baicalin on renal fibrosis in rats with diabetic nephrop- III (Col- III) athy (DN) and to investigate its mechanism of action. Methods A rat model of diabetic nephropathy was constructed. The rats were randomly divided into control group, model group, baicalin low dose group, baicalin medium dose group, baicalin high dose group and metformin group, with 10 rats in each group. Except for the control group, all rats in each group were fed with streptozotocin 65 mg • kg -

Mechanism of Blood-activating and Toxin-removing Method in Treatment of Coronary Heart Disease and Cognitive Dysfunction Based on Treating Different Diseases with Same Method / 中国实验方剂学杂志

As China is about to enter an era of deep aging， the coexistence of multiple diseases is gradually increasing. Coronary heart disease （CHD） and cognitive dysfunction also show increasing incidence year by year. The two diseases affect and cause each other， becoming the major chronic diseases harmful to the health of the elderly. It is of great clinical significance to explore the methods integrating traditional Chinese and western medicine for the prevention and treatment of the two diseases. The relationship between CHD and cognitive dysfunction in traditional Chinese medicine （TCM） was first recorded in Huangdi’s Internal Classic （Huang Di Nei Jing）. As the understanding of CHD and cognitive dysfunction is deepening， the influences of stasis and toxin on both diseases have attracted increasing attention. According to the theories of TCM， CHD and cognitive dysfunction have common points in the etiology and pathogenesis. Therefore， the theory of treating different diseases with same method provides a theoretical basis for the clinical treatment of different diseases with the same pathogenesis. Moreover， this theory conforms to the principle of integrated and individualized prevention and treatment of multi-disease coexistence in modern medicine. This paper systematically proposed that the coexistence of stasis and toxin is a major pathogenesis of CHD and cognitive dysfunction. We then explored the possible mechanisms of the blood-activating and toxin-removing method in the treatment of CHD and cognitive dysfunction based on the theory of treating different diseases with same method. The mechanisms include the regulation of ceramide metabolism， activation of silent mating-type information regulation 2 homolog 1 （SIRT1）， inhibition of pyroptosis， regulation of mitogen-activated protein kinase/nuclear factor-κB （MAPK/NF-κB） signaling pathway， inhibition of mitochondrial division， and regulation of DNA methylation. We hope this paper will provide an idea for the future research on the prevention and treatment of CHD and cognitive dysfunction with TCM.

Anti-herpes simplex virus effect of aristolochic acids in vitro and in vivo / 中国药理学通报

Aim To investigate the inhibition effects and mechanisms of aristolochic acids(AAs)against herpes simplex virus(HSV)in vitro and in vivo. Methods The cytopathic effect(CPE), plaque assay, indirect immunofluorescence and others were used to explore the anti-HSV effects and mechanisms of aristolochic acid in Vero cells, and the in vivo anti-HSV activity of AAs was evaluated using HSV-1 infected BALB/c mouse model. Results The IC

Effect of different parts of Pinelliae Rhizoma Decoction against airway inflammation and analysis of effective components / 中国中药杂志

This study investigated the material basis and mechanism of Pinelliae Rhizoma Decoction in the treatment of airway inflammation. The cigarette smoke combined with lipopolysaccharide(LPS) was used to induce an airway inflammation model in mice. The expression levels of IL-6 and IL-8 in the bronchoalveolar lavage fluid(BALF) and the phosphorylation levels of p38 and IκB in the lungs of mice were taken as indexes to screen the effective extracts by system solvent extraction from Pinelliae Rhizoma Decoction(dichloromethane extract, ethyl acetate extract, n-butanol extract, etc.). Meanwhile, the human bronchial epithelial(16-HBE) cell model of cigarette smoke extract(CSE)-induced injury was established, and the mRNA expression levels of IL-6 and IL-8 and the phosphorylation levels of p38 and IκB proteins were also taken as indexes to evaluate the anti-inflammatory effect of different extracts of Pinelliae Rhizoma Decoction. The results showed that Pinelliae Rhizoma Decoction significantly antagonized airway inflammation in mice by down-regulating the expression levels of IL-6 and IL-8 in mice with airway inflammation and 16-HBE cells with CSE-induced injury and inhibiting the phosphorylation levels of p38 and IκB. The dichloromethane and ethyl acetate extracts of Pinelliae Rhizoma Decoction showed significant anti-inflammatory effects, while such effects of other extracts were not prominent. Furthermore, the database of Pinelliae Rhizoma composition was constructed, and the components in effective extracts were analyzed by HPLC-TOF-MS and Nano-LC-MS/MS. As revealed by the results, the compositions of the two effective extracts were similar with 36 common components. They were combined and then divided into Pinelliae Rhizoma alkaloids(PTAs) and Pinelliae Rhizoma non-alkaloids(PTNAs) by 732 cation-exchange resin. Further in vitro investigation confirmed the significant anti-inflammatory effect of PTNAs, while such effect of PTAs was not manifest. The MS analysis showed 172 peptides and 7 organic acids in PTNAs. The peptide content in PTNAs was 63.5% measured by quantitative analysis of BCA assay, and the organic acid content was 9.92% by potentiometric titration method. The findings of this study suggested that Pinelliae Rhizoma Decoction could antagonize airway inflammation in mice by inhibiting phosphorylation of p38 and IκB and blocking the activation of MAPK and NF-κB signaling pathways, and the effective components were related to the peptides and organic acids in PTNAs. The above results lay a foundation for the research on the mechanism and material basis of Pinelliae Rhizoma in antagonizing airway inflammation.

Effect of Euphorbia helioscopia Alcohol Extract on MAPK/NF-κB Inflammation Pathway on Mice with Acute Lung Injury Induced by LPS / 中国实验方剂学杂志

Objective:To study the protective effect of Euphorbia helioscopia alcohol extract on lipopolysaccharide (LPS) -induced acute lung injury in mice and explore its possible mechanism. Method:The 50 Balb/c male mice were randomly divided into 5 groups, including normal group, model group, dexamethasone group (1.5 mg·kg-1), E. helioscopia alcohol extracts group (7.5，3.75 g·kg-1). Except for the normal group, the other groups used intranasal instillation of LPS to establish a model of acute lung injury in mice. The type and number of inflammatory cells in bronchoalveolar lavage fluid (BALF) were detected by automatic blood analyzer and Wright-Giemsa composite staining. The lung tissue damage was observed by hematoxylin-eosin (HE) staining. The contents of the inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in BALF were detected by flow cytometry. The protein expressions of nuclear factor kappa-B p65(NF-κB p65), phospho-NF-κB p65 (p-NF-κB p65), inhibitor of NF-κBα (IκBα), phospho-IκBα (p-IκBα) in NF-κB pathway and c-Jun N-terminal kinase (JNK), phospho-JNK (p-JNK), p38 protein (p38), phospho-p38 (p-p38), extracellular regulated protein kinases (ERK1/2), phospho-ERK1/2 (p-ERK1/2) in mitogen-activated protein kinase (MAPK) pathway were determined by Western blot. Result:Compared with normal control group, the lung tissue of the model group showed obvious damage, in which a large number of inflammatory cells infiltrated, and the integrity of the alveoli was destroyed. Inflammatory factors TNF-α, IL-6 in BALF and p-NF-κB p65, p-JNK, p-p38, p-ERK protein expression levels in lung tissue were significantly increased (P<0.01). Compared with model group, the pathological damage of lung tissue in mice with high dose of E. helioscopia alcohol extract and dexamethasone positive group was significantly alleviated. The levels of TNF-α and IL-6 in BALF and the expression levels of p-NF-κB p65, p-JNK, p-p38 and p-ERK1/2 protein in lung tissue were significantly down-regulated (P<0.01). Conclusion:The E. helioscopia alcohol extract has a protective effect on LPS-induced acute lung injury in mice, its mechanism may be related to the regulation of the NF-κB/MAPK signaling pathway.

Effects of p38MAPK inhibitor on fetal lung injury in a rat model of acute pancreatitis in late pregnancy / 中华急诊医学杂志

Objective To investigate the effect and underlying mechanisms of p38 mitogenactivated protein kinase inhibitor SB203580 on fetal lung injury in a rat model of acute pancreatitis in late pregnancy.Methods Twenty-four pregnant Sprague-Dawley rats in last gestation were randomly(random number) divided into the SO group,APILP group,and SB203580 treatment (SB) group.APILP model was induced by retrograde injection of 5％ sodium taurocholate into the biliary-pancreatic duct.SB203580 administration (10 mg/kg body weight,intraperitoneal injection) was performed 0.5 h before surgery.All the rats in the SO and APILP groups received intraperitoneal injection of equivoluminal solvent at the same time point.Animals were sacrificed at 12 h after the induction of APILP,then the blood and tissue samples were harvested.Serum levels of AMY and TNF-α were analyzed.Histopathological changes of maternal pancreas and fetal lung were observed and evaluated.The expression and location of NF-κB in fetal lungs were detected by immunohistochemistry and MPO expression in fetal lungs was examined by immunofluorescence.The expression ofp-p38MAPK,p38MAPK,TNF-α and ICAM-1 was determined by Western blot.One-way ANOVA and Tukey's multiple comparison tests were used for statistical analysis.Results The levels of AMY and TNF-α in maternal serum were markedly increased after APILP [(7871.3±623.5) vs (1 915.3±452.3),(193.8±25.4) vs (107.0±±13.3),(P＜0.05)].Obvious pathological changes presented in matemal pancreas and fetal lung after the attack of APILP,and their pathological scores were significantly higher than those of the SO group [(12.44±1.08) vs (1.56±0.56),(2.50±0.53) vs (0.88±0.64),(P＜0.05)].The number of NF-κB and MPO positive cells in fetal lungs were significantly higher than those in the SO group [(150.63±34.58) vs(29.50±8.80),(53.38±8.30) vs (11.75±3.33);P＜0.05)].In addition,the expression and nuclear translocation were pervasive in fetal lungs in the APILP group.Furthermore,the levels of p-p38MAPK [(0.6367±0.0386) vs (0.2282±0.0220)],TNF-α [(0.6313±0.0395) vs (0.0725±0.0076)],ICAM-1 [(0.8958±0.0776) vs (0.1372±0.0388)] and HMGB1 [(0.6478±0.0209) vs (0.2825±0.0533)] expression in fetal lungs were significantly increased after the establishment of APILP model (P＜0.05).However,with the pre-administration of SB203580,the pathological scores of matemal pancreases (9.38±1.58) and fetal lungs (1.63±0.52) were decreased significantly (P＜0.05),as well as the levels of AMY (4162.1±642.1) and TNF-α (139.6±21.1) in maternal serum (P＜0.05).The number of NF-κB (93.00±18.88) and MPO (27.38±4.75) positive cells in fetal lungs were dramatically reduced (P＜0.05) and fewer nuclear translocation was observed in the SB group.Interestingly,the expression levels of p-p38MAPK (0.2578±0.0170),TNF-α (0.3240±0.0326),ICAM-1 (0.4177±0.0823) and HMGB1 (0.4923±0.0457) in fetal lungs were markedly decreased with the treatment of SB203580 (P＜0.05).Conclusions P38MAPK and its downstream inflammatory signaling pathway were involved in the process of APILP-related fetal lung injury;SB203580 administration could significantly attenuate fetal lung injury induced by APILP,which may be closely related to the inhibition of p38MAPK phosphorylation and inflammatory cascade caused by the activation of downstream signal pathways.

Protective effects of magnolol against cardiac injuries via attenuating of mitogen-activated protein kinase (MAPK)/nuclear factor κB (NF-κB)-mediated inflammatory response in type 1 diabetic mice / 中草药

Objective To investigate the protective effects and mechanism of magnolol on diabetic cardiomyopathy in type 1 diabetic mice. Methods Using type 1 diabetic mice induced by streptozotocin (STZ), the mice in the magnolol-treated groups were treated intragastrically (ig) with magnolol by the dose of 10 mg/kg or 20 mg/kg respectively. After 12-week treatment, animals were then euthanized. The levels of creatine kinase (CK), MB isoenzyme of creatine kinase (CK-MB) and lactate dehydrogenase (LDH) in serum were detected by enzyme-linked-immunosorbent serologic assay (ELISA). The histopathology of heart tissue was detected by hematoxylin and eosin (HE) and Masson staining. Inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) were evaluated by qRT-qPCR assay. The alteration of MAPK and NF-κB signaling pathway was detected by Western blotting. Results Compared with the control group, the mice in diabetic group showed a significantly increase in the level of CK, CK-MB and LDH in serum (P andlt; 0.05), and cardiac pathological lesions were also observed. With the TNF-α and IL-6 mRNA expression in cardiac tissue increased (P and lt; 0.05), extracellular regulated protein kinases (ERK), C-Jun N-terminal kinase (JNK) and P38 phosphorylation level, as well as IκB degradation, were significantly increased in type 1 diabetic mice model. Compared with the model group, the level of cardiac serum markers (CK, CK-MB, and LDH) of mice in the magnolol-treated groups was significantly decreased (P and lt; 0.05). Also, magnolol can improve the abnormalities of serum indexes and histopathological damage induced by diabetes in mice. It reduced cardiac tissue TNF-α and IL-6 mRNA expression level (P andlt; 0.05). In addition to IκB degradation, phosphorylation of ERK, JNK and p38 were inhibited by treatment with magnolol (P andlt; 0.05). Moreover, the effect of dosage 20 mg/kg magnolol was significantly superior to 10 mg/kg magnolol on the reduction of IκB degradation in NF-κB signaling pathway (P andlt; 0.05). Conclusion Magnolol could attenuate the inflammation-mediated diabetic myocardial injuries via inhibiting activation of MAPK/NF-κB signaling pathway.

The effects of IGF-1 on the proliferation and apoptosis of cultured condylar chondrocytes / 实用口腔医学杂志

Objective:To investigate the effects of IGF-1 and IL-1β on the proliferation and apoptosis of cultured human condylar chondrocytes( CCs) of temporomandibular joint( TMJ) . Methods:Cultured CCs were derived from human TMJ condylar cartilage tis-sue, and identified by immunocytochemistry staining. The cultured cells were divided into 6 groups:control group, IL-1β(10 μg/L) group and IL-1 group (10 μg/L) + IGF-1 group (0, 1, 10, 50 and 100 μg/L, respectively). The cell proliferation ability was de-tected by MTT assay. The cell cycle and apoptosis were detected by flow cytometry. The expression of apoptosis-associated factors Bcl-2, Bax and p38 MAPK/NF-κB proteins were detected by Western blot. Results:Type II collagen was positively expressed in cultured CCs. IL-1β treatment decreased cell proliferation, increased cell apoptosis with concomitant increase of the percentage of early apopto-sis and late apoptotic cells, increased Caspase-3 expression, decreased Bcl-2/Bax ratio, and increased the expression of p38 MAPK/NF-κB proteins. Whereas, with 1-100 μg/L IGF-1 pretreatment, the proliferation ability and Bcl-2/Bax ratio of the cells were in-creased(P<0. 05), the apoptotic cells were decreased, the expression of Caspase-3 and p38 MAPK/NF-κB proteins was decreased ( P<0. 05) in a dose-dependent manner. Conclusion:IGF-1 may inhibit IL-1β-induced cell apoptosis and attenuate the activation of p38 MAPK/NF-κB of human condylar chondrocytes.

Berberine regulates MMPs/TIMP via inhibition of P38 MAPK/NF-κB phosphorylation and anti-inflammation in rat experimental periodontitis / 西安交通大学学报(医学版)

ABSTRACT:Objective To investigate the effects of berberine on matrix metalloproteinases/tissue inhibitors of matrix metalloproteinases (MMPs/TIMPs) in rat periodontitis .Methods Adult male Sprague‐Dawley rats were subjected to thread ligation and porphyromonas gingivalis ( P . gingivalis ) inoculation resulting in periodontitis . Berberine [150 mg/(kg · d)] or vehicle was administered by oral gavage for 4 weeks .Alveolar bone loss and soft‐tissue destruction were determined by micro‐computed tomography (μ‐CT) and HE staining .The contents of tumor necrosis factor‐α(TNF‐α) and interleukin‐1β(IL‐1β) of gingival tissue were examined by ELISA .The expressions of MMP‐2 ,MMP‐9 and TIMP‐2 as well as the phosphorylation of P38 MAPK and NF‐κB were determined by Western blot .Results Significant increases were observed in alveolar bone loss and periodontal soft‐tissue destruction with higher levels of TNF‐α, IL‐1β and MMP‐2/9 expressions and the activities of P38 MAPK and NF‐κB in the experiment periodontitis group .Berberine of [150 mg/(kg · d)] not only improved the periodontal tissue and decreased alveolar bone loss ,but also reduced the contents of TNF‐α,IL‐1βand MMP‐2/9 and increased TIMP‐2 .In addition ,berberine inhibited the phosphorylation of P38 MAPK/NF‐κB .Conclusion Berberine protects against periodontal tissue damage via decreasing MMP‐2 and MMP‐9 expressions but increasing TIMP‐2 expression , which may be induced by inhibition of P38 MAPK/NF‐κB and the anti‐inflammatory effect on rat periodontitis .

Sangxingtang inhibits the inflammation of LPS-induced acute lung injury in mice by down-regulating the MAPK/NF-κB pathway / 中国天然药物

In the present study, we investigated anti-inflammatory effects of Sangxingtang (SXT) on acute lung injury using a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. The cell counting in the bronchoalveolar lavage fluid (BALF) was performed. The degree of lung edema was evaluated by measuring the wet/dry weight (W/D) ratio. The superoxidase dismutase (SOD) and myeloperoxidase (MPO) activities were assayed by SOD and MPO kits, respectively. The levels of inflammatory mediators, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), were assayed by the enzyme-linked immunosorbent assay methods. Pathological changes of lung tissues were observed by Hematoxylin and eosin (HE) staining. The inflammatory signaling pathway-related proteins nuclear factor mitogen activated protein kinases (P38MAPK), extracellular regulated protein kinases (Erk), c-Jun N-terminal kinase (Jnk) and nuclear transcription factor (NF-κB) p65 expressions were measured by Western blotting. Our results showed that the treatment with the SXT markedly attenuated the inflammatory cell numbers in the BALF, decreased the levels of P-P38MAPK, P-Erk, P-Jnk and P-NF-κB p65 and the total protein levels in lungs, improved the SOD activity and inhibited the MPO activity. Histological studies demonstrated that SXT substantially reduced the LPS-induced neutrophils in lung tissues, compared with the untreated LPS group. In conclusion, our results indicated that SXT had protective effects on LPS-induced ALI in mice.