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 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 Improve Renal Injury in Mice with Systemic Lupus Erythematosus by Regulating TLR9/MyD88/NF-κB Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the intervention effect of total glucosides of paeony （TGP） on the renal injury of MRL/lpr mice based on the Toll-like receptor 9 （TLR9）/myeloid differentiation factor 88 （MyD88）/nuclear transcription factor-κB （NF-κB） signaling pathway and explore the immunological mechanism of TGP in preventing and treating systemic lupus erythematosus （SLE）. MethodMRL/lpr female mice of SPF grade were randomly divided into a model group， a dexamethasone group （0.15 g·kg-1）， and high- （0.078 g·kg-1） and low-dose （0.039 g·kg-1） TGP groups， and female C57BL/6J mice were assigned to a blank group， with 7 mice in each group. Mice in each group were treated with corresponding drugs or normal saline by gavage at the same time every day. After 4 weeks， samples were collected. The kidney and spleen were weighed， and the organ index was calculated. Serum creatinine （SCr） and blood urea nitrogen （BUN） levels in each group were detected by biochemical assay. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes in the kidney. The degree of renal fibrosis was evaluated by Masson staining. The serum levels of interleukin （IL）-2， interferon （IFN）-α， IL-4， and anti-nuclear antibody （ANA） were detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA expression of TLR9， MyD88， and NF-κB p65 in renal tissues was detected by real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression of TLR9 and NF-κB p65 in renal tissues was detected by immunofluorescence. The protein expression of TLR9， MyD88， and NF-κB p65 in renal and spleen tissues was tested by Western blot. ResultCompared with the blank group， the model group showed increased SCr， BUN， spleen index， and kidney index （P<0.05）， deteriorated pathological injury and fibrosis in renal tissues， elevated serum levels of IFN-α， IL-4， and ANA， decreased level of IL-2 （P<0.05）， and up-regulated TLR9， MyD88， and NF-κB p65 mRNA and protein levels in the kidney and spleen （P<0.05）. Compared with the model group， the TGP groups displayed reduced SCr， BUN， spleen index， and kidney index （P<0.05）， relieved pathological damage and fibrosis in renal tissues， decreased serum levels of IFN-α， IL-4， and ANA （P<0.05）， increased level of IL-2， and declining mRNA and protein expression levels of TLR9， MyD88， and NF-κB p65 in the kidney and spleen （P<0.05）. ConclusionTGP may inhibit the expression of downstream inflammatory factors to regulate immunity and resist SLE-induced renal injury by regulating the TLR9/MyD88/NF-κB signaling pathway.

Regulatory Mechanism of Total Glucosides of Paeony on Gut Microenvironment in Non-obese Diabetic Mice with Sjogren's Syndrome / 中国实验方剂学杂志

Objective:To investigate the effects of total glucosides of paeony （TGPs） on intestinal motility， barrier function， and gut microbiota in non-obese diabetic （NOD） mice with Sjogren's syndrome （SS）. Method:Thirty NOD mice were randomly assigned into the model group （deionized water）， prebiotic fructo-oligosaccharide （FOS） group （700 mg∙kg^-1）， and the low- （160 mg∙kg^-1）， medium- （320 mg∙kg^-1）， and high-dose （640 mg∙kg^-1） TGP groups， with six mice in each group. Moreover， the BALB/c mice were employed as the normal control and administered with deionized water. The food and water intakes， number of discharged fecal particles， and fecal moisture content were observed to evaluate the effect of TGPs on intestinal motility in SS mice. The levels of <italic>D</italic>-lactate （<italic>D</italic>-Lac） content， diamine oxidase （DAO）， and junction-associated protein zonula occludens-1 （ZO-1） in mouse serum were detected by enzyme linked immunosorbent assay （ELISA）. The fecal samples collected at different time points were determined by spread plate method and gas chromatography for uncovering the intestinal microbial communities and the content of short-chain fatty acids. Result:Compared with the normal group， the model group exhibited decreased food and water intakes （<italic>P</italic><0.01）， weakened intestinal propulsion （<italic>P</italic><0.01）， elevated <italic>D</italic>-Lac and DAO （<italic>P</italic><0.05，<italic>P</italic><0.01）， lowered ZO-1 and SCFAs （<italic>P</italic><0.05，<italic>P</italic><0.01）， and reduced number of intestinal bacteria （<italic>P</italic><0.01）. The comparison with the model group revealed that TGPs significantly increased the number of discharged fecal particles and fecal moisture content （<italic>P</italic><0.05，<italic>P</italic><0.01）， enhanced intestinal propulsion （<italic>P</italic><0.05， <italic>P</italic><0.01）， decreased serum <italic>D</italic>-Lac and DAO levels （<italic>P</italic><0.05，<italic>P</italic><0.01）， and up-regulated ZO-1 expression （<italic>P</italic><0.01）. Apart from increasing the proportions of <italic>Bifidobacterium</italic> and <italic>Lactobacillus</italic> and decreasing the proportion of<italic> Enterobacter </italic>in intestinal flora （<italic>P</italic><0.05，<italic>P</italic><0.01）， TGPs also accelerated the production of acetic acid and butyric acid （<italic>P</italic><0.05，<italic>P</italic><0.01）. Conclusion:TGPs attenuate SS-mediated constipation and restore the impaired intestinal barrier function in mice by increasing fecal moisture content， boosting intestinal motility， regulating intestinal microbial communities， elevating acetic acid and butyric acid levels， and up-regulating tight junction protein expression.

Clinical Efficacy of Shashen Maidongtang Plus Total Glucosides of Paeony Capsule in Treatment of Primary Sjogren's Syndrome with Based on Theory of Fluid Metabolism / 中国实验方剂学杂志

Objective:To investigate the clinical efficacy of Shashen Maidongtang plus total glucosides of paeony capsule on primary Sjogren's syndrome (pSS) based on the theory of fluid metabolism. Method:In this study, 84 patients of Qi-Yin deficiency type pSS admitted in Zhengzhou Chinese Medicine Hospital from January 2018 to January 2019 were divided into observation group (42 cases) and control group (42 cases) on the basis of random number table. The control group was orally given total glucosides of paeony capsule and iguratimod tablet, while the observation group was orally given Shashen Maidongtang combined with glucosides of paeony capsule. After 3 months of continuous treatment to all subjects, the clinical efficacy was evaluated, and side effects were recorded. Before and after the treatment, the saliva flow rate and basal tear secretion Schirmer I test (SIt) value were measured, European League Against Rheumatism Sjogren's syndrome patient reported index and Sjogren's syndrome disease activity index (ESSPRI and ESSDAI) were scored, the erythrocyte sedimentation rate (ESR) was determined by Westergren, and the levels of serum rheumatoid factor (RF) and immunoglobulin (Ig) G were tested by immunoturbidimetry and rate scattering turbidimetry, respectively. Result:The overall effective rate of the observation group was 90.48% (38/42), which was much higher than 69.05% (29/42) of the control group (χ2=5.974，P<0.05). After treatment, the saliva flow rates and SIt values of both groups got significantly increased compared with those before the treatment (P<0.05), but the saliva flow and SIt of the observation group were significantly better than those of the control group over the same period after treatment (P<0.05). After treatment, both groups had a great decrease in ESSPRI and ESSDAI scores compared with those before the treatment (P<0.05), and the above scores of the observation group were dramatically lower than those of the control group over the same period (P<0.05). After treatment, ESR, serum RF, and IgG levels of both groups were significantly lower than those before the treatment (P<0.05), and the observation group showed higher levels of ESR, serum RF and IgG than the control group over the same period after treatment (P<0.05). Side effects were few and mild in both groups. Conclusion:In treating patients of Qi-Yin deficiency type pSS, Shashen Maidongtang plus total glucosides of paeony capsule was proven to be effective generally. It could significantly inhibit excessive inflammation and hyperhumoral immunity in patients, and control their disease activity. This may be related to the effect of Shashen Maidong decoction and its decomposed recipes in correcting body fluid infusion and metabolic disorder in patients of Qi-Yin deficiency type pSS.

Effects of Total Glucosides of Paeonia lactiflora Combined with Cisplatin on Tumor Inhibition and Renal Injury Improvement in Model Rats with Gastric Cancer / 中国药房

OBJECTIVE：To study the improvement effects of total glucosides of Paeonia l actiflora（TGPL）combined with cisplatin on tumor inhibition and renal injury in gastric cancer model rats. METHODS ：Totally 75 rats were divided into control group（normal saline ，i.g.），model group （normal saline ，i.g.），cisplatin group （25 mg/kg，i.p.），TGPL group （200 mg/kg，i.g.）， TGPL+cisplatin group （200 mg/kg TGPL ，i.g.+25 mg/kg cisplatin ，i.p.），with 15 rats in each group. Except for control group ， gastric cancer rat models were established in other groups by subcutaneous inoculation of gastric cancer BGC 823 cell suspension. After modeling ，they were given relevant medicine intraperitoneally/intragastrically ，for consecutive 28 d. The tumor weight and tumor inhibition rate were measured. The apoptosis rate in tumor tissue was detected by flow cytometry ；Western blotting assay was used to detect the levels of Bcl- 2 and Bax in tumor tissue ；ELISA or biochemical analyzer were used to determine the levels of IL-18 and KIM- 1 in urine ，BUN and Scr in serum ，as well as SOD， MDA and GSH in renal tissue ； histopathological 015）changes of renal tissue in rats were detected by HE staining. 65896961。E-mail：taolitianxia999@163.com RESULTS： Compared with control group ， there was no statistical significance in the levels of IL- 18 and KIM- 1 in urine，serum levels of BUN and Scr ，the levels of SOD MDA and GSH in renal tissue of model group （P＞0.05）；no obvious histopathological change was found in renal tissue. Compared with model group ，tumor weight in cisplatin group was decreased significantly ，while cell apoptosis was increased significantly，while expression level of Bax in tumor tissue was increased significantly ，the expression level of Bcl- 2 was decreased significantly（P＜0.05）；the levels of IL- 18 and KIM- 1 in urine ，BUN and Scr in serum and MDA in kidney were increased significantly（P＜0.05）；the levels of SOD and GSH in renal tissue were decreased significantly （P＜0.05）；renal tubules were dilated，vacuoles of epithelial cells in basal layer and cast in renal tubules formed . Compared with cisplatin ，tumor weight in TGPL+cisplatin group was decreased significantly ，while apoptotic rate was increased significantly ，while the level of Bax was increased significantly ，expression level of Bcl- 2 was decreased significantly （P＜0.05）；the levels of IL- 18 and KIM- 1 in urine ， BUN and Scr in serum and MDA in renal tissue were significantly reduced （P＜0.05）；the levels of SOD and GSH in renal tissue were increased significantly （P＜0.05）；there was no tubule dilation ，but vacuoles were occasionally found in basal epithelial cells，and the cast formation in renal tubules was rare. Compared with TGPL group，tumor weight in TGPL +cisplatin group was significantly reduced ，the tumor inhibition rate was significantly increased ，the apoptosis rate was significantly increased ，while the expression level of Bax in tumor tissue was increased significantly ，expression level of Bcl- 2 was decreased significantly （P＜ 0.05）；there was no statistical significance in the levels of IL- 18 and KIM- 1 in urine ，the levels of BUN and Scr in serum ，the levels of SOD ，MDA and GSH in renal tissue （P＞0.05）；a small amount of inflammatory cells infiltrated occasionally in renal tissue. CONCLUSIONS ：TGPL combined with cisplatin can inhibit tumor growth ，promote tumor cell apoptosis and improve renal injury induced by cisplatin.

Clinical Effect of Total Glucosides of Paeonia as the adjuvant therapy on Hematuria and Proteinuria Purpura Nephritis and Its Effect on Serum Cytokines / 中国综合临床

Objective To investigate the efficacy of total glucosides of paeony ( TGP ) in the treatment of hematuria and proteinuria purpura nephritis ( HSPN ) and serum interleukin?6 ( IL?6 ), interleukin?1 beta (IL?1 beta) and interleukin?18 (IL?18).Methods From June 2017 to December 2018, 64 cases of children with primary hematuria and proteinuria purpura nephritis admitted to the department of pediatrics affiliated hospital of Xuzhou medical university were selected as study subjects,and were divided into control group (33 cases) and observation group (31 cases) according to random number method.The children in the control group were given oral administration of poniasone acetate,and the observation group was treated with TGP on the basis of the control group.Both groups received continuous treatment for 4 weeks.Two groups′ before and after treatment expression level of serum interleukin?6, interleukin?1β and interleukin?18,and level of clinic indicator such as Urinary red biood cell (URBC),24 hour urinary protein quantity, urinary immune globulin G ( IGU ), micro?albuminuria ( urinary microalbumin, MAU ), α?Microglobulin (α1?MG) and urinary transferrin ( TFRU) is made a comparison.Results After 4weeks of treatment,the total clinical effective rate of the observation group (93.5%(29／31)) was significantly higher than that of the control group (72.7%(24／33)),and the difference between the two groups was statistically significant (χ2＝4.868,P＜0.05).Before treatment,difference between serum interleukin?6,interleukin?1β and interleukin?18 from two groups and each clinic indicators level has no statistic significance (all P＞0.05) .After treatment,in the observation group,Serum IL?6 ( (16.68±6.83) ng／L and (32.24±6.99) ng／L,t＝12.373),IL?1β((63.83 ±8.97)ng／L and (85.59±9.42) ng／L,t＝9.758),IL?18((64.52±5.46) ng／L and (88.50±5.54) ng／Ll,t＝18.899),24 h urinary protein quantification ( 0.3 (0.21,0.36) g／24 h and 1.0 (0.65,1.23) g／24 h,Z＝－4.861),URBC (15.30 (3.80,36.80)×106／L and 168.9 (58.4, 324.0)×106／L,Z＝－4.840),were lower than before treatment ( all P＜0.05); After treatment, in the control group,Serum IL?6 ((23.62±5.95) pg／ml and (33.44±4.68) pg／ml,t＝9.149),IL?1β ((68.67 ±6.31) pg／ml and (86.59±8.71) pg／ml,t＝10.617),IL?18((71.25±9.69) pg／ml and (89.87±6.68) pg／ml,t＝11.506),24 h urinary protein quantification (0.42 (0.33,0.56) g／24 h and 0.94 (0.74,1.25) g／24 h,Z＝－5.013),URBC ( 57.00 ( 39.25,77.50)×106／L and 145.60 ( 58.20,360.85)×106／L,Z＝－4.762),were lower than before treatment ( all P＜0.05).The difference between the two groups was statistically significant (P＜0.05).Conclusion The adjuvant effect of total glucoside of white peony root on hematuria and proteinuria purpura nephritis is significant, which can reduce the level of hematuria and proteinuria and improve the renal symptoms of children.Its mechanism of action may be to reduce renal inflammation and protect the kidney by down?regulating the expression of serum IL?6,IL?1 and IL?18.

Benefits and Safety of Tripterygium Glycosides and Total Glucosides of Paeony for Rheumatoid Arthritis: An Overview of Systematic Reviews / 中国结合医学杂志

OBJECTIVE@#To summarize the evidence from systematic reviews (SRs) on the benefits and safety of Tripterygium glycosides (TG) and total glucosides of paeony (TGP), commonly used to treat rheumatoid arthritis (RA) in China, for patients with RA.@*METHODS@#SRs of randomized controlled trials (RCTs) on TG or TGP in treating RA were included, by searching 8 databases from their inception until December 2017. Two authors extracted data independently. We assessed the quality of SRs using AMSTAR and graded the quality of evidence according to the GRADE approach.@*RESULTS@#Eleven SRs containing an average of 7.6 RCTs, involving a total of 7,012 participants were included in this overview. On the basis of included SRs, TG and TGP could improve the following indexes for RA patients: American College of Rheumatology (ACR) 20 response rate, ACR50 response rate and ACR70 response rate, swollen joint count, tender joint count, erythrocyte sedimentation rate and C-reactive protein. Moreover, TGP could reduce incidence of hepatotoxicity. The most common adverse effects of TG were gastrointestinal discomfort and gonad toxicity, while for TGP was mild to moderate diarrhea. The overall quality of evidence for these findings ranged from "low" to "moderate".@*CONCLUSIONS@#TG and TGP might be 2 potentially effective complementary and alternative drugs for patients with RA. Nevertheless, due to gonad toxicity, TG should only be considered in elderly patients or patients without reproductive needs. More evidence from high quality RCTs and SRs is warranted to support the use of TG and TGP for RA patients.

Study on Efficacy Enhancing Effects of Compatibility of Aconitum carmichaeli Liposoluble Alkaloids and Total Glucosides of Peony in the Treatment of Wind-Cold-Dampness Type Bi-Syndrome Model Rats / 中国药房

OBJECTIVE： To study the efficacy enhancing effect of compatibility of Aconitum carmichaeli liposoluble alkaloids and total glucosides of peony in the treatment of wind-cold-dampness type bi-syndrome model rats. METHODS： Totally 100 SD male rats were randomly divided into blank group （water）， model group （water）， rotundine group [positive control， 10.0    mg/（kg·d）]， dexamethasone group [positive control， 0.3 mg/（kg·d）]，A. carmichaeli alkaloids low-dose and high-dose groups [A. carmichaeli  liposoluble alkaloid extract 12.5， 25.0 mg/（kg·d）]， total glucosides of peony low-dose and high-dose groups [total glucosides of peony powder 200.0，400.0 mg/（kg·d）]， compatibility low-dose and high-dose groups [A. carmichaeli  liposoluble alkaloid+total glucosides of peony powder were 12.5 mg/（kg·d）+400.0 mg/（kg·d）， 25.0 mg/（kg·d）+800.0 mg/（kg·d） respectively]， with 10 rats in each group. Except for blank group， other groups were given complete Freund’s adjuvant 0.1 mL on the right hind paw and wind-cold-dampness stimulation to induce wind-cold-dampness type bi-syndrome model. Nineteen days after modeling， they were given relevant medicine or water intragastrically， once a day， for consecutive 14 d. The joint tenderness threshold （except for dexamethasone group） and joint swelling index （except for rotundine group） were measured at 0 （before medication）， 3rd and 6th day after administration respectively. HE staining was used to observe the pathological changes of synovial membrane of ankle joint in rats （except for rotundine group）. ELISA assay was used to determine anti-cyclic citrullinated peptide （CCP） antibody in serum of rats （except for rotundine group）， and compatibility index （CI） were calculated. RESULTS： Compared with blank group， joint tenderness threshold of rats were decreased significantly in model group at different time points， while joint swelling index was increased significantly （P＜0.01）. Inflammatory lesions in synovial tissue were obvious， and the content of anti-CCP antibody in serum was significantly increased （P＜0.01）. Compared with model group， the joint tenderness threshold， joint swelling index， synovial tissue pathological changes and anti-CCP antibody content in serum of rats in medication groups were improved in varying degrees， most of the indicators had significant difference （P＜0.05 or P＜0.01）， and the improvement effect of the compatibility groups was better than single component treatment groups. CI value calculated based on anti-CCP antibody content was 0.213，suggesting that the compatibility of the two components had synergistic effect. CONCLUSIONS： The compatibility of A. carmichaeli liposoluble alkaloids and total glucosides of peony in the treatment of wind-cold-dampness type bi-syndrome model rats has analgesia，anti-inflammation and synovial tissue protection， with synergistic efficacy-enhancing effect.

Study on Improvement Effects of Different Proportions of Total Ginsenoside of Ginseng ，Total Glucosides of Moutan Cortex and Paeonol Containing Serum on HUVEC Injury Induced by H 2O2 / 中国药房

OBJECTIVE： To study improvement effects of different proportions of total glucosides of ginseng （TGG）， total glucosides of moutan cortex （TGM） and paeonol containing serum on the injury of human umbilical vein endothelial cells （HUVEC） injury induced by hydrogen peroxide （H2O2）， screen the optimal proportion and investigate its mechanism. METHODS： The rats were randomly divided into blank group （distilled water）， TGG group （TGG， 2.025 g/kg）， TGM group （TGM， 4.05      g/kg） and paeonol group （paeonol， 1.08 g/kg）， with 12 rats in each group. They were given relevant medicine twice a day for consecutive 7 days. 1 h after last medication， the blood samples were collected via abdominal aorta to prepare drug containing serum. Using survival rate of HUVEC as evaluation indexes， different proportions of TGG， TGM and paeonol containing serum as factors， L9（34） orthogonal test was designed to optimize the optimal proportion of 3 kinds of drug containing serum. HUVEC were divided into blank group， model group， TGG group， TGM group， paeonol group and optimal proportion group. Except that blank group were treated with relevant medium， other group were treated with 1.2 mmol/L H2O2 to induce HUVEC injury， and then TGG group （volume fraction of drug containing serum was 0.000 5％）， TGM group （volume fraction of drug containing serum was 0.000 5％）， paeonol group （volume fraction of drug containing serum was 1％） and optimal proportion group were intervened with drug containing serum. The levels of LDH， NO and ET-1 in cells were detected by microplate method and ELISA. RESULTS： The optimal proportion of drug containing serum were TGG 0.000 5％， TGM 0.000 5％ and paeonol 1％. Compared with blank group， the levels of LDH and ET-1 were higher in model group （P＜0.01）， while NO level was lower （P＜0.05）. Compared with model group， the levels of NO were higher in TGG group， TGM group and optimal proportion group （P＜0.01）， while the levels of LDH and ET-1 were lower （P＜0.05 or P＜0.01）. Compared with TGG group， TGM group and paeonol group， the level of LDH was lower in optimal proportion group （P＜0.05 or P＜0.01）， while the level of NO was higher （P＜0.05 or P＜0.01）. CONCLUSIONS： TGG and TGM combined with paeonol can significantly improve HUVEC injury induced by H2O2， and the mechanism of which may be associated with the decrease of LDH and ET-1 and the increase of NO.

Curative effect of leflunomide combined with total glucosides of paeony on rheumatoid arthritis / 中国基层医药

Objective To observe the clinical effect of leflunomide combined with total glucosides of paeony (TGP) on rheumatoid arthritis (RA).Methods From September 2014 to June 2016,83 RA patients in Jiuquan People's Hospital were selected in the research,and according to time sequence seeing doctors,the patients were divided into control group (41 patients) and treatment group (42 patients).The patients of the two groups were orally given leflunomide (20 mg,1 time/d),while the treatment group was added with TGP (0.6 g,3 times/d).The patients of the two groups were treated for one month.The changes of clinical indicators such as RF,ESR,CRP,2-dimer of the two groups before and after treatment were observed.Results Before treatment,the RF,ESR,CRP,2-dimer between the two groups had no statistically significant differences (all P ＞ 0.05).After treatment,the RF,ESR,CRP,2-dimer of treatment group were (76.9 ±25.6)U/L,(18.5 ±6.3)mm/h,(15.4 ±6.3) rmg/L,(5.22 ±4.65) mg/L,respectively,which of the control group were (99.6 ±32.7)U/L,(27.8±8.6) mm/h,(21.7 ±7.8) mg/L,(14.08 ±5.76)mg/L,respectively,the differences between the two groups were statistically significant (t =3.480,5.230,4.680,4.513,all P ＜ 0.05).The total effective rate of the treatment group was 83.33 ％,which was higher than 58.54％ of the control group,the difference was statistically significant (x2 =5.330,P ＜ 0.05).Conclusion The clinical effect of leflunomide combined with TGP in the treatment of RA is better than leflunomide.

Effect of Total Glucosides of White Paeony Capsules on Psychological Ethology and Hypothalamic Neuroendocrine System of Stress Rats / 医药导报

Objective To observe the effects of total glucosides of white paeony(GWP) on psychological ethology and neuroendocrine system of stress rats. Methods Ten male Sprague-Dawley rats were treated as normal control group,the others (n=40) were constructed by isolated custody and chronic unpredictable stimuli to build the model of stress rats.Stress rats were randomly divided into 4 groups:model control group,GWP high dose group and low dose(66,33 mg·kg-1) group,fluoxetine(5. 0 mg·kg-1) group,each group had 10 rats.The changes of rat behavior were monitored by locomotor activity system.The change of emotion was observed by tail suspension test.The pathology change of adrenal was observed by HE staining.The levels of CorT and ACTH in serum were measured by radioimmunoassay.The expression of CRH mRNA of hypothalamic were detected by RT-PCR. Results The activity of the level scoring and vertical scoring of GWP high dose group was obviously improved as compared to that in model control group,while static time was significantly shortened,Adrenal index of GWP groups were increased significantly(P<0.05),thymus index of the treatment group was declined(P<0.05),CorT and ACTH content were decreased (P<0.05) and hypothalamus CRH mRNA of GWP group was decreased(P<0.05). Conclusion The improvement of activity and related hormone anomalous changes were observed in rats treated with GWP.The mechanism of its actions might be involved adjusting the endocrine function,decreasing CorT and ACTH content and the expression of hypothalamic CRH mRNA of stress rats.

Clinical Observation of NB-UVB Combined with Total Glucosides of White Paeony Capsules and Urea Cream in the Treatment of Psoriasis Vulgaris / 中国药房

OBJECTIVE:To observe therapeutic efficacy and safety of NB-UVB combined with Total glucosides of white paeony(TGP)capsules and Urea cream in the treatment of psoriasis vulgaris. METHODS:A total of 75 patients with psoriasis vulgaris in dermatology department of our hospital during Jan. 2015-Dec. 2016 were divided into control group(37 cases)and observation group(38 cases)according to random number table. Control group was given TGP capsules 0.6 g orally,3 times a day,reducing to 0.3 g,3 times a day if diarrhea or stool increased significantly after taking the medicine+Urea cream,smearing on the skin,day and evening,for consecutive 12 weeks. Observation group was additionally given NB-UVB irradiation with initial dose of 0.36 J/cm2,2 min/time,every other day,adjusted according to skin reaction for consecutive 8 weeks,on the basis of control group. Clinical efficacies of 2 groups were observed,and PASI scores before and after treatment and the occurrence of ADR were observed. RESULTS:One patient of observation group withdrew from therapy after suffering from obvious edematous erythema with pain due to irradiation. All patients of control group completed treatment. Total response rate of observation group (86.49%)was significantly higher than that of control group(56.76%),with statistical significance(P<0.05). Before treatment, there was no statistical significance in PASI scores between 2 groups(P>0.05). After treatment,PASI scores of 2 groups were significantly lower than before treatment,and observation group was significantly lower than control group,with statistical significance(P<0.05). There was no statistical significance in total incidence of ADR between 2 groups(P>0.05). CONCLUSIONS:NB-UVB combined with TGP capsules and Urea cream show good therapeutic efficacy and safety for psoriasis vulgaris,and can significantly decrease PASI score of patients.

The Alleviating Effects and the Underlying Mechanism of the Total Glucosides from Paeonia lactiflora on Irritable Bowel Syndrome / 中国药学杂志

OBJECTIVE: To clarify the effect of total glucosides from paeony(PTG) on irritable bowel syndrome (IBS), and to explore the molecular mechanism of PTG on alleviating diarrhea symptoms and abdominal pain.METHODS: The diarrhea model was conducted by exposing rat to restraint stress stimulation and bellyache model was conducted by subcutaneous injection of neostigmine to mice. Based on these two models, the curative effect of PTG on IBS was investigated. To investigate the regulative effects of PTG on Caco-2 cells, the Caco-2 monolayer cell model with barrier dysfunction was established by trypsin stimulation, and the inflammatory Caco-2 cell model was established by interleukin-1β (IL-1β) stimulation.RESULTS: PTG could significantly reduce the frequency of defecation in diarrhea rat model (P<0.05) and relieve abnormal bowel movements in bellyache mice model (P<0.05). After PTG treatment, the TEER value of Caco-2 monolayer was significantly increased (P<0.01), the transmittance of fluorescence yellow was significantly decreased (P<0.001) and the expression of tight junction (ZO-1)protein was notably up-regulated (P<0.001). In addition, the gene and protein expression of nuclear factor profilin kappa B(IκBα)in inflammatory Caco-2 cell model was significantly improved (P<0.001) after PTG treatment.CONCLUSION: PTG significantly ameliorates IBS symptoms by protecting the barrier function of Caco-2 cell monolayer and relieving inflammation of Caco-2 cells.

Preparation and in vitro transdermal diffusion characteristics of Centella asiatica total glucosides liposome / 中草药

Objective To optimize the preparation technology for Centella asiatica total glucosides (CTG) liposome and to investigate its percutaneous permeability in vitro. Methods Liposomes were prepared by reverse-phase evaporation technique. Taking the entrapment efficiency of madecassoside and asiaticoside as indexes, the preparation of liposome was optimized by using single factor and Box-Behnken response surface method. The properties of liposomes including morphology, entrapment efficiency, mean diameter, Zeta potential, and accumulative release were studied. Results The optimal formulation was lecithin-cholesterol (4:1), lecithin-CTG (23.22:1), and organic- aqueous (7:1). The liposome was smooth and spherieal in appearance, mean diameter, and Zeta potential were 201.7 nm and -15.7 mV, respectively. The entrapment efficiency of madecassoside and asiaticoside were 75.85% and 84.94%. The in vitro 12 h accumulative release was 52.10% and 45.97%. The equations for the permeation rate of madecassoside and asiaticoside in liposomes were Q = 67.93 t1/2-50.34, R2 = 0.988, Q = 139.74 t1/2-241.2, R2 = 0.987, respectively. The retention amount in the skin was 76 μg/cm2 and 48.7 μg/cm2, which were 1.56 and 1.18 times higher than those of solution. Conclusion The optimized process is rational, feasible, and good stability. The CTG liposome prepared in this study have the smaller size, the higher encapsulation efficiency, higher retain in skin and obvious sustained-release effects.

Clinical effect of semiconductor laser combined with total glucosides of paeony capsules for the treatment of erosive oral lichen planus / 口腔疾病防治

Objective @# To investigate the short-term clinical effect of semiconductor laser exposure combined with total glucosides of paeony (TGP) capsules for the treatment of erosive oral lichen planus (OLP).@*Methods@#Sixty-four patients with erosive oral lichen planus were randomly divided into two groups: the experimental group and the control group. Patients in the control group were treated with TGP capsules, while patients in the experimental group were treated with TGP capsules and semiconductor laser irradiation. The clinical effects were evaluated 3 months after treatment. The data were analyzed using the SPSS 17.0 software package.@*Results @#Three months after treatment, the effective rate in the experimental group was 90.6%, which was significantly higher than that in the control group (59.4%, χ 2=5.62, P < 0.05). The physical condition and visual analogue scale (VAS) scores in the experimental group were 2.17 ± 1.49 and 1.25 ± 1.29, respectively. The physical condition and VAS scores in the control group were 3.55 ± 1.41 and 2.09 ± 1.24, respectively. The physical condition and VAS scores in both groups were significantly higher after treatment than before (P < 0.05). Three months after treatment, the physical condition score (t=3.805) and VAS score (t=2.655) in the experimental group were significant higher than those in the control group (P < 0.05).@*Conclusion@#Semiconductor laser irradiation combined with TGP capsules can improve the short-term clinical efficacy in the treatment of erosive OLP.

Efficacy and adverse reaction of total glucosides of paeony compared with vitamin B2 in recurrent aphthous ulcers / 中国生化药物杂志

Objective To explore and analyze the clinical efficacy and adverse reactions of total glucosides of paeony (TGP) and vitamin B2 in the treatment of recurrent aphthous ulcers (RAU) . Methods 120 patients of RAU were randomly divided into TGP group and vitamin B2 group, 60 cases in each group. The TGP group received TGP capsules after meals, three times a day, 0.6g/d. Vitamin B2 group received vitamin B2 tablets, three times a day, 5mg/d, 8 weeks for one course. The ulcer change, visual analogue scale (VAS) and efficacy were observed. Results After treatment, the VAS scores were significantly reduced in two groups(P<0.05), and the above indicators of TGP group were better than vitamin B2 group(P<0.05). The total efficacy in TGP group was higher than that in vitamin B2 group (P<0.05). There was minor adverse reactions in TGP group and no significant adverse reactions in vitamin B2 group.Conclusion TGP has good efficacy and safety in the treatment of recurrent aphthous ulcers. The TGP has significant effect than that of vitamin B2.

Research progress of pharmacokinetics and pharmacodynamics of total glucosides of peony in hepatoprotective effects / 中国中药杂志

Total glucosides of peony (TGP), containing the effective components of paeoniflorin (Pae), albiflorin (Alb) and so on, are effective parts of Radix Paeoniae Alba. And it possesses extensive pharmacological actions, one of which is hepatoprotective effect. In recent years, abundant of pharmacokinetics and pharmacodynamics research of TGP in hepatoprotective effects have been performed. However, the relative medicine of TGP in hepatoprotective effect has not been developed for clinical application. In order to provide reference for the development and rational clinical application of TGP, the research progresses of pharmacokinetics and pharmacodynamics of TGP in hepatoprotective effect were summarized in this paper. Pharmacokinetics research has clarified the process of absorption, distribution, metabolism and excretion of TGP in vivo, and liver injury disease can significantly influence its metabolic processes. Pharmacodynamics studies suggested that TGP can protect against acute liver injury, non-alcoholic fatty liver diseases (NAFLD), chronic liver fibrosis and liver cancer. However, the action mechanism and in vivo process about hepatoprotective effects of TGP have not been clearly revealed. How liver injury influences the metabolism of TGP and its integrated regulation through multiple targets need to be further studied. The combined pharmacokinetics and pharmacodynamics studies should be performed in favour of medicine development and clinical application of TGP in hepatoprotective effects.

Study on clinical effects of total glucosides of paeony capsules combined with acitretin and compound flumethasone on psoriasis vulgaris / 医学研究生学报

Objective Psoriasis vulgaris (PV) is easy to prone to recur and hard to cure and little research has been done on combined treatment on PV.The article was to study the clinical effects of total glucosides of paeony capsules (TGP) combined with acitretin and compound flumethasone on PV as well as the peripheral blood cytokine levels.Methods 126 patients with PV who visited our hospital from October 2015 to January 2017 were randomly divided into combined treatment group (63 cases) and control group (63 cases).Both groups were treated with oral acitretin and topical compound flumethasone, what's more, the compound flumethasone group received oral TGP treatment, 8 weeks for a course.The clinical therapeutic effects were evaluated by the levels of peripheral blood IL-17, IL-18, IL-23, TNF-α level, PASI score and percentage of total skin lesions before and after the treatment.Results After the treatment, the concentration of IL-17, IL-18, IL-23 significantly decreased(P<0.05), which was significantly less in combined treatment group compared with control group (IL-17 [61.18±8.91] vs [78.64±7.85], IL-18 [68.56±17.95] vs [79.49±18.64], IL-23 [70.13±12.16] vs [91.18±16.89] pg/ML)(P<0.05).Moreover, the TNF-α level, the PASI score and the percentage of total skin lesions significantly decreased in both groups after treatment(P<0.05), which was significantly less in combined treatment group compared with control group (TNF-α level [14.47±7.53] vs [23.49±8.12]ng/L, PASI score [4.09±1.29] vs [7.29±5.13], the percentage of total skin lesions [6.17±4.59]% vs [8.09±5.18]%) (P<0.05).Conclusion TGP combined with acitretin and compound flumethasone can significantly enhance the clinical therapeutic effects and effectively regulate the levels of the IL-17, IL-18, IL-23 and TNF-α level, which results in treating psoriasis vulgaris.