Anti-inflammatory Effect and Mechanism of Artesunate： A Review / 中国实验方剂学杂志

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.

Study on anti-inflammatory effects and mechanism of Zhuang medicine Tongfeng li’an capsules on gouty arthritis / 中国药房

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.

Research progress on metformin in the prevention and treatment for oral diseases / 口腔疾病防治

@#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

Role of IL-37 in childhood immune diseases / 国际儿科学杂志

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.

Reduning Injection prevents carrageenan-induced inflammation in rats by serum and urine metabolomics analysis / 中草药·英文版

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

Anti-inflammatory Effect of Huanglian Jiedutang and Clinical Application: A Review / 中国实验方剂学杂志

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.

Screening of Anti-inflammatory Active Sites of Water Extract of Iris halophila Root and Analysis of Its Chemical Constituents / 中国实验方剂学杂志

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.

Effects of PNU 282987 on Improving Cardiac Remodeling and JAK 2/STAT3 Signaling Pathway / 中国药房

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.

Study on Anti-inflammatory Effect and Mechanism of Jingulian Capsule on Inflammatory Model Rats / 中国药房

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.

The Role Of Platelet Rich Plasma And Quercetin In Alleviating Dimethylnitrosamine-Induced Acute Spleen Injury Through Regulating Oxidative Stress, Inflammation And Apoptosis

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.

Establishment of HPLC Fingerprint of Lonicera japonica and Study on Its Anti-inflammatory Spectrum-effect Relationship / 中国药房

OBJECTIVE：To establish fingerprint of Lonicera japonica ，and to study its anti-inflammatory spectrum-effect relationship. METHODS ：HPLC was adopted. The determination was performed on Diamonsil C 18 column with mobile phase consisted of 0.1％ formic acid solution-acetonitrile （gradient elution ）at the flow rate of 1.0 mL/min. The column temperature was 30 ℃，and detection wavelength was 238 nm. The sample size was 10 μL. Using chlorogenic acid as reference，HPLC fingerprint of 10 batches of L. japonica from different production areas was established according to TCM Chromatographic Fingerprint Similarity Evaluation System （2012 edition）. By comparing with reference substance ，chemical constituents corresponding to common peaks were identified ，and the similarity analysis was conducted. Acute and chronic inflammatory models of mice induced by xylene ，carrageenan and cotton ball were used to evaluate inhibition rate of 10 batches of L. japonica to ear，foot and granuloma swelling； the average value was calculated as the comprehensive pharmacodynamic index. The spectrum-effect relationship with HPLC fingerprint of L. japonica and anti-inflammatory effect was analyzed by grey relational analysis （GRA）and partial least squares regressiosn （PLSR）based on common peak area and comprehensive pharmacodynamic index . Chromatographic peaks with correlation＞0.7 and regression coefficient of PLSR model ＞0 were characteristic peaks. The percentage of peak areas of characteristic peaks to peak areas of common peak was calculated in 10 batches of L. japonica （e.g.“peak ratio ”）. RESULTS ： There were 25 common peaks in HPLC fingerprints of 10 batches of L. japonica ，with similarity of 0.775-0.994. Totally 9 peaks were confirmed ，i.e. rutin （peak 18），hyperoside（peak 20），isochlorogenc acid B （peak 22），galuteolin（peak 21），chlorogenc acid（peak 9），loganin（peak 10），neochlorogenic acid （peak 2），isochlorogenic acid C （peak 25），isochlorogenic acid A （peak 23）. All 10 batches of L. japonica had inhibitory effects on ear swelling ，foot swelling and granuloma ，with average inhibitory rate of 47.95％-56.52％. The correlation by GRA was peak 8＞12＞18＞16＞3＞11＞20＞22＞19＞21＞1＞9＞10＞13＞24＞14＞2＞ 17＞25＞23＞5＞4＞15，and all of correlations were greater than 0.7. The regression coefficient of PLSR for peaks 2，4，5，7，8， 10，12，13，14，15，16，17，18，20，21，22，24 were all greater than 0；those peaks were positively correlated with anti-inflammatory effect and were characteristic peaks except for peak 7； among them ，VIP values of peaks 5，8，10，16，18， 20，24 were greater than 1. The peak ratio of 10 batches of L. japonica was 58.61％-71.19％. CONCLUSIONS ：HPLC fingerprint of 10 batches of L. Japonica is successfully established. 10 batches of samples have similar components ，and the content of anti-inflammatory components is relatively high. The proportion of characteristic peaks to common peaks should not be less than 51.8％.

Mechanism on moxibustion for rheumatoid arthritis based on PD-1/PD-L1 signaling pathway / 中国针灸

OBJECTIVE@#To explore the mechanism of moxibustion on the treatment of rheumatoid arthritis (RA) in the perspective of programmed cell death-1 and its ligand 1 (PD-1/PD-L1).@*METHODS@#A total of 30 Japanese big ear white rabbits were randomly divided into a control group, a model group and a moxibustion group, 10 rabbits in each one. In the model group and the moxibustion group, RA model was prepared by the injection of Freund's complete adjuvant (FCA) into the hind knee joint cavities of each rabbit. In the control group, 0.9% sodium chloride solution of the same dose was injected. On the 8th day of experiment, in the moxibustion group, moxibustion was applied to "Shenshu" (BL 23) and "Zusanli" (ST 36), 5 cones at each acupoint, on the bilateral sides alternatively, once a day, 6 treatments as one course, with an interval of 1 days between the treatment courses. Totally, 3 courses of treatment were required. On the 1st, 7th, 14th, 21st and 28th days of experiment, successively, the circumference of the bilateral knee joints was measured with the tape. On the 28th day of experiment, H.E. staining was adopted to observe the histopathological morphology and to evaluate the score of knee synovial tissue. ELISA was used to determined the concentrations of soluble PD-1 (sPD-1) and its ligand 1 (sPD-L1), the interleukin 2 (IL-2) and IL-17 in knee synovial fluid and the concentrations of sPD-1 and sPD-L1 in serum. The histochemistry method was used to determine the expressions of membrane PD-1 (mPD-1) and its ligand 1 (mPD-L1) in spleen tissue.@*RESULTS@#On the 14th, 21st and 28th days of experiment, the circumference of both knee joints was increased in each of the rabbits in the model group as compared with the control group (<0.01), and it was reduced significantly in the moxibustion group as compared with the model group (<0.01). Compared with the control group, the hyperplasia of synovial tissue and fibrous tissue, as well as inflammatory cell infiltration were increased obviously in the model group (<0.01), and they were reduced significantly in the moxibustion group as compared with the model group (<0.01, <0.05). Compared with the control group, the concentrations of IL-2 and IL-17 in knee synovial fluid were increased in the rabbits of the model group (<0.01). Compared with the model group, after the intervention with moxibustion, the concentrations of IL-2 and IL-17 in knee synovial fluid were reduced in the rabbits of the moxibustion group (<0.05). Compared with the control group, the concentrations of sPD-1 and sPD-L1 in knee synovial fluid and serum in the rabbits of the model group were all increased (<0.05). Compared with the model group, the concentration of sPD-1 in the knee synovial fluid and serum were reduced in the rabbits of moxibustion group (<0.05). Compared with the control group, the expressions of mPD-1 and mPD-L1 in spleen tissue were increased obviously in the rabbits of the model group (<0.05). Compared with the model group, the expression of mPD-L1 in spleen tissue was up-regulated in the rabbits of the moxibustion group (<0.05).@*CONCLUSION@#Moxibustion could inhibit the over-activation of T cells by enhancing the negative regulation of PD-1/PD-L1 signaling pathway so as to play its effect in treatment of RA.

Moxibustion combined with acupoint catgut embedding promotes recovery of injured colonic mucosa by suppressing inflammation in ulcerative colitis rats / 针刺研究

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.

CORM-2-entrapped ultradeformable liposomes ameliorate acute skin inflammation in an ear edema model

The short release half-life of carbon monoxide (CO) is a major obstacle to the effective therapeutic use of carbon monoxide-releasing molecule-2 (CORM-2). The potential of CORM-2-entrapped ultradeformable liposomes (CORM-2-UDLs) to enhance the release half-life of CO and alleviate skin inflammation was investigated in the present study. CORM-2-UDLs were prepared by using soy phosphatidylcholine to form lipid bilayers and Tween 80 as an edge activator. The deformability of CORM-2-UDLs was measured and compared with that of conventional liposomes by passing formulations through a filter device at a constant pressure. The release profile of CO from CORM-2-UDLs was evaluated by myoglobin assay.

Establishment of UPLC-Q-TOF-MS/MS Fingerprint of Fritillaria thunbergii and Analysis of Anti-inflammatory Quality Markers / 中国药房

OBJECTIVE： To establish UPLC-Q- TOF-MS/MS fingerprint of Fritillaria thunbergii ， and to define its anti-inflammatory quality markers. METHODS ：The determination was performed on Eclipse Plus C 18 column with mobile phase consisted of methanol- 0.1％ formic acid solution （gradient elution ）at the flow rate of 0.4 mL/min. The column temperature was set at 30 ℃，and injection volume was 2 µL. The electrospray ion source was used to scan in the range of m/z 50-1 200 with positive and negative ion detection mode. UPLC-Q-TOF-MS/MS fingerprints of 10 batches of F. thunbergii from different habitats were established by using the Similarity Evaluation System of TCM Chromatographic Fingerprints （2004A edition ）. With ear swelling degree，the serum levels of MDA and NO as anti-inflammatory indexes ，the correlation between the relative area of common peaks in fingerprint and the anti-inflammatory indexes was analyzed by using bivariate correlation analysis and grey correlation analysis ， and the quality markers were screened and identified. RESULTS ：In positive and negative ion mode ，10 batches of F. thunbergii had 26 peaks and 10 peaks. Based on bivariate correlation analysis and grey correlation analysis ，nine quality markers related to anti-inflammatory effect were found ，which were identified as peiminine ，peimine，cyclobalamine，daucidin，polyphyllin Ⅴ， bitumen podophyllotoxin ，phytosterol，ent-kaur-15-en-17-ol，ent-17-norkauran-16-one. CONCLUSIONS ：Established UPLC-Q- TOF-MS/MS fingerprint can be used to evaluate the quality of F. thunbergii ；peiminine，peimine and cyclobalamine and so on may be the quality markers of anti-inflammatory effect of F. thunbergii .

Potential synergic mechanism of Wutou-Gancao herb-pair by inhibiting efflux transporter P-glycoprotein / 药物分析学报

Wutou-Gancao herb-pair is extensively used to attenuate the toxicity and enhance the efficacy of aconite. In this study, potential synergic mechanism of the herb pair was investigated by utilizing multiple ap-proaches. In silico and in vitro Caco-2 cell models were applied to study the potential binding mode of bioactive ingredients existing in liquorice with P-glycoprotein (P-gp), as well as the inhibition effects on P-gp. Additionally, anti-inflammatory activity of aconitine (AC) combined with active ingredients of liquorice, as well as pharmacokinetic patterns of AC after co-administration was investigated. Anti-inflammatory effect of AC (1 mg/kg) in rats was enhanced in combination with bioactive ingredients of liquorice (10 mg/kg). In the meanwhile, the exposure of AC in vivo was altered, in terms of Cmax and AUC. For instance, the Cmax and AUC were increased to 1.9 and 1.3 folds, respectively, when used in combination with liquiritigenin. The in silico study revealed the potential binding mode with outward facing conformation of P-gp. The resulting data obtained from transport of rhodamine-123 (Rh-123) across Caco-2 cell monolayer further indicated that the function of P-gp was inhibited by chemicals in liquorice. The synergic effect was therefore proposed to be attributed to inhibition of P-gp by liquorice since AC has been demonstrated to be the substrate of P-gp. The resuls revealed that potential synergic mechanism of Wutou-Gancao herb-pair by inhibiting function of key efflux transporter P-gp to enhance the exposure of AC in systematic circulation, and further the anti-inflammatory effect, which helps clarify the compatibility rationale of these two herbs.

Study on Protective Effects of the Ethanol Extract of Garcinia oblongifolia on LPS-induced RAW 264.7 Cell Inflammatory Injury / 中国药房

OBJECTIVE：To investigate the anti-inflammatory activity of 70％ ethanol extracts from Garcinia oblongifolia （GOEE）on LPS-induced RAW 264.7 cells and its potential molecular mechanism. METHODS ：GOEE was obtained after the fresh G. oblongifolia epicarp refluxed with 70％ ethanol. The contents of total phenol and total flavonoids were determined by Folin-Ciocalteau assay and UV spectrophotometer. MTT assay was used to detect the cytotoxicity of different doses of GOEE. The inflammatory model was induced in RAW 264.7 cells by lipopolysa- ccharide （LPS）. Using dexamethasone and N-acetyl-L-cysteine as positive control ，Griess assay and 2′，7′-dichloro- fluorescein assay were used to detect the contents of NO in cell culture medium and ROS in cells. The levels of TNF-α，IL-6，and IL- 1β in cell culture medium were measured by ELISA. The protein expression of p 65，p-p65，IκBα，p-IκBα，HO-1 in cells and NRF 2 in nucleus were determined by using Western blotting assay. RESULTS：The contents of total phenol and flavonoids in GOEE were （20.191±1.264）and（12.571±0.020）mg/g，respectively. At the concentration below 500 μ g/mL， GOEE had no significantly effect on survival rate of RAW 264.7 cells（P＞ 294043）0.05）. Compared with control group ，the contents of NO and ROS，the levels of TNF-α，IL-6 and IL- 1β，ratio of p-p 65 top65，ratio of p-IκBα to IκBα，protein expression of NRF 2 were increased significantly in LPS model group （P＜0.05 or P＜0.01）. Compared with LPS model group ，the contents of NO（except for GOEE 50 μg/mL group）and ROS ，the levels of TNF-α，IL-6 and IL- 1β，ratio of p-p 65 to p 65 and ratio of p-IκBα to IκBα were decreased significantly in GOEE groups and positive control groups ，while protein expression of HO- 1 and NRF 2 were increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS：GOEE attenuates LPS-induced macrophages inflammation injury by inhibiting the inflammatory response and the phosphorylation of NF-κB pathway，promoting NRF 2 protein transportation to the nucleus.

Restoration of the inflammatory gene expression by horse oil in DNCB-treated mice skin

Comparison Of Efficacy Of The Anti-Inflammatory Effect Of Topical 0.1% Dexamethasone Sodium And Topical 0.05% Difluprednate Eye Drops After Small Incision Cataract Surgery

Aims: The study aims to compare the efficacy of the anti-inflammatory effect of 0.1% dexamethasone sodium and 0.05%difluprednate eye drops after small incision cataract surgery (SICS).Study Design: A prospective, randomized, and clinical study was conducted on patients.Place and Duration of Study: This study was conducted in the Department of Ophthalmology, VCGS Government MedicalCollege, Srinagar, Uttarakhand, between December 2017 and November 2018.Materials and Methods: This study included two groups of 40 patients each (a total of 80 patients). 40 patients in GroupA wererandomly started on 0.1% dexamethasone eye drops postoperatively and another 40 patients in Group B were randomly started0.05% difluprednate eye drops postoperatively. Response to the therapy was recorded on day 1, 7, and 40 on the parametersof post-operative anterior chamber reaction and post-operative visual acuity, and the results were compared.Results: All results were correlated with final visual outcome, and post-operative flare, which showed 0.05% difluprednate, isclinically and statistically more effective in early post-operative period than 0.1% dexamethasone sodium to control inflammationin uneventful SICS.Conclusions: After the comparison of the data in both the groups, the patients started on 0.05% difluprednate eye dropspostoperatively showed better response to therapy (P < 0.0001) with respect to the parameters of best-corrected visual acuityand post-operative flare as compared to the patients started on 0.1% dexamethasone sodium eye drop therapy postoperatively,indicating that 0.05% difluprednate eye drops have a better anti-inflammatory effect.

Antinociceptive local activity of 4-allyl-1-hydroxy-2-methoxybenzene (eugenol) by the formalin test: an anti-inflammatory effect

Eugenol has been employed for decades as a condiment, an antimycotic, an antibacterial, an antiviral, and an antioxidant, and it is one of the natural analgesics most frequently utilized for pain and inflammation. Our objective was to determine the analgesic/anti-inflammatory effect of eugenol compared with diclofenac, naproxen, and tramadol using the formalin test. The formalin method was used in 6- to 10-week-old Wistar rats (weighing 250 g each) divided into six groups: saline (0.9%); formalin (5%); diclofenac (250 µg/kg); naproxen (400 µg/kg); tramadol (500 µg/kg), and eugenol (1,400 µg/kg), in the intraplantar part of the hind-end trunk of the rats, with n = 5 per group. Eugenol diminished 44.4% of nociceptive behavior in phase 1 and 48% in phase 2 (p ≤0.05 vs formalin). Eugenol was shown to be 1.14 times more effective than diclofenac, but 1.62 and 1.75 times less effective than naproxen and tramadol, respectively, in phase 1 and 1.45 times less effective than diclofenac and naproxen and 1.66 less effective than tramadol in phase 2 (p ≤0.05). These data suggest that eugenol possesses moderate activity in the acute pain phase and greater activity in inflammatory-type pain, and both effects are comparable to those produced by diclofenac and are less than the effects produced by naproxen and tramadol in the formalin test