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ObjectiveTo investigate the effect of modified Weijingtang on the pyroptosis of RAW264.7 macrophages via the cysteinyl aspartate-specific protease-1 (Caspase-1)/gasdermin D (GSDMD) pathway. MethodLipopolysaccharide (LPS) was used to induce pyroptosis of RAW264.7 cells. The blank group was treated with the blank serum, and the intervention groups were treated with the sera containing different doses of modified Weijingtang. After 24 h, the viability of cells in different groups was examined by the cell counting kit-8 (CCK-8). The pyroptosis and morphology of cells in each group were observed by a scanning electron microscope and a phase-contrast microscope, respectively. The mRNA and protein levels of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), Caspase-1, and GSDMD in each group were determined by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot, respectively. The levels of interleukin (IL)-18 and IL-1β in each group were measured by enzyme-linked immunosorbent assay. ResultUnder the electron microscope, RAW264.7 cells presented the best morphology and structure in the blank group and obvious pyroptosis and leakage of cell contents in the model (LPS) group. Compared with the model group, the intervention groups showed reduced pyroptosis to varying degrees, and the high-dose group had the closest cell morphology and structure to the blank group. Under the optical microscope, RAW264.7 cells were spherical in the blank group and irregular with protrusions in the model group. Compared with the model group, the intervention groups showed improved cell morphology, and the cell morphology in the group with the dose of 20% was the closest to that in the blank group. The mRNA and protein levels of NLRP3, Caspase-1, and GSDMD in the model group were higher than those in the blank group (P<0.05). Compared with the model group, each intervention group showed down-regulated expression of the above indicators (P<0.05). Compared with the blank group, the model group presented elevated levels of IL-18 and IL-1β (P<0.05), which were lowered in the intervention (10%, 20%) groups (P<0.01). ConclusionModified Weijingtang inhibits the pyroptosis of macrophages by down-regulating the Caspase-1/GSDMD pathway and reducing the release of proinflammatory cytokines.
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Inflammation is involved in the development of various acute and chronic diseases in the body. Sustained inflammatory responses are key driving factors for diseases such as cancer, neurodegenerative diseases, cardiovascular diseases, metabolic syndrome, inflammatory bowel disease, and arthritis. Therefore, finding anti-inflammatory drugs is crucial for the prevention and treatment of various diseases. In recent years, there has been increasing attention to finding natural drugs with minimal toxic side effects. Lonicerae Japonicae Flos and Lonicerae Flos, as traditional Chinese medicines potent in clearing heat and removing toxins, have strong biological activity and multiple pharmacological effects. They are widely distributed in the plant world and have significant medicinal value. With the continuous advancement of the research on Lonicerae Japonicae Flos and Lonicerae Flos, they have been widely used in the medical field and possess great development potential. Currently, research mainly focuses on the anti-inflammatory mechanisms of Lonicerae Japonicae Flos and Lonicerae Flos, while systematic summaries of their anti-inflammatory active ingredients are rare. Therefore, this paper focuses on the differential analysis of the anti-inflammatory active components of Lonicerae Japonicae Flos and Lonicerae Flos. In addition, it reviewed the possible mechanisms by which extracts and active ingredients of Lonicerae Japonicae Flos and Lonicerae Flos may exert anti-inflammatory effects through various pathways, such as influencing the release of cellular inflammatory factors, regulating inflammatory signaling pathways such as nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), signal transducer and activator of transcription 3 (STAT3), MAPK/extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/NF-κB, and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathways, increasing antioxidant stress capacity, enhancing immune defense capabilities, and improving intestinal microbiota, aiming to provide a theoretical basis for the rational clinical application of Lonicerae Japonicae Flos and Lonicerae Flos.
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BACKGROUND:Resistance to the inflammatory response is an important part of promoting the repair of damaged tissue and improving the local inflammatory response caused by medical bio-implant materials has been a key issue to be addressed in recent years. OBJECTIVE:To summarize the anti-inflammatory effects of common metal ions and related molecular mechanisms to provide some theoretical references for improving the early inflammatory response of hosts caused by bio-implant materials. METHODS:A computer search of the relevant literature in PubMed,Web of Science,CNKI and WanFang databases was conducted using"metal ions,magnesium ion,zinc ion,silver ion,copper ion,inflammation,anti-inflammatory effects,oxidative stress,immunoregulation,signaling pathways"as Chinese and English search terms.Preliminary screening was conducted by reading the titles and abstracts.Finally,80 papers were included for result analysis and summary. RESULTS AND CONCLUSION:(1)Metal ions such as magnesium,zinc,silver and copper have a good anti-inflammatory effect.The strength of this anti-inflammatory effect is strongly correlated with the dose and duration of action.In the future,consideration can be given to controlling the release rate of ions and adjusting the appropriate therapeutic concentration to achieve the best anti-inflammatory effect.(2)Magnesium ions and zinc ions exhibit excellent anti-inflammatory activity,with magnesium ions often being beneficial in anti-inflammatory therapy in the form of compounds such as magnesium sulfate and zinc ions regulating the body's inflammatory response with zinc feed as the main source of zinc supplementation.(3)Silver and copper ions have some anti-inflammatory effects,but are still predominant for their excellent antibacterial activity,mainly in the form of nanoparticles and bio-coatings.(4)Magnesium and zinc metal ions can be combined with natural extracts to form complexes to exert anti-inflammatory effects,and this method has the advantage of being inexpensive and widely available and is a sustainable and green approach,which is worthy of clinical promotion.(5)Metal ions such as magnesium,zinc,silver and copper exert anti-inflammatory effects by reducing host oxidative stress damage,modulating immune cells and inhibiting inflammatory signaling pathways such as nuclear factor-κB,Toll-like receptor,STAT3 and NOD.(6)The molecular mechanism related to the anti-inflammation of metal ions is a complex network,which is not the effect of a single pathway,but should be a combination of multiple signaling pathways.There are still many potential mechanisms that have not yet been explored,and more systematic elucidation of the interconnections between various signaling pathways is needed in the future.
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ObjectiveTo study the anti-inflammatory effects of Blumea balsamifera (L.) DC oil (BBO) based on nuclear factor kappa-B (NF-κB) nonclassical and arachidonic acid (AA) pathway. MethodsEffects of BBO on the production of slow reacting substance of anaphylaxis (SRS-A) were detected by the ileal smooth muscle method. The contents of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) in lipopolysaccharides (LPS) -induced macrophages were detected by ELISA kit. The expression of COX-2, 5-LOX, FLAP and RelB were detected by qRT-PCR. Western blot was performed to detect the effects of BBO on the level of NF-κB nonclassical pathway proteins TNF receptor associated factor 3 (TRAF3), TNF receptor associated factor 2 (TRAF2), NF-κB-inducing kinase (NIK), p100 and RelB. ResultsThe contractile tension of guinea pig ileum was reduced (P<0.001), and the SRS-A production inhibition rate reached 65.34% at 1mg·mL-1 BBO concentration. Compared with LPS group, BBO reduced the concentrations of PGE2 (P<0.05) and LTB4 (P<0.05), and decreased the expressions of COX-2 (P<0.05), 5-LOX (P<0.05) and FLAP (P<0.05) in AA pathway at concentrations of 40-80 μg·mL-1. Moreover, 40-80 μg·mL-1 BBO decreased the concentrations of TRAF3 (P<0.05), TRAF2 (P<0.05), and NIK (P<0.05), and further inhibited the phosphorylation of p100 (P<0.05), as well as the level of the transcription factor RelB in genes (P<0.05) and proteins (P<0.05) in nonclassical NF-κB pathway, whereas BBO did not cause such changes. ConclusionBBO may potentially exert its anti-inflammatory effects by suppressing the regulatory proteins TRAF3 and TRAF2 and the transcription factor RelB in NF-κB nonclassical pathway. The inhibitory action extending to the induction kinase function of NIK, further hindering the phosphorylation of p100 and its binding with the transcription factor RelB. Consequently, downstream elements in the AA pathway, including the pivotal rate-limiting enzymes COX-2, 5-LOX and FLAP, were altered. This modulation influences the levels of inflammatory mediators such as PGE2 and LTB4.
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Long-term inflammation will develop into chronic inflammation and become inflammatory diseases.Antibiotics are commonly used in clinical practice to treat inflammatory diseases.But patients are prone to drug resistance.So we need to find new treatment.Chlorogenic acid is an organic compound extracted from honeysuckle and other plants.Its anti-inflammatory activity is strong,and it has a significant anti-inflammatory effect on inflammatory diseases in various systems.It has been shown that chlorogenic acid can regulate inflammation-related signaling pathways,such as nuclear factor κB(NF-κB)canonical signaling pathway,NF-κB atypical signaling pathway,nuclear factor-erythroid 2-related factor 2(Nrf2)canonical signaling pathway,and Nrf2 atypical signaling pathway,etc.It can up-regulate the expression of anti-inflammatory cytokines such as interleukin(IL)-4,IL-10,IL-13 and down-regulate the expression of pro-inflammatory cytokine such as IL-1β,IL-6,and IL-8.Although chlorogenic acid has a strong anti-inflammatory effect,but clinical trials and application still face many difficulties.In the future,the anti-inflammatory molecular mechanism of chlorogenic acid should be further studied to explore its clinical application value and improve new ideas for the treatment of inflammatory diseases.
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OBJECTIVE To investigate the anti-inflammatory effects and mechanism of Zhuang medicine Tongfeng li’an capsules on gouty arthritis in combination with in vivo and in vitro experiments. METHODS Sixty rats were randomly divided into normal group, model group, positive control group (27 mg/kg allopurinol+0.27 mg/kg colchicine), Tongfeng li’an capsules low- dose, medium-dose and high-dose groups (2.2, 4.5, 9.0 g/kg), with 10 rats in each group. Except for normal group, gouty arthritis model of rats was induced in other groups. Rats in each administration group were given corresponding drugs intragastrically, and rats in the normal group and model group were given equal volume of water intragastrically for 14 consecutive days. The degree of ankle joint swelling, serum level of interleukin-1β (IL-1β) and protein expressions of nuclear factor kappa-B (NF-κB) in synovial tissue were detected, and the histopathological changes of synovium tissue in the ankle joint of rats were observed. The inflammation model was established by stimulating RAW264.7 cells with lipopolysaccharide. After Tongfeng li’an capsules (62.5, 125, 250 μg/mL) were given, the levels of nitric oxide (NO), reactive oxygen species (ROS) and IL-1β in the cells and protein expression of NF-κB were detected, and NF-κB localization in the cells was also determined. RESULTS Results of in vivo experiment showed that compared with normal group, the swelling degree of the ankle joint, serum IL-1β level and protein expression of NF-κB in synovium tissue were all increased significantly in model group (P<0.05); pathological changes such as synovial hyperplasia, edema, vascular congestion, capillary hyperplasia, and increased inflammatory cells were observed. Compared with model group, the levels of above indexes were all decreased significantly in Tongfeng li’an capsules high-dose group (P<0.05), and most of the above indexes were significantly reduced in Tongfeng li’an capsules medium-dose and low-dose groups (P<0.05); synovial hyperplasia of the ankle joint improved, and the infiltration of inflammatory cells 2019BS044) decreased. Results of in vitro experiment showed that Tongfeng li’an capsule could significantly reduce the levels of NO, ROS and IL-1β and protein expression of NF-κB(P<0.01), and inhibit NF- κB nucleation. CONCLUSIONS Tongfeng li’ancapsules have good anti-inflammatory effect on gouty arthritis, and its mechanism may be related to the inhibition of NF-κB signaling pathway activity.
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We herein report a patient who complained persistent exudate at navel in spite of adequate antibiotics therapy after laparoscopic cholecystectomy was successfully treated with Kampo therapy. The pharmacological effect of this Kampo formulation i.e. senkinnaitakusan is still unknown, but this formulation has been used for persistent infectious diseases. According to the description in the classic textbook, this formulation is suggested to encourage metabolic function and exhibit anti-inflammatory function. There have been no reports of Kampo therapy for the superficial incisional site infection associated with laparoscopic surgery. The authors propose that Kampo medicine is another promising option in the management of surgical site infection (SSI).
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Inflammation, the basic pathological process of many diseases, can occur in various tissues and organs of the body and cause many diseases including cancer. So far, there are thousands of anti-inflammatory drugs on the market, but most of these drugs have adverse reactions of gastrointestinal injury, and can even cause greater damage to the body. In recent years, the research on the repurpose of Chinese medicine is in the ascendant, and the innovative research on the specific antimalarial drug artemisinin has attracted extensive attention from scholars in China and abroad. Artesunate is a water-soluble derivative of artemisinin, which has the characteristics of quick effect and low toxicity. In addition to its significant therapeutic effect on malaria, artesunate also has a potential anti-inflammatory effect. In this review, the anti-inflammatory effect and mechanism of artesunate were elaborated in detail by consulting the relevant literature. It was found that artesunate had good anti-inflammatory effects in the respiratory system, liver injury, osteoarthritis, dermatitis, kidney inflammation, colitis, neuroinflammation, and even in novel coronavirus disease 2019 (COVID-19). It was concluded that artesunate mainly participated in apoptotic signal transduction, mediated immune regulation, and improved oxidative stress to play an anti-inflammatory role by acting on nuclear factor-κB (NF-κB), nuclear factor E2-related factor 2 (Nrf2), phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/tumor necrosis factor receptor-associated factor 6 (TRAF6), high mobility group box 1 (HMGB1)/receptor for advanced glycation endproduct (RAGE), and other pathways. Through the review of the anti-inflammatory effect and mechanism of artesunate, it is expected to provide a reference for the application of artesunate in inflammation resistance and further development and utilization of artesunate in the future.
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@#Metformin is currently the first-line drug for the treatment of diabetes. In addition to its hypoglycemic effect, it has also been found to have other potential effects, such as anti-inflammatory, odontogenic differentiation-promoting, osteogenic differentiation-promoting, and antitumor effects. Previous studies have shown that metformin can promote the healing of periapical lesions, and its mechanism may be related to the promotion of osteogenic differentiation and the induction of dental pulp cell differentiation by activation of adenylate-activated protein kinase by dimethyldiphosphate. Clinical indexes, such as the probing depth, attachment loss level and probing bleeding index, were significantly improved in patients with periodontitis treated with metformin, which may play a role in the prevention and treatment of periodontal disease by promoting the proliferation, migration and osteogenic differentiation of periodontal ligament stem cells. Metformin has been proven to inhibit the growth and proliferation of tumor cells and plays an important role in the prevention and treatment of oral tumors such as oral squamous cell carcinoma. At present, research remains in the in vitro and animal experimental stage, and the related mechanism needs to be further explored. Clinical trials remain in the evaluation of clinical indicators, so large-scale, long-term, multicenter, randomized controlled clinical trials need to be further developed
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Interleukin-37(IL-37)is an anti-inflammatory cytokine in the IL-1 family that suppresses both innate and adaptive immune responses in two ways: intracellular complex formation and extracellular binding to membrane receptors.Studies have shown that IL-37 plays an important anti-inflammatory role in childhood immune diseases such as juvenile idiopathic arthritis, Kawasaki disease, inflammatory bowel disease, asthma, hand, foot and mouth disease and autism spectrum disease by regulating gene transcription, cell metabolism, cell proliferation and cytokine expression.This article reviews the biological characteristics, signaling pathway of IL-37 and its anti-inflammatory mechanism in childhood immune diseases.
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Objective To explore the anti-inflammatory and hepatoprotective mechanism of Shuganning injection through establishing the active ingredients-targets network and protein interactions network. Methods The main active ingredients of Artemisiae scopariae, Fructus gardenia, Radix scutellariae, Radix isatidis and Ganoderma in Shuganning injection were obtained by TCMSP; GeneCards and OMIM were used to screen the hepatitis-related targets among the corresponding targets of the active ingredient of Shuganning injection; The Cytoscape software was used to construct the active ingredient-targets network of Shuganning injection. The protein interactions network was constructed using the String database and Cytoscape software. The GO and KEGG pathways involved in the targets were analyzed by DAVID database. Results The results showed that 20 active ingredients and 83 targets of Shuganning injection were involved. GO analysis showed that Shuganning injection mainly affected the regulation of cellular processes and biological processes, as well as the response to chemical stimulation and stress. KEGG pathway analysis showed that the targets of the anti-inflammatory and hepatoprotective effect of Shuganning injection mainly involved in signaling pathways such as TNF, IL-17, and MAPK. Conclusion The anti-inflammatory and hepatoprotective effect of Shuganning injection have the characteristics of multiple components, multiple targets and multiple pathways, which may play a role by regulating pathways such as TNF、IL-17 and MAPK .
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Objective: To elucidate the anti-inflammatory mechanism of Reduning Injection (RDN) by analyzing the potential biomarkers and metabolic pathways of the carrageenan-induced inflammatory model from the overall metabolic level. Methods: Rat inflammatory model was established by carrageenan. UPLC-Q-TOF/MS was used to detect and analyze changes of endogenous metabolites in the serum and urine of carrageenan-induced inflammatory rats. Combined with multivariate analysis and databases analysis, inflammatory-related potential biomarkers were screened and identified to analyze possible metabolic pathways. The reliability and biological significance of these biomarkers was verified by metabolic network analysis and correlation analysis with pharmacodynamic indicators. Results: A total of 16 potential biomarkers were screened and identified by multivariate analysis and metabolite databases, among which 13 species could be adjusted by RDN. The metabolism pathway analysis revealed that histidine metabolism, sphingolipid metabolism, and tyrosine metabolism were greatly disturbed. Their biomarkers involved urocanic acid, sphingosine, and norepinephrine, all of which showed a callback trend after RDN treatment. The three biomarkers had a certain correlation with some known inflammatory-related small molecules (histamine, arachidonic acid, Leukotriene B4, and PGE
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Aim To explore the anti-inflammatory effect of natural compound Ginkgetin on lipopolysaccharide-induced mouse primary peritoneal macrophages and the underlying mechanism, in order to provide a theoretical basis for the development of clinical drug candidates. Methods MTT test kit was used to detect the cytotoxicity of Ginkgetin on mouse primary peritoneal macrophages; ELISA and RT-qPCR methods were used to detect the anti-inflammatory effect of different concentrations of Ginkgetin on LPS-induced cell inflammation injury model; Western blot was used to detect the anti-inflammatory mechanism of ginkgo flavonoids. Results Compared with LPS stimulation group, Ginkgetin treatment group produced a concentration-dependent anti-inflammatory effect, which could be attributed to the fact that Ginkgetin could inhibit LPS-induced activation of NF-κB signaling pathway. MTT results also showed that ginkgo flavonoids had little toxicity to mouse primary peritoneal macrophages. Conclusions Ginkgelin alleviates LPS-induced inflammatory injury of mouse primary peritoneal macrophages by inhibiting the activation of NF-κB signaling pathway. It is expected to be a natural monomer antiinflammatory drug candidate.
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Objective:To investigate the anti-inflammatory effects of water extract of the<italic> Iris halophila</italic> root on lipopolysaccharide(LPS) stimulated RAW264.7 cells and analyze its chemical constituents. Method:The supernatant of YWG prepared by water extraction and alcohol precipitation was separated by AB-8 macroporous adsorption resin column chromatography to obtain ethanol eluates with different concentrations (YWG,YWG-0%,YWG-20%,YWG-40%,and YWG-60%). Cell counting kit-8(CCK-8) assay was used to determine the effects of YWG-0%,YWG-20%,YWG-40%,and YWG-60% on the viability of RAW264.7 cells. Griess assay was employed to detect the nitric oxide (NO) level in LPS-stimulated RAW264.7 cells. The release of tumor necrosis factor(TNF)-<italic>α</italic>,interleukin(IL)-6,IL-10,and IL-1<italic>β</italic> was detected by enzyme-linked immunosorbent assay(ELISA). YWG and the elution site with the most robust anti-inflammatory activity were identified and compared by ultra-high performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UHPLC-Q-TOF-MS/MS). Result:Ethanol eluates with different concentrations inhibited the release of NO,TNF-α,IL-1<italic>β</italic>, and IL-6 in the supernatant of LPS induced RAW264.7 cells (<italic>P<</italic>0.05),and promoted the release of IL-10 (<italic>P<</italic>0.05). YWG-60% displayed a highly significant effect (<italic>P</italic><0.01). A total of 127 constituents were detected from the comparison of YWG and YWG-60% by UHPLC-Q-TOF-MS/MS in the positive and negative ion modes,including 61 flavonoids. YWG-60% contained 25 flavonoids with elevated content as compared with YWG. Conclusion:YWG-60% showed potent anti-inflammatory effect,and the effective anti-inflammatory constituents were presumedly flavonoids. The findings of this study are expected to provide a scientific theoretical basis for the basic research on the medicinal effect of the water extract of YWG.
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As a typical representative of heat-clearing and detoxifying prescriptions, Huanglian Jiedutang (HJT) has various pharmacological activities and is widely used in clinical practice. The articles concerning the effect and clinical application of HJT published in recent years were retrieved from such databases as China National Knowledge Infrastructure (CNKI) and PubMed to figure out HJT efficacy, especially in anti-inflammation, the corresponding action pathways, and its clinical application. It was found that the anti-inflammatory effect mainly resulted from HJT regulation of multiple pathways including interleukin-17 (IL-17) signaling pathway, tumor necrosis factor (TNF) signaling pathway, Toll-like receptor 4 (TLR4) signaling pathway, and neutrophil chemotaxis. The inflammatory cytokines in the serum were reduced via these pathways and thus the inflammation was inhibited. Because of its unique anti-inflammatory advantage, HJT has been widely used for the treatment of cardiovascular and cerebrovascular diseases, digestive system diseases, skin inflammation, sepsis, and other infectious diseases. In view of this, the paper reviewed the anti-inflammatory effect and clinical application of HJT, aiming to provide a reference for further research.
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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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OBJECTIVE:To st udy the effects of α7 nicotinic acetylcholine receptor agonists (PNU282987)on improving cardiac remodeling of mice and Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)signaling pathway. METHODS:Male Kunming mice were randomly divided into normal control group ,model group ,propranolol group (positive control,i.g. 40 mg/kg)and PNU 282987 low-dose,medium-close and high-dose groups (intraperitoneal injection of 0.5,1.0,3.0 mg/kg),with 10 mice in each group. Except for the normal control group ,mice in the other groups were given isoproterenol (ISO,30 mg/kg) subcutaneously for 7 days to induce the cardiac remodeling model. After 30 minutes of ISO injection , administration groups were given relevant liquid ,once a day ,for 7 consecutive days. Twelve hours after last administration ,the left ventricular ejection fraction (EF)and left ventricular short axis shortening rate (FS)of mice in each group were measured ,and the whole heart mass index (HMI)was calculated ;the pathological changes of myocardium were observed. The serum contents of lactate dehydrogenase (LDH),creatine kinase (CK),tumor necrosis factor α(TNF-α),interleukin 6(IL-6),the protein expression of intercellular adhesion molecule 1(ICAM-1)and adhesion molecule 1(VCAM-1)were also determined. The ratios of p-JAK2/JAK2,p-STAT3/STAT3 in myocardial tissue were detected. RESULTS :Compared with normal control group ,EF and FS of model group were significantly reduced ,HMI,the contents of LDH,CK,TNF-α and IL-6,the protein expression of ICAM- 1 and VCAM- 1,the ratio of p-JAK 2/JAK2 and p-STAT 3/STAT3 were increased significantly (P<0.05 or P<0.01); blue collagen deposition in the interstitium of myocardium was obvious,and the degree of fibrosis was severe. Compared with model group , the EF and FS of the mice in the medium-dose and high-dose groups were increased significantly , HMI (except for PNU 282987 medium-dose group ),the contents of LDH (except for PNU 282987 medium-dose group ),CK,TNF-α and IL-6,the protein expression of ICAM- 1 and VCAM- 1,the ratio of p-JAK 2/JAK2 and p-STAT 3/STAT3 were decreased significantly (P<0.05 or P< 0.01);blue collagen deposition in the myocardial interstitium was significantly reduced ,and the degree of myocardial fibrosis was significantly reduced. There was no significant difference in the comparison of the above indicators in PNU 282987 low-dose group (P>0.05). CONCLUSIONS :PNU282987 can improve cardiac remodeling of mice ,the mechanism of which may be associated with inhibiting JAK 2/STAT3 signaling pathway.
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Objective: Excessive oxidative stress is implicated in spleen injury. Platelet-rich plasma (PRP) and quercetin (QUR) have been shown to protect cells against oxidative stress. This study was designed to investigate their effect on dimethyl nitrosamine (DMN) induced spleen injury in male rats. Methods: Forty male Wistar rats were divided into four groups; Group (1): Negative control group (Con), Group (2): DMN group, DMN was given intraperitonealy at a dose of 4 mg/kg b. wt/day for four weeks for sub-chronic injury of spleen tissue, Group (3): DMN+PRP, rats were injected intraperitonealy with DMN at a dose of 4 mg/kg b. wt/day for four weeks then treated i. v. by single dose 50 μL of PRP, then left for a period of four weeks without any treatments, Group(4): DMN+QUR, rats received intraperitonealy DMN at a dose of 4 mg/kg b. wt/day for four weeks, then treated with quercetin orally at a dose of 50 mg/kg b. wt. in aqueous suspension daily using an intragastric tube for four weeks. Results: DMN inoculation resulted in significant elevations of oxidative stress, as evidenced by the increased malondialdehyde, hydrogen peroxide and xanthine oxidase levels associated with a significant decrease in Superoxide dismutase and catalase activities in the spleen tissue as compared to the normal control group. Moreover, DMN caused an up-regulation in the values of the splenic C-reactive protein (CRP), interleuckin-6 (IL-6), nuclear factor kappa B (NF-κB), leukotriene-C4 (LT-C4), P53 and Fas levels with a significant decline in anti-apoptotic protein B-cell lymphoma 2 level as compared to the normal control group. PRP and QUR significantly attenuated the DMN-evoked spleen oxidative stress and modulated the activities of antioxidant enzymes as compared to DMN group. In addition, treatment of DMN group with PRP or QUR resulted in an improvement in CRP, IL-6, NF-κB, LT-C4, P53 and Fas levels as compared to DMN group. Caspase-3 expression was positive in DMN group while no difference was present in control, PRP and Quercetin groups. However, the VEGF immunopositive reaction was found in DMN, PRP and Quercetin groups compared to control group. Histopathological results showed degeneration, haemorrhage, inflammatory cells and necrotoic areas in splenic tissue from DMN group compared to the treated groups where signs of recovery were observed in the whole splenic tissue. Conclusion: These data suggest that PRP and QUR protect rat spleen from DMN-induced oxidative stress, probably via their antioxidant activity, anti-inflammatory and anti-apoptotic effects. So, PRP and QUR are promising pharmacological agents for preventing the potential spleen injury of DMN following occupational or environmental exposures.
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OBJECTIVE: To observe the effect of moxibustion and acupoint catgut embedding (ACE) at "Tianshu"(ST25) "Dachangshu"(BL25) and "Shangjuxu"(ST37) on changes of body mass, stool property, histopathological conditions and expression levels of interleukin 6 (IL-6) in colonic mucosa of ulcerative colitis (UC) rats, so as to reveal its anti-inflammatory mechanisms underlying improvement of UC. METHODS: SD rats were randomized into normal, model, moxibustion, ACE and moxibustion+ACE groups (n=6 in each group). The UC model was established by enema of trinitro-benzene-sulfonic acid and ethanol. Moxibustion was applied to bilateral ST25, BL25 and ST37 for 10 min, once daily for 14 days, and ACE applied to the same 3 acupoints, once a week for two weeks. After the treatment, the rats' general conditions were observed, and the severity of UC was assessed by using disease activity index (DAI) score. Colonic mucosal pathological changes were observed under microscope after hematoxylin eosin (H.E.) stain, and the expression levels of IL-6 in the colonic mucosa tissue detected by using immunohistochemical stain and Western blot, respectively. RESULTS: After modeling, the DAI score, and expression level of colonic IL-6 protein detected by immunohistochemistry and Western blot were obviously increased in the model group relevant to the normal group (P<0.01). Following the intervention, the increase of DAI score and IL-6 expression were reversed in moxibustion, ACE and moxibustion+ACE groups (P<0.01, P<0.05). The therapeutic effects of moxibustion+ACE were considerably superior to those of simple ACE and simple moxibustion in down-regulating the levels of DAI score and IL-6 expression (P<0.01). H.E. staining showed severe defect of the colonic mucosal epithelium with infiltration of a large number of inflammatory cells in the model group, which was milder in moxibustion, ACE and moxibustion+ACE groups. CONCLUSION: Moxibustion combined with ACE is able to improve the inflammatory injury of colonic mucosa in UC rats, which may be related with its effect in suppressing the expression of colonic IL-6; and the efficacy of moxibustion+ACE is apparently superior to that of moxibustion and ACE alone.
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