Total Glucosides Of Paeony Group Research Articles

Total glucosides of paeony alleviates experimental Sjögren's syndrome through inhibiting NLRP3 inflammasome activation of submandibular gland cells.

The mechanisms by which total glucosides of paeony (TGP) mitigates Sjögren's syndrome (SS) remains elusive. In the present study, we aim to explore the relationship between the therapeutic effects of TGP in the treatment of SS and NLRP3 inflammasome activation in submandibular gland (SG) cells. Female non-obese diabetic (NOD) mice were selected as the model of SS. The mice were divided into PBS and TGP treatment group. For treatment, TGP (400mg·kg-1) was administered intragastrically every day for 4 weeks. The SS-like symptoms and pathological changes of the SG of mice were compared between the PBS and TGP group. The activation of NLRP3 inflammasome in SG was detected by RT-qPCR, immunohistochemistry and western blot. The SG cells stimulated by lipopolysaccharide (LPS) and adenosine triphosphate (ATP) for activation of NLRP3 inflammasome were treated with or without TGP. Then, NLRP3 inflammasome activation was assessed. The IL-1β and IL-18 in homogenate of SG, serum and supernatant were detected by ELISA. Compared with balb/c mice, NOD mice showed SS-like symptoms and lymphocyte infiltration in SG, and the expression of NLRP3 inflammasome in SG was significantly increased. The SS-like symptoms were alleviated, and lymphocyte infiltration in SG was reduced, and the level of NLRP3 inflammasome in SG mice was decreased after TGP treatment. TGP also significantly inhibit the activation of NLRP3 inflammasome of SG cells in vitro. Collectively, our results indicated that TGP alleviates SS through inhibition of the activation of NLRP3 inflammasome of SG. These findings clarified the mechanism underlying the therapeutic effects of TGP on SS, and provided new evidence for the further application of TGP in the treatment of SS.

Efficacy and safety of total glucosides of paeony in the treatment of recurrent aphthous ulcers: a single-center, double-blind, randomized, placebo-controlled clinical trial.

Introduction: There has been a lack of treatments available to lower the frequency of recurrent aphthous ulcers (RAUs) until now. Total glucosides of paeony (TGP) is a botanical drug extracted from the dried roots of Paeonia lactiflora Pall. [Ranunculaceae; Paeoniae Radix Alba]. This study aims to evaluate the efficacy and safety of TGP in the treatment of RAU. Methods: This study was registered with the Chinese Clinical Trial Registry (ChiCTR1900025623). Patients were randomly assigned to the TGP or placebo group and treated with 1.8g/day for 24weeks. Participants were observed for a total of 36weeks and were asked to record ulcer severity, medication, and adverse reactions in the form of diaries or apps every day. The primary outcome was the monthly ulcer-free interval. Results: A total of 79 individuals were enrolled, with 40 assigned to the TGP group and 39 to the placebo group. The dropout rate was 18.18%. In the TGP group, the monthly ulcer-free interval was significantly longer than baseline (median, 9.6days) since weeks 13-24 (median, 18.5days) (p < 0.05), and after discontinuation, it was further prolonged (median, 24.7days) than in weeks 13-24 (p < 0.05). In addition, the monthly ulcer-free interval was longer in the TGP group than in the placebo group (median, 15.9days) at weeks 25-36 (p < 0.001). There were better improvements in the monthly number of ulcers and monthly area of ulcers, and visual analog scoring in the TGP group at weeks 25-36 (p < 0.001). Conclusion: TGP had a good long-term therapeutic effect on RAU with frequent occurrence. Systematic Review Registration: www.chictr.org.cn, identifier ChiCTR1900025623.

Efficacy and safety of Tripterygium glycosides in Sjögren's syndrome treatment: evidence from 12 randomized controlled trials.

Tripterygium glycosides (TGs) has been widely used in the treatment of Sjögren's syndrome (SS). Seven databases, PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Medical Database, China Science and Technology Journal Database, and the Chinese Biomedicine database, were selected to collect randomized controlled trials (RCTs) related to the treatment of SS with TGs alone or in combination. The participants, intervention, comparison, outcome, and study design principle were adopted for the inclusion of related studies. The risk of bias was assessed using the Cochrane Collaboration's tool. Meta-analysis was conducted using RevMan 5.3, with risk ratios (RRs) or standard mean differences (SMDs) and 95% confidence intervals (CIs). Overall, 12 trials involving 668 patients were analyzed. The results of the meta-analysis showed that TGs in combination with total glucosides of paeony (TGP) had significantly lower symptom scores than TGs alone on dry eyes (SMD =-0.61, 95% CI: -1.12 to -0.10, P=0.02) or dry mouth (SMD =-1.29, 95% CI: -1.84 to -0.74, P<0.00001). The efficacy rates of TG + TGP vs. TGs (P<0.00001) and TG + HM vs. TGs (P=0.01) were significantly different. In addition, compared to hydroxychloroquine (HCQ), TGs could induce expression of C-reactive protein (P=0.007), globulin (P<0.00001), and immunoglobulin A (IgA) (P=0.006), whereas the TG + TGP group had lower levels of immunoglobulin G (IgG) (P<0.00001), immunoglobulin M (IgM) (P=0.02), and IgA (P<0.00001), as well as saliva flow rate (P<0.00001) and lacrimal gland function (P<0.00001). The adverse events between TGs and HCQ were not evident, and there was no increase in the risk of adverse reactions when combined with other drugs. TGs are potentially effective for treating SS without increasing the risk of adverse events. High-quality, multi-center, and large-scale RCTs are required.

Total Glucosides of Paeony protects against collagen-induced mouse arthritis via inhibiting follicular helper T cell differentiation

BackgroundThe development of rheumatoid arthritis (RA) is related to germinal center (GC) response and autoreactive T cells, which mediate adaptive immunity and play an important role in stimulating the production of autoantibodies and pro-inflammatory cytokines by B cells and macrophages. Total Glucosides of Paeony (TGP) has anti-inflammatory, immunomodulatory and analgesic effects and is widely used to treat RA. However, few studies investigated whether the therapeutic effect of TGP is associated with the inhibition of autoimmune response. PurposeThe aim of this study was to investigate the effects and mechanisms of TGP on RA. Study DesignType II collagen-induced arthritis (CIA) mouse model was used, and TGP and paeoniflorin were intragastrically treated. MethodsDBA/1 mice were divided into 5 groups: control, model, positive drug (paeoniflorin) and high- and low-dose TGP group. After 21 days of intragastric administration, the pathological change, inflammation expression and molecular mechanism of each group of mice were detected by Micro-CT, histochemical analysis, ELLSA, Western blot, RT-qPCR and flow cytometry. ResultsOur study found that TGP treatment effectively improved inflammation and joint destruction in CIA mice. It reduced the production of serum IgG2a and pro-inflammatory cytokines, including serum interleukin (IL)-21, tumor necrosis factor (TNF)-α and IL-6, and the phosphorylation of NF-κB p65 and STAT3 in a dose-dependent manner. More importantly, TGP could suppress the frequency of germinal center B cells and Tfh cells in the spleen. ConclusionTGP can not only improve symptoms, but also inhibit bone destruction. The therapeutic effect of TGP on CIA is mainly achieved by inhibiting spleen Tfh cell differentiation and GC formation through STAT3 signaling pathway.

Efficacy and safety of total glucosides of paeony combined with methotrexate and leflunomide for active rheumatoid arthritis: a meta-analysis.

Purpose: Total glucosides of paeony (TGP) have been confirmed to reduce hepatotoxicity caused by methotrexate (MTX) and leflunomide (LEF) in rheumatoid arthritis (RA). Nevertheless, high-quality evidence-based meta-analysis data on the issue are unavailable. This study aimed to evaluate the efficacy and safety of this combination treatment for RA.Materials and methods: PubMed, EMBASE, Web of Science, Cochrane Library, ClinicalTrials, Chinese Biomedical Literature database, China National Knowledge Internet, Wan Fang, and VIP were searched up to February 2019. Randomized controlled trials (RCTs) on the efficacy and safety of TGP combined MTX and LEF for RA were included.Results: Eight RCTs were included in the final meta-analysis. Pooled results showed better therapeutic effects against RA in the TGP-treated group (RR =1.10, 95% CI: 1.04 −1.16). The TGP+MTX+LEF group showed a reduced erythrocyte sedimentation rate (MD = −2.80 mm/h, 95% CI: −5.08 - −0.52), C-reactive protein level (MD = −4.17 mg/L, 95% CI: −7.84 - −0.51), and rheumatoid factor (MD = −12.09 IU/mL, 95% CI: −14.05 - −10.14). Besides, the combination treatment tended to benefit lipid profiles (total cholesterol: 95% CI: −1.27–0.06; triglycerides: 95% CI: −0.49 - −0.08; high-density lipoprotein cholesterol: 95% CI: 0.15–0.83; and low-density lipoprotein cholesterol: 95% CI: −0.54 - −0.02). Adverse events, hepatotoxicity in particular, significantly decreased (RR =0.55, 95% CI: 0.38–0.80) in the TGP group.Conclusion: Compared to MTX and LEF therapy, TGP combination treatment may be a more effective and safer strategy. It is advisable to apply TGP as an adjuvant given its hepatoprotective and possible lipid-regulating effect. However, further large-scale and high-quality clinical trials are warranted, and the efficacy of TGP in terms of its effect on lipid profiles should be further confirmed.

Clinical and immunological consequences of total glucosides of paeony treatment in Sjögren's syndrome: A randomized controlled pilot trial

BackgroundThe total glucosides of paeony (TGP) can inhibit inflammation and alleviate symptoms in autoimmune diseases. This study investigated the clinical and immunological consequences of TGP treatment in patients with primary Sjögren's syndrome (SS). MethodsWe conducted a randomized, double-blinded, placebo-controlled clinical trial in 45 patients with primary SS. Patients were randomized at 2:1 ratio to either TGP group (n=29) or placebo group (n=16) and followed up for 24weeks. The primary outocme was the European League Against Rheumatism Sjögren's Syndrome Patient Reported Index (ESSPRI). The secondary outcomes were stimulated and unstimulated salivary flow rate, Schirmer's test and erythrocyte sedimentation rate (ESR), immuneglobulin (Ig), anti-nuclear antibody (ANA), anti-SSA, and anti-SSB. The proportions of B cells in peripheral blood and the levels of serum inerleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and B cell activating factor belonging to the TNF family (BAFF) were measured at baseline and at the end of follow up of 24weeks. ResultsThe average score of ESSPRI in both groups had no statistical significance at 24th week. The mean of ESSPRI in the dry-mouth part of questionnaire in patients who scored 3 to 6 points was significantly reduced in the TGP group changed from (4.81±0.60) at baseline to (4.20±1.46) (P=0.027) at week 24. Stimulated salivary flow rate increased at week 24 from (1.80±0.39) to (2.01±0.51) (P=0.031) and unstimulated salivary flow rate increased from (0.65±0.46) to (0.78±0.45) (P=0.011) in the TGP group, but the placebo group showed no significant difference. Erythrocyte sedimentation rate (ESR) was decreased significantly compared to the placebo group at 12- and 24-week from (40.9±18.0) to (29.4±12.2) (P=0.003) and (30.4±17.3) (P=0.024). The percentage of naive B cells decreased at week 24 in the TGP group from (77.34±12.20) to (64.59±15.60) (P=0.005) while memory B cells increased from (21.79±11.97) to (34.21±15.48) (P=0.006) respectively. The concentrations of TNF-α and IFN-γ decreased in the TGP group at week 24 from (32.51±26.67) to (24.22±13.56) (P=0.017) and (10.71±8.94) to (6.55±4.88) (P=0.022), respectively. No significant difference in ANA titer, anti-SSA antibodies, anti-SSB antibodies, C3 concentration or C4 concentration was observed between the two groups. ConclusionTGP appears to improve the glandular secreting function and decrease the level of inflammatory cytokines.

Clinical study of total glucosides of paeony for the treatment of diabetic kidney disease in patients with diabetes mellitus.

Total glucosides of paeony (TGP), an active compound extracted from dried roots of Paeonia lactiflora Pall, have anti-inflammatory effects. This study investigated the efficacy and safety of TGP for treating diabetic kidney disease (DKD) in type 2 diabetes mellitus patients. An open-label, prospective, randomized, parallel-group, single-site study involving 76 patients with DKD. Patients were randomized into two groups: losartan group (n=38), treated with losartan 100mg/day for 6months and TGP group (n=38), treated with TGP 1800mg/day and losartan 100mg/day for 6months. Serum hs-CRP, MCP-1, and TNF-α were determined before and after treatment. Urinary albumin excretion rate (UAER), fasting blood glucose, serum creatinine, and lipid profiles were examined. At the end-point, UAER decreased in the TGP group compared with baseline. UAER in the losartan group decreased to a level lower than before treatment. The rate of decline in the losartan group was significantly lower than the TGP group. There were no significant differences in serum creatinine and albumin levels between TGP and losartan groups at the end-point. Serum hs-CRP, MCP-1, and TNF-α levels were significantly lower in both groups after treatment. After treatment, serum hs-CRP, MCP-1, and TNF-α in the TGP group decreased more than the losartan group. Positive correlations were observed between UAER and hs-CRP, MCP-1, and TNF-α. No statistically significant difference in side effects was observed between groups. Our study showed that TGP treatment could reduce the albuminuria and inflammatory markers in type 2 diabetes mellitus patients with DKD.

Effect of total glucosides of paeony on Wnt/β-catenin signal transduction pathway expression in kidney of diabetic rats

The study is to explore the effect of total glucosides of paeony (TGP)on Wnt/β-catenin signal transduction pathway expression in kidney of diabetic rats, and discuss the protection of TGP in diabetic nephropathy and possible mechanism. Ninety male SD rats of 8 weeks age were randomly divided into normal control group (n = 10) and model group (n = 80). Rats of the normal control group were fed with regular diet, while rats of the model group were fed with high-fat high-sugar diet and 4 weeks later were given an intraperitoneal injection of 35 mg x kg(-1) streptozotocin (STZ). The successfully induced type 2 diabetic rat models were then randomly divided into DM group, three TGP (50, 100, 200 mg x kg(-1) x d(-1)) treatment group and tripterygium wilfordii glycosides (8 mg x kg(-1) x d(-1)) control group. Rats of DM group and each treatment group were given high-fat high-sugar diet. At week 14, the levels of blood sugar, 24 hour urine protein, serum creatinine and blood urea nitrogen were tested. The rats were then sacrificed. Renal pathological changes were examined. Renal tissue Wnt-1 and β-catenin expressions were detected by immunohistochemical assay. Wnt-1 mRNA and β-catenin mRNA expression was semi-quantified by RT-PCR. Wnt-1 protein and β-catenin protein expression was semi-quantified by Western blot. The Result show that Wnt-1 and β-catenin expression increased in kidney of high-fat high-sugar induced type 2 diabetic rats. Compared with diabetic group, the level of serum creatinine, blood urea nitrogen, 24 h urine protein, mean glomerular area and mean glomerular volume were decreased, renal histopathology were improved, expression of Wnt-1 and β-catenin mRNA and protein was reduced in TGP group. Tripterygium wilfordii glycosides had the similar effect. In conclusion, these results showed that Wnt/β-catenin abnormal activation in kidney of type 2 diabetic rats, TGP can improve kidney damage in diabetic rats and delay the development of diabetic nephropathy by inhibit the Wnt/β-catenin signaling pathway.

Reduced hepatotoxicity by total glucosides of paeony in combination treatment with leflunomide and methotrexate for patients with active rheumatoid arthritis

Combination use of methotrexate (MTX) and leflunomide (LEF) has been proved effective in the treatment of active rheumatoid arthritis (RA). However, previous trials have documented that both are associated with increased incidence of liver toxicity. As active compounds extracted from the roots of the traditional Chinese herb Paeonia lactiflora Pall, total glucosides of paeony (TGP) have been shown to have anti-inflammatory, hepatoprotective and immuno-regulatory activities, without evident toxicity or side effects. In this 24-week, open label, randomized multicenter clinical trial, we investigated the efficacy of TGP and the protective effect on hepatotoxicity in the combination treatment with LEF and MTX for patients with active RA. A total of 204 patients with active RA (DAS28>3.2) recruited from 3 regional referral centers were enrolled and received MTX and LEF combination therapy (MTX 10mg/week plus LEF 20mg/day) with or without TGP for up to 24weeks by randomization. Hepatotoxicity was defined as an increase of at least 1.5-fold the upper limits of normal (ULN) of alanine aminotransferase (ALT) or aspartate aminotransferase (AST). Significantly less frequent hepatotoxicity was observed in patients with TGP than those without (9.5% vs 34.8%, p<0.001) at 12weeks. The proportion of patients whose ALT or AST levels were >1.5 to ≤2 times and >2 to ≤3 times the ULN were lower in TGP group than the control (1.9% vs 10.1%, 2.9% vs 12.4%, p<0.05 respectively). More patients in the TGP group achieved a European League Against Rheumatism (EULAR) good response or moderate response at 12weeks, although there is no statistical significance. Similar results were observed at 24weeks. Our preliminary study demonstrates the hepatoprotective and additive role of TGP in combination with MTX and LEF in the treatment of active RA.

Effects of total glucosides of paeony for delaying onset of Sjogren's syndrome: An animal study

ObjectiveTo investigate the effectiveness of total glucosides of paeony (TGP) on Sjogren's syndrome (SS) using non-obese diabetic (NOD) mice model. Study designTwenty-seven 8-week-old female NOD mice were assigned into TGP group, hydroxychloroquine (HCQ) group and normal saline (NS) group, receiving corresponding drugs respectively and sacrificed at 24-week-old. Saliva flow rate (SFR), ration of regulatory T cells, level of anti-SSA/SSB, histological changes in submandibular glands (SMG) and microarray analysis were assessed. The data were analyzed using SPSS. ResultsCompared to NS group, in TGP group, SFR, SMG index and the ration of regulatory T cells were significantly higher, while anti-SSA/SSB and lymphocytic foci were significantly lower. HCQ group demonstrated similar results except SMG index. Altered gene expression was found in 10.71% of TGP and 13.09% of HCQ of the profile. ConclusionTGP demonstrated a similar effectiveness as HCQ in delaying the onset of SS-like disease in NOD mice.