Total glucosides of paeony attenuates animal psoriasis induced inflammatory response through inhibiting STAT1 and STAT3 phosphorylation

OBJECTIVE Psoriasis is an immune system meditated disease,especially T cells.It disturbed many people around the world and hard to therapy.Paeonia lactiflora Pall has been used as a medicine in china for thousands of years.Recent studies has found that the main component of Paeonia lactiflora Pall can alleviates the immune response in many diseases.In this study,we researched the effects and possible mechanisms of total glucosides of paeony(TGP)on animal psoriasis in order to study the therapeutic effects and mechanisms of TGP in 5%propranolol creaminduced psoriasis in guinea pigs and Imiquimod(IMQ)cream-induced psoriasis in mice.METHODS The effect of TGP was evaluated using a psoriasis-like model of guinea pigs and mice.Ear thickness was accessed,and pathology injury was observed by HE staining.The levels of serum IL-1β,IL-6,IL-12,IL-17,IL-23,TNF-α,and IFN-γ,skin IL-17A,IL-22 and orphan nuclear receptor(RORγt)mRNA expression,proliferating cell nuclear antigen(PCNA),total or phosphorylated signal transducers and activators of transcription(STAT1 and STAT3)were determined by ELISA,real time PCR,immu⁃nohistochemical staining,and Western blotting,respectively.RESULTS Compared with model group,TGP treatment decreased the ear thickness,improved pathology of psoriasis,alleviated IMQ-induced keratinocyte proliferation,reduced the inflammatory cytokine,and downregulated IL-17A,IL-22,and RORγt mRNA in mice.Further study indicated that TGP inhibited STAT1 and STAT3 phosphorylation in lesion skins of psoriasis-like mice.CONCLUSION TGP alleviates the symptoms of psoriasis-like guinea pigs and mice,and the possible mechanism may relate to inhibit T helper 17(TH17)cell differentiation and keratinocytes proliferation by inhibiting STAT1 and STAT3 phosphorylation.

Protective Effects of Total Glucosides of Paeony against the Liver Injury Induced by Anti-tuberculosis Drugs

[Objectives] This study was conducted to elucidate the mechanism of action of total glucosides of paeony （TGP） against the liver injury induced by isoniazid （INH） and rifampicin （RFP）, and to provide experimental evidence for rational use of anti-tuberculosis drugs.[Methods] Liver injury in mice was induced by the combination of INH and RFP in mice. After the mice were given different doses of Total Glucosides of White Paeony Capsules （TGP） for 10 d, the hepatosomatic index, biochemical indices in serum and liver homogenate were measured, and histopathological changes in liver tissue were observed. Glucurolactone was used as the positive control, and 0.9% sodium chloride was used as the negative control in the experiment.[Results] TGP reduced the activities of alanine transaminase （ALT） and aspartate transferase （AST） in serum and the level of malondialdehyde （MDA） in liver tissue, and increased the level of glutathione （GSH） and the activity of superoxidase dismutase （SOD） in liver tissue.[Conclusions] TAP has a protective effect against the liver injury induced by INH and RFP.

Total glucosides of paeony alleviates Sjogren syndrome through inhibiting inflammatory responses in mice

OBJECTIVE To study the therapeutic effects of TGP on SS both in C57BL/6J mice immunized by immu⁃nological induction(SS mice)and NOD/ShiltJNju(NOD)mice.METHODS TGP(180,360,720 mg·kg^-1)was intragastri⁃cally administered for 6 or 16 weeks for SS mice and NOD mice,respectively.Weekly food and water intake,saliva flow,submandibular gland(SMG)and spleen index,and SMG pathology were measured.ELISA was used to evaluate serum interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ)and autoantigens(SSA/Ro,SSB/La,andα-fodrin).Real-time PCR and Luminex liquid suspension chip assay were applied to analyze SMG inflammatory cytokines mRNA TNF-α,IL-17A,CXCL9,CXCL13,and B-cell activating factor(BAFF)and protein(IL-1β,IL-6,TNF-α,and IFN-γ)expres⁃sion.RESULTS Compared with SS mice,TGP(720 mg·kg^-1)treatment increased saliva flow,reduced organ indexes,and decreased serum IL-6 and IFN-γ concentration.TGP(360 mg·kg^-1)treatment decreased serum IFN-γ concentra⁃tion.TGP(180,360,720 mg·kg^-1)treatment improved SMG pathological damage.Compared with NOD mice,the saliva flowincreased from 9 to 15 weeks of administration.After 2 weeks of administration,TGP(720 mg·kg^-1)treatment decreased serum SSA/Ro,SSB/La and a-fodrin concentration,increased SMG index,inhibited SMG IFN-γ concentra⁃tion,and down-regulated SMG TNF-α,IL-17A,CXCL9,CXCL13 and BAFF mRNA expression.TGP(360 mg·kg^-1)treat⁃ment decreased serum SSB/La and a-fodrin,and SMG TNF-α and IFN-γ concentration,and down-regulated SMG TNF-α,IL-17A,CXCL9 and BAFF mRNA expression.TGP(180 mg·kg^-1)treatment decreased serum SSB/La,a-fodrin,and SMG IL-1β concentration,and down-regulated SMG TNF-α,IL-17A and BAFF mRNA expression.After 8 weeks of administration,TGP(180,360,720 mg·kg^-1)treatment increased SMG index,and decreased serum a-fodrin concentra⁃tion.TGP(720 mg·kg^-1)treatment down-regulated mRNA expression of SMG TNF-α,IL-17A,CXCL9,CXCL13,and BAFF.TGP(360 mg·kg^-1)treatment reduced mRNA expression of TNF-α,CXCL9,CXCL13 and BAFF,and concentra⁃tion of IL-6 and TNF-α.TGP(180 mg·kg^-1)treatment down-regulated mRNA expression of TNF-α,CXCL9,and CXCL13,and decreased IL-6 and TNF-αconcentration in SMG.After 16 weeks of administration,TGP(180,360,720 mg·kg^-1)treatment reduced serum SSA/Ro and a-fodrin concentration,increased SMG index,and decreased SMG CXCL13 and BAFF mRNA expression.TGP(360,720 mg·kg^-1)treatment decreased serum SSB/Laconcentration and SMG TNF-α,IL-17A and CXCL9 mRNA expression.Besides,TGP(180,360,720 mg·kg^-1)treatment alleviated the pathological damage of SMG after 2 and 16 weeks of administration.CONCLUSION TGP has a certain therapeutic effect onmice through inhibiting inflammatory responses.

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.

Effect of total glucosides of paeony on serum cytokines in patients with psoriasis and its clinical efficacy:A meta-analysis

Objective:To evaluate the relationship between the changes of inflammatory cytokines and clinical efficacy in patients with psoriasis treated with Total glucosides of paeony by Meta analyses,and to explore the microcosmic mechanism of effective treatment of psoriasis with Total glucosides of paeony from the point of view of evidence-based medicine.Methods:The databases of CNKI,Wanfang,VIP,SinoMed,PuMed,Embase and Cochrane Library were searched by computer,and the time range was from the establishment of the database to May 2020.After screening,data extraction and bias risk assessment,Revman5.3 software was used for statistical analysis.Results:A total of 998 patients were included in 11 clinical studies,including 502 patients in the trial group and 496 patients in the control group.The results of Meta analysis showed that there was significant difference in the expression of cytokines between the two groups(MD=-10.97,95%Cl[-15.56,-6.37]).The effective rate of treatment(OR=3.57,95%Cl[2.58,4.94])and the decrease of PASI score(MD=-4.55,95%Cl[-5.91,-3.20])in the combined use of Total glucosides of paeony group were superior to those in the control group.Conclusion:Total glucosides of paeony can regulate immune and inflammatory response and improve skin lesions by inhibiting the expression of cytokines such as IL-2,IL-8,IL-23 and TNF-αin serum of patients with psoriasis.In view of the low overall quality of the included studies,larger samples and higher quality clinical trials are still needed to obtain more sufficient evidence.

Systematic review/meta-analysis re-evaluation of clinical effects of total glucosides of paeony in the treatment of rheumatoid arthritis

Objective: To re-evaluate the systematic review of Rheumatoid arthritis (RA) treatmentwith total glucosides of paeony (TGP) to provide evidence-based evidence for the treatmentof RA with TGP in the clinic. Methods: A total of eight databases including CNKI, Wan FangData, CBM, VIP, PubMed, Embase, Cochrane Library, and Web of Science were searched bycomputer for the systematic reviews/meta-analyses concerning the treatment of RA withTGP. The retrieval period was from the establishment of the database to May 2, 2022.Literature screening was conducted based on the randomized controlled trial, and thematerials of the included literature were extracted. Using the preferred reporting items forsystematic reviews and meta-analyses statement. The a measurement tool to assesssystematic reviews 2 scale and grades of recommendation, assessment, development, andevaluation system evaluated the reporting quality, methodological quality, and outcomeindicators evidence levels included in the literature. Results: Six systematicreviews/meta-analysis literature were finally included. Evaluation of the preferred reportingitems for systematic reviews and meta-analyses statement showed that the overall reportingquality of included literature was low, and only one piece with high quality was included.The results of the a measurement tool to assess systematic reviews 2 scale evaluationshowed that the qualities of included literature were all low-level and highly low-level. Thegrades of recommendation, assessment, development, and evaluation evidence qualityevaluation showed a total of 39 outcome indicators in the six included literature, and alloutcome indicators were intermediate, low-level, and extremely low in evidence evaluation.Conclusion: Many pieces of evidence show that TGP has certain advantages in alleviatingclinical symptoms, reducing adverse reactions, and reducing hepatotoxicity in the treatmentof RA, but this conclusion lacks high-level evidence to support it, which needs to be provedby more studies in the future.

基于TLR4/NF-κB/NLRP3信号通路探究白芍总苷对自身免疫性甲状腺炎大鼠炎症损伤的影响

目的探讨白芍总苷对自身免疫性甲状腺炎(AIT)大鼠炎症损伤及TLR4/NF-κB/NLRP3通路的影响。方法实验分为对照组(Control)、模型组(Model)、白芍总苷组(TGP)、TLR4抑制剂组(TLR4 inhibitor)和TGP+TLR4激动剂组(TGP+TLR4 agonist),每组各10只。除Control组外,其余各组大鼠采用皮下注射甲状腺球蛋白与弗氏佐剂诱导AIT大鼠模型。给药6周后,苏木精-伊红(HE)染色观察甲状腺组织病理学变化;酶联免疫吸附法(ELISA)测定血清TPOAb、TgAb、TSH、T3、T4、TNF-α、INF-γ、IL-1β、IL-18水平;RT-qPCR和Western blot检测甲状腺组织TLR4/NF-κB/NLRP3信号通路mRNA和蛋白表达。结果与Control组相比,Model组大鼠甲状腺滤泡上皮明显受损,TPOAb、TgAb、TSH、T3、T4、TNF-α、INF-γ、IL-1β、IL-18水平升高(P<0.01),TLR4/NF-κB/NLRP3信号通路mRNA和蛋白表达升高(P<0.01)。与Model组相比,TGP组、TLR4 inhibitor组大鼠甲状腺滤泡上皮损伤减轻,TPOAb、TgAb、TSH、T3、T4、TNF-α、INF-γ、IL-1β、IL-18水平降低(P<0.01),TLR4/NF-κB/NLRP3信号通路mRNA和蛋白表达降低(P<0.01)。与TGP组相比,TGP+TLR4 agonist组大鼠甲状腺滤泡上皮损伤加重,TPOAb、TgAb、TSH、T3、T4、TNF-α、INF-γ、IL-1β、IL-18水平升高(P<0.05或P<0.01),TLR4/NF-κB/NLRP3信号通路mRNA和蛋白表达增加(P<0.05或P<0.01)。结论TGP通过抑制TLR4/NF-κB/NLRP3信号通路,改善甲状腺组织炎症损伤发挥甲状腺保护作用。

白芍总苷胶囊联合艾拉莫德片对原发性干燥综合征患者的临床疗效

目的考察白芍总苷胶囊联合艾拉莫德片对原发性干燥综合征患者的临床疗效。方法80例患者随机分为对照组和观察组,每组40例,对照组给予艾拉莫德片,观察组在对照组基础上加用白芍总苷胶囊,疗程3个月。检测临床疗效、中医证候评分、ESSDAI、ESSPRI、外分泌腺功能指标(泪腺分泌量、自然唾液流率)、IgG、CD4^(+)、CD8^(+)、Th17/Treg、IL-17、TNF-α、不良反应发生率变化。结果观察组总有效率高于对照组(P<0.05)。治疗后,2组中医证候评分、ESSDAI、ESSPRI、IgG、CD8^(+)、Th17/Treg、IL-17、TNF-α降低(P<0.05),外分泌腺功能指标、CD4^(+)升高(P<0.05)。2组不良反应发生率比较,差异无统计学意义(P>0.05)。结论白芍总苷胶囊联合艾拉莫德片可安全有效地调节原发性干燥综合征患者T淋巴细胞水平和Th17/Treg平衡,降低IgG水平,改善免疫功能和临床症状,抑制机体炎症,提高外分泌腺功能。

白芍总苷胶囊联合益生菌芦荟发酵凝胶治疗复发性阿弗他溃疡的疗效分析

目的探讨白芍总苷胶囊联合益生菌芦荟发酵凝胶治疗复发性阿弗他溃疡的临床疗效。方法选取2023年1月至12月在西安市红会医院治疗的复发性阿弗他溃疡患者80例进行随机对照试验,采用随机数字表法分为两组,各40例。对照组男22例、女18例,年龄(31.88±6.12)岁,病程(11.15±2.70)个月,采用益生菌芦荟发酵凝胶治疗,共治疗2周;观察组男20例、女20例,年龄(31.76±6.00)岁,病程(11.22±2.16)个月,采用白芍总苷胶囊联合益生菌芦荟发酵凝胶治疗,共治疗2周。对比两组患者临床疗效、用药后疼痛评分[采用视觉模拟评分法(VAS)]、溃疡面积、炎性因子[肿瘤坏死因子-α(TNF-α)、白细胞介素-2(IL-2)、γ干扰素(IFN-γ)]与不良反应发生情况。统计学方法采用t检验、χ^(2)检验。结果观察组治疗总有效率为95.00%(38/40),高于对照组的80.00%(32/40),差异有统计学意义(χ^(2)=4.114,P=0.043)。治疗前,两组患者VAS评分、溃疡面积及炎性因子水平比较,差异均无统计学意义(均P>0.05)。治疗后,观察组VAS评分及TNF-α、IL-2水平均低于对照组[(1.30±0.22)分比(2.20±0.36)分、(3.58±0.81)g/L比(5.35±1.48)g/L、(0.30±0.07)g/L比(0.62±0.10)g/L],溃疡面积小于对照组[(0.68±0.12)cm^(2)比(1.45±0.28)cm^(2)],FN-γ水平高于对照组[(77.50±12.97)mmol/L比(63.68±12.49)mmol/L],差异均有统计学意义(t=13.492、6.635、16.580、15.986、4.854,均P<0.05)。两组患者不良反应发生率比较,差异无统计学意义(χ^(2)=0.263,P=0.608)。结论白芍总苷胶囊联合益生菌芦荟发酵凝胶治疗复发性阿弗他溃疡可提高治疗效果,减轻疼痛程度与炎性反应,缩小溃疡面积,且不会明显增加不良反应的发生。

白芍总苷缓释干混悬剂质量评价研究

目的:对自制的白芍总苷缓释干混悬剂的质量进行评价。方法:采用制剂学方法、含量测定和释放度测定三大途径评价该制剂质量,其中制剂学方法包括形态考察、沉降体积比(F)和重新分散性实验等;通过线性关系的考察、加样回收实验、精密度实验、重现性实验和稳定性实验进行方法学考察,并对白芍总苷缓释干混悬剂进行含量测定;以对照品芍药苷为指标,按照2020年版《中华人民共和国药典》四部中溶出度测定法的桨法测定该缓释干混悬剂的释放效果。结果:自制的三批白芍总苷缓释干混悬剂F均大于0.90;重新分散次数较少,平均值为4 r/min。方法学考察中线性范围为0.124~0.746μg,精密度实验、重现性实验和稳定性实验相对标准偏差(RSD)均小于2%,说明方法学考察中线性关系良好,精密度较高;加样回收实验中回收率为97.27%~101.56%,说明方法的准确度较高。芍药苷含量为2.51~2.84 mg/g;释放度测定结果显示制剂在12 h内持续释放药物,三批制剂在12 h内释放度平均值为99%。结论:制剂学评价中F均符合2020年版《中华人民共和国药典》口服混悬剂F小于0.90标准,较少的重新分散次数说明该制剂分散性优良;含量测定和释放度测定结果从质量检测角度说明该制剂达到了一定的缓释效果。

白芍及白芍总苷治疗自身免疫性皮肤病的作用及机制研究进展

药理研究表明白芍具有抗炎、免疫调节、保肝、镇痛等作用,在临床上白芍及白芍总苷常用于治疗自身免疫性疾病。随着白芍及白芍总苷在抗炎和免疫调节中的作用机制逐步被认识,它们在免疫相关性、炎症性皮肤病中的临床应用得到了不断扩展,通过抗炎、免疫调节和抗氧化等机制在增效减毒、降低疾病复发率方面发挥重要作用。本文对白芍及白芍总苷治疗免疫相关性、炎症性皮肤病的作用及机制的研究进展进行综述,为其深入研究提供依据。

基于网络药理学探讨白芍总苷治疗类风湿关节炎肺间质纤维化的机制研究

[目的]通过网络药理学结合动物试验探究白芍总苷(TGP)主要药物成分与类风湿关节炎(RA)肺间质纤维化之间的作用靶点,揭示白芍总苷治疗RA肺间质纤维化的分子机制。[方法]通过检索多个数据库,根据2个ADEM参数口服生物利用度(oral bioavailability, OB)>30%、类药性(drug likeness, DL)>0.18,筛选出白芍总苷中的主要活性成分及作用的基因靶点;检索DrugBank、GeneCards、OMIM、TTD、DisGenet等数据库筛选RA和肺间质纤维化的基因靶点,通过UniProt数据库进行靶点蛋白的基因名转换,收集白芍总苷治疗RA和肺间质纤维化的作用靶点。获取化合物和疾病靶点取交集,制作韦恩图;将靶点交集导入到STRING数据库绘制PPI网络图,利用DAVID数据库进行GO功能和KEGG信号通路富集分析,深入分析其治疗类风湿关节炎合并肺间质纤维化的机制。将Wistar大鼠分为空白组、模型组、白芍总苷组和托法替布组,通过测定肺脏指数反映肺脏组织的水肿炎症反应,HE染色观察各组肺组织和踝关节滑膜租住的炎症反应,Masson染色观察肺脏组织的胶原沉积状况。[结果]检索TCMSP数据库,筛选得到85种白芍总苷的药物成分,根据OB>30%、类药性>0.18,共筛选9种主要成分;从DrugBank、DisGenet、OMIM、TTD和GeneCards等数据库筛选RA疾病靶点1 625个,肺间质纤维化的疾病靶点1 930个。通过GO功能和KEGG信号通路富集分析共获得分子功能65条目,细胞组分37条目,生物过程350条目和141个富集通路。通过中药-靶点-通路网络图,将Degree排名前十的肿瘤坏死因子(TNF)、白细胞介素-6(IL6)、AKT丝氨酸/苏氨酸激酶1(AKT1)、血管内皮生长因子A(VEGFA)、基质金属蛋白酶9 (MMP9)、转录因子Jun(JUN)、过氧化物酶体增殖物激活受体γ(PPARG)、胱天蛋白酶3(CASP3)、前列腺素内过氧化物合酶2(PTGS2)、细胞间黏附分子-1(ICAM1)作为白芍总苷治疗RA肺间质纤维化的关键作用靶点。动物试验结果显示,与模型组相比,治疗组的关节炎评分和肺脏指数降低;HE染色发现,白芍总苷组的关节和肺脏组织炎性细胞的浸润减少;Masson染色发现,白芍总苷可减少条索状的纤维化灶,表明白芍总苷不但可治疗RA,还能延缓肺间质纤维化的胶原沉积和减少炎症反应。[结论]白芍总苷通过多种成分作用于炎症反应、免疫调节和细胞分化增殖等方面的多靶点和多通路,通过靶点和通路间的协同相互作用来延缓RA肺间质纤维化疾病的发展进程。

基于NF-κB和STAT3探讨白芍总苷对化学性肝损伤肝阴虚证大鼠的作用机制

[目的]基于核因子-κB(NF-κB)和信号转导和转录激活因子3(STAT3)研究白芍总苷对化学性肝损伤肝阴虚型大鼠的保护作用机制。[方法]将雄性SD大鼠随机分为空白组、模型组、一贯煎组(6.35 g/kg)、白芍总苷组(50 mg/kg)。采用20%四氯化碳(CCL4)橄榄油溶液联合30 mg/kg甲状腺片造模,造模的同时给药,时间为6周。观察大鼠体质量、肛温、摄食量、摄水量、舌面干湿度,以及测定血清环磷酸腺苷(cAMP)、环磷酸鸟苷(cGMP)含量、cAMP/cGMP。测定血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、γ-谷氨酰转肽酶(γ-GT)、碱性磷酸酶(ALP)、总胆红素(TBIL)、总胆汁酸(TBA)的含量变化并取肝脏进行Masson染色评估肝纤维化程度;测定血清白细胞介素-1(IL-1)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、白细胞介素-10(IL-10)、白细胞介素-1受体拮抗剂(IL-1Ra)的水平及大鼠肝脏NF-κB p65、STAT3 mRNA及蛋白水平。[结果]与模型组相比,白芍总苷组体质量上升(P>0.05);白芍总苷组肛温下降(P<0.01),24 h摄食量和饮水量减少(P<0.01),舌面干湿度增加(P<0.01);白芍总苷组cAMP降低,cGMP升高,cAMP/cGMP下降(P<0.01);白芍总苷组ALT、AST、γ-GT、ALP、TBIL均下降(P<0.01),TBA含量无统计意义(P>0.05);白芍总苷组肝纤维化程度明显减轻;白芍总苷组IL-1、IL-6、TNF-α均下降,IL-10、IL-1Ra水平均上升(P<0.05或P<0.01);白芍总苷组NF-κB p65 mRNA和蛋白表达显著下降(P<0.01),STAT3 mRNA和蛋白表达升高(P<0.01)。[结论]研究结果显示,白芍总苷对肝阴虚型肝损伤具有较好的保护作用,可能通过抑制NF-κB的激活,促进STAT3的表达,从而减少促炎细胞因子分泌,增加抗炎细胞因子释放。

白芍总苷对H_(2)O_(2)诱导下黑色素细胞的保护及作用机制

为了探究白芍总苷治疗白癜风的潜在作用机理,对人正常黑色素细胞PIG1进行体外培养,用不同浓度的白芍总苷对细胞进行预处理并施加H_(2)O_(2)刺激,用CCK-8法检测细胞活力,用流式细胞术检测细胞凋亡和活性氧的产生,用蛋白免疫印迹法检测细胞色素c、cleaved caspase-3、cleaved caspase-9含量以及MAPK家族成员p38及其磷酸化的表达.结果显示:①白芍总苷可有效抑制H_(2)O_(2)诱导的PIG1细胞毒性,且呈剂量依赖性;②白芍总苷减少了H_(2)O_(2)诱导的细胞活性氧的产生和细胞色素c的释放,下调了cleaved caspase-3和cleaved caspase-9的激活;③白芍总苷有效阻碍了H_(2)O_(2)诱导的p38 MAPK磷酸化.上述结果表明,白芍总苷可作为一种有效的抗氧化剂,保护黑色素细胞免受H_(2)O_(2)诱导的氧化应激损伤.

白芍总苷调节磷脂酰肌醇3-激酶/蛋白激酶B信号通路对大鼠原发性痛经的改善作用实验研究

目的:探讨白芍总苷(TGP)调节磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)信号通路对大鼠原发性痛经(PDM)的改善作用。方法:将雌性SD大鼠采用随机数字表法分为正常对照组(Nor组)、PDM模型组(PDM组)、低剂量TGP组(TGP-L组)、高剂量TGP组(TGP-H组)和高剂量TGP+PI3K激活剂740Y-P组(TGP-H+740Y-P组),每组12只。除Nor组外,其余各组大鼠采用苯甲酸雌二醇联合缩宫素制备大鼠PDM模型,并分别用50、100 mg/kg TGP干预TGP-L组、TGP-H组大鼠,TGP-H+740Y-P组大鼠另需10 mg/kg 740Y-P干预。末次给药后观察大鼠的扭体反应,记录扭体次数和潜伏期,行扭体反应评分。HE染色观察大鼠子宫组织的病理学变化,行病理学评分。ELISA法检测大鼠子宫组织前列腺素F2α(PGF2α)、前列腺素E2(PGE2)水平以及血清β-内啡肽(β-EP)水平。免疫印迹法测量子宫组织PI3K、Akt表达及其磷酸化水平。结果:与Nor组比较,PDM组子宫病理损伤严重,子宫组织病理学评分、PGF2α以及p-PI3K、p-Akt水平升高,子宫组织PGE2及血清β-EP水平降低(均P<0.05)。与PDM组比较,TGP-L组、TGP-H组大鼠扭体反应潜伏期延长,扭体反应次数减少,扭体反应评分降低,子宫组织病理损伤减轻,子宫组织病理学评分、PGF2α以及p-PI3K、p-Akt水平降低,子宫组织PGE2及血清β-EP水平升高(均P<0.05)。高剂量TGP对大鼠PDM的改善作用更显著,而740Y-P减弱了TGP对大鼠PDM的改善作用。结论:TGP可能通过抑制PI3K/Akt信号通路改善大鼠PDM。

白芍总苷治疗原发性干燥综合征的疗效及安全性Meta分析

[目的]系统评价白芍总苷(TGP)治疗原发性干燥综合征(pSS)的疗效及安全性。[方法]计算机检索中国知网(CNKI)、维普数据库(VIP)、中国生物医学文献数据库(CBM)、万方数据库(Wanfang)、PubMed、EMBASE、Cochrane(截至2022年10月29日),收集TGP治疗pSS的随机对照试验(RCTs)。2名评价人员独立筛选文献、录入数据并进行文献质量评价,采用RevMan 5.4软件进行Meta分析。[结果]共检索到368篇文献,筛选后纳入10项RCTs,包括受试者874例。Meta分析显示,单用TGP治疗pSS时在Schirmer试验[MD=1.31,95%CI(0.74,1.88),P<0.000 01]、唾液流率[MD=0.12,95%CI(0.02,0.21),P=0.02]和红细胞沉降率(ESR)[MD=-7.30,95%CI(-16.64,1.24),P=0.000 4]方面疗效显著,TGP联用西药时在Schirmer试验[MD=1.10,95%CI(0.36,3.17),P=0.01]、唾液流率[MD=-6.96,95%CI(-8.34,-5.57),P<0.000 01]、ESR[MD=-9.87,95%CI(-12.64,-7.10),P<0.000 01]、类风湿因子(RF)[MD=-9.95,95%CI(-13.45,-6.45),P<0.000 01]、C反应蛋白(CRP)[MD=-1.76,95%CI(-2.92,-0.60),P=0.003]、免疫球蛋白G(IgG)[MD=-3.19,95%CI(-4.22,-2.17),P<0.000 01]、IgA[MD=-0.97,95%CI(-1.36,-0.58),P<0.000 01]和IgM[MD=-0.44,95%CI(-0.72,-0.16),P=0.002]方面疗效显著,有效率均显著提高,且不良反应较少,差异均具有统计学意义(P<0.05)。[结论]当前研究证据表明,TGP对于pSS患者在改善外分泌功能(Schirmer试验和唾液流率),降低炎症指数(ESR、RF和CRP)和免疫球蛋白(IgG、Ig A和IgM)方面疗效显著,改善血清γ球蛋白、ESSPRI等指标均具有一定优势,同时其不良反应少且症状较轻,安全性较好。但受纳入研究样本量、方法学质量、结局指标等限制,该结论有待更多高质量研究进行验证。

白芍总苷胶囊联合甲氨蝶呤治疗类风湿关节炎患者的效果

目的:观察白芍总苷胶囊联合甲氨蝶呤治疗类风湿关节炎患者的效果。方法:选取2021年1月—2023年9月蚌埠医科大学第二附属医院收治的71例类风湿关节炎患者作为研究对象,按照随机数表法将患者分为研究组(n=36)和对照组(n=35)。对照组给予甲氨蝶呤治疗,研究组在对照组基础上给予白芍总苷胶囊,比较两组治疗效果、免疫功能、中医症候积分、炎症因子、骨代谢及不良反应。结果:研究组治疗总有效率高于对照组,差异有统计学意义(P<0.05)。治疗后,治疗后,两组CD3^(+)、CD4^(+)、N端骨钙素(N-terminal middle osteocalcin,N-MID)、总I型胶原氨基端延长肽(total typeⅠcollagen amino terminal extension peptide,T-PⅠNP)、骨碱性磷酸酶(bone alkaline phosphatase,BALP)水平高于治疗前,中医症候积分和CD8^(+)、β-骨胶原交联(β-crosslaps,β-CTX)、白细胞介素-6(interleukin-6,IL-6)、红细胞沉降率(erythrocyte sedimentation rate,ESR)、C反应蛋白(C-reactive protein,CRP)水平低于治疗前,且研究组优于对照组,差异有统计学意义(P<0.05)。研究组不良反应发生率高于对照组,但差异无统计学意义(P>0.05)。结论:白芍总苷胶囊联合甲氨蝶呤治疗类风湿关节炎能显著缓解关节炎症刺激,改善机体免疫功能和骨代谢,促进临床症状好转,治疗安全性和实用性较高。

白芍总苷对脂多糖诱导的小鼠急性肺损伤的保护作用及机制

目的探讨白芍总苷(total glucosides of paeony,TGP)治疗急性肺损伤小鼠的效果及机制。方法24只雌性C57小鼠采用数字表法随机分为4组:对照组、脂多糖(lipopolysaccharide,LPS)模型组、白芍总苷组(LPS+TGP)和地塞米松(dexamethasone,DEX)组(LPS+DEX),每组6只。采用LPS(4 ng/kg)经鼻吸入,连续5 d建立小鼠急性肺损伤模型;LPS+TGP组、LPS+DEX组分别给予50 mg·kg^(-1)·d^(-1) TGP和5 mg·kg^(-1)·d^(-1) DEX灌胃;观察记录各组小鼠的体质量变化;取肺组织做苏木精-伊红(hematoxylin-eosin,HE)染色观察肺病理损伤情况;流式细胞术检测外周血、脾脏、肺脏组织树突状细胞(dendritic cell,DC)、中性粒细胞和巨噬细胞比例变化,肺脏组织M1型、M2型巨噬细胞的比例变化;酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)分析支气管肺泡灌洗液中白细胞介素-1β(interleukin-1β,IL-1β)和白细胞介素-6(interleukin-6,IL-6)浓度;实时荧光定量聚合酶链反应(real time quantitative polymerase chain reaction,RT-qPCR)检测肺组织IL-1β、IL-6和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)mRNA表达水平;蛋白印迹法(Western blotting)检测核转录因子-κB p65(nuclear transcription factor-κB p65,NF-κB p65)和磷酸化型核转录因子-κB p65(phospho-nuclear factor-κB p65,pNF-κB p65)蛋白含量。结果TGP和DEX可明显改善LPS引起的小鼠体质量减轻;HE染色显示LPS组小鼠肺脏组织炎性细胞浸润、肺泡间隔破坏和肺泡间质增厚,LPS+TGP组、LPS+DEX组小鼠肺部病理改变程度较LPS组减轻。外周血流式细胞结果显示:与LPS组相比,LPS+TGP组、LPS+DEX组中性粒细胞比例明显降低,DC细胞和巨噬细胞比例无明显改变;脾脏组织流式细胞结果显示:与LPS组相比,LPS+TGP组、LPS+DEX组小鼠中性粒细胞、DC细胞和巨噬细胞比例均显著下降,肺组织流式细胞分析结果显示:与LPS组相比,LPS+TGP组、LPS+DEX组肺组织巨噬细胞比例无明显改变,M1型细胞比例显著下降,M2型巨噬细胞比例升高,中性粒细胞比例下降。ELISA结果显示:与LPS组相比,支气管肺泡灌洗液中IL-6、IL-1β水平明显下降。RT-qPCR结果显示:与LPS组相比,LPS+TGP组和LPS+DEX组肺组织IL-1β、IL-6和TNF-αmRNA表达水平显著下降;Western blotting结果显示:与LPS组相比,LPS+TGP组和LPS+DEX组NF-κB p65蛋白表达无明显改变,而pNF-κB p65蛋白表达较LPS组明显降低。结论TGP改善LPS诱导的急性肺损伤,具体机制可能与其降低外周血、肺脏中性粒细胞和脾脏炎症细胞比例,抑制肺巨噬细胞向M1型极化,抑制NF-κB炎症信号通路激活和炎症因子释放有关。

Total Glucosides of Paeony Regulate Immune Imbalance Mediated by Dermal Mesenchymal Stem Cellsin 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.

白芍总苷胶囊联合来氟米特对类风湿关节炎Th1/Th2细胞平衡和外周血单核细胞TLR4/NF-κB信号通路的影响

目的探讨白芍总苷胶囊联合来氟米特对类风湿关节炎(rheumatoid arthritis,RA)患者辅助性T细胞(helper T cell,Th)1/Th2细胞平衡和外周血单核细胞Toll样受体4(toll-like receptor 4,TLR4)/核因子κB(nuclear factorκB,NF-κB)信号通路的影响。方法按照信封抽签法将锦州医科大学附属第一医院2021年4月至2023年12月期间接收的129例RA患者分为对照组(n=64,来氟米特片治疗)和观察组(n=65,白芍总苷胶囊联合来氟米特片治疗)。对比两组疗效、临床症状、病情评分、疾病相关指标、Th1/Th2细胞平衡和TLR4/NF-κB信号通路相关指标,同时观察两组不良反应发生情况。结果观察组的临床总有效率高于对照组(P<0.05)。与对照组相比,观察组治疗2个月后晨僵时间缩短,关节肿胀数和关节压痛数减少,疼痛视觉模拟量表(visual analog scale of pain,VAS)评分和RA患者病情评价(disease activity score 28,DAS28)评分下降,C反应蛋白、红细胞沉降率、类风湿因子下降,Th2细胞升高,Th1细胞、Th1/Th2下降,TLR4信使核糖核酸(messenger ribonucleic acid,mRNA)、NF-κB mRNA下降(P<0.05)。两组不良反应发生率对比无差异(P>0.05)。结论白芍总苷胶囊联合来氟米特治疗RA患者,可促进患者症状改善,提高临床治疗效果,可能与调节Th1/Th2细胞平衡和抑制外周血单核细胞TLR4/NF-κB信号通路激活有关。