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1.
Article de Chinois | WPRIM | ID: wpr-1006582

RÉSUMÉ

Osteoarthritis (OA), rheumatoid arthritis (RA), gouty arthritis (GA), and intervertebral disc degeneration (IVDD) are the most common bone and joint-related diseases in clinical practice. They can all affect related joints, leading to joint pain, swelling, dysfunction, and other symptoms. The difference is that OA is mainly caused by joint wear and age-related degradation and is manifested as joint pain, stiffness, and limited movement. RA is an autoimmune disease, manifested as joint pain, swelling, morning stiffness, and systemic symptoms. GA is caused by abnormal uric acid metabolism, manifested as acute arthritis, and IVDD is caused by intervertebral disc degeneration. Studies have shown that the mechanism of the occurrence and development of these bone and joint diseases is extremely complex. Pyroptosis is closely related to these bone and joint-related diseases by participating in bone and joint inflammation, cartilage metabolism imbalance, extracellular matrix degradation, and pathological damage of bone and joint. Inhibition of bone and joint-related pyroptosis will effectively prevent and treat bone and joint-related diseases. At the same time, many studies have confirmed that traditional Chinese medicine (TCM) has a prominent curative effect and obvious advantages in the prevention and treatment of bone and joint-related diseases. TCM can reduce the inflammatory reaction of bone and joints, improve the pathological damage of bone and joint diseases, and relieve bone and joint pain by inhibiting pyroptosis. Therefore, this article aims to briefly explain the relationship between pyroptosis and the occurrence and development of bone and joint-related diseases and summarize the latest research reports on the intervention of pyroptosis in the treatment of bone and joint-related diseases by TCM monomers, TCM extracts, and TCM compounds. It offers new ideas for the in-depth study of the pathogenesis and drug treatment of bone and joint diseases and provides a basis for the clinical use of TCM to prevent and treat bone and joint diseases.

2.
Article de Chinois | WPRIM | ID: wpr-1017814

RÉSUMÉ

Objective To investigate the expression characteristics of serum resistin(RETN)and Beclin-1 in patients with gouty arthritis(GA),and to analyze the relationship between RETN and GA clinical charac-teristics and clinical efficacy.Methods A total of 82 GA patients(GA group)and 60 healthy volunteers(con-trol group)in Dongguan People's Hospital from January 2019 to December 2022 were enrolled in the study.The expressions of serum RETN and Beclin-1 in GA patients were detected before and after treatment(on the physical examination day of the control group),and the differences of serum RETN and Beclin-1 in GA pa-tients with different clinical characteristics and efficacy were compared.Pearson correlation analysis was used to investigate the correlation between serum RETN,Beclin-1 expression and uric acid(UA)level in GA pa-tients.The diagnostic value of serum RETN and Beclin-1 in GA was analyzed using the receiver operating characteristic(ROC)curve.Results The serum RETN level in the GA group was higher than that in the con-trol group,and the expression of Beclin-1 was lower than that in the control group(P<0.05).The serum RETN levels in GA patients with acute stage,disease duration≥5 years,affected joints≥5,annual attack fre-quency≥3 times were higher than those in GA patients with chronic stage and intermittent stage,disease du-ration<5 years,affected joints<5,annual attack frequency<3 times(P<0.05),and the expression of Bec-lin-1 were lower than those in GA patients in chronic and intermittent stages,disease duration<5 years,af-fected joints<5,annual frequency<3 times(P<0.05).The serum UA level in GA patients was positively correlated with RETN(r=0.674,P<0.05),and negatively correlated with Beclin-1 expression(r=-0.568,P<0.05).After treatment,the serum expression of level RETN in the effective group was lower than that in the ineffective group,while the level Beclin-1 was higher than that in the ineffective group(P<0.05).The ar-ea under the curve of combined RETN and Beclin-1 diagnosis for GA was 0.921,which was higher than that of individual diagnosis(Z=3.752,3.154,P<0.05).Conclusion Serum RETN level increases,and Beclin-1 ex-pression decreases in GA patients,which is associated with increased UA level,prolonged acute stage and course of GA,increased number of affected joints and annual attack frequency,and treatment ineffectiveness.RETN and Beclin-1 could serve as biomarkers for GA diagnosis.

3.
Article de Chinois | WPRIM | ID: wpr-1021387

RÉSUMÉ

BACKGROUND:In chronic gout patients,sodium urate is deposited in bone joints and around synovial membranes,eroding and destroying bone,leading to serious complications such as gouty arthritis and deformity.Research on the mechanisms by which sodium urate crystals erode and destroy bone can help early clinical intervention in gouty diseases and prevent and delay the complications caused by bone destruction. OBJECTIVE:To explore the destructive effects of gout crystals on bone through clinical imaging studies and experimental basic research,review the current progress and development prospects of research on the phenomenon and mechanism of bone destruction caused by gout,guide the clinical early intervention of gouty bone destruction,and guide the direction of research on the role of bone destruction. METHODS:The Chinese search terms were"gout,bone destruction,bone erosion"and the English search terms were"tophi,gout,RANKL,bone destruction,bone erosion,"which were used in the computer search of WanFang and PubMed databases.Finally,64 articles were selected for review according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:The specific manifestations of clinical studies(imaging,histopathology)to some extent elaborate the osteolytic process of gout,and in basic studies,the mechanism of gout-causing bone destruction can be divided into the five aspects:(1)Sodium acid crystals have an important role in bone destruction,directly affecting osteocytes,chondrocytes,osteoblasts and proresorptive factors that promote bone destruction;(2)Receptor activator of nuclear factor-κB ligand and other proresorptive factors are involved in bone destruction;(3)T cell-mediated cellular immunity functions as a bridge in bone destruction,and activated T cells induce osteoclast differentiation;(4)Monocytes/macrophages are not only precursors of osteoclast-like cells,but also induce the expression of proresorptive factors such as Receptor activator of nuclear factor-κB ligand;(5)Neutrophils affect the morphology of osteoclast arrangement,and neutrophil extracellular trap networks promote osteolysis by promoting osteoclast differentiation.

4.
Article de Chinois | WPRIM | ID: wpr-1021983

RÉSUMÉ

BACKGROUND:The activation of NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome has been found to be an important factor in the pathogenesis of gouty arthritis,and the activation of NLPR3 inflammasome can be effectively inhibited by regulating the PTEN-induced kinas 1(PINK1)/Parkin signaling pathway. OBJECTIVE:To investigate the effect of Duhuo Jisheng Decoction on the PINK1/Parkin/NLRP3 signaling pathway. METHODS:(1)Animal experiment:Male Sprague-Dawley rats were randomly divided into control group,model group,positive control group(Qiushuixian tablets 0.3 mg/kg),and low-,medium-,and high-dose Duhuo Jisheng Decoction groups(6.9,13.8,and 27.6 g/kg,respectively).A rat gouty arthritis model was constructed by injecting monosodium urate crystal suspension into the right hind ankle joint cavity of rats in all the groups except for the control group.(2)Cell experiment:Human monocytes(THP-1)were divided into blank control group,model group,Duhuo Jisheng Decoction-containing serum group,and PINK1 siRNA+Duhuo Jisheng Decoction-containing serum group.The cells in each group except the blank control group were stimulated with sodium urate to establish an in vitro gouty arthritis model.(3)The swelling degree,joint circumference,gait score,joint inflammation index and degree of pathological grading in the ankle joints of rats were observed.Enzyme-linked immunosorbent assay was used to detect the levels of uric acid,C-reactive protein,NLRP3,and interleukin 1β.Immunoblotting assay was used to detect the levels of proteins related to the PINK1/Parkin/NLRP3 pathway.Tetramethyl azolidine blue assay was used to detect cell activity.Immunofluorescent double staining was performed to detect the level of mitophagy.Immunofluorescence was used to detect the expression of NLRP3 and interleukin 1β. RESULTS AND CONCLUSION:(1)Compared with the control group,rats in the model group showed elevated ankle swelling and ankle circumference at 6-48 hours(P<0.05),elevated gait scores and joint inflammation indexes at 24 and 48 hours(P<0.05),elevated serum uric acid and C-reactive protein levels,degree of pathological classification,expression of PINK1,Parkin,and NLRP3 proteins,and interleukin 1β level in synovial tissues(P<0.05).Compared with the model group,the protein expression levels of PINK1 and Parkin in all the Duhuo Jisheng Decoction groups were elevated,while the levels of the other indexes were decreased(P<0.05).(2)Compared with the model group,NLRP3 activity,interleukin 1β level and mitochondrial outer membrane translocator protein 20 protein level in the Duhuo Jisheng Decoction-containing serum group were decreased(P<0.05),while the proliferation inhibition rate,PINK1,Parkin and LC3B protein level were increased(P<0.05).Compared with the model group,the mitochondrial autophagy level of cells in the Duhuo Jisheng Decoction-containing serum group was elevated(P<0.05),while NLRP3 and interleukin 1β protein levels were decreased(P<0.05).(3)Compared with the Duhuo Jisheng Decoction-containing serum group,the mitochondrial autophagy level of cells in the PINK1 siRNA+Duhuo Jisheng Decoction-containing serum group was decreased(P<0.05),and the expression levels of NLRP3 and interleukin 1β were elevated(P<0.05).To conclude,Duhuo Jisheng Decoction inhibits the activation of NLRP3 inflammasome by regulating the PINK1/Parkin signaling pathway, thereby exerting a therapeutic effect on gouty arthritis.

5.
Article de Chinois | WPRIM | ID: wpr-1031872

RÉSUMÉ

ObjectiveTo investigate the effect of modified Simiaosan on miR-223-3p and NOD-like receptor thermal protein domain associated protein 3 (NLRP3)/interleukin-1β (IL-1β) signaling pathway in rat model with acute gouty arthritis (AGA) and explore the anti-inflammatory mechanism of modified Simiaosan on AGA. MethodA total of 72 8-week-old male SD rats were selected. They were divided into blank group, model group, colchicine group (0.3 mg·kg-1), high-dose modified Simiaosan group (31.75 g·kg-1), medium-dose modified Simiaosan group (15.75 g·kg-1), and low-dose modified Simiaosan group (7.875 g·kg-1) according to random number table method, with 12 rats in each group. Except for the blank group, monosodium urate (MSU) crystal suspension was injected into the right ankle joint of rats by the Coderre method in other groups to replicate the rat model with AGA. The drug administration groups were given the corresponding drug solution by gavage, and the model group and the blank group were given an equal volume of sterile sodium chloride solution by gavage for one week. The circumference of the rats' ankle joint was measured, and the swelling degree of the ankle joint was calculated. Hematoxylin-eosin (HE) staining was used to detect the pathological morphological changes in the synovial tissue of the ankle joint. The levels of IL-1β, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in the serum of rats in each group were detected by enzyme-linked immunosorbent assay (ELISA). Western blot was used to detect the protein expressions of NLRP3, Caspase-1, and apoptosis-related spot-like protein (ASC) in synovial tissue of rats in each group, and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expressions of NLRP3, Caspase-1, and ASC and the expression of miR-223-3p in synovial tissue of rats. ResultCompared with that in the normal group, the swelling degree of the ankle joint in the model group was higher (P<0.01), and the synovial tissue structure was disordered. Synovial cells proliferated obviously, and a large number of inflammatory cells were infiltrated. The levels of IL-1β, IL-6, and TNF-α in the serum of the model group increased significantly (P<0.01), and the protein and mRNA expressions of NLRP3, Caspase-1, and ASC increased, while expression of miR-223-3 decreased. Compared with the model group, the swelling degree of ankle joint in the colchicine group and high-dose and medium-dose modified Simiaosan groups was lower (P<0.05). Synovial cell proliferation and inflammatory cell infiltration of the colchicine group and high-dose, medium-dose, and low-dose modified Simiaosan groups were reduced to varying degrees, among which the colchicine group and high-dose modified Simiaosan group improved most obviously. The levels of IL-1β, IL-6, and TNF-α in the serum of rats in different dose groups of modified Simiaosan and colchicine group decreased significantly (P<0.01), while the protein and mRNA expressions of NLRP3, Caspase-1, and ASC increased (P<0.01). The expression of miR-223-3p in synovial tissue of the medium-dose and high-dose modified Simiaosan groups and colchicine group increased significantly (P<0.01). Compared with those in the colchicine group, the levels of IL-1β, IL-6, and TNF-α in the low-dose modified Simiaosan group increased greatly (P<0.01). In the medium-dose modified Simiaosan group, the protein expressions of NLRP3, Caspase-1, and ASC increased, and the expression of miR-223-3p decreased (P<0.05). In the low-dose modified Simiaosan group, the levels of IL-1β, IL-6, and TNF-α increased greatly (P<0.01), as well as the protein and mRNA expressions of NLRP3, Caspase-1, and ASC, while the expression of miR-223-3p was decreased (P<0.01). ConclusionModified Simiaosan may play an anti-inflammatory role by intervening in the NLRP3/IL-1β signaling pathway via regulating miR-223-3p.

6.
Article de Chinois | WPRIM | ID: wpr-1039586

RÉSUMÉ

Objective @#To compare the ultrasound signs of symptomatic joint lesions in rheumatoid arthritis (RA) and gouty arthritis ( GA) , musculoskeletal ultrasound ( MSUS) was utilized. @*Methods @#A retrospective analysis was performed for 85 hospitalized patients with RA and 55 hospitalized patients with GA in the same period , and the differences in general data , diseased joints and ultrasound signs between the two groups were compared. @*Results@#The gender, age and diseased joints of the two groups were statistically significant (all P < 0. 05) . The detection rate of knee joint lesions was the highest; the RA group had high sensitivity , high specificity of meniscal injury , and high diagnostic efficiency of bone erosion , while the diagnostic performance of the three combined ultrasound signs of punctate strong echo , double track sign and tophi in the GA group was higher than that of any individual diagnosis , and the sensitivity and specificity were also higher. The course of disease in the RA group was positively correlated with bone erosion (P < 0. 05) , and the course in the GA group was positively correlated with tophi (P < 0. 05) .@*Conclusion @#The ultrasound signs of RA and GA are different , and MSUS has good value in the diagnosis and differential diagnosis of the two.

7.
Article de Chinois | WPRIM | ID: wpr-980793

RÉSUMÉ

OBJECTIVE@#To observe the immediate analgesic effect of electroacupuncture (EA) combined with diclofenac sodium on acute gouty arthritis (AGA).@*METHODS@#A total of 90 patients with AGA were randomly divided into a low-dose medication (LM) group (30 cases, 1 case was eliminated, 1 case dropped off), a conventional medication (CM) group (30 cases, 1 case dropped off) and a combination of acupuncture and medication (AM) group (30 cases ). The LM group was given oral administration of 50 mg diclofenac sodium sustained-release capsule; the CM group was given oral administration of 100 mg diclofenac sodium sustained-release capsule; on the basis of the treatment of LM group, the AM group was treated with electroacupuncture at ashi points, Dadu (SP 2), Taichong (LR 3), Taibai (SP 3), Neiting (ST 44), Sanyinjiao (SP 6), Zusanli (ST 36) and Yinlingquan (SP 9) on the affected side, and Taichong (LR 3) and Zusanli (ST 36), Sanyinjiao (SP 6) and Yinlingquan (SP 9) were connected to electroacupuncture respectively, continuous wave, 2 Hz in frequency. The visual analogue scale (VAS) scores of pain before treatment and after 10 min, 2 h, 4 h and 6 h of treatment completion, joint tenderness and swelling scores before treatment and after 10 min and 6 h of treatment completion were compared, and the rate of diclofenac sodium addition within 24 h after treatment completion was recorded among the three groups.@*RESULTS@#After 10 min of treatment completion, the scores of VAS, joint tenderness and joint swelling in the AM group were lower than those before treatment (P<0.05), and the VAS score in the AM group was lower than that in the other two groups (P<0.05). After 2, 4 and 6 h of treatment completion, the VAS scores of the three groups were lower than those before treatment (P<0.05), and the scores in the AM group were lower than those in the LM group (P<0.05). After 6 h of treatment completion, the joint tenderness scores of the three groups and the joint swelling scores of the AM group and the CM group were lower than those before treatment (P<0.05), and the joint tenderness and swelling scores of the AM group were lower than those of the LM group (P<0.05). The rate of diclofenac sodium addition was 3.3 % (1/30) and 3.4 % (1/29) in the AM group and the CM group, respectively, which were lower than 17.9% (5/28) in the LM group (P<0.05).@*CONCLUSION@#Electroacupuncture combined with diclofenac sodium have a good immediate analgesic effect in the treatment of AGA, and have the advantages of small dosage of analgesic drugs and less adverse reactions.


Sujet(s)
Humains , Diclofenac , Électroacupuncture , Goutte articulaire/traitement médicamenteux , Préparations à action retardée , Thérapie par acupuncture , Arthralgie
8.
Article de Anglais | WPRIM | ID: wpr-971324

RÉSUMÉ

OBJECTIVE@#To investigate and reveal the underlying mechanism of the effect of total saponins from Dioscoreae nipponica Makino (TSDN) on the arachidonic acid pathway in monosodium urate (MSU) crystal-induced M1-polarized macrophages.@*METHODS@#M1 polarization of RAW264.7 cells were induced by 1 µ g/mL lipopolysaccharide (LPS). The methylthiazolyldiphenyl-tetrazolium bromide method was then used to screen the concentration of TSDN. MSU (500 µ g/mL) was used to induce the gouty arthritis model. Afterwards, 10 µ g/L TSDN and 8 µ mol/L celecoxib, which was used as a positive control, were added to the above LPS and MSU-induced cells for 24 h. The mRNA and protein expressions of cyclooxygenase (COX) 2, 5-lipoxygenase (5-LOX), microsomal prostaglandin E synthase derived eicosanoids (mPGES)-1, leukotriene B (LTB)4, cytochrome P450 (CYP) 4A, and prostaglandin E2 (PGE2) were tested by real-time polymerase chain reaction and Western blotting, respectively. The enzyme-linked immunosorbent assay was used to test the contents of M1 markers, including inducible nitric oxid synthase (NOS) 2, CD80, and CD86.@*RESULTS@#TSDN inhibited the proliferation of M1 macrophages and decreased both the mRNA and protein expressions of COX2, 5-LOX, CYP4A, LTB4, and PGE2 (P<0.01) while increased the mRNA and protein expression of mPGES-1 (P<0.05 or P<0.01). TSDN could also significantly decrease the contents of NOS2, CD80, and CD86 (P<0.01).@*CONCLUSION@#TSDN has an anti-inflammation effect on gouty arthritis in an in vitro model by regulating arachidonic acid signaling pathway.


Sujet(s)
Acide urique/métabolisme , Acide arachidonique/métabolisme , Dioscorea , Goutte articulaire , Lipopolysaccharides , Saponines/pharmacologie , Macrophages , Transduction du signal , ARN messager/métabolisme
9.
Acta Pharmaceutica Sinica B ; (6): 678-693, 2023.
Article de Anglais | WPRIM | ID: wpr-971718

RÉSUMÉ

The NLRP3 inflammasome's core and most specific protein, NLRP3, has a variety of functions in inflammation-driven diseases. Costunolide (COS) is the major active ingredient of the traditional Chinese medicinal herb Saussurea lappa and has anti-inflammatory activity, but the principal mechanism and molecular target of COS remain unclear. Here, we show that COS covalently binds to cysteine 598 in NACHT domain of NLRP3, altering the ATPase activity and assembly of NLRP3 inflammasome. We declare COS's great anti-inflammasome efficacy in macrophages and disease models of gouty arthritis and ulcerative colitis via inhibiting NLRP3 inflammasome activation. We also reveal that the α-methylene-γ-butyrolactone motif in sesquiterpene lactone is the certain active group in inhibiting NLRP3 activation. Taken together, NLRP3 is identified as a direct target of COS for its anti-inflammasome activity. COS, especially the α-methylene-γ-butyrolactone motif in COS structure, might be used to design and produce novel NLRP3 inhibitors as a lead compound.

10.
Article de Chinois | WPRIM | ID: wpr-972295

RÉSUMÉ

ObjectiveTo study the clinical efficacy of the Qingre Lishi Huazhuo method on patients with chronic gouty arthritis of dampness-heat obstruction syndrome and the effect on nucleotide-binding oligomerization domain-like receptor 3(NLRP3)/interleukin-1β (IL-1β) signaling pathway to preliminarily explore its mechanism. MethodSixty patients with chronic gouty arthritis of dampness-heat obstruction syndrome were enrolled and divided into a treatment group (30 cases) and a control group (30 cases) according to the random number table method. Thirty people were assigned to the healthy group. Patients in the control group were treated with oral Febuxostat, while those in the treatment group were treated with modified Simiaosan combined with Febuxostat. Treatment lasted four weeks. The general clinical data, traditional Chinese medicine (TCM) syndrome scores, serum uric acid (UA), serum creatinine (SCr), blood urea nitrogen (BUN), fasting blood glucose (FPG), low-density lipoprotein (LDL), triglyceride (TG), total cholesterol (TC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) of patients were recorded. Enzyme-linked immunosorbent assay (ELISA) was employed to measure the levels of IL-1β,TNF-α, and IL-6,and the levels of NLRP3,cysteinyl aspartate-specific protease-1 (Caspase-1), and apoptosis-associated speck-like protein containing a CARD (ASC) were detected by Western blot. ResultBefore treatment, the levels of body mass index (BMI), systolic blood pressure (SBP),diastolic blood pressure (DBP),UA,SCr,BUN,FPG,LDL,TG,and TC in both groups significantly increased (P<0.05,P<0.01),and the levels of HDL significantly decreased as compared with those in the healthy group(P<0.05). Additionally, the levels of IL-1β, TNF-α, and IL-6 in both groups significantly increased before treatment (P<0.01). Compared with the results before treatment, patients in the two groups had significant reductions in tube pain, joint tenderness, joint swelling,joint fever, activity disorders, body fatigue, sliminess, bitter mouth, yellow and red urine, and tongue manifestation scores (P<0.05,P<0.01). Compared with patients in the control group after treatment, those in the treatment group had a significant decrease in joint fever, body fatigue, sliminess, bitter mouth,sticky stool,yellow and red urine, tongue manifestation score, and pulse score (P<0.05). The total effective rate in the treatment group was 80.0% (24/30), higher than 56.7% (17/30)in the control group(χ2=11.916,P<0.05). Compared with the results before treatment, BMI, SBP, DBP, UA, SCr, BUN, FPG, LDL, TG, TC, ESR,CRP, IL-1β, TNF-α, IL-6 levels, and VAS score in both groups significantly decreased (P<0.05,P<0.01). Compared with patients in the control group after treatment, those in the treatment group had decreased DBP,ESR, IL-1β levels, and VAS score (P<0.05). Western blot results showed that before treatment, the protein expression of NLRP3, Caspase-1, and ASC in peripheral blood mononuclear cells (PBMCs) of patients in both groups were higher than those in the healthy group (P<0.01). Compared with the results before treatment, the protein expression of NLRP3, Caspase-1, and ASC in PBMCs in patients of both groups after treatment decreased (P<0.05,P<0.01). Compared with the control group after treatment, the treatment group showed decreased expression levels of NLRP3 and Caspase-1(P<0.05). ConclusionThe Qingre Lishi Huazhuo method can effectively improve the clinical symptoms and reduce inflammation of chronic gouty arthritis of dampness-heat obstruction syndrome with good safety. The mechanism may be related to the inhibition of the NLRP3/IL-1β signaling pathway.

11.
Article de Chinois | WPRIM | ID: wpr-997651

RÉSUMÉ

ObjectiveTo observe the effect of Huanglian Jiedutang on the inflammatory injury in the mouse model of acute gouty arthritis (AGA) and to explore the mechanism of Huanglian Jiedutang in treating AGA. MethodForty male C57BL/6J mice were randomized into blank, model, colchicine (0.83 mg·kg-1), and Huanglian Jiedutang (5 g·kg-1) groups. The mouse model of AGA was established by injecting monosodium urate (MSU) crystals into the ankle joint. The swelling degree of the right ankle joint of each mouse was measured every day for 7 days, and the pathological changes of the ankle joint were detected by hematoxylin-eosin (HE) staining after 7 days. The other 40 C57BL/6J mice were grouped as above. After 18 hours of modeling, the right ankle joint was collected, and real-time polymerase chain reaction was employed to measure the mRNA levels of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6, NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), and Caspase-1. The expression levels of IL-1β, TNF-α, and IL-6 were measured by the enzyme-linked immunosorbent assay. Western blot was employed to determine the protein levels of NLRP3 inflammasome, Toll-like receptor 4 (TLR4), and nuclear factor-κB (NF-κB). ResultCompared with the blank group, the model group showed swelling right ankle joint (P<0.01), obvious foreign body granuloma in the ankle joint with inflammatory cell infiltration. After the treatment with Huanglian Jiedutang, the ankle joint swelling was relieved (P<0.05, P<0.01), and the size of foreign body granuloma was reduced. Compared with the blank group, the model group showed up-regulated mRNA levels of IL-1β, TNF-α, and IL-6 in the ankle joint tissue (P<0.01), up-regulated mRNA levels of NLRP3 and Caspase-1 in the NLRP3 inflammasome (P<0.05, P<0.01), and up-regulated protein levels of NLRP3, Caspase-1, TLR4, and NF-κB (P<0.05, P<0.01). Huanglian Jiedutang down-regulated the mRNA levels of IL-1β, TNF-α, IL-6, NLRP3, and Caspase-1 (P<0.05, P<0.01) and the protein levels of IL-1β, TNF-α, IL-6, NLRP3, Caspase-1, TLR4, and NF-κB (P<0.05 or P<0.01). ConclusionInjecting MSU crystal resulted in local inflammatory injury of the joints in the mouse model of AGA. The treatment with Huanglian Jiedutang may alleviate the inflammatory injury by regulating the NLRP3 inflammasome and TLR4/NF-κB signaling pathway.

12.
Acta Pharmaceutica Sinica ; (12): 2424-2433, 2023.
Article de Chinois | WPRIM | ID: wpr-999144

RÉSUMÉ

Gouty arthritis is a type of metabolic rheumatic disease caused by autoimmune abnormalities. Currently, the use of Western medicine in the clinical treatment of gouty arthritis has been associated with a high risk of adverse reactions. Therefore, there is a growing interest in exploring therapeutic drugs from traditional Chinese medicine as a potential alternative. According to the theory of traditional Chinese medicine, gouty arthritis has been classified as damp-heat arthralgia syndrome. Shirebi granules has been found to have good clinical efficacy in treating gouty arthritis. However, its underlying pharmacological mechanisms remain unclear. To address this problem, the study first established the interaction network of candidate targets for Shirebi granules, which is used to treat damp-heat syndrome of gouty arthritis. Then, the key candidate targets of Shirebi granules for treating gouty arthritis with damp-heat syndrome were screened by calculating the topological features of the network nodes. Then, the functional mining of the key candidate targets revealed that the candidate targets of Shirebi granules may intervene in the biological process of inflammatory response and lipid metabolism through the crosstalk of Wnt/β-catenin signaling. To verify the effectiveness of Shirebi granules in treating gouty arthritis with damp-heat syndrome, a rat model was established. The results demonstrated that the granules significantly improved the severity of arthritis in rats with this condition, reduced joint inflammation, gait score, swelling index, increased mechanical pain threshold (P < 0.05), and reduced the content of serum inflammatory factors IL-1β, IL-6, and TNF-α in gouty arthritis rats with damp-heat syndrome (P < 0.01) gouty. It was also found that Shirebi granules effectively alleviated the symptoms of dampness heat syndrome such as local joint fever and dry mouth by reducing the temperature of the joints in acute gouty arthritis with damp-heat syndrome (AD) rats, increasing the threshold of heat pain, increasing water intake (P < 0.01), and inhibiting abnormal changes in the content of fatty acid oxidation related enzymes (P < 0.01). Western blot analysis showed that Shirebi granules increased the protein expression levels of Wnt and β-catenin (P < 0.01) while decreasing the protein expression of p65, p-p65 and PPARγ (P < 0.01) in rats with gouty arthritis and damp-heat syndrome. The results showed that Shirebi granules may reverse the "inflammation-immune" imbalance and lipid metabolism disorder by regulating the crosstalk of Wnt/β-catenin signaling, and play a role in alleviating the severity of the disease. This study provides a methodological reference for elucidating the pharmacological mechanisms of traditional Chinese medicine formulas. It also presents research ideas for the appropriate clinical use of Chinese patent medicines and the development of new clinical drugs for gouty arthritis therapy. The animal welfare and experiment procedures of this study were performed in accordance with the regulations of the Experimental Animal Ethics Committee of Experimental Research Center, China Academy of Chinese Medical Sciences (grant No. ERCCACMS11-2302-08).

13.
Article de Chinois | WPRIM | ID: wpr-996513

RÉSUMÉ

ObjectiveTo investigate the effects of Biling Qutong prescription (BLQT) on serum levels of NOD-like receptor thermal protein domain associated protein 3 (NLRP3), purinergic ligand-gated ion channel 7 receptor (P2X7R), fibronectin (FN), and hepatic steatosis in patients with type 2 diabetes mellitus (T2DM) complicated with gouty arthritis (GA). MethodSixty-four patients diagnosed with T2DM comorbid with GA and treated at the First Affiliated Hospital of Anhui University of Chinese Medicine from January 2019 to December 2022 were enrolled and randomly divided into a BLQT group (Chinese medicine group, 32 cases) and the ibuprofen group (western medicine group, 32 cases). Thirty healthy individuals who underwent routine health examinations during the same period were assigned to the control group. The BLQT group and the western medicine group received basic treatment along with BLQT and ibuprofen, respectively. After 8 weeks of continuous treatment, the traditional Chinese medicine syndrome score (TCMSS) of the patients was evaluated before and after treatment. The differences in fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (2 h PG), glycated hemoglobin (HbA1c), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), serum uric acid (SUA), serum creatinine (SCr), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), alanine aminotransferase (ALT), aspartate aminotransferase (AST), controlled attenuation parameter (CAP), liver stiffness measurement (LSM), NLRP3, P2X7R, and FN levels before and after treatment were compared. Adverse drug reactions that occurred during treatment were recorded. ResultThe TCMSS for joint redness, swelling, pain, joint burning, yellow urine, and red tongue with yellow and greasy coating, as well as total score were significantly reduced in both the BLQT group and the western medicine group as compared with those before treatment (P<0.05, P<0.01). The BLQT group also showed a significant reduction in symptom scores such as dry mouth, polyuria, polydipsia, and slippery and rapid pulse (P<0.01). Compared with the western medicine group after treatment, the BLQT group exhibited a more significant reduction in all symptom scores and total score (P<0.05, P<0.01). The BLQT group and the western medicine group showed a decrease in FPG, 2 h PG, HbA1c, SCr, SUA, TG, TC, and LDL-C levels (P<0.05, P<0.01) after treatment, and the BLQT group showed decreased HOMA-IR, ALT, AST, and HDL-C levels (P<0.05, P<0.01) compared with those before treatment. When compared with the western medicine group after treatment, the BLQT group showed a more significant reduction in all laboratory parameters except for HDL-C (P<0.05, P<0.01). Before treatment, NLRP3, P2X7R, and FN levels in both the BLQT group and the western medicine group were higher than those in the control group (P<0.01). After treatment, NLRP3 and P2X7R levels in both groups significantly decreased (P<0.01), and FN levels in the BLQT group also decreased significantly (P<0.01). When compared with the western medicine group after treatment, the BLQT group showed a more significant reduction in NLRP3, P2X7R, and FN levels (P<0.01). Before treatment, CAP and LSM levels in both the BLQT group and the western medicine group were higher than those in the control group (P<0.01). After treatment, CAP and LSM levels in both groups decreased (P<0.05, P<0.01). Compared with the western medicine group after treatment, the BLQT group showed a more significant reduction in CAP and LSM (P<0.01). The incidence of adverse reactions was 3.13% (1/32) in the BLQT group and 15.63% (5/32) in the western medicine group, with no significant difference. ConclusionBLQT has good efficacy in patients with T2DM complicated with GA, which can significantly alleviate joint redness, swelling, heat, pain, limited mobility, dry mouth, and polydipsia, reduce blood glucose, uric acid, and lipid levels, suppress the high expression of NLRP3, P2X7R, and FN, and improve hepatic steatosis.

14.
Article de Chinois | WPRIM | ID: wpr-996826

RÉSUMÉ

The prevalence of osteoporosis, osteoarthritis, gouty arthritis, rheumatoid arthritis, and intervertebral disc degeneration is increasing year by year with the growing number of elderly people, and the common clinical manifestations of these diseases include severe pain in different areas, which seriously affects the daily life of the patients. Therefore, how to relieve the pain and reduce the prevalence of bone and joint diseases and improve the quality of life of the patients is a hot spot in the medical field. Studies have confirmed that NOD-like receptor family, pyrin domain-containing protein 3 (NLRP3) inflammasomes, as pattern recognition receptors, are involved in the inflammation, chondrocyte proliferation, osteoblast and osteoclast differentiation, intervertebral disc cell inflammation and scorching, extracellular matrix degradation and apoptosis, mitochondrial dysfunction, endoplasmic reticulum stress, and reactive oxygen species damage, demonstrating close link with the development of bone and joint diseases. Chinese medicine has a long history and demonstrates remarkable therapeutic effects in the treatment of bone and joint diseases. It can mitigate the pathological changes of bone and joint diseases by inhibiting NLRP3 inflammasomes to alleviate the pain, playing a role in preventing and treating these diseases. Therefore, this paper briefly describes the relationship between NLRP3 inflammasomes and the development of bone and joint diseases by reviewing the latest research progress at home and abroad. We summarize the latest studies about the active components, extracts, and compound prescriptions of Chinese medicines in the treatment of bone and joint diseases via regulating NLRP3 inflammasomes. This review is expected to offer new insights into the in-depth research on the pathogenesis and drug treatment of bone and joint diseases and provide a basis for the clinical application of Chinese medicine in the prevention and treatment of such diseases.

15.
Article de Chinois | WPRIM | ID: wpr-962648

RÉSUMÉ

Gouty arthritis (GA) is a metabolic disease caused by disorders of purine metabolism and/or abnormal excretion of uric acid in the body. Its pathogenesis is mostly related to dietary structure as well as excessive intake of protein, sugar and fat, and the clinical manifestations are joint redness, swelling, heat and pain, which seriously affect the daily life of patients. Therefore, it is urgent to carry out research on anti-GA drugs. Western drugs for the treatment of GA, such as colchicine, can relieve pain in the short term, but with obvious side effects in long-term treatment. Traditional Chinese medicine has definite efficacy and high safety in the treatment of GA and is more acceptable to patients than western medicine. Modern medical research has concluded that inflammatory factors, oxidative stress, apoptosis and intestinal dysbacteriosis are closely related to the pathogenesis of GA. In-depth research has found that single traditional Chinese medicine and its compounds can regulate Toll-like receptors/myeloid differentiation factor 88 (TLRs/MyD88) signaling pathway, NLR family pyrin domain containing 3 (NLRP3) inflammasome, nuclear transcription factor-κB (NF-κB) and other inflammatory signaling pathways, and further intervene in the downstream cytokines such as interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), peroxisome proliferator-activated receptor γ (PPARγ), nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-α(IκB-α) and aspartate-specific cysteine protease 1 (Caspase-1) to reduce inflammatory factors and increase anti-inflammatory factors, thereby exerting the anti-GA role. Therefore, this paper summarized and elaborated the experiments of inflammatory response mediated by traditional Chinese medicines and their compounds via regulating inflammatory signaling pathways in recent years, which provides new ideas and theoretical basis for finding more related anti-inflammatory traditional Chinese medicines for the treatment of GA.

16.
China Pharmacy ; (12): 814-818, 2023.
Article de Chinois | WPRIM | ID: wpr-969577

RÉSUMÉ

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.

17.
Article de Anglais | WPRIM | ID: wpr-1010281

RÉSUMÉ

OBJECTIVE@#To explore the mechanism of effects of total saponin fraction from Dioscorea Nipponica Makino (TSDN) on M1/M2 polarization of monocytes/macrophages and arachidonic acid (AA) pathway in rats with gouty arthritis (GA).@*METHODS@#Seventy-two Sprague Dawley rats were randomly divided into 4 groups (n=18 in each): normal, model, TSDN at 160 mg/kg, and celecoxib at 43.3 mg/kg. Monosodium urate crystal (MSU) was injected into the rats' ankle joints to induce an experimental GA model. Blood and tissue samples were collected on the 3rd, 5th, and 8th days of drug administration. Histopathological changes in the synovium of joints were observed via hematoxylin and eosin (HE) staining. The expression levels of arachidonic acid (AA) signaling pathway were assessed via real-time polymerase chain reaction (qPCR) and Western blot. Flow cytometry was used to determine the proportion of M1 and M2 macrophages in the peripheral blood. An enzyme-linked immunosorbent assay (ELISA) was used to detect interleukine (IL)-1 β, tumor necrosis factor-alpha (TNF-α), IL-4, IL-10, prostaglandin E2 (PGE2), and leukotriene B4 (LTB4).@*RESULTS@#HE staining showed that TSDN improved the synovial tissue. qPCR and Western blot showed that on the 3rd, 5th and 8th days of drug administration, TSDN reduced the mRNA and protein expressions of cyclooxygenase (COX)2, microsomal prostaglandin E synthase-1 derived eicosanoids (mPGES-1), 5-lipoxygenase (5-LOX), recombinant human mothers against decapentaplegic homolog 3 (Smad3), nucleotide-binding oligomerization domain-like receptor protein 3 (NALP3), and inducible nitric oxide synthase (iNOS) in rats' ankle synovial tissues (P<0.01). TSDN decreased COX1 mRNA and protein expression on 3rd and 5th day of drug administration and raised it on the 8th day (both P<0.01). It lowered CD68 protein expression on days 3 (P<0.01), as well as mRNA and protein expression on days 5 and 8 (P<0.01). On the 3rd, 5th, and 8th days of drug administration, TSDN elevated the mRNA and protein expression of Arg1 and CD163 (P<0.01). Flow cytometry results showed that TSDN decreased the percentage of M1 macrophages while increasing the percentage of M2 in peripheral blood (P<0.05 or P<0.01). ELISA results showed that on the 3rd, 5th, and 8th days of drug administration, TSDN decreased serum levels of IL-1 β, TNF-α, and LTB4 (P<0.01), as well as PGE2 levels on days 3rd and 8th days (P<0.05 or P<0.01); on day 8 of administration, TSDN increased IL-4 serum levels and enhanced IL-10 contents on days 5 and 8 (P<0.05 or P<0.01).@*CONCLUSION@#The anti-inflammatory effect of TSDN on rats with GA may be achieved by influencing M1/M2 polarization through AA signaling pathway.


Sujet(s)
Rats , Humains , Animaux , Goutte articulaire/traitement médicamenteux , Monocytes/anatomopathologie , Interleukine-10/métabolisme , Acide arachidonique/pharmacologie , Dioscorea/composition chimique , Rat Wistar , Facteur de nécrose tumorale alpha/métabolisme , Saponines/usage thérapeutique , Interleukine-4/métabolisme , Leucotriène B4/pharmacologie , Rat Sprague-Dawley , Macrophages , Transduction du signal , ARN messager/métabolisme
18.
Article de Chinois | WPRIM | ID: wpr-973135

RÉSUMÉ

ObjectiveTo study the mechanism of Danggui Sinitang in mitigating gouty arthritis (GA) in rats by regulating autophagy via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. MethodSixty male SD rats were randomly assigned into normal, model, colchicine (0.3 mg·kg-1), and low-, medium-, and high-dose Danggui Sinitang (6.54, 13.08, and 26.16 g·kg-1) groups (n=10) and administrated with corresponding drugs by gavage. The rats in the normal group and model group were administrated with equal volume of normal saline by gavage for 7 days. One hour after administration on day 5, the GA model was established by injecting sodium urate suspension (50 g·L-1) into the right ankle joint of rats in other groups except the normal group, and the rats in the normal group were injected with sterile normal saline of the same volume. The swelling and pathological changes of the ankle joint were observed. The serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β were determined. Western blot was employed to determine the protein levels of PI3K, phosphorylated PI3K (p-PI3K), protein kinase B (Akt), phosphorylated Akt (p-Akt), mTOR, phosphorylated mTOR (p-mTOR), microtubule-associated protein 1 light chain 3 Ⅱ/Ⅰ (LC3Ⅱ/Ⅰ), autophagy effector Beclin-1, and ubiquitin-binding protein p62 in the synovial tissue. Real-time fluorescent quantitative PCR (Real-time PCR) was employed to determine the mRNA levels of PI3K, Akt, mTOR, LC3, Beclin-1 and p62. ResultCompared with the normal control, the model group showed increased joint swelling index (P<0.01), elevated serum levels of TNF-α, IL-6, and IL-1β, inflammatory cell infiltration, and fibrous tissue hyperplasia. In addition, the model group showed up-regulated protein levels of PI3K, p-PI3K, Akt, p-Akt, mTOR, p-mTOR, and p62 and mRNA levels of PI3K, Akt, mTOR, and p62 in the synovial tissue, while it showed down-regulated protein levels of LC3Ⅱ/Ⅰ and Beclin-1 and mRNA levels of LC3 and Beclin-1 (P<0.01). Compared with the model group, medium- and high-dose Danggui Sinitang alleviated the joint swelling (P<0.01), lowered the serum levels of TNF-α, IL-6, and IL-1β (P<0.05), and relieved the inflammatory cell infiltration in the synovial tissue of the ankle joint and the fibrous tissue hyperplasia. Moreover, they down-regulated the protein levels of PI3K, p-PI3K, Akt, p-Akt, mTOR, p-mTOR, and p62 and the mRNA levels of PI3K, Akt, mTOR, and p62 in the synovial tissue (P<0.05), while they up-regulated the protein levels of LC3Ⅱ/Ⅰ and Beclin-1 and the mRNA levels of LC3 and Beclin-1 (P<0.05). ConclusionDanggui Sinitang, especially at a high dose, can inhibit PI3K/Akt/mTOR signaling pathway to improve autophagy in the synovial tissue, thereby mitigating GA.

19.
Article de Chinois | WPRIM | ID: wpr-973147

RÉSUMÉ

ObjectiveIn the treatment of acute gouty arthritis (AGA), western medicine is mostly used for anti-inflammatory and analgesic purposes to control the blood uric acid level, but some patients are still at risk of poor control and recurrent attacks. Chinese medicinal prescriptions, potent in resisting inflammation and relieving pain, are able to stabilize the blood uric acid level, reduce acute attacks, and improve the clinical efficacy of western medicine. However, there is a lack of evidence to support their use as evidence-based medicine. This study employed network Meta-analysis (NMA) to evaluate the efficacy and safety of common Chinese medicinal prescriptions in the treatment of AGA, aiming to provide evidence-based medical evidence for the clinical use of Chinese medicinal prescriptions in the treatment of AGA. MethodChinese and English databases were searched for prospective cohort studies and randomized controlled trials (RCTs) on Chinese medicinal prescriptions against AGA from database inception to December 1, 2022. Stata software and Review Manager were used for statistical analysis. ResultForty-four papers with 3 564 cases involved were included in the current NMA. In terms of reducing blood uric acid, the cumulative probability results showed that Mahuang Lianyao Chixiaodou Tang showed optimal efficacy (87.60%). In terms of relieving joint pain, Danggui Niantongtang and Guizhi Shaoyao Zhimutang showed optimal efficacy (92.00% and 82.30%). In terms of improving erythrocyte sedimentation rate (ESR), Simiaowan was superior to other prescriptions (87.00%). In terms of reducing C-reactive protein (CRP), Simiaowan and Baihutang modified with Guizhitang showed superior efficacy (76.00% and 66.10%). In terms of safety, except for the basic treatment group, Mahuang Lianyao Chixiaodou Tang had the lowest probability of adverse events, and Danggui Niantongtang had the highest probability of adverse reactions during treatment. According to the results of cluster analysis, Mahuang Lianyao Chixiaodou Tang and Simiaowan are effective and safe. ConclusionAccording to the results of NMA, Chinese medicinal prescriptions can assist in the treatment of AGA and improve the effectiveness of western medicine. For patients with AGA, clinicians can choose Mahuang Lianyao Chixiaodou Tang or Simiaowan as an auxiliary drug for routine western medicine treatment.

20.
Article de Chinois | WPRIM | ID: wpr-973748

RÉSUMÉ

ObjectiveTo explore the efficacy and mechanism of the alcohol extract DH50 of Angelicae Pubescentis Radix in treating gouty arthritis induced by monosodium urate (MSU) crystals in vivo and in vitro. MethodFifty male SD rats were randomly assigned into five groups (n=10): a normal group, a model group, a dexamethasone (DXMS, 0.07 mg·kg-1) group, and low- (DH50-D, 9 mg·kg-1) and high-dose (DH50-G, 18 mg·kg-1) DH50 groups. The rats in the normal group and model group were administrated with the same amount of pure water. On day 5, the gouty arthritis model was established by injecting MSU into the right ankle joint of rats. The toe volume and joint inflammation index were measured 4, 8, 24, and 48 h after modeling. The pathological changes of the synovial tissue were detected by hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was employed to measure the levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and IL-6 in the synovial tissue. Western blot was employed to measure the protein levels of NOD-like receptor protein 3 (NLRP3), cysteine-aspartic protease-1 (Caspase-1), apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC), IL-1β, and cyclooxygenase-2 (COX-2) in the synovial tissue. Furthermore, the cell inflammation model was established with RAW264.7 cells stimulated with MSU (75 mg·L-1). The cell experiments were carried out with 6 groups: a normal group, a model group, a positive drug (DXMS, 100 μmol·L-1) group, and low- (DH50-D, 25 mg·L-1), medium- (DH50-Z, 50 mg·L-1), and high-dose (DH50-G, 100 mg·L-1) DH50 groups. Methyl thiazolyl tetrazolium (MTT) assay was employed to determine the cell viability, ELISA to determine the content of TNF-α in the supernatant of cell culture, and Western blot to determine the protein levels of NLRP3, cleaved Caspase-1, IL-1β, TNF-α, and COX-2. ResultCompared with the normal group, the rat model group showed increased toe swelling degree and joint inflammatory index (P<0.01), serious infiltration of the synovium, elevated levels of inflammatory cytokines in the tissue homogenate (P<0.01), and up-regulated protein levels of NLRP3, Caspase-1, ASC, IL-1β, and COX-2 (P<0.05, P<0.01). Compared with the rat model group, low- and high-dose DH50 mitigated the toe swelling degree, decreased the joint inflammatory index, alleviated the inflammatory infiltration, lowered the levels of inflammatory cytokines in the tissue homogenate (P<0.01), and down-regulated the expression of related proteins (P<0.05, P<0.01). Compared with the normal group, the cell model group showed elevated level of TNF-α in the supernatant (P<0.01) and up-regulated protein levels of NLRP3, cleaved Caspase-1, IL-1β, TNF-α, and COX-2 (P<0.05). Compared with the model group, low, medium, and high doses of DH50 lowered the level of TNF-α in the supernatant of cell culture in a dose-dependent manner and down-regulated the expression of related proteins (P<0.05, P<0.01). ConclusionDH50 can mitigate gouty arthritis both in vitro and in vivo by inhibiting the activation of NLRP3 inflammasomes and the production of inflammatory cytokines.

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