Comparison of efficacy of acupuncture-related therapies in treating Acute Gouty Arthritis: A Network Meta-Analysis of Randomized Controlled Trials.

Background: and purpose: Acupuncture and moxibustion, as a complementary and alternative therapy, has been widely used in the treatment of acute gouty arthritis (AGA). However, there are various forms of acupuncture and moxibustion, and the curative effect of different forms is different. This study evaluated the clinical efficacy of different acupuncture therapies in treating AGA by network meta-analysis. Methods: Computer searches of English databases (including PubMed, The Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Embase) and Chinese databases (including China National Knowledge Infrastructure (CNKI), VIP Database, Wanfang Database and China Biomedical Literature Database) were conducted for randomized controlled trials (RCTs) of acupuncture therapies in treating AGA. We set the search time from the database establishment to May 2022. Data analysis was performed using Stata14.2 software. Results: Thirty-two RCTs involving 2434 patients with AGA were screened out. The results showed that in terms of the improvement of pain visual analogue scale (VAS) scores, the top ones were acupoint application (100%), electroacupuncture + Western medicine (73.5%) and acupuncture + Western medicine (69.2%); In terms of total effective rate, acupoint application (85.2%), acupuncture (75.2%) and acupuncture + Western medicine (63%) ranked the top; In terms of reducing serum uric acid (SUA) levels, the top ones were acupoint application (95%), acupuncture + Western medicine (87.5%) and acupuncture (66.2%); In terms of the reduction of erythrocyte sedimentation rate (ESR), acupuncture (95%), acupoint application (84.7%), and electroacupuncture + Western medicine (52.8%) were the most prominent. Conclusion: The existing evidence shows that acupoint application has more advantages in improving the total effective rate, improving pain and reduce SUA levels, and acupuncture has an advantage in reducing ESR levels and adverse events. However, due to the low qualities of the original studies, the quality of this evidence is poor. Therefore, it is recommended that more scientific research be performed to confirm the efficacy of acupuncture.

Traditional herbal medicine: Therapeutic potential in acute gouty arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Acute gouty arthritis (AGA) is characterized by a rapid inflammatory reaction caused by the build-up of monosodium urate (MSU) crystals in the tissues surrounding the joints. This condition often associated with hyperuricemia (HUA), is distinguished by its symptoms of intense pain, active inflammation, and swelling of the joints. Traditional approaches in AGA management often fall short of desired outcomes in clinical settings. However, recent ethnopharmacological investigations have been focusing on the potential of Traditional Herbal Medicine (THM) in various forms, exploring their therapeutic impact and targets in AGA treatment. AIM OF THE REVIEW: This review briefly summarizes the current potential pharmacological mechanisms of THMs - including active ingredients, extracts, and prescriptions -in the treatment of AGA, and discusses the relevant potential mechanisms and molecular targets in depth. The objective of this study is to offer extensive information and a reference point for the exploration of targeted AGA treatment using THMs. MATERIALS AND METHODS: This review obtained scientific publications focused on in vitro and in vivo studies of anti-AGA THMs conducted between 2013 and 2023. The literature was collected from various journals and electronic databases, including PubMed, Elsevier, ScienceDirect, Web of Science, and Google Scholar. The retrieval and analysis of relevant articles were guided by keywords such as "acute gouty arthritis and Chinese herbal medicine," "acute gouty arthritis herbal prescription," "acute gouty arthritis and immune cells," "acute gouty arthritis and inflammation," "acute gouty arthritis and NOD-like receptor thermoprotein domain associated protein 3 (NLRP3)," "acute gouty arthritis and miRNA," and "acute gouty arthritis and oxidative stress." RESULTS: We found that AGA has a large number of therapeutic targets, highlighting the effectiveness the potential of THMs in AGA treatment through in vitro and in vivo studies. THMs and their active ingredients can mitigate AGA symptoms through a variety of therapeutic targets, such as influencing macrophage polarization, neutrophils, T cells, natural killer (NK) cells, and addressing factors like inflammation, NLRP3 inflammasome, signaling pathways, oxidative stress, and miRNA multi-target interactions. The anti-AGA properties of THMs, including their active components and prescriptions, were systematically summarized and categorized based on their respective therapeutic targets. CONCLUSION: phenolic, flavonoid, terpenoid and alkaloid compounds in THMs are considered the key ingredients to improve AGA. THMs and their active ingredients achieve enhanced efficacy through interactions with multiple targets, of which NLRP3 is a main therapeutic target. Nonetheless, given the intricate composition of traditional Chinese medicine (TCM), additional research is required to unravel the underlying mechanisms and molecular targets through which THMs alleviate AGA.

Efficacy and safety of Huzhang Granule, a compound Chinese herbal medicine, for acute gouty arthritis: A double-blind, randomized controlled trial.

BACKGROUND: Acute gouty arthritis (AGA) is an inflammatory joint disease with a high prevalence. Typical medical interventions, including nonsteroidal anti-inflammatory drugs, colchicine and glucocorticoids, can have serious adverse reactions. Huzhang Granule (HZG), a compound Chinese herbal medicine, has been used to treat AGA for more than 30 years with satisfactory effects and no significant adverse reactions. However, the efficacy and safety of HZG in AGA patients remains unknown. OBJECTIVE: The present investigation was designed to examine the efficacy and safety profile of HZG in managing AGA patients. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: The current study was conducted as a noninferiority, randomized controlled clinical trial on 180 eligible enrolled participants. Participants were randomly assigned into the HZG and etoricoxib groups. Treatments were administered for 5 d, during which the HZG group received HZG and placebo etoricoxib, while the etoricoxib group received etoricoxib and placebo HZG in the same ratio (1:1). MAIN OUTCOME MEASURES: The primary outcome was pain experienced by the patient in the gout-afflicted joint from days 2 to 5 of the treatment window. The pain level was measured via a visual analogue scale, ranging from 0 mm to 100 mm. The secondary outcomes comprised joint tenderness and swelling, reduction of inflammatory biomarkers, and the patient's and investigator's global evaluations of therapeutic response. RESULTS: The mean reduction in pain was -51.22 mm (95% confidence interval [CI], [-53.42, -49.03] mm) for the HZG and -52.00 mm (95% CI, [-54.06, -49.94] mm) for the etoricoxib groups. The mean difference between the two groups was 0.78 mm (95% CI, [-2.25, 3.81] mm). All additional efficacy endpoints, covering decreased inflammation and pain relief, yielded compelling proof of noninferiority. Patients in the HZG group exhibited a comparatively lower rate of adverse events compared to those in the etoricoxib group (4.44% vs 13.33%; P ≤ 0.05). CONCLUSION: HZG and etoricoxib groups demonstrated similar levels of analgesic effectiveness. The safety and efficacy of HZG indicates that it can be used as a potential therapeutic option for treating AGA. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2000036970). Please cite this article as: Wang H, Chen ST, Ding XJ, Kuai L, Hua L, Li X, Wang YF, Zhang M, Li B, Wang RP, Zhou M. Efficacy and safety of Huzhang Granule, a compound Chinese herbal medicine, for acute gouty arthritis: A double-blind, randomized controlled trial. J Integr Med. 2024; 22(3): 270-278.

Efficacy of Qingpeng ointment (a Tibetan medicine) for acute gouty arthritis: a multi-center, randomized, double-blind, placebo-controlled trial.

BACKGROUND: This study aims to assess the efficacy and safety of Qingpeng ointment (QPO), a Tibetan medicine for alleviating symptoms in individuals with acute gouty arthritis (AGA). METHODS: This study was a randomized, double-blind, placebo-controlled trial that involved individuals with AGA whose joint pain, as measured on a visual analog scale (VAS) from 0 to 10, was equal to or greater than 3. The participants were randomly assigned to either the QPO or the placebo group and received their respective treatments twice daily for seven consecutive days. In case of intolerable pain, the participants were allowed to use diclofenac sodium sustained-release tablets as a rescue medicine. The primary outcomes measured were joint pain and swelling, while the secondary outcomes included joint mobility, redness, serum uric acid levels, C-reactive protein levels, and the amount of remaining rescue medicine. Any adverse events that occurred during the trial were also recorded. RESULTS: A total of 203 cases were divided into two groups, with balanced baselines: 102 in the QPO group and 101 in the placebo group. For joint pain, differences between the groups were notable in the VAS scores [1.75 (0, 3.00) versus 2.00 (1.00, 3.50); P = 0.038], changes in VAS [5.00 (3.00, 6.00) versus 4.00 (2.00, 6.00); P = 0.036], and disappearance rate [26.47% compared to 15.84%; P = 0.046] after treatment. Concerning joint swelling, significant between-group differences were observed in the VAS scores [1.00 (0, 2.30) versus 2.00 (0.70, 3.00); P = 0.032] and disappearance rate [33.33% compared to 21.78%; P = 0.046] at treatment completion. The QPO group exhibited a statistically significant mobility improvement compared to the placebo group (P = 0.004). No significant differences were found in other secondary outcomes. Five patients, four from the QPO group and one from the other, encountered mild adverse events, primarily skin irritation. All of these cases were resolved after dosage reduction or discontinuation of the medication. CONCLUSIONS: Compared to the placebo, QPO exhibits positive effects on AGA by alleviating pain, reducing swelling, and enhancing joint mobility, without causing significant adverse effects. TRIAL REGISTRATION: ISRCTN34355813. Registered on 25/01/2021.

[Immediate analgesic effect of electroacupuncture combined with diclofenac sodium on acute gouty arthritis: a randomized controlled trial].

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.

Relief effects of Laoshan cherry extracts as a dietary supplement against the symptoms of acute gouty arthritis in rats induced by urate crystals.

We evaluated the effects of Laoshan cherry as a food or dietary supplement on relieving the symptoms of acute gouty arthritis in rats induced by urate crystals. Rats in groups of 10 were given Laoshan cherry functional extracts at doses of 5, 10, and 20 mg/kg by oral gavage for 21 days and then injected with a sodium nitrate suspension in the rear ankle area as an induced acute gouty arthritis model. The ankle swelling and inflammations in the model (no treatment) group increased significantly compared with blank group; the ankle inflammations reduced in experimental groups receiving three different doses of the cherry extract and the joint swelling reduced in the high-dose group by 43% compared with the model group. Serum uric acid and xanthine oxidase activities were also elevated in the model group and these parameters were reduced by a maximum of 8% and 33%, respectively, in the rats receiving the cherry extracts. The serum levels of the inflammatory cytokine IL-1ß in the high-dose group decreased by 12% compared with the model group. These results demonstrated that the cherries possess a functional substance that has a significant alleviating effect on the symptoms of gouty arthritis in rats induced by sodium urate injection.

Qingre Huazhuo Jiangsuan Decoction promotes autophagy by inhibiting PI3K/AKT/mTOR signaling pathway to relieve acute gouty arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Gout belongs to the category of "arthralgia syndrome" in traditional Chinese medicine. It is believed that gout is caused by stagnation of blood stasis, heat, and turbid toxin. Qingre Huazhuo Jiangsuan Decoction (QHJD) is a traditional Chinese medicine prescription developed from the classic Chinese medicine prescription Simiao powder to clear heat, remove turbidity, reduce acid, and reduce inflammation. Now Traditional Chinese Medicine (TCM) physicians often apply it to treat acute gouty arthritis (AGA). However, the mechanism of QHJD in relieving acute gouty arthritis is still unclear, and further research is needed. AIM OF THE STUDY: Here, we aim to explore the potential mechanism of QHJD in relieving acute gouty arthritis. MATERIALS AND METHODS: Acute gouty arthritis model was established by injecting monosodium urate (MSU) suspension into knee joint. The pathological state of synovial tissue in each group was evaluated by hematoxylin-eosin (HE) staining. The level of TNF-α, IL-6, and IL-1ß were detected by enzyme-linked immunosorbent assay (ELISA). qRT-PCR was used to detect the mRNA expression of NLRP3, ATG5, ATG7, PI3K, AKT, and mTOR. The protein expression of LC3II/I, p62, ULK1, P-ULK1, Beclin-1, PI3K, AKT, mTOR, P-PI3K, P-AKT, and P-mTOR were detected by Western blot. RESULTS: (1) The level of autophagy protein (mRNA) was significantly up-regulated in QHJD group and rapamycin, while the expression of autophagy protein (mRNA) was significantly downregulated in the 3-methyladenoenoic acid (3 MA) group; (2) QHJD and rapamycin significantly inhibited PI3K/AKT/mTOR pathway, while 3 MA group activated this pathway. (3) It was worth noting that after treatment with QHJD and rapamycin, the inflammatory pathological state of AGA synovial tissue was significantly reduced with the activation of the autophagy gene in knee synovial tissue, and the inhibition of PI3K/AKT/mTOR pathway. CONCLUSIONS: This research revealed that QHJD activates autophagy by inhibiting PI3K/AKT/mTOR pathway, thereby relieving acute gouty arthritis.

Electroacupuncture for acute gouty arthritis: a systematic review and meta-analysis of randomized controlled trials.

Acute gouty arthritis (AGA) is a metabolic disorder in which recurrent pain episodes can severely affect the quality of life of gout sufferers. Electroacupuncture (EA) is a non-pharmacologic therapy. This systematic review aimed to assess the efficacy and safety of electroacupuncture in treating acute gouty arthritis. We searched eight Chinese and English databases from inception to July 30, 2023, and 242 studies were retrieved. Finally, 15 randomized controlled trials (n=1076) were included in a meta-analysis using Review Manager V.5.4.1. meta-analysis results included efficacy rate, visual rating scale (VAS) for pain, serum uric acid level (SUA), immediate analgesic effect, and incidence of adverse events. Electroacupuncture (or combined non-pharmacologic) treatment of AGA was significantly different from treatment with conventional medications (RR = 1.14, 95% confidence interval CI = 1.10 to 1.19, P < 0.00001). The analgesic effect of the electroacupuncture group was superior to that of conventional Western drug treatment (MD = -2.26, 95% CI = -2.71 to -1.81, P < 0.00001). The electroacupuncture group was better at lowering serum uric acid than the conventional western drug group (MD =-31.60, CI -44.24 to -18.96], P < 0.00001). In addition, electroacupuncture combined with Western drugs had better immediate analgesic effects than conventional Western drug treatment (MD = -1.85, CI -2.65 to -1.05, P < 0.00001). Five studies reported adverse events in the electroacupuncture group versus the drug group, including 19 cases of gastrointestinal symptoms and 6 cases of neurological symptoms (RR = 0.20, 95% CI = 0.04 to 0.88, P = 0.03). Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=450037, identifier CRD42023450037.

Immediate analgesic effect of electroacupuncture combined with diclofenac sodium on acute gouty arthritis: a randomized controlled trial / 中国针灸

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.

Efficacy and safety of Tibetan medicine Qingpeng ointment for acute gouty arthritis: protocol for a multi-center, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Acute gouty arthritis (AGA) is an inflammatory arthritis clinically characterized by severe pain, swelling, and restricted movement of joints, which may cause physical disability and decrease quality of life. The use of recommended first-line treatment agents for AGA may be limited by adverse events. There has been a traditional use of alternative therapies for AGA. Tibetan medicine Qingpeng ointment is one of the on-market herbal products used for symptom relief of AGA. Previous clinical studies indicated that Qingpeng ointment can relieve pain, swelling, redness, and dysfunction of joints in patients with AGA. However, there is no rigorous randomized trial to demonstrate its benefit for AGA. In order to evaluate the efficacy and safety of Qingpeng ointment for AGA, we designed a randomized controlled trial. METHODS: This study is designed as a multi-center, randomized, double-blind, placebo-controlled trial. Two hundred and six adults with acute flare of gout, and visual analogue scale (VAS) score of joint pain ≥ 3 points will be recruited. Participants will be randomly assigned to herbal treatment or placebo group at a ratio of 1:1. Qingpeng ointment, or equal placebo ointment, will be applied topically at involved joints twice a day for consecutive 7 days. Patients in both groups would be allowed giving diclofenac sodium sustained-release tablets as rescue therapy when VAS score of joint pain ≥ 7 points during the treatment. The primary outcomes will be joint pain measured by VAS score, and joint swelling measured using width and thickness of affected joints and VAS score. Other outcome measures will be joint mobility, joint redness, C-reactive protein, serum uric acid, and the use of rescue medicine as well as adverse effect. DISCUSSION: To the best of our knowledge, this study is the first multi-center, randomized, double-blind, and placebo-controlled clinical trial to assess the efficacy of Tibetan medicine Qingpeng ointment for AGA. The findings of this study would provide evidence for its use to relieve symptoms of AGA. TRIAL REGISTRATION: ISRCTN ISRCTN34355813 . Registered on 25 January 2021.

Effect of Baihu and Guizhi decoction in acute gouty arthritis: study protocol for a randomized controlled trial.

BACKGROUND: The prevalence rates of gout worldwide have increased annually. Acute gouty arthritis (AGA) accounts for a large proportion of gout patients and causes severe physical and mental pain in patients. Controlling the occurrence and development of gout inflammation is the first step in the treatment of gout. The main treatment drugs in gout are non-steroid anti-inflammatory drugs (NSAIDs), colchicine, and glucocorticoids, but these treatments have many adverse reactions which limit their clinical application. Baihu and Guizhi decoction (BHGZ) is one of the classic prescriptions in the Synopsis of the Golden Chamber and is a good prescription for AGA. Previous clinical studies have shown that BHGZ confers a strong benefit for treating AGA. However, the literature shows a lack of high-quality RCT research on BHGZ with respect to AGA. Therefore, in this study, we use a randomized, double-blind, controlled study with a placebo to evaluate the clinical efficacy and safety of BHGZ on the AGA of moist heat arthralgia spasm syndrome. METHODS: This study is a randomized, double-blind, controlled clinical trial. A total of 102 adult participants with AGA of moist heat arthralgia spasm syndrome will be enrolled, with balanced treatment allocation (1:1). The experimental intervention will be BHGZ plus the low-dose colchicine, and the control intervention will be placebo plus the low-dose colchicine for 10 days. To study the clinical efficacy (including VAS score; joint tenderness, joint swelling, joint movement disorder; TCM evidence efficacy score) and the changes of inflammatory indexes. At the same time, the improvement of joint inflammation in patients with AGA will be observed from musculoskeletal ultrasound imaging, and the safety evaluation will be carried out. DISCUSSION: This study will be the first placebo-controlled RCT to assess whether BHGZ plus low-dose colchicine have beneficial effects on changing reducing inflammation of joints for patients with AGA of moist heat arthralgia spasm syndrome. The results of this trial will help to provide evidence-based recommendations for clinicians. TRIAL REGISTRATION: Chinese Clinical Trials Register ChiCTR1900024974 . Registered on 5 August 2019.

[Mechanism and experimental verification of "Polygoni Cuspidati Rhizoma et Radix-Ligustri Lucidi Fructus" combination in treatment of acute gouty arthritis based on network pharmacology].

Based on network pharmacology, the mechanism of Polygoni Cuspidati Rhizoma et Radix-Ligustri Lucidi Fructus(PL) combination against acute gouty arthritis(AGA) was explored and preliminarily verified by animal experiment. The chemical components and corresponding targets of PL were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The active components with oral bioavailability(OB)≥30% and drug-likeness(DL)≥0.18 were screened based on literature, and the related protein targets were collected. Then the protein targets were standardized with the help of UniProt database. The AGA-related targets were searched from GeneCards, NCBI, and DrugBank. The common targets of the disease and the medicinals were yielded by FunRich V3, and the protein-protein interaction(PPI) network was constructed to screen the key targets, followed by Gene Ontology(GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis of the key targets. Afterwards, some of the key targets were verified by sodium urate crystal-induced AGA mouse model. A total of 25 active components and 287 targets of PL, 811 targets of AGA, and 88 common targets were screened out. PPI network analysis showed that tumor necrosis factor(TNF), interleukin-6(IL-6), and interleukin-1ß(IL-1ß) may be the core targets of PL in the treatment of AGA. The key targets were mainly involved in 566 GO terms(P<0.05), including multiple biological processes such as inflammatory response and immune response. Moreover, they were related to 116 KEGG pathways and these pathways were involved in inflammation and immunity, mainly including NOD-like receptor signaling pathway and TNF signaling pathway. Animal experiment confirmed that PL can alleviate ankle swelling, improve abnormal gait, and down-regulate the protein expression of TNF-α, IL-6, and IL-1ß in AGA mice, indicating that PL can treat AGA through TNF-α, IL-6, and IL-1ß and the feasibility of network pharmacology to predict drug targets. This study preliminarily discussed the key targets and biological signaling pathways involved in the treatment of AGA with PL combination, which reflected the multi-pathway and multi-target action characteristics of Chinese medicine. Moreover, this study laid a scientific basis for research on the treatment of AGA with PL combination, as well as the mechanism of action.

Influence of intervention treatment by "heat-clearing and diuresis-promoting" prescription on NALP3, an inflammatory factor in acute gouty arthritis.

BACKGROUND: To investigate the efficacy of Qingre Lishi Decoction(QLRD), in the treatment of acute gouty arthritis, and its influence on the expression levels of inflammatory factor nucleotide-binding oligomerization domain-like receptor(NALP 3) in patients. METHODS: A total of 78 patients with acute gouty arthritis admitted to our hospital were randomly divided into the control group and the observation group, with 39 cases in each group. The control group was given basic treatment and colchicine tablets, and the observation group was given "heat-clearing and diuresis-promoting" prescription for intervention treatment. The main symptom score, treatment effective rate and laboratory indexes of the two groups were compared 7 days after treatment. RESULTS: After treatment, the scores of joint redness, hot pain, joint flexion and extension disorder, oliguria and constipation were improved in both groups, and the improvement degree in observation group was higher than that in control group (P < 0.05); the clinical effective rate in the observation group (94.87%) was higher than that in the control group (76.92%). The serum uric acid (UA), erythrocyte sedimentation rate (ESR), interleukin-1ß (IL-1ß) and NALP3 showed a decreasing trend, and the decrease degree of each index in observation group was higher than that in control group (P < 0.05). CONCLUSION: The "heat-clearing and diuresis-promoting" prescription for intervention treatment can effectively improve the clinical symptoms of patients with acute gouty arthritis and reduce the level of inflammatory factor NALP3, maintaining remarkable effect.

Effects of Gentiopicroside on activation of NLRP3 inflammasome in acute gouty arthritis mice induced by MSU.

Acute gouty arthritis is a self-limiting inflammatory disease resulting from the deposition of monosodium urate (MSU) crystals. It has been shown that Gentiopicroside (GPS) possesses anti-inflammatory and analgesic functions. The aim of this study was to parse out whether GPS has an effect on acute gouty arthritis. We established an acute gouty arthritis model by the injection of MSU into the paw, and found that GPS relieves MSU-induced mechanical, thermal hyperalgesia, and paw swelling. Furthermore, GPS down-regulated the release of pro-inflammatory cytokines in paw tissues, including IL-1ß, IL-6, IL-18, and TNF-α. The results of H&E staining and MPO activity measurement showed that GPS inhibits neutrophil infiltration. And the over-expressions of NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and Caspase-1 induced by MSU were inhibited by treatment with GPS. These results revealed that GPS can treat acute gouty arthritis based on anti-inflammatory and analgesic properties in vivo, which might be ascribed to the inhibition on NLRP3 inflammasome. Furthermore, we performed in vitro study to confirm the results of in vivo study. Consistently, the results proved that GPS could inhibit the activation of NLRP3 inflammasome in RAW264.7 macrophages stimulated by LPS-MSU. In conclusion, this study provides an experimental basis for the application of GPS and expands the potential value of GPS in the therapy of acute gouty arthritis.

Modified Baihu decoction therapeutically remodels gut microbiota to inhibit acute gouty arthritis.

Background: Acute gouty arthritis (AGA) is the most common first symptom of gout, and the development of gout as a metabolic and immune inflammatory disease is also correlated with the gut microbiota. However, the mechanism of the effect of changes in the gut microbiota on AGA remains unclear. The intestinal flora can not only affect purine metabolism or regulate inflammation, but also influence the therapeutic effect of drugs on AGA. The aim of this study was to investigate the exact mechanism of modified Baihu decoction (MBD) in the treatment of AGA and whether it is related to the regulation of the structure of the intestinal flora. Methods: On the 21st day of MBD administration by continuous gavage, a rat acute gouty arthritis model was constructed using sodium urate (0.1 mL/rat, 50 mg/mL), and the ankle joint swelling was measured before and 4 h, 8 h, 24 h, and 48 h after the injection of sodium urate. After 48 h of sodium urate injection, serum, liver, kidney, ankle synovial tissue and feces were collected from rats. The collected samples were examined and analyzed using H&E, Elisa, Immunohistochemistry, Histopathology, 16S rDNA, and Biochemical analysis. To investigate the mechanism of MBD to alleviate AGA using pro-inflammatory factors and intestinal flora. Results: MBD (5.84, 35 g/kg) was administered orally to AGA rats and diclofenac sodium tablets (DS-tablets) were used as standard treatment control. Serum biochemical assessment confirmed that MBD is a safe drug for the treatment of AGA. In addition, our findings confirmed that MBD relieved AGA-related symptoms, such as toe swelling. Lowering serum levels of uric acid, IL-1ß, and TGF-ß1 immunohistochemical results also confirmed that MBD reduced the expression of inflammatory elements such as IL-1ß, NLRP3, ASC, and Caspase-1 in synovial tissue.Furthermore, compared with control group, the 16s rDNA sequencing of AGA rat faeces revealed an increase in the relative abundance of Lachnospiraceae, Muribaculaceae, and Bifidobacteriaceae species. While the relative abundance of Lactobacillaceae, Erysipelotrichaceae, Ruminococcaceae, Prevotellaceae and Enterobacteriaceae showed a relative decrease in species abundance. Of these, the reduction in species abundance of Enterobacteriaceae was associated with a reduction in amino acid metabolism and environmental perception. After MBD therapeutic intervention, the disturbance of the intestinal flora caused by AGA was restored. Conclusion: In summary, MBD is an effective agent for the treatment of AGA, with the potential mechanism being the regulation of intestinal flora to control inflammation. This would help to promote the therapeutic effect of MBD on AGA.

Mechanism and experimental verification of "Polygoni Cuspidati Rhizoma et Radix-Ligustri Lucidi Fructus" combination in treatment of acute gouty arthritis based on network pharmacology / 中国中药杂志

Based on network pharmacology, the mechanism of Polygoni Cuspidati Rhizoma et Radix-Ligustri Lucidi Fructus(PL) combination against acute gouty arthritis(AGA) was explored and preliminarily verified by animal experiment. The chemical components and corresponding targets of PL were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The active components with oral bioavailability(OB)≥30% and drug-likeness(DL)≥0.18 were screened based on literature, and the related protein targets were collected. Then the protein targets were standardized with the help of UniProt database. The AGA-related targets were searched from GeneCards, NCBI, and DrugBank. The common targets of the disease and the medicinals were yielded by FunRich V3, and the protein-protein interaction(PPI) network was constructed to screen the key targets, followed by Gene Ontology(GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis of the key targets. Afterwards, some of the key targets were verified by sodium urate crystal-induced AGA mouse model. A total of 25 active components and 287 targets of PL, 811 targets of AGA, and 88 common targets were screened out. PPI network analysis showed that tumor necrosis factor(TNF), interleukin-6(IL-6), and interleukin-1β(IL-1β) may be the core targets of PL in the treatment of AGA. The key targets were mainly involved in 566 GO terms(P<0.05), including multiple biological processes such as inflammatory response and immune response. Moreover, they were related to 116 KEGG pathways and these pathways were involved in inflammation and immunity, mainly including NOD-like receptor signaling pathway and TNF signaling pathway. Animal experiment confirmed that PL can alleviate ankle swelling, improve abnormal gait, and down-regulate the protein expression of TNF-α, IL-6, and IL-1β in AGA mice, indicating that PL can treat AGA through TNF-α, IL-6, and IL-1β and the feasibility of network pharmacology to predict drug targets. This study preliminarily discussed the key targets and biological signaling pathways involved in the treatment of AGA with PL combination, which reflected the multi-pathway and multi-target action characteristics of Chinese medicine. Moreover, this study laid a scientific basis for research on the treatment of AGA with PL combination, as well as the mechanism of action.

Study on the compatibility effect and active constituents of Atractylodis Rhizoma in Ermiao Wan against Acute Gouty Arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Ermiao Wan (EMW), composed of Atractylodis Rhizoma (AR) and Phellodendri Chinensis Cortex (PC), is a classical traditional Chinese medicine prescription having been used to treat the disease named "Tong Feng", which is described as "ache in bones and joints" with the same symptom of modern disease named acute gouty arthritis for many years in TCM clinical practice. Besides, both PC and AR were considered to be effective in anti-inflammatory according to modern pharmacological research. AIM OF THE STUDY: Present study was undertaken to probe the compatibility rationality between the two herbs PC and AR in EMW and the active constituents of AR against acute gouty arthritis (AGA). MATERIALS AND METHODS: Rat model of AGA was induced by intra-articular injection of monosodium urate (MSU) crystal suspension, and PC combined with or without different AR extracts were used for AGA treatment. Ankle joint swelling, proinflammatory cytokines in serum and pathological changes of synovium were investigated. Using the developed UHPLC-QQQ-MS method, the plasma concentrations of the primary alkaloids in PC, such as berberine, phellodendrine, magnoflorine, jatrorrhizine, berberrubine, palmatine, and tetrahydropalmatine, in AGA rat were determined, and pharmacokinetics properties were compared following oral administration of PC, PC combined with or without different AR extracts. RESULTS: PC, PC combined with AR volatile oil (VO) extract or PC combined with whole AR extract significantly attenuated the ankle joint swelling of AGA rats. Besides, the combination of PC and VO extract of AR showed superior efficacy than other groups in ameliorating ankle joint swelling, reducing the IL-6 expression in serum and improving tissue lesions of ankle joints. Furthermore, it turned out that the VO extract of AR increased the blood exposure level of PC related alkaloids than non-volatile oil (NVO) extract of AR, by comparing the pharmacokinetic results of each group. CONCLUSIONS: The VO components of AR were the key compatible materials to combine with PC in EMW for AGA treatment. Moreover, the enhanced anti-AGA activity of PC after combining with VO extract of AR may attribute to the influence of VO on the pharmacokinetics of PC. This study may provide useful information for elucidating the compatibility effects of AR in EMW against AGA.

[Cathepsin-B involved in effect of electroacupuncture by inhibiting the activation of NLRP3 inflammasome in rats with acute gouty arthritis].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on Cathepsin-B in the synovium of the knee joint of acute gouty arthritis(AGA) rats, so as to explore the mechanism of EA in the treatment of AGA. METHODS: A total of 60 male Wistar rats were randomly divided into normal control,model, medication and EA groups, with 15 rats in each group. Rat model of AGA was established by injection of 0.2 mL sodium urate crystal suspension into the left knee joint cavity. The rats in the medication group were treated with colchicine by gavage(0.3 mg·kg-1·d-1), and the rats in the EA group were treated with EA at the left "Sanyinjiao" (SP6) and "Zusanli"(ST36) for 10 min each time, once a day for a week. The Coderre gait grading standard was used to score the gait of rats. The pathological morphology of synovial tissue of the left knee joint was observed by H.E. staining. The expression levels of Cathepsin-B protein and Nod-like receptor pyrin domain 3(NLRP3), apoptosis-associated speck-like protein containing CARD (ASC),Caspase-1, interleukin-1ß(IL-1ß) and IL-18 mRNAs were detected by Western blot and real-time fluorescence quantitative PCR, respectively. RESULTS: Compared with the normal control group, the degree of synovitis infiltration in the model group was more serious. And the gait score，the protein expression level of Cathepsin-B and the mRNA expression levels of NLRP3,ASC,Caspase-1, IL-1ß,IL-18 were significantly increased (P<0.01).After the interventions, the degree of inflammatory infiltration was mild, The gait score, the protein expression level of Cathepsin-B and the mRNA expression levels of NLRP3 and ASC,Caspase-1，IL-1ß,IL-18 were significantly decreased in both medication and EA groups in contrast to the model group (P<0.01, P<0.05). Compared with medication group, the mRNA expression levels of Caspase-1 and IL-18 in the EA group were increased (P<0.05). CONCLUSION: EA may inhibit the activation of NLRP3 inflammasome by reducing the activity of Cathepsin-B in the synovium of the knee joint, so as to treat AGA.

Silencing of Gasdermin D by siRNA-Loaded PEI-Chol Lipopolymers Potently Relieves Acute Gouty Arthritis through Inhibiting Pyroptosis.

Gasdermin D (GSDMD) plays a causal role in NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis eruption, which has been regarded as a potential therapeutic target for pyroptosis-related diseases including acute gouty arthritis. In the present study, the synthesized PEI-Chol (cholesterol grafted polyethylenimine) was assembled with GSDMD small interfering RNA (siRNA) to form PEI-Chol/siGSDMD polyplexes, which provided high transfection efficiency for siRNA-mediated GSDMD knockdown. Then we evaluated the effect of GSDMD siRNA-loaded PEI-Chol on inflammatory cascades in bone-marrow-derived macrophages (BMDMs) and acute gouty arthritis animal models under MSU exposure. When accompanied by pyroptosis blockade and decreased release of interleukin-1 beta (IL-1ß), NLRP3 inflammasome activation was also suppressed by GSDMD knockdown in vivo and in vitro. Moreover, in MSU-induced acute gouty arthritis mice, blocking GSDMD with siRNA significantly improved ankle swelling and inflammatory infiltration observed in histopathological analysis. Furthermore, investigation using a mouse air pouch model verified the effect of siGSDMD-loaded PEI-Chol on pyroptosis of recruited macrophages and related signaling pathways in response to MSU. These novel findings exhibited that GSDMD knockdown relieved acute gouty arthritis through inhibiting pyroptosis, providing a possible therapeutic approach for MSU-induced acute gouty arthritis molecular therapy using PEI-Chol as a nucleic acid delivery carrier.

Effects of external application of compound Qingbi granules on acute gouty arthritis with dampness-heat syndrome: a randomized controlled trial.

BACKGROUND AND AIM: The use of anti-inflammatory and analgesic drugs such as nonsteroidal anti-inflammatory drugs(NSAIDs) for treating acute gout has limitations, such as adverse reactions in the gastrointestinal tract and toxicity in the liver, kidney, and heart. Hence, a new safe and effective treatment approach needs to be explored to reduce the use of anti-inflammatory and analgesic drugs, incidence of adverse reactions, and patients' burden. This randomized controlled clinical trial aimed to investigate the clinical efficacy and safety of the external application of compound Qingbi granules (CQBG) in treating acute gouty arthritis(AGA), providing evidence for designing a safe, effective, and optimized protocol for AGA comprehensive treatment. METHODS: A total of 90 patients in line with the diagnostic standard of AGA were recruited and randomly divided into control, T1, and T2 groups (30 in each group). All the participators in the three groups all received Western-medicine-basic treatment (low-purine diet, drinking water more than 2000 mL/days, oral loxoprofen, and NAHCO3). Besides, the T1 group received an external application of diclofenac diethylamine emulgel, while the T2 group received an external application of CQBG. The participants in the control group received single-use Western-medicine-basic treatment. With a treatment course of 7 days and a follow-up of 7 days, the three groups were compared in terms of primary outcome indicators, including swelling, pain improvement, and change in pain duration and secondary outcome indicators, including serum C-reactive protein (CRP) level, uric acid (UA) level, and change in the thickness of the inflammatory synovium of joints under ultrasound. Meanwhile, the safety of the protocol was evaluated. RESULTS: The three groups of patients had no apparent differences in age, body mass index, history of gout, complications, and so on before recruitment. A comparison between pretreatment and post-treatment revealed remarkable reductions in the arthralgia visual analog scale score(VAS) and the swelling score in the three groups after the treatment and the improvements in the T2 group were more significant than those in the T1 and control groups (P < 0.05). Regarding the onset time of pain improvement and pain duration, the T2 group had more significant efficacy compared with the other two groups (P < 0.05). The serum CRP and blood UA levels in the three groups significantly decreased after the treatment, but with no significant intergroup difference. The improvement in the thickness of the inflammatory synovium in joints tested by ultrasound was more significant in the T2 group than in the control group (P < 0.05). For safety evaluations, no significant difference in the incidence of adverse events was found. CONCLUSIONS: The external application of CQBG combined with Western-medicine-basic treatment in patients with AGA improved arthralgia and swelling, shortened the period of taking NSAIDs, and reduced the levels of CRP and serum UA. Its therapeutic effect was significantly better than the effect of single-use Western-medicine-basic treatment. The study provided evidence for the clinical application of CQBG combined with Western medicine in treating AGA. TRIAL REGISTRATION: ChiCTR, ChiCTR1800018020. Registered 27 August 2018, https://www.chictr.org.cn/showproj.aspx?proj=27138.