Efficacy and safety of total glucosides of paeony in the treatment of recurrent aphthous ulcers: a systematic review and meta-analysis.

Background: Recurrent aphthous ulcer (RAU) had high prevalence and lacked widely recognized treatment. Total glucosides of paeony (TGP) was used in the treatment of RAU in recent years. This study was to summarize the efficacy and safety of TGP in the treatment of RAU. Methods: We searched eight commonly used databases for relevant studies that published before 1 November 2023. Primary outcome was visual analogue scale (VAS). Secondary outcomes included overall response rate, significant response rate, ulcer healing time, interval, number of ulcers, and serum inflammatory factors. We conducted the meta-analysis, assessed risk of bias and the confidence of the evidence, by using Stata 15.0, Review Manager 5.4, and Gradepro. Results: Nine randomized controlled trials (RCTs) encompassing 883 patients with RAU were included in the final analysis. The VAS in the TGP group was lower than that in the control group (MD = -1.18, 95% CI = -1.58 to -0.78, p < 0.001, moderate-certainty evidence), subgroup analysis suggested longer (>8 weeks) medication and observation led to a more significant reduction in pain (p = 0.02). Moreover, TGP had higher overall response rate (RR = 1.18, 95% CI = 1.04 to 1.33, p = 0.008, very low-certainty evidence) and significant response rate (RR = 1.72, 95% CI = 1.38 to 2.14, p < 0.001, very low-certainty evidence), accelerated ulcer healing (MD = -1.79, 95% CI = -2.67 to -0.91, p < 0.001, low-certainty evidence), and extended intervals (MD = 23.60, 95% CI = 14.17 to 33.03, p < 0.001, very low-certainty evidence). The efficacy of TGP in reducing the number of ulcers showed no significant difference compared to the control group (MD = -1.66, 95% CI = -3.60 to 0.28, p = 0.09, low-certainty evidence). Moreover, TGP treatment was associated with a higher incidence of abdominal symptoms (RR = 3.27, 95% CI = 1.62 to 6.60, p < 0.001). Conclusion: TGP appears to hold promise as a widely-used clinical therapeutic option for treating RAU. Nevertheless, further rigorous studies of high quality are required to validate its effectiveness. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=471154, Identifier CRD42023471154.

Effects of total glucosides of paeony on serum inflammatory cytokines in animal models of rheumatoid arthritis: a systematic review and meta-analysis.

Background: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic synovitis of the affected joints. Total glucosides of paeony (TGP) capsules have been widely used clinically for the treatment of RA with good efficacy and safety. However, its effect on inflammatory cytokines remains unclear. Objectives: This study aimed to summarize the effect of TGP on the expression level of serum inflammatory cytokines in RA animal models and its potential mechanisms. Methods: Six databases were searched up to 14 August 2023, relevant animal experiment studies were screened, data were extracted, and the SYRCLE animal experiment bias risk assessment tool was used for risk assessment. Results: A total of 24 studies were included, including 581 animals. Results showed that compared with the model control group, TGP decreased the levels of TNF-α, IL-1ß, IL-6, and PGE2 and increased the levels of TGF-ß1 after 1-2 weeks of intervention, decreased the levels of TNF-α, IL-1ß, IL-6, IL-2, IL-17, IL-17α, IL-21, VEGF, IFN-γ and PGE2 and increased the levels of IL-10 and IL-4 after 3-4 weeks of intervention, decreased the levels of TNF-α, IL-6, IL-17α and increased the level of IL-10 after 8 weeks of intervention. There was no significant difference in the effects of TGP on the levels of IL-10, IL-17, and IFN-γ after 1-2 weeks of intervention and IL-1 and TGF-ß1 after 3-4 weeks of intervention. Conclusion: In summary, based on the existing studies, this study found that compared with the control group of the RA animal model, TGP can reduce the levels of serum pro-inflammatory cytokines such as TNF-α, IL-1ß, and IL-6 and increase the levels of serum anti-inflammatory cytokines such as IL-10, exerting an anti-inflammatory effect by regulating and improving the levels of inflammatory cytokines, and thus alleviating the disease. Given the low quality of the included studies and the lack of sufficient evidence, more high-quality studies are still needed to validate the results of this study.

The immunoregulatory effects of total glucosides of paeony in autoimmune diseases.

Total glucoside of paeonia (TGP) and its main active ingredient paeoniflorin, extracted from the Chinese herb Paeonia Lactiflora Pallas, exhibit potent immunomodulatory effects. TGP has been shown to inhibit inflammatory responses and disease progression in experimental models of multiple autoimmune diseases (AIDs), including rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, psoriasis, etc. TGP shows broad immunomodulatory effects on many immune cells such as T cells, macrophages, and dendritic cells, by regulating their activation, proliferation, differentiation, and production of effector molecules. Mechanistically, TGP modulates intracellular signaling transductions including JAK/STAT, NF-κB, MAPK, and PI3K/AKT/mTOR pathways. Moreover, TGP has been applied in the clinical treatment of various AIDs with satisfactory therapeutic outcomes and minor side effects. Thus, available studies have demonstrated that TGP and its bioactive constituents exhibit anti-inflammatory and immunomodulatory functions and may have extensive applications in the treatment of AIDs.

Prolonged administration of total glucosides of paeony improves intestinal immune imbalance and epithelial barrier damage in collagen-induced arthritis rats based on metabolomics-network pharmacology integrated analysis.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial inflammation and joint damage with complex pathological mechanisms. In recent years, many studies have shown that the dysregulation of intestinal mucosal immunity and the damage of the epithelial barrier are closely related to the occurrence of RA. Total glucosides of paeony (TGP) have been used clinically for the treatment of RA in China for decades, while the pharmacological mechanism is still uncertain. The purpose of this study was to investigate the regulatory effect and mechanism of TGP on intestinal immunity and epithelial barrier in RA model rats. The results showed that TGP alleviated immune hyperfunction by regulating the ratio of CD3+, CD4+ and CD8+ in different lymphocyte synthesis sites of the small intestine, including Peyer's patches (PPs), intraepithelial lymphocytes (IELs), and lamina propria lymphocytes (LPLs). Specially, TGP first exhibited immunomodulatory effects on sites close to the intestinal lumen (IELs and LPLs), and then on PPs far away from the intestinal lumen as the administration time prolonged. Meanwhile, TGP restores the intestinal epithelial barrier by upregulating the ratio of villi height (V)/crypt depth (C) and expression of tight junction proteins (ZO-1, occludin). Finally, the integrated analysis of metabolomics-network pharmacology was also used to explore the possible regulation mechanism of TGP on the intestinal tract. Metabolomics analysis revealed that TGP reversed the intestinal metabolic profile disturbance in CIA rats, and identified 32 biomarkers and 163 corresponding targets; network pharmacology analysis identified 111 potential targets for TGP to treat RA. By intersecting the results of the two, three key targets such as ADA, PNP and TYR were determined. Pharmacological verification experiments showed that the levels of ADA and PNP in the small intestine of CIA rats were significantly increased, while TGP significantly decreased their ADA and PNP levels. In conclusion, purine metabolism may play an important role in the process of TGP improving RA-induced intestinal immune imbalance and impaired epithelial barrier.

Combined use of total glucosides of paeony and hydroxychloroquine in primary Sjögren's syndrome: A systematic review.

OBJECTIVE: To assess the effectiveness and safety of the total glucosides of paeony (TGP) combined with hydroxychloroquine (HCQ) on the treatment of primary Sjögren's syndrome (pSS) by conducting a meta-analysis. METHODS: Eight databases were searched for randomized controlled trials (RCTs) reporting the use of TGP combined with HCQ for pSS, which are before May 10, 2022. Meta-analyses were performed on disappeared clinical symptoms (dry mouth and dry eyes), Schirmer's test, saliva flow test, erythrocyte sedimentation rate (ESR), index of immunoglobulin G (IgG), immunoglobulin M (IgM), immunoglobulin A (IgA), and adverse events (AEs). The Revman 5.4 software was used for this meta-analysis. RESULTS: Seven RCTs which included 632 participants were identified. The pooled results showed significant differences in clinical symptoms disappear (dry mouth and dry eyes) (p = .0004), IgM (p < .00001), IgA (p < .00001), salivary flow rate (p < .00001) and Schirmer's test (p = .02) in the comparison of TGP combined with HCQ and HCQ alone. For the IgG and ESR, both pooled and subgroup analyses showed that TGP + HCQ was superior to HCQ alone. For the safety analysis, no significant differences in AEs (p = .39) was revealed. The more frequently seen adverse reactions were diarrhea, vomit and there was no severe adverse events were reported in TGP + HCQ group. CONCLUSION: Therefore, TGP + HCQ can be considered to be a potentially valid and safe combination for the treatment of pSS in the clinic.

Total Glucosides of Paeony Ameliorate Myocardial Injury in Chronic Heart Failure Rats by Suppressing PARP-1.

Total glucosides of paeony (TGP) have a potential protective effect on chronic heart failure (CHF) rats, but the mechanism remains unclear. PARP inhibition prevents the decrease in myocardial contractility. Therefore, we aim to investigate the effects and mechanisms of TGP on CHF and the role of PARP-1 in CHF. Left anterior descending ligation rats and adriamycin-treated H9C9 cells were used as CHF models, and captopril as a positive control for in vivo experiments. We found that TGP alleviated myocardial remodeling and improved cardiac morphology and function. TGP also reduced myocardial apoptosis and autophagy, decreased inflammatory factor release, and inhibited the PARP-1 and NF-κB proteins. Through cell transfection, we found that PAPR-1 knockdown inhibited NF-κB nuclear translocation. Additionally, TGP inhibited apoptosis, autophagy, and inflammation in CHF cells, while PARP-1 overexpression partially antagonized them. In conclusion, TGP has the potential to improve CHF and PARP-1 may be a potential target.

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 1.8 g/day for 24 weeks. Participants were observed for a total of 36 weeks 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, 9.6 days) since weeks 13-24 (median, 18.5 days) (p < 0.05), and after discontinuation, it was further prolonged (median, 24.7 days) 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, 15.9 days) 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 total glucosides of paeony in the treatment of 5 types of inflammatory arthritis: A systematic review and meta-analysis.

OBJECTIVE: To evaluate efficacy and safety of total glucosides of paeony in the treatment of 5 types of inflammatory arthritis METHODS: Databases such as Pubmed, Cochran Library, Embase were searched to collect RCTs about TGP in the treatment of inflammatory arthritis. Then, the RCTs were assessed for risk of bias and RCT data were extracted. Finally, RevMan 5.4 was used for the meta-analysis. RESULTS: A total of 63 RCTs were finally included, involving 5293 participants and 5 types of types of inflammatory arthritis: rheumatoid arthritis (RA), ankylosing spondylitis (AS), osteoarthritis (OA), juvenile idiopathic arthritis (JIA), psoriatic arthritis. For AS, TGP may improve AS disease activity score (ASDAS), decrease erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tumor necrosis factor (TNF)- α and interleukin (IL)- 6; for RA, TGP may improve disease activity of 28 joints (DAS28), decrease ESR, CRP, rheumatoid factor (RF), TNF-α and IL-6; for psoriatic arthritis, TGP may improve psoriasis area and severity index (PASI) and decrease ESR; for OA, TGP may improve visual analogue scale (VAS) and decrease nitric oxide (NO); for JIA, TGP may increase total efficiency rate, decrease ESR, CRP and TNF-α. For safety, RCTs showed that the addition of TGP did not increase adverse events, and may even reduce adverse events. CONCLUSION: TGP may improve symptoms and inflammation levels in patients with inflammatory arthritis. However, due to the low quality and small number of RCTs, large-sample, multi-center clinical trials are still needed for revision or validation.

Total Glucosides of Paeony Regulate Immune Imbalance Mediated by Dermal Mesenchymal Stem Cells in Psoriasis Mice.

OBJECTIVE: To investigate the therapeutic effects of total glucosides of paeony (TGP) on psoriasis based on the immunomodulatory effect of dermal mesenchymal stem cells (DMSCs). METHODS: A total of 30 male BALB/c mice were divided into 6 groups (n=5 in each) by a random number table method, including control, psoriasis model (model, 5% imiquimod cream 42 mg/d), low-, medium- and high-dose TGP (50, 100, and 200 mg/kg, L, M-, and H-TGP, respectively), and positive control group (2.5 mg/kg acitretin). After 14 days of continuous administration, the skin's histopathological changes, apoptosis, secretion of inflammatory cytokines, and proportion of regulatory T cells (Treg) and T helper cell 17 (Th17) were evaluated using hematoxylin-eosin (HE) staining, TdT-mediated dUTP nick end labeling staining, enzyme-linked immunosorbent assay, and flow cytometry, respectively. DMSCs were further isolated from the skin tissues of normal and psoriatic mice, and the cell morphology, phenotype, and cycle were observed. Furthermore, TGP was used to treat psoriatic DMSCs to analyze the effects on the DMSCs immune regulation. RESULTS: TGP alleviated skin pathological injury, reduced epidermis layer thickness, inhibited apoptosis, and regulated the secretion of inflammatory cytokines and the proportion of Treg and Th17 in the skin tissues of psoriatic mice (P<0.05 or P<0.01). There was no significant difference in cell morphology and phenotype between control and psoriatic DMSCs (P>0.05), however, more psoriatic DMSCs remained in G0/G1 phase compared with the normal DMSCs (P<0.01). TGP treatment of psoriatic DMSCs significantly increased cell viability, decreased apoptosis, relieved inflammatory response, and inhibited the expression of toll-like receptor 4 and P65 (P<0.05 or P<0.01). CONCLUSION: TGP may exert a good therapeutic effect on psoriasis by regulating the immune imbalance of DMSCs.

Identification and hepatoprotective activity of total glycosides of paeony with high content of paeoniflorin extracted from Paeonia lactiflora Pall.

The aims of this work were to obtain total glucosides of paeony (TGP) with high content of paeoniflorin and evaluate the hepo-protective properties of TGP. After optimization by response surface methodology, optimized conditions were as follows: extraction time 33.0 min, extraction temperature 48 °C, ethanol content 44%, and the yield of TGP was 47.68 mg/g. Moreover, under established macroporous resin purification, paeoniflorin content of TGP achieved 67.6% in 1.5 L scale-up verification experiment. Purified TGP (p-TGP) was further analyzed by UHPLC-Q-Orbitrap-MS/MS, and 35 compouds including paeoniflorin were identified. The obtained p-TGP effectively reduced biochemical indexes and inflammatory cytokines in liver tissue of acute alcoholic liver injury mice model. Depending on this work, TGP with definitive compound composition exhibited great protective effect against acute alcoholic liver injury in vivo. Furthermore, the finding of this work will be helpful to understand the relationship between compound composition and functional properties of Chinese herb extracts.

Clinical effect of compound phellodendron gargle with total glucosides of paeony capsule in the treatment of erosive oral lichen planus / 药学实践杂志

Objective To observe the short-term clinical effect of compound phellodendron gargle combined with the total glucosides of paeony (TGP) in the treatment of erosive oral lichen planus (OLP). Methods 62 patients were divided into observation group and control group through a designed parallel randomized controlled study. All the patients used the total glucosides of paeony capsule , the patients in the observation group also used the compound phellodendron gargle. The pain condition, the healing condition of face, and the treatment effective in both group were evaluated through physical signs and VAS scores evaluations by SPSS 22.0, which could further evaluate the short-term clinical efficacy of compound phellodendron. Results After 30 days, the scores of VAS and physical signs of each group are much better than before. And the scores of VAS and treatment effective of observation group were significantly better than those of the other control groups (P<0.05). Conclusion The application of phellodendron gargle with total glucosides of paeony capsule could improve the treatment effect of OLP patients and reduce the oral pain , which could be used widely in clinical practice.

Study on the effects and mechanism of total glucosides of paeony on enhancing efficacy and reducing toxicity of Tripterygium wilfordii polyglycoside in the treatment of eczema / 中国药房

OBJECTIVE To investigate the effects of total glucosides of paeony （TGP） on enhancing efficacy and reducing toxicity of Tripterygium wilfordii polyglycoside （TWP） in the treatment of eczema. METHODS Totally 50 SD male rats were collected to establish eczema model by sensitizing with 2，4-dinitrofluorobenzene-acetone olive oil solution （volume ratio was 4∶1） on the abdominal area and provoking on the back and ear. Model rats were randomly divided into model group， loratadine group （0.9 mg/kg）， TWP group （9.45 mg/kg）， TGP group （162 mg/kg） and compatibility group （TWP 9.45 mg/kg+TGP 162 mg/kg）， with 10 rats in each group. Other 10 rats were collected to set as normal group. Three days after the first sensitization， administration groups were given relevant medicine intragastrically， and normal group and model group were given constant volume of 0.1% CMC-Na solution intragastrically， once a day， for consecutive 21 d. Twenty-four hours later after the final administration， the general condition of rats in each group was observed， and the eczema area and severity index （EASI） were scored； ear swelling degree of rats was measured， and the skinhistomorphology observation and pathological score were performed； protein expressions of p38 mitogen-activated 13938427612@126.com protein kinase （p38 MAPK）， phosphorylated p38 MAPK （p- MAPK） and phosphorylation level of p38 MAPK in rat skin tissue were detected； the levels of inflammatory indexes （interleukin-4， interferon- γ）， liver and kidney function indexes [glutamic-pyruvic transaminase （GPT）， glutamic-oxaloacetic transaminase （GOT）， serum creatinine （SCr） and blood urea nitrogen （BUN）] and oxidant stress indexes [total superoxide dismutase （T-SOD） and malondialdehyde （MDA）] were measured. RESULTS Compared with normal group， EASI score， ear swelling degree， pathological score， protein expressions of p38 MAPK and p-p38 MAPK， phosphorylation level of p38 MAPK， the levels of inflammatory indexes and BUN were all increased significantly in model group （P＜0.05）. Compared with model group， EASI scores， ear swelling degree， pathological scores， protein expressions of p38 MAPK and p-p38 MAPK， phosphorylation levels of p38 MAPK and levels of inflammatory indexes were all improved significantly in administration groups （P＜0.05）. The levels of GPT， GOT， SCr and BUN were increased significantly in TWP group， while the serum levels of GOT and SCr in TGP group and serum level of SCr in loratadine group were all decreased significantly （P＜0.05）. The levels of T-SOD in liver and kidney tissue were all decreased significantly in TWP group and compatibility group， while the levels of MDA were increased significantly （P＜0.05）. The compatibility group showed more obvious effect in improving the ear swelling degree， pathological score， p38 MAPK expression and its phosphorylation level and levels of inflammatory indexes， and could reverse the abnormality of liver and kidney indexes caused by TWP （P＜0.05）. CONCLUSIONS The combination of TGP and TWP has the effects of anti-inflammatory， synergistic and hepatorenal detoxification in eczema model rats. Its mechanism may be associated with down-regulating the expression of serum proinflammatory indexes and inhibiting the activation of p38 MAPK pathway.

Total Glucosides of Paeony Regulate Immune Imbalance Mediated by Dermal Mesenchymal Stem Cells in Psoriasis Mice / 中国结合医学杂志

OBJECTIVE@#To investigate the therapeutic effects of total glucosides of paeony (TGP) on psoriasis based on the immunomodulatory effect of dermal mesenchymal stem cells (DMSCs).@*METHODS@#A total of 30 male BALB/c mice were divided into 6 groups (n=5 in each) by a random number table method, including control, psoriasis model (model, 5% imiquimod cream 42 mg/d), low-, medium- and high-dose TGP (50, 100, and 200 mg/kg, L, M-, and H-TGP, respectively), and positive control group (2.5 mg/kg acitretin). After 14 days of continuous administration, the skin's histopathological changes, apoptosis, secretion of inflammatory cytokines, and proportion of regulatory T cells (Treg) and T helper cell 17 (Th17) were evaluated using hematoxylin-eosin (HE) staining, TdT-mediated dUTP nick end labeling staining, enzyme-linked immunosorbent assay, and flow cytometry, respectively. DMSCs were further isolated from the skin tissues of normal and psoriatic mice, and the cell morphology, phenotype, and cycle were observed. Furthermore, TGP was used to treat psoriatic DMSCs to analyze the effects on the DMSCs immune regulation.@*RESULTS@#TGP alleviated skin pathological injury, reduced epidermis layer thickness, inhibited apoptosis, and regulated the secretion of inflammatory cytokines and the proportion of Treg and Th17 in the skin tissues of psoriatic mice (P<0.05 or P<0.01). There was no significant difference in cell morphology and phenotype between control and psoriatic DMSCs (P>0.05), however, more psoriatic DMSCs remained in G0/G1 phase compared with the normal DMSCs (P<0.01). TGP treatment of psoriatic DMSCs significantly increased cell viability, decreased apoptosis, relieved inflammatory response, and inhibited the expression of toll-like receptor 4 and P65 (P<0.05 or P<0.01).@*CONCLUSION@#TGP may exert a good therapeutic effect on psoriasis by regulating the immune imbalance of DMSCs.

Clinical Evaluation of Dexamethasone Plus Gentamycin Mouthwash Use in Combination with Total Glucosides of Paeony for Treatment of Oral Lichen Planus without Fungal Infection: A Comparative Study with Long-Term Follow-Up.

Background: Oral lichen planus (OLP) is a common chronic inflammatory disease of the oral mucosa and considered a potential malignant disease, for which a method for complete cure is lacking. The dexamethasone and gentamicin mouthwash, combined with total glucosides of paeony (TGP), was tested in the treatment of OLP patients without fungal infection, with a view to provide evidence that may assist in resolving the dilemma. Methods: A randomized and single-blind clinical trial of 48 non-erosive and erosive OLP patients was conducted, with the patients divided into two groups. Group A was treated with dexamethasone plus gentamycin mouthwash and Group B received an additional TGP capsule together with the aforementioned mouthwash. All the patients were followed up with four times, at 2 weeks, 1 month, 3 months, and 6 months. The clinical manifestations, sign score, and VAS scale were recorded. The total effective rate (%) was defined as (cases of complete resolution + cases of partial resolution)/total cases observed × 100%. Results: A total of 43 patients completed all follow-up appointments. Among the 21 patients in Group A, the total effective rate was 61.9%. Of the 22 patients in Group B, the total effective rate was 89.66%. The clinical manifestation, sign score, and VAS of the two groups all indicated improvements, and there were significant differences between the two groups (p < 0.05). Conclusions: Dexamethasone plus gentamycin mouthwash combined with TGP treatment for OLP patients is a safe and effective treatment of OLP.

Efficacy and safety of total glucosides of paeony in the treatment of systemic lupus erythematosus: A systematic review and meta-analysis.

Background: Total glucosides of paeony (TGP), extracted from the Chinese medicine Paeonia lactiflora Pall., have been proven to be effective in various autoimmune diseases. We aim to systematically evaluate the efficacy and safety of TGP combined with different conventional therapeutic agents in the treatment of systemic lupus erythematosus (SLE). Methods: Eight databases were searched for randomized controlled studies of TGP for SLE. The search time was set from the establishment of the databases to March 2022. The risk of bias was assessed by the Cochrane Evaluation Manual (5.1.0), RevMan 5.3 software was used for meta-analysis, and the certainty of the evidence was assessed by the GRADE methodology. Results: A total of 23 articles were included, including 792 patients overall in the treatment group and 781 patients overall in the control group. The meta-analysis results showed that TGP combined with conventional treatments was superior to the conventional treatments in reducing the SLE disease activity and the incidence of adverse reactions (SMDTGP+GC+CTX = -1.98, 95% Cl = [-2.50, -1.46], p < 0.001; SMDTGP+GC+HCQ = -0.65, 95% Cl = [-1.04, -0.26], p <0.001; SMDTGP+GC+TAC = -0.94, 95% Cl = [-1.53, -0.34], p < 0.05; SMDTGP+GC = -1.00, 95% Cl = [-1.64, -0.36], p < 0.05; and RRTGP+GC+CTX = 0.37, 95% Cl = [0.21, 0.64], p < 0.001). The results also showed that TGP helped improve other outcomes related to SLE disease activity, such as complement proteins (C3 and C4), immunoglobulins (IgA, IgM and, IgG), ESR, CRP, 24 h urine protein, and recurrence rate. In addition, TGP may also be effective in reducing the average daily dosage of glucocorticoids (GCs) and the cumulative dosage of cyclophosphamide (CTX). The certainty of the evidence was assessed as moderate to low. Conclusion: TGP is more effective and safer when used in combination with different conventional therapeutic agents. It helped reduce the disease activity of SLE and the incidence of adverse reactions. However, we should be cautious about these conclusions as the quality of the evidence is poor. Future studies should focus on improving the methodology. High-quality randomized controlled trials (RCTs) will be necessary to provide strong evidence for the efficacy of TGP for SLE. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42021272481.

Efficacy and safety of total glucosides of paeony as an add-on treatment in adolescents and adults with chronic urticaria: A systematic review and meta-analysis.

Background: Total glycosides of paeony (TGP), an active compound extracted from the dried roots of Paenoia lactiflora Pall., has been widely used to treat chronic urticaria (CU) in China. This study aims to systematically evaluate the efficacy and safety of TGP as an add-on treatment for the treatment of CU in adolescents and adults. Methods: Eight literature databases and two clinical trial registries were searched from their inception to 31 May 2022. Randomized controlled trials on TGP as an add-on treatment for CU in adolescents and adults were included. The Cochrane Collaboration's risk of bias tool was used for the methodological quality assessment, and RevMan 5.3 software and Stata 12.0 software were used for data analyses. Results: A total of 30 studies with 2,973 participants were included in this meta-analysis. The methodological qualities of all included studies were suboptimal. The pooled results showed that TGP combined with H1-antihistamine was superior to H1-antihistamine alone in the cure rate (risk ratio (RR) = 1.54, 95% confidence interval (CI) = 1.39 to 1.71, p < 0.00001), total efficacy rate (RR = 1.33, 95%CI = 1.26 to 1.40, p < 0.00001), urticaria activity score 7 (mean difference (MD) = -4.03, 95%CI = -6.62 to -1.44, p = 0.002), recurrence rate (RR = 0.31, 95%CI = 0.20 to 0.46, p < 0.00001), and the level of IgE in serum (standardized mean difference (SMD) = -1.96, 95%CI = -3.02 to -0.90, p = 0.0003). In terms of safety, the incidence of diarrhea (RR = 6.19, 95%CI = 3.39 to 11.29, p < 0.00001) was significantly increased in the TGP plus H1-antihistamine groups, and no abnormal results of laboratory tests and electrocardiogram were reported in two groups. The qualities of evidences were evaluated as moderate to low. Conclusions: TGP as an add-on treatment could provide a good effect for CU in adolescents and adults with mild and tolerable adverse events. However, in view of poor methodological quality, high-quality and long-term clinical trials are needed in the future to confirm and update the evidence.

Total Glucosides of Paeony Attenuates Ulcerative Colitis via Inhibiting TLR4/NF-κB Signaling Pathway.

The therapeutic effects and mechanisms of action of total glucosides of paeony (TGP) in treating ulcerative colitis remain to be clarified. Mouse model of ulcerative colitis was treated with TGP and the indexes including scores of disease activity index, gross morphologic damage and histological damage, and inflammatory and oxidative stress markers were determined. Patients with ulcerative colitis received TGP capsule therapy and the indexes including efficacy of colonoscopy and histology, scores of Ulcerative Colitis Activity Index (UCAI) and Short Inflammatory Bowel Disease Questionnaire (SIBDQ), and inflammatory parameters were assessed. The expressions of toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) were measured in colonic tissues of mice and patients. TGP treatment significantly increased weight, decreased scores of disease activity index, gross morphologic damage and histological damage, and reduced the levels of tumor necrosis factor-α, interleukin-1ß, malondialdehyde and myeloperoxidase in mouse model. Patients treated with TGP capsule had significantly higher relief rates of diarrhea, abdominal pain, and bloody purulent stool, decreased UCAI and increased SIBDQ scores, and lower levels of erythrocyte sedimentation rate, C-reactive protein and CD4+/CD8+ T-cell ratio than those patients with routine therapy. The overall response rate of TGP capsule was significantly higher than that of routine therapy. TGP treatment significantly suppressed the expressions of TLR4 and NF-κB in colonic tissues of both mouse model and patients with UC. TGP shows a good therapeutic effect on ulcerative colitis in animals and human patients, and the underlying mechanisms may be related to the inhibition of TLR4/NF-κB signaling by TGP.

Successful treatment of Morbihan disease with total glucosides of paeony: A case report.

BACKGROUND: Morbihan disease is a rare cutaneous disorder characterized by non-pitting edema and erythema of the upper two-thirds of the face. In severe cases, orbital and facial contour changes may affect the visual field, and there is no guideline for the standard treatment of this disease. Existing treatment methods have been reported to be associated with long medication cycle, easy recurrence after drug withdrawal, and multiple adverse reactions. CASE SUMMARY: A 55-year-old Chinese woman presented to our hospital with non-pitting edema and erythema of the upper two thirds of her face for 5 mo. Physical examination showed obvious edema and erythema on the upper face. The boundary was unclear, the lesions were hard and non-pitting, and infiltration was obvious by touch. Pathological examination revealed mild hyperkeratosis of the epidermis, nodular inflammatory lesions in the dermis, epithelioid granuloma, and inflammatory cell infiltration with lymphocytes and histiocytes around skin appendages and blood vessels. Alcian blue staining, acid fast staining, silver staining and periodic acid-Schiff staining were negative. The patient was diagnosed with Morbihan disease. She was treated with prednisone acetate and tripterygium wilfordii polyglycoside tablets for 4 mo, and the edema was slightly reduced, but transaminase levels were significantly increased. Compound glycyrrhizin capsules were administered for liver protection for 1 mo; however, facial edema did not significantly improve and transaminase levels continued to increase. Total glucosides of paeony capsules were then administered for 4 mo, and transaminase level returned to normal and the patient's facial edema disappeared completely. CONCLUSION: Total glucosides of paeony has a remarkable effect in Morbihan disease, without adverse reactions.

Total glucosides of paeony inhibits liver fibrosis and inflammatory response associated with cirrhosis via the FLI1/NLRP3 axis.

BACKGROUND: Total glucosides of paeony (TGP) has a myriad of hepatoprotective activities. However, its role in cirrhosis, a major risk factor for hepatocellular carcinoma, remains largely unexplored. Here, we determined the impact of TGP on liver fibrosis and inflammation in mice modeled by carbon tetrachloride with an aim to explore a possible molecular mechanism. METHODS: Liver fibrosis and inflammation in mice were evaluated using ELISA, hematoxylin-eosin, Masson's trichrome, immunohistochemical staining and TUNEL methods. The impact of TGP on gene expression in the liver tissues of the mice was investigated using microarray analysis, showing the most significant increase in expression of friend leukemia integration 1 transcription factor (FLI1). After loss-of-functions assays of FLI1, the downstream gene of FLI1 was searched by bioinformatics analysis and verified. RESULTS: TGP reduced liver tissue damage, inhibited apoptosis, and alleviated liver fibrosis and inflammation in cirrhotic mice. FLI1 was downregulated in the liver of cirrhotic mice and lipopolysaccharide-treated hepatocytes, and TGP promoted the expression of FLI1. FLI1 depletion inhibited the effects of TGP on alleviating liver fibrosis and inflammatory responses in mice. FLI1 repressed Nod-like receptor protein 3 (NLRP3) transcription by binding to its promoter. Further silencing of NLRP3 in the presence of shFLI1 alleviated histopathological changes, inhibited apoptosis, and attenuated liver fibrosis and inflammatory responses in the liver of cirrhotic mice. CONCLUSIONS: TGP promotes the expression of FLI1, which in turn inhibits NLRP3 expression, thereby reducing cirrhosis-induced liver fibrosis and inflammatory response in mice.

Total Glucosides of Paeonia lactiflora for Safely Reducing Disease Activity in Systemic Lupus Erythematosus: A Systematic Review and Meta-Analysis.

Background: Total glucosides of paeony (TGP), extracted from the dried roots of Paeonia lactiflora Pall., are proven to regulate immune function in various rheumatic diseases. We aim to systematically evaluate the efficacy and safety of TGP in reducing disease activity in systemic lupus erythematosus (SLE). Methods: We searched trials in seven electronic databases and two clinical trail registries. Randomized controlled trials (RCTs) evaluating efficacy and safety of TGP for SLE were identified. The Cochrane Risk of Bias Tool 2.0 was used for quality assessment of the included trials, and RevMan 5.4 software was used for meta-analysis. Results: A total of 14 RCTs were included, including 978 participants, 492 in the intervention group and 486 in the control group. Regarding the efficacy of TGP for SLE, results showed that TGP plus conventional treatments (CTs) was superior to CTs alone in reducing disease activity (MD SLEDAI-1m = -3.54, 95% CI = -4.08 to -3.00, p < 0.00001; MD SLEDAI-2m = -3.80, 95% CI = -4.51 to -3.09, p < 0.00001; MD SLEDAI-3m = -1.62, 95% CI = -2.60 to -0.64, p < 0.0001; MD SLEDAI-6m = -1.97, 95% CI = -3.18 to -0.76, p = 0.001). The results also showed that TGP contributed to a betterment in improving other outcomes related to lupus activity, such as ESR, CRP, complement proteins (C3, C4), and immunoglobulins (IgA, IgM). In addition, TGP significantly decreased average daily glucocorticoid dosage and cumulative cyclophosamide dosage, as well as disease recurrence rate. In terms of safety, TGP may reduce the incidence of adverse reactions (RR = 0.51, 95% CI = 0.29 to 0.88, p = 0.01). The certainty of the evidence were assessed as moderate to low. Conclusion: TGP appears potentially effective and generally safe in reducing disease activity in SLE. However, in view of high risk of bias, the findings need to be confirmed in high-quality trials. Systematic Review Registration: https://www.crd.york.ac.uk/prospero, identifier CRD42021274850.