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OBJECTIVE：To study the anti- inflammatory effect and mechanism of Jingulian capsule on inflammatory model rats. METHODS ：Totally 48 rats were randomly divided into blank control group ，model group ，Jingulian capsule low-dose ， medium-dose and high-dose groups （0.66，1.32，2.64 g/kg），dexamethasone group （positive control ，0.945 mg/kg），with 8 rats in each group. Blank control group and model group were given constant volume of water intragastrically ，and other groups were given relevant medicine intragastrocally ，twice a day ，for consecutive 3 days. Thirty minutes after last administration ，model group and administration groups were given lipopolysaccharide （10 mg/kg）intraperitoneally to induce inflammatory model. Six hours after intraperitoneal injection ，the contents of TNF-α，IL-1β，IL-6，PGE2 in serum were detected by ELISA. The wet to dry weight （W/D）ratio of lung tissue were determined. HE staining was used to observe the pathological changes of lung tissue . RT-PCR was used to detect the mRNA expression of TNF-α，IL-6，PGE2 and IL- 1β in lung tissue. Western blot assay was used to detect the phosphorylation of NF-κB p65 protein and the expression of IκBα protein in lung tissue. RESULTS：Compared with blank ； control group ，the contents of TNF-α，IL-1β，IL-6 and PGE 2 in serum ，the W/D ratio of lung tissue ，the expression of TNF-α，IL-1β，IL-6 and PGE 2 mRNA and the phosphorylation level of NF-κB p65 protein in lung tissue of model group weresignificantly increased ，and the expression of IκBα proteinwas significantly decreased （P＜0.05 or P＜0.01）；a large number of alveolar atrophy and collapse ，alveolar wall thickening ，lung consolidation ，and a large number of inflammatory cell infiltration could be seen in lung tissue. Compared with model group ，the contents of TNF-α，IL-1β（except for low-dose group ）， IL-6 and PGE 2 in serum ，as well as the expression of TNF-α（except for high-dose group ），IL-1β，IL-6（except for low-dose ， high-dose groups ）and PGE 2 mRNA in lung tissue were decreased significantly in Jingulian capsule groups （P＜0.05 or P＜0.01）； the W/D ratio of lung tissue was decreased significantly in Jingulian high-dose group （P＜0.05 or P＜0.01）；the expression of phosphorylation level of NF-κB p65 protein in lung tissue of Jingulian medium-dose group were decreased significantly （P＜0.05 or P＜0.01），while the expression of IκBα protein was increased significantly（P＜0.05）；the alveolar structure was clear ，the alveolar wall was slightly thickened ， and a small amount of inflammatory cell infiltration was seen in lung tissue. CONCLUSIONS：Jingulian capsule has good anti-inflammatory effect on inflammatory model rats ，the mechanism of which may be related to the inhibition of NF-κB signal pathway.
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The coronavirus disease 2019 (COVID-19), originated in Wuhan city, Hubei Province, China in December 2019, and then quickly spread to most provinces and regions in China and even spread to many countries abroad. COVID-19 is characterized by wide epidemic, strong infectivity, rapid onset and critical condition. In the face of this epidemic, all parts of the country quickly set off a peak in the fight against COVID-19, but no effective drug for COVID-19 has been developed in the short term. Recently, many hospitals have combined traditional Chinese medicine with western medicine in treatment, and the clinical effect is remarkable, which proves the antiviral effect of traditional Chinese medicine. A large number of pharmacological and clinical studies have proved that the Chinese materia medica S. flavescens has significant antiviral effect. In this paper, the mechanism of anti-coronavirus effect of S. flavescens is expounded from multiple pathways, such as type I interferon, NF-κB signal pathway, ERK signal pathway, PI3K/Akt signal pathway and matrine alkaloids, etc. It is intended to provide reference for clinical treatment of coronavirus infection pneumonia and research and development of related drugs of S. flavescens.
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OBJECTIVE: To discuss the effect of Sanbi granules on type Ⅱ collagen induced arthritis (CIA) rats by regulating the TLR4/MAPKs/NF-κB signal pathway. METHODS: Sixty of Wistar rats were randomly divided into normal control group (CTL group, n=10), model group (n=10), positive control group (n=10) and low dose of Sanbi group (n=10), middle dose of Sanbi group (n=10), high dose of Sanbi group (n=10). The collagen induced arthritis (CIA) model of rats was adopted and treated for 20 days by intragastric administration from 2 weeks after primary immune. After exposure to sanbi for 35 d, the rats status, paw swelling, arthritis index (AI) and pathological change of synovial tissue were observed. The serum IL-1β, IL-6, tumor necrosis factor α (TNF-α) levels were detected by ELISA. And the expressions of Toll-like receptor 4 (TLR4), nuclear factor κB (NF-κB) (p65), p-NF-κB (p65), p38, p-p38, extracellular signal-regulated kinase 1/2 (ERK1/2), p-ERK1/2, c-Jun NH2-terminal kinase (JNK), p-JNK mRNA or proteins in synovial tissues were detected by qRT-PCR and Western blot. RESULTS: At the end of experiment, compared with model group, the paw swelling degree and arthritis index (AI) of CIA rats in DXM group and low, middle, high dose of Sanbi groups were lower (P0.05). Besides, compared with CTL group, TLR4, p-NF-κB (p65), p-p38, p-ERK1/2, p-JNK mRNA and proteins in synovial tissues of CIA rats in model group, DXM group and low, middle, high dose of Sanbi groups were higher (P<0.05). And these mRNAs and proteins in DXM group and low, middle, high dose of Sanbi groups were lower than these in model group, particularly in DXM group and high dose of Sanbi group (P<0.05). CONCLUSION: There are significant evidences that Sanbi granules could protect joint synovial tissues injury by down-regulation TLR4/MAPKs/NF-κB signal pathway on CIA rats.
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Sepsis is a kind of systemic inflammatroy response syndrome (SIRS) induced by severe infection,operation,and trauma,with high mortality rate,treatment cost,and high consumption of medical resources.It has caused a great burden to the medical industry and even the national economy.Therefore,it is urgent to find effective treatment methods for sepsis.At present,the sepsis has been treated with certain drugs pointing at its pathogenesis,such as antibiotics,glucocorticoids,and vasoactive drugs.,but the therapeutic effect is not ideal,with many side effects,poor prognosis,and high clinical mortality.Based on the overall macro-dialectical thinking mode,and with the unique effect and low side effect,traditional Chinese medicine (TCM) has attracted the attention from researchers and clinicians around the world for treatment of sepsis.In recent years,some traditional Chinese medicine prescriptions,Chinese patent medicines,single Chinese medicines and active ingredients are increasingly used as new drugs to prevent and treat sepsis.Such treatment methods have been widely recognized and have reduced the mortality and inflammatory indexes of patients to a certain extent,playing an important role in the prevention and treatment of sepsis.In this paper,the actions of nuclear factor kappa B (NF-κB) signal pathway in sepsis as well as the advances in research of NF-κB signal pathway-related proteins in Chinese medicine for sepsis were reviewed.
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Dynamic balance of bone metabolism is one of the important factors to maintain normal osseous tissue function. When the balance is broken, it causes bone damage and even bone metabolic disease. However, the mechanism of bone metabolism is still unclear, the signal pathway is complex, and the treatment of diseases is still under study. The research on the mechanism of bone metabolism by Chinese materia medica has become a new direction in the treatment of bone metabolism diseases. At present, common mechanisms in bone metabolism include OPG/RANKL/RANK signal pathway, Wnt/β-catenin signal pathway, TGF-β/BMP/Smad signal pathway, and NF-κB signal pathway. In this paper, the research on the above pathways was reviewed, so as to provide a reference for further exploring the treatment of bone metabolism diseases with Chinese materia medica.
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Aim To observe the effect of pyrimidine dithiocarbamate (PDTC) on the variance of disc morphology and the expressions of TNF-α, MMP-9 in the cervical disc in cervical dynamic equilibrium rat models, and to investigate the roles of PDTC in the process of intervertebral disc degeneration and the mechanism involved.Methods Fifty-four SD rats were divided into three groups randomly, then the dynamic equilibrium rat model was established by cutting the nuchal superficial and deep muscle of the rats.The dynamic equilibrium rats with PDTC solution intraperitoneal injection after operations were defined as PDTC group (group A), the models with saline intraperitoneal injection after operations as saline group (group B), the rats of fake operation with saline intraperitoneal injection as blank group (group C), and the animals were sacrificed in batches 10 weeks, 12 weeks, 16 weeks respectively after operation.The C5, C6 vertebrae and C5/6 discs were harvested, and the disc morphology was observed.TNF-α, MMP-9 mRNA expressions were detected by q-PCR and protein expression was observed by Western blot.Results Compared with the saline group, the morphology of disc in PDTC group was destructed slightly and fiber ring arranged orderly.TNF-α, MMP-9 gene and protein expressions had no obvious changes (P>0.05) in blank group (group C) at each time point.The expressions of IL-6, MMP-9 mRNA increased with time in group B, but the amount increased fast firstly, and slow lately, reaching peak in 12 weeks.The expression of TNF-α, MMP-9 protein became steady in group B from 10 weeks compared with other time points(P>0.05).TNF-α, MMP-9 genes and proteins expression decreased obviously in PDTC group (group A) compared with saline group (group B) (P<0.01) at each time point, but higher than blank group C(P<0.01) at each time point.Conclusions TNF-α and MMP-9 are important inflammatory factors involved in rat cervical disc degeneration, PDTC relieves the degeneration of rat cervical disc by reducing the expression of TNF-α and MMP-9 via disturbing the NF-κB signal pathway probably, and PDTC may become potential medicine for disc degeneration.
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Objective To investigate the therapeutic effect and possible mechanism of adenosine A2A receptor agonist (CGS21680) combined with bone marrow mesenchymal stem cells (BMMSC) transplantation in acute liver failure (ALF).Methods Fifty male C57BL/6 mice, 6-8 weeks old, were fed with standard diet for 1 week and randomly divided into 5 groups according to random number table: healthy control group (n=6), model group (n=11), BMMSC group (n=11), CGS21680/BMMSC group (n=11) and CGS21680 group (n=11).Except healthy control group, the other mice were injected with D-GalN and lipopolysaccharide (LPS) to establish ALF model.Ten hours later, CGS21680/BMMSC group and CGS21680 group were injected intraperitoneally with adenosine A2A receptor agonist CGS21680 (2.1 mg/kg).In addition, the BMMSC group and CGS21680/BMMSC group were injected BMMSC (1×10.6) through tail vein.After 24 hours, pathological changes of liver tissue was observed by hematoxylin and eosin staining.The change of proportion of mouse splenic Treg among CD4+T lymphocytes was detected by flow cytometry.Toll-like receptor (TLR)4 and nuclear factor (NF)-κB expression levels in liver tissue were detected by real-time fluorescence quantitative polymerase chain reaction (PCR) and Western blot.One-way analysis of variance (one-way ANOVA) and SNK-q test was conducted for data analysis.Results Serum IL-6 levels were (23.67±2.97) pg/mL in healthy control group, (151.47±6.03) pg/mL in model control group, (72.10±3.74) pg/mL in BMMSC group, (53.35±2.50) pg/mL in CGS21680/BMMSC group and (84.85±3.25) pg/mL in CGS21680 group.The differences between healthy control group and the other 4 groups were all statistically significant (t=46.02, 25.51, 19.58 and 34.03, respectively, all P<0.01).Serum TNF-ɑ levels were (24.62±3.19) pg/mL in healthy control group, (102.25±2.10) pg/mL in model control group, (54.71±2.23) pg/mL in BMMSC group, (42.20±4.72) pg/mL in CGS21680/BMMSC group and (81.76±3.50) pg/mL in CGS21680 group.The differences between healthy control group and the other 4 groups were all statistically significant (t=46.49, 19.97, 7.72 and 29.57, respectively, all P<0.01).The differences of spleen Treg proportion in healthy control group were statistically significant compared with model control group, BMMSC group, CGS21680/BMMSC group and CGS21680 group (t=51.67, 12.22, 5.91 and 18.21, respectively, all P<0.01).The differences of TLR4 mRNA levels of liver tissue in healthy control group were statistically significant compared with model control group, BMMSC group, CGS21680/BMMSC group and CGS21680 group (t=26.31, 21.33, 13.24 and 27.14, respectively, all P<0.05).The differences of NF-κB mRNA level of liver tissue in healthy control group were statistically significant compared with model control group, BMMSC group, CGS21680/BMMSC group and CGS21680 group (t=16.56, 16.34, 7.83 and 13.11, respectively, all P<0.05).The differences of TLR4 protein level in liver tissue of healthy control group were statistically significant compared with model control group, BMMSC group, CGS21680/BMMSC group and CGS21680 group (t=35.60, 10.38, 6.05 and 18.02, respectively, all P<0.05).The differences of liver NF-κB protein level in the healthy control group were statistically significant compared with model control group, BMMSC group, CGS21680/BMMSC group and CGS21680 group (t=10.80, 7.30, 4.61 and 13.24, respectively, all P<0.05).Conclusions Adenosine A2A receptor agonist combined with BMMSC can significantly up-regulate the proportion of Treg cells in acute liver failure mice and inhibit the TLR4/NF-κB pathway activation, with both coordinated regulation, and further inhibit the liver inflammation.
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Objective To explore the mechanism of azithromycin for intervening with inflammation of rats with chronic ob‐structive pulmonary disease (COPD) via TLR‐4/NF‐κB signal pathway .Methods Thirty‐six SD rats were divided into health con‐trol group ,model group and azithromycin group .The rat COPD model in the model group and the azithromycin group was estab‐lished by smoking and intratracheal administration of lipopolysaccharide for 1 month .At 30 min before smoking ,the azithromycin group was given azithromycin 50 mg/kg by gavage ,while the health control group and model group were given the equal amount of normal saline .One month later ,rats were sacrificed and lung tissue was obtained .The pathological morphology of the lung was ob‐served by the HE staining .The enzyme linked immunosorbent assay (ELISA) method was used to detect the level of TNF‐α,IL‐1βand IL‐6 from lung tissue homogenate .The expression of TLR4 ,NF‐κB and pp65 mRNA was detected by RT‐PCR .The expression of TLR4 ,NF‐κB ,pp65 ,MMP‐2 and MMP‐9 protein was detected by Western blot .The cytological classification and count in bron‐choalveolar lavage fluid (BALF) were performed .Results Compared with the model group ,the azithromycin group could improve the lung tissue morphology ,decreased the neutrophil granulocyte count(P< 0 .01) ,reduced the secretion of TNF‐α,IL‐1β,IL‐6 , MMP‐2 and MMP‐9 in lung tissue homogenates(P<0 .01) ,and suppressed the expression of TLR4 and pp65 phosphorylation level (P<0 .01) .Conclusion Azithromycin can intervene with inflammation of rats with COPD .
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Objective To investigate the protective effect of diacerein on monosodium iodoacetate (MIA) induced injury in rat osteoarthritis chondrocytes .Methods The experiment was divided into five groups ,including the normal group ,model group (4μM MIA) ,diacerein low ,middle and high doses groups (1 ,10 ,100μM) .The viability of chondrocytes was detected by MTT assay . The activity of cysteinyl aspartate specific proteinase‐3 (Caspase‐3) was measured by spectrophotography .The activation of nuclear factor kappa B (NF‐κB) signaling pathway and expression level of downstream target molecule cell Bax ,Bcl‐2 ,matrix metalloprotei‐nase‐9 (MMP‐9) and MMP‐13 were detected by Western blot .Results 1 ,10 ,100μM diacerein could increase the viability of MIA‐induced chondrocytes and reduce the activity of Caspase‐3(P<0 .05) .10 ,100μM diacerein could decrease the phosphorylation level of IκBαand NF‐κB p65 ,furthermore downregulated the level of Bax ,MMP‐9 and MMP‐13 protein ,and upregulated the level of Bcl‐2 protein (P<0 .05) .Conclusion Diacerein could inhibit cell apoptosis and degradation of extracellular matrix in MIA‐induced rat chondrocytes ,which might be related to the NF‐κB signal pathway .
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Objective To explore the inhibition effect of glutamine on the inflammation of rats with pneumonia induced by Klebsiella pneumoniae.Methods Thirty-six SD rats were randomly divided into the normal group,model group and glutamine treatment group.The rat pneumonia model was established by intratracheal instillation of Klebsiella Bacillus pneumonia.Results Compared with the model group,the glutamine treatmernt group could reduce the ratio of W/D(5.98±0.29)vs.(4.32±0.33)(P＜ 0.05),alleviated the lung tissue edema,inflammatory cell infiltration and then improved the morphology of the lung tissue,inhibited the IL-6,IL-1 and TNF-α secretion in serum and lung homogenate(P＜0.05),and inhibited the level of NF-κB p65 and IκBα phosphorylation.Conclusion Glutamine inhibits the inflammation of rats with pneumonia induced by Klebsiella pneumoniae,which might be related to NF-κB signal pathway.
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To investigate the inhibitory effects of acteoside (ACT) on BV-2 microglial cells and the potential mechanism,LPS was used to treat BV-2 cells with or without ACT (12.5,25,50 μmol•L ⁻¹). Then, the expressions of inflammatory factors (NO,TNF-α,IL-6) and inflammation related proteins (iNOS,COX-2,p-IKKβ,IKKβ,p-ⅠκB,ⅠκB) were detected. In addition,the nuclear translocation of NF-κB was explored. The results showed that ACT could significantly suppress the inflammatory response against LPS stimulation by decreasing the expressions of NO,IL-6,TNF-α,iNOS,COX-2 and the phosphorylations of IKKβ and IκB. Moreover,the nuclear translocation of NF-κB p65 was inhibited by ACT. Taken together, ACT could significantly inhibit the inflammatory response of BV-2 microglial cells which were induced by LPS via inhibition of NF-κB signaling pathway.
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OBJECTIVE: To study the effects of fibroblast growth factor-21 (FGF-21) on acute inflammation induced by lipopolysaccharide (LPS) and its mechanism. METHODS: Mouse model of acute inflammation was established by injection of LPS and treated with FGF-21 at high, medium and low doses, the pathological changes were detected with HE staining, the expression level of TNF-α, IL-1β, IL-6 and IL-17 in serum and peritoneal macrophage were determined by ELISA and Real-time PCR. NF-κB p65 in macrophage cells was analyzed by confocal laser scanning microscope and Western-blotting. RESULTS: FGF-21 treatment reduced lung damage and inflammatory cell infiltration and decreased the expression level of TNF-α, IL-1β, IL-6 and IL-17 in both serum and peritoneal macrophage. The results of confocal laser scanning microscope and Western-blotting both showed that FGF-21 could inhibit NF-κB transferring to the nucleus. CONCLUSION: FGF-21 could regulate the immune system by acting on macrophage. Relieving the inflammatory response in mice through NF-κB signal pathway may be one of the mechanisms FGF-21 regulating immune system.
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This study was aimed to explore the molecular mechanism of nano-realgar in treatment of systematic lupus erythematosus (SLE) lupus nephritis (LN). Intragastric administration of equal volume of high-, middle-, low-dose nano-realgar suspension, and normal saline (NS) were given to MRL/lpr mice, respectively. The observations were made on levels of ANA, ds-DNA antibody, IgG and IgM in blood serum, as well as TWEAK, NF-κB, MCP-1 mRNA and protein expression levels in renal tissues. The results showed that compared with the NS group, levels of ANA, ds-DNA antibody, IgG and IgM were obviously reduced (P < 0.05); the levels of TWEAK, NF-κB and MCP-1 mRNA were obviously reduced (P < 0.05); the protein expression levels of TWEAK, NF-κB and MCP-1 mRNA were obviously reduced (P < 0.05) in the high-, middle-, low-dose nano-realgar group. It was concluded that nano-realgar intervened the TWEAK-NF-κB signal pathway through downregulating MCP-1 expression among MRL/lpr mice, in order to reduce the levels of ANA, ds-DNA antibody, IgG and IgM for relieving autoimmune damages in the treatment of SLE (LN).
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Ulcerative colitis (UC) is a chronic and relapsing condition of the intestinal inflammation of unknown etiology and remains one of the most intractable gastrointestinal diseases, impairing quality of life and carrying a high risk of colorectal cancer in patients with UC. Currently, aminosalicylic acid, steroid hormone, and immunosuppressor are the main drugs for treating UC. However, all of them can not cure UC once and for all. In recent years, many scholars attempted to find new drugs in the extracts and active compounds from herbs for the prevention and treatment of UC. The paper summarized the status of nuclear factor kappa B (NF-κB) signal pathway of UC, and those anti-inflammation Chinese materia medica regarded proteins and enzymes of NF-κB pathway as targets.
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Objective To explore mechnism and effect of fentanyl on proliferation of gastric cancer SGC-7901 cell.Methods Gastric cancer SGC-7901 cell was cultured with fentanyl of 0 (negative control), 0.5, 5 and 50 nmol/L, MTT method was used to detect the effect of fentanyl on SGC-7901 viability.The effect of fentanyl on SGC-7901 cell cycle was measured by flow cytometry.The level of cell related protein,cell cycle protein cyclin D1, Bcl-2.Results Compared with control group, fentanyl (0.5, 5, 50 nmol/L) could inhibit SGC-7901 cell viability, and the inhibitory rate was highest at 48 h.0.5, 5, 50 nmol/L fentanyl made cell cycle arrested in G1 phase.Compared with control group, fentanyl can significantly inhibit cyclinD1 and Bcl-2 expression with drug concentration increasing(P<0.05).Conclusion These results suggeste fentanyl inhibit proliferation of gastric cancer SGC-7901 cell.
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Objective: To investigate the effects of Tongsaimai Prescription (TSMP) and TSMP without Achyranthis Bidentatae Radix (ABR) on ischemic brain injuries in rats. Methods: The male SD rats were divided into Sham, model, Nimodipine (32.4 mg/kg), TSMP (crude drug 31.74 g/kg), and TSMP without ABR (crude drug 27.77 g/kg) groups. Except the Sham and model groups, the rats were ig administered once daily, for 3 d. After the treatment, except the Sham group, the cerebral ischemic stroke model was established. After 24 h, the blood and brain tissue were taken, the brain tissue was stained with TTC, and the cerebral infarction ratio was measured. The pathological changes were observed, and the contents of HMGB1, TNF-α, and IL-1β in serum were detected. The expression of NF-κB in ischemia tissue was observed by immunohistochemisty method. Results: The expression of HMGB1, TNF-α, and IL-1β increased obviously (P < 0.05). TSMP and TSMP without ABR could decrease the contents of HMGB1, TNF-α, and IL-1β, inhibit the expression of NF-κB (P < 0.05), and the effect of TSMP without ABR on decreasing IL-1β was stronger. Conclusion: Both TSMP and TSMP without ABR could inhibit the activation of HMGB1-related NF-κB signal pathway with the function of anti-imflammation, alleviated encephaledema, and protecting nerve cells. TSMP without ABR has the similar effect on the ischemic brain injuries and the better effect on inhibiting the secretion of inflammatory factor IL-1β.