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 ...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.展开更多
[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 experimenta...[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.展开更多
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 admini...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.展开更多
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 fie...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.展开更多
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 microco...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.展开更多
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 ...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.展开更多
A simple, sensitive and specific high performance liquid chromatography-tandem mass spectrometry （HPLC-MS/MS）method combined with solid phase extraction has been developed and validated for the simultaneous quantifi...A simple, sensitive and specific high performance liquid chromatography-tandem mass spectrometry （HPLC-MS/MS）method combined with solid phase extraction has been developed and validated for the simultaneous quantification of paeoniflorinand albiflorin in rats plasma and tissue homogenate after administration of total glycosides of paeony （TGP）. Chromatographicseparation was achieved on a C15 column （150 mmx4.6 mm, 5 pro） with mobile phase consisted of acetonitrile-0.05% formicacid aqueous （20： 80, v/v） at a flow rate of 0.5 mL/min. The analytes were detected with triple-quadrupole mass spectrometer usingturbo ion spray with negative ionization in the multiple reaction-monitoring （MRM） modes. The results of method validationconformed to the requirements for the determination of biological samples. This method was successfully applied to thepharmacokinetics and tissue distribution study of TGP in rats. The results showed that paeonifiorin and albiflorin wereabsorbed and reached peak value quickly, and had the similar pharmacokinetic characteristics. Both of them underwent a rapid andwide distribution in the tissues throughout the whole body, among which stomach was the main distribution tissue. Moreover, theyhad the ability to cross the blood-brain barrier.展开更多
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...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.展开更多
Objective： To assess the effect and adverse reaction of total glucosides of paeony capsule （TGPC） in combining with citirizine for the treatment of chronic urticaria. Methods： A total of 120 patients were assigned...Objective： To assess the effect and adverse reaction of total glucosides of paeony capsule （TGPC） in combining with citirizine for the treatment of chronic urticaria. Methods： A total of 120 patients were assigned to two groups by lottery, 65 in the treated group and 55 in the control group. They all were orally treated with citirizine tablet 10 mg per day, but to the treated group, additional 0.2 g TGPC was given three times per day, the therapeutic course for both groups was 4 weeks. The effectiveness of treatment was observed, and the changes of total symptom score, serum levels of interleukin-4 （IL-4）, and immunoglobulin E （IgE） were measured before and after treatment. Moreover, a follow- up was carded out one month after ending the treatment. Results： The dropped cases were two in the treated group and seven in the control group; so, the study was accomplished on 63 patients in the treated group and 48 patients in the control group. The total effective rate was assessed at 73.02% （46/63） in the treated group, which was significantly higher than 47.92% （23/48） in the control group （P〈0.01）. After treatment, the total symptom score decreased in both groups, but the decrement in the treated group was more significant （P〈0.05）. Serum levels of IL-4 and IgE in the treated group lowered significantly, while the changes in the control group were insignificant, so statistical significant differences were shown between groups （P〈0.01）. A follow-up study showed that the relapse rate in the treated group was 30.00% （6/20）, while that in the control group was 90.00% （9/10）, and the former was lower than the latter （P〈0.01）. Adverse reactions, revealed as drowsiness, dizziness, and weakness, were seen in eight cases and seven cases in the two groups, respectively. Besides, mild diarrhea occurred in two cases of the treated group. Conclusions： The treatment of TGPC combining citirizine shows definite curative effect in treating chronic urticaria, with low relapse rate and without evident adverse reaction. Its therapeutic effect might be realized by means of regulating patients＇ immune function. Besides, the medication should be continued for a rather long peried to achieve the full effect.展开更多
Objective： To observe the efficacy and safety of total glucosides of paeony capsule （TGPC） in patients with mild and moderate alopecia areata. Methods： A total of 86 outpatients were randomly allocated into two gr...Objective： To observe the efficacy and safety of total glucosides of paeony capsule （TGPC） in patients with mild and moderate alopecia areata. Methods： A total of 86 outpatients were randomly allocated into two groups of TGPC （treatment, 44 cases） and compound glycyrrhizin tablet （control, 42 cases）. The treatment group was given oral TGPC, three times daily and 600 mg per time; the control group was given oral compound glycyrrhizin tablets, three times daily and 50 mg per time. In addition, both groups were given 10 mg of vitamin B2 and tapped the bold patches with massage. The treatment course was three months for both groups. Peripheral blood T-cell subsets （CD3^＋CD4^＋, CD3^＋CD8^＋, Th, Ts, Th/Ts） of 10 patients randomly selected from each group respectively were tested before and after three months of treatment. The effectiveness and adverse reaction of all cases were observed each month. The safety was evaluated according to the incidence rate of adverse reaction. Results： In the treatment group, the cured and markedly effective rate was 36.36% （16/44）, 50.00% （22/44） and 68.18% （30/44） at the end of first, second and third month of treatment, respectively, and the incidence rate of adverse reaction was 13.64% （6/44）. In the control group, the cured and markedly effective rate was 38.10% （16/42）, 57.14% （24/42） and 71.43% （30/42）, respectively, and the incidence rate of adverse reaction was 16.67% （7/42）. The cured and markedly effective rate and the incidence rate of adverse reaction were similar in both groups （P〉0.05）. TGPC and compound glycyrrhizin tablet can inhibit CD3^＋CD4^＋ and CD3^＋CD8^＋, and decrease the ratio of Th/Ts （P〈0.05）. Conclusion： TGPC is effective and safe in the treatment of alopecia areata.展开更多
Boiling processing is commonly used in post-harvest handling of White Paeony Root （WPR）, in order to whiten the herbal materials and preserve the bright color, since such WPR is empirically considered to possess a h...Boiling processing is commonly used in post-harvest handling of White Paeony Root （WPR）, in order to whiten the herbal materials and preserve the bright color, since such WPR is empirically considered to possess a higher quality. The present study was designed to investigate whether and how the boiling processing affects overall quality of WPR. First, an ultra-high performance liquid chromatography quadrupole/time-of-flight mass spectrometry-based metabolomics approach coupled with multivariate statistical analysis was developed to compare the holistic quality of boiled and un-boiled WPR samples. Second, ten major components in WPR samples boiled for different durations were quantitatively determined using high performance liquid chromatography to further explore the effects of boiling time on the holistic quality of WPR, meanwhile the appearance of the processed herbal materials was observed. The results suggested that the boiling processing conspicuously affected the holistic quality of WPR by simultaneously and inconsistently altering the chemical compositions and that short-time boiling processing between 2 and 10 rain could both make the WPR bright-colored and improve tile contents of major bioactive components, which were not achieved either without boiling or with prolonged boiling. In conclusion, short-term boiling （2-10 min） is recommended for post-harvest handling of WPR.展开更多
OBJECTIVE: To investigate the mechanism underlying anti-inflammatory and immunoregulatory effect of total glucosides of paeony(TGP) based on toll-like receptor 2(TLR2) mediated tumor necrosis factor(TNF) receptor-asso...OBJECTIVE: To investigate the mechanism underlying anti-inflammatory and immunoregulatory effect of total glucosides of paeony(TGP) based on toll-like receptor 2(TLR2) mediated tumor necrosis factor(TNF) receptor-associated factor 6(TRAF6)/nuclear factor-kappa B(NF-κB) pathway activation in rats with rheumatoid arthritis.METHODS: Adjuvant arthritis(AA) model was developed by complete freund’s adjuvant(CFA) immunization. TGP(100, 50, 25 mg/kg) and celecoxib(2.8 mg/kg) were administered by intragastric administration for 21 d. Right hind paw swelling was assessed every 2 d. After 21 d, synovial changes of the ankle were detected by histopathology. CD4+and CD8+ T cell amounts in peripheral blood were measured by flow-cytometrically. Gene and protein levels of toll-like receptor(TLR)2, TRAF6, tumor necrosis factor ligand superfamily member 6(FASLG)in the spleen were assessed by RT-qPCR and Western Bolt, respectively. Nuclear expression of NF-κB p65 was detected by NF-κB p65 Assay Kit.RESULTS: Paw swelling and synovium lesions were obviously aggravated in AA rats. These symptoms were significantly relieved by TGP.The ratio of CD4+/CD8+ T cell was increased in AA rats, while TGP reduced this increased ratio.Gene and protein levels of splenic TLR2, TFAR6 and FASLG, and nuclear NF-κB p65 in AA rats were significantly increased, but overtly inhibited by TGP.CONCLUSION: These findings suggest that TGP’s anti-inflammatory effect onRA in rats with CFA may be related to the downregulation of TLR2/TRAF6/NF-κB pathway and the regulation of T cell subsets.展开更多
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 ...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.展开更多
Total paeony glycoside（TPG） is obtained from Radix Paeoniae Rubra with a variety of bioactivities. However, the low solubility and bioavailability limit its application. The present study aimed to develop TPG nanocr...Total paeony glycoside（TPG） is obtained from Radix Paeoniae Rubra with a variety of bioactivities. However, the low solubility and bioavailability limit its application. The present study aimed to develop TPG nanocrystals to increase the dissolution and then improve the oral bioavailability. TPG nanocrystals were prepared via precipitation and high-pressure homogenization method. The physical-chemical properties of the optimal TPG nanocrystals in terms of particle size, zeta potential, morphology and crystallinity were evaluated. The results showed that TPG nanocrystals had a mean particle size of（210.2±2.5） nm, a polydispersity index of 0.191±0.033 and a zeta potential of（–22.4±1.2） mV. The result of differential scanning calorimetry showed that the nanocrystals were still in crystalline state after the preparation procedure. Transmission electron microscopy（TEM） results showed that the nanosuspension was in spherical shape. The pharmacokinetics of TPG nanocrystals for rats was investigated by liquid chromatography-tandem mass spectroscopy（LC-MS/MS）. Compared with the TPG coarse suspension, TPG nanocrystals exhibited significant increase in AUC0–∞（approximately 1.85-fold）. Taken together, TPG nanocrystals could be used as a promising drug delivery system due to the enhanced oral bioavailability of TPG.展开更多
Objective:To explore and validate the potential targets of Paeoniae Radix Alba(P.Radix,Bai Shao)in protecting against chemical liver injury through network pharmacology,molecular docking technology,and in vitro cell e...Objective:To explore and validate the potential targets of Paeoniae Radix Alba(P.Radix,Bai Shao)in protecting against chemical liver injury through network pharmacology,molecular docking technology,and in vitro cell experiments.Methods:Network pharmacology was used to identify the common potential targets of P.Radix and chemical liver injury.Molecular docking was used to fit the components,which were subsequently verified in vitro.A cell model of hepatic fibrosis was established by activating hepatic stellate cell(HSC)-LX2 cells with 10 ng/mL transforming growth factor-β1.The cells were exposed to different concentrations of total glucosides of paeony(TGP),the active substance of P.Radix,and then evaluated using the cell counting kit-8 assay,enzyme-linked immunosorbent assay,and western blot.Results:Analysis through network pharmacology revealed 13 key compounds of P.Radix,and the potential targets for preventing chemical liver injury were IL-6,AKT serine/threonine kinase 1,jun protooncogene,heat shock protein 90 alpha family class A member 1(HSP90AA1),peroxisome proliferator activated receptor gamma(PPARG),PTGS2,and CASP3.Gene Ontology(GO)enrichment analysis indicated the involvement of response to drugs,membrane rafts,and peptide binding.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis revealed that the main pathways involved lipid and atherosclerosis and chemical carcinogenesis-receptor activation.Paeoniflorin and albiflorin exhibited strong affinity for HSP90AA1,PTGS2,PPARG,and CASP3.Different concentrations of TGP can inhibit the expression of COL-I,COL-III,IL-6,TNF-a,IL-1β,HSP-90a,and PTGS2 while increasing the expression of PPAR-γand CASP3 in activated HSC-LX2 cells.Conclusion:P.Radix primarily can regulate targets such as HSP90AA1,PTGS2,PPARG,CASP3.TGP,the main active compound of P.Radix,protects against chemical liver injury by reducing the inflammatory response,activating apoptotic proteins,and promoting the apoptosis of activated HSCs.展开更多
Objective： To investigate the effects and mechanism of the active components of Red Paeonia and Fthizoma chuanxiong （Xiongshao Capsule, 芎芍胶囊, XSC） on angiogenesis in atherosclerosis plaque in rabbits. Metbods：...Objective： To investigate the effects and mechanism of the active components of Red Paeonia and Fthizoma chuanxiong （Xiongshao Capsule, 芎芍胶囊, XSC） on angiogenesis in atherosclerosis plaque in rabbits. Metbods： Fifty New Zealand rabbits were randomly divided into the normal group, the model group, and the three medicated groups treated respectively with Simvastatin （2.5 mg/kg per day）, low-dose （0.24 g/kg per day） and high-dose （0.48 g/kg per day） XSC, 10 in each group. Rabbits in the normal group were fed with regular diet. To those in the other four groups, high fat diet was given, and a balloon angioplasty was performed two weeks later to establish abdominal aortic atherosclerosis model. Then, the model rabbits were fed continuously with high fat diet, and to those in the medicated groups, the testing drugs were added in the forage correspondingly for 6 successive weeks. Levels of blood lipids were measured at the end of the experiment. Meantime, serum levels of high sensitivity C-reactive protein （hsCRP） and tumor necrosis factor α （TNF-α） were detected with enzyme-linked immunoassay; the plaque area （PA）, cross-sectional vascular area （CVA） and correcting plaque area （PNCVA） were determined quantitatively using imaging software; and the protein expression of vascular endothelial growth factor （VEGF） and factor Ⅷ related antigen （FⅧRAg） in plaque was detected using immunohistochemical method. Results： As compared with the model group, the content of total cholesterol （TC） in the three medicated groups, and contents of triglyceride （TG） and low-density lipoprotein cholesterol （LDL-C） in the Simvastatin group were lower to various extents （P〈0.05, P〈0.01）. The serum level of hsCRP in all modeled rabbits was higher than that in the normal group, but in the three treated groups it was significantly lower than that in the model group （P〈0.05, P〈0.01）. Expressions of VEGF and FⅧRAg, as well as PNCVA in the three medicated groups were significantly lower than those in the model control group （P〈0.05, P〈0.01）. Conclusion： The active components of Red Paeonia and Rhizoma chuanxiong have definite effects in delaying the genesis and development of atherosclerosis, its mechanism might be related with the inhibition on angiogenesis in plaque, and also with its actions of lipo-metabolism regulation and anti-inflammation.展开更多
基金China Pharmaceutical University "Double First-Class" University project(CPU2018GY32)National Science and Technology Major Project of China(2016ZX09101031)
文摘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.
基金Supported by Student Research Training Program of Jiaxing University(85171737)
文摘[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.
文摘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.
文摘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.
基金Special of State Key Laboratory of TCM Wet Syndrome(No.SZ2020ZZ15)。
文摘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.
基金National Natural Science Foundation of China(NO.81804050)Henan province traditional Chinese medicine scientific research special major subject(NO.20-21ZYZD05)Henan province traditional Chinese medicine scientific research special general subject(NO.2022ZY1062).
文摘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.
基金Natural Science Foundation of Hebei Province of China(Grant No.C2011206158,08B031)Hundreds of Innovative Talents Project of Hebei Education Department of China
文摘A simple, sensitive and specific high performance liquid chromatography-tandem mass spectrometry （HPLC-MS/MS）method combined with solid phase extraction has been developed and validated for the simultaneous quantification of paeoniflorinand albiflorin in rats plasma and tissue homogenate after administration of total glycosides of paeony （TGP）. Chromatographicseparation was achieved on a C15 column （150 mmx4.6 mm, 5 pro） with mobile phase consisted of acetonitrile-0.05% formicacid aqueous （20： 80, v/v） at a flow rate of 0.5 mL/min. The analytes were detected with triple-quadrupole mass spectrometer usingturbo ion spray with negative ionization in the multiple reaction-monitoring （MRM） modes. The results of method validationconformed to the requirements for the determination of biological samples. This method was successfully applied to thepharmacokinetics and tissue distribution study of TGP in rats. The results showed that paeonifiorin and albiflorin wereabsorbed and reached peak value quickly, and had the similar pharmacokinetic characteristics. Both of them underwent a rapid andwide distribution in the tissues throughout the whole body, among which stomach was the main distribution tissue. Moreover, theyhad the ability to cross the blood-brain barrier.
基金Supported by the National Natural Science Foundation of China(No.81673941,81603588 and 81804042)
文摘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.
文摘Objective： To assess the effect and adverse reaction of total glucosides of paeony capsule （TGPC） in combining with citirizine for the treatment of chronic urticaria. Methods： A total of 120 patients were assigned to two groups by lottery, 65 in the treated group and 55 in the control group. They all were orally treated with citirizine tablet 10 mg per day, but to the treated group, additional 0.2 g TGPC was given three times per day, the therapeutic course for both groups was 4 weeks. The effectiveness of treatment was observed, and the changes of total symptom score, serum levels of interleukin-4 （IL-4）, and immunoglobulin E （IgE） were measured before and after treatment. Moreover, a follow- up was carded out one month after ending the treatment. Results： The dropped cases were two in the treated group and seven in the control group; so, the study was accomplished on 63 patients in the treated group and 48 patients in the control group. The total effective rate was assessed at 73.02% （46/63） in the treated group, which was significantly higher than 47.92% （23/48） in the control group （P〈0.01）. After treatment, the total symptom score decreased in both groups, but the decrement in the treated group was more significant （P〈0.05）. Serum levels of IL-4 and IgE in the treated group lowered significantly, while the changes in the control group were insignificant, so statistical significant differences were shown between groups （P〈0.01）. A follow-up study showed that the relapse rate in the treated group was 30.00% （6/20）, while that in the control group was 90.00% （9/10）, and the former was lower than the latter （P〈0.01）. Adverse reactions, revealed as drowsiness, dizziness, and weakness, were seen in eight cases and seven cases in the two groups, respectively. Besides, mild diarrhea occurred in two cases of the treated group. Conclusions： The treatment of TGPC combining citirizine shows definite curative effect in treating chronic urticaria, with low relapse rate and without evident adverse reaction. Its therapeutic effect might be realized by means of regulating patients＇ immune function. Besides, the medication should be continued for a rather long peried to achieve the full effect.
文摘Objective： To observe the efficacy and safety of total glucosides of paeony capsule （TGPC） in patients with mild and moderate alopecia areata. Methods： A total of 86 outpatients were randomly allocated into two groups of TGPC （treatment, 44 cases） and compound glycyrrhizin tablet （control, 42 cases）. The treatment group was given oral TGPC, three times daily and 600 mg per time; the control group was given oral compound glycyrrhizin tablets, three times daily and 50 mg per time. In addition, both groups were given 10 mg of vitamin B2 and tapped the bold patches with massage. The treatment course was three months for both groups. Peripheral blood T-cell subsets （CD3^＋CD4^＋, CD3^＋CD8^＋, Th, Ts, Th/Ts） of 10 patients randomly selected from each group respectively were tested before and after three months of treatment. The effectiveness and adverse reaction of all cases were observed each month. The safety was evaluated according to the incidence rate of adverse reaction. Results： In the treatment group, the cured and markedly effective rate was 36.36% （16/44）, 50.00% （22/44） and 68.18% （30/44） at the end of first, second and third month of treatment, respectively, and the incidence rate of adverse reaction was 13.64% （6/44）. In the control group, the cured and markedly effective rate was 38.10% （16/42）, 57.14% （24/42） and 71.43% （30/42）, respectively, and the incidence rate of adverse reaction was 16.67% （7/42）. The cured and markedly effective rate and the incidence rate of adverse reaction were similar in both groups （P〉0.05）. TGPC and compound glycyrrhizin tablet can inhibit CD3^＋CD4^＋ and CD3^＋CD8^＋, and decrease the ratio of Th/Ts （P〈0.05）. Conclusion： TGPC is effective and safe in the treatment of alopecia areata.
基金supported by a special fund of China State Administration of Traditional Chinese Medicine(No.201307008-2)National High Technology Research and Development Plan of China(863 Plain)(No.2014AA022204)+1 种基金Jiangsu Province Six Talent Project(YY-007)Jiangsu Branch of China Academy of Chinese Medical Science(No.JSBN1301)
文摘Boiling processing is commonly used in post-harvest handling of White Paeony Root （WPR）, in order to whiten the herbal materials and preserve the bright color, since such WPR is empirically considered to possess a higher quality. The present study was designed to investigate whether and how the boiling processing affects overall quality of WPR. First, an ultra-high performance liquid chromatography quadrupole/time-of-flight mass spectrometry-based metabolomics approach coupled with multivariate statistical analysis was developed to compare the holistic quality of boiled and un-boiled WPR samples. Second, ten major components in WPR samples boiled for different durations were quantitatively determined using high performance liquid chromatography to further explore the effects of boiling time on the holistic quality of WPR, meanwhile the appearance of the processed herbal materials was observed. The results suggested that the boiling processing conspicuously affected the holistic quality of WPR by simultaneously and inconsistently altering the chemical compositions and that short-time boiling processing between 2 and 10 rain could both make the WPR bright-colored and improve tile contents of major bioactive components, which were not achieved either without boiling or with prolonged boiling. In conclusion, short-term boiling （2-10 min） is recommended for post-harvest handling of WPR.
基金Supported by Natural Science Foundation of China(No.81273900):Studies on Epigenetic Mechanisms Associated with the Classical Decoction of HanBi(Wutou Decoction)and ReBi(Baihu Plus Guizhi Decoction)Natural Science Foundation of China(No.81773972):Based on succinate/GPR91 Pathway Connected Abnormal Glucose Metabolism Exacerbates Inflammation to Investigate the"Dispelling Pyretic Arthralgia"Mechanism of Baihu Guizhi Decoction
文摘OBJECTIVE: To investigate the mechanism underlying anti-inflammatory and immunoregulatory effect of total glucosides of paeony(TGP) based on toll-like receptor 2(TLR2) mediated tumor necrosis factor(TNF) receptor-associated factor 6(TRAF6)/nuclear factor-kappa B(NF-κB) pathway activation in rats with rheumatoid arthritis.METHODS: Adjuvant arthritis(AA) model was developed by complete freund’s adjuvant(CFA) immunization. TGP(100, 50, 25 mg/kg) and celecoxib(2.8 mg/kg) were administered by intragastric administration for 21 d. Right hind paw swelling was assessed every 2 d. After 21 d, synovial changes of the ankle were detected by histopathology. CD4+and CD8+ T cell amounts in peripheral blood were measured by flow-cytometrically. Gene and protein levels of toll-like receptor(TLR)2, TRAF6, tumor necrosis factor ligand superfamily member 6(FASLG)in the spleen were assessed by RT-qPCR and Western Bolt, respectively. Nuclear expression of NF-κB p65 was detected by NF-κB p65 Assay Kit.RESULTS: Paw swelling and synovium lesions were obviously aggravated in AA rats. These symptoms were significantly relieved by TGP.The ratio of CD4+/CD8+ T cell was increased in AA rats, while TGP reduced this increased ratio.Gene and protein levels of splenic TLR2, TFAR6 and FASLG, and nuclear NF-κB p65 in AA rats were significantly increased, but overtly inhibited by TGP.CONCLUSION: These findings suggest that TGP’s anti-inflammatory effect onRA in rats with CFA may be related to the downregulation of TLR2/TRAF6/NF-κB pathway and the regulation of T cell subsets.
基金Supported by Hebei Provincial Administration of Traditional Chinese Medicine(No.2020016)。
文摘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.
基金Innovation Team Project(Grant No.LT2015011)from the Education Department of Liaoning ProvinceImportant Sci entific and Technical Achievements Transformation Project(Gr ant No.Z17-5-078)+1 种基金Applied Basic Research Project(Grant No.F16205144)of Science and Technology Bureau of Shenyangthe Liaoning Provincial Education Department Project of China(Grant No.L2015192)
文摘Total paeony glycoside（TPG） is obtained from Radix Paeoniae Rubra with a variety of bioactivities. However, the low solubility and bioavailability limit its application. The present study aimed to develop TPG nanocrystals to increase the dissolution and then improve the oral bioavailability. TPG nanocrystals were prepared via precipitation and high-pressure homogenization method. The physical-chemical properties of the optimal TPG nanocrystals in terms of particle size, zeta potential, morphology and crystallinity were evaluated. The results showed that TPG nanocrystals had a mean particle size of（210.2±2.5） nm, a polydispersity index of 0.191±0.033 and a zeta potential of（–22.4±1.2） mV. The result of differential scanning calorimetry showed that the nanocrystals were still in crystalline state after the preparation procedure. Transmission electron microscopy（TEM） results showed that the nanosuspension was in spherical shape. The pharmacokinetics of TPG nanocrystals for rats was investigated by liquid chromatography-tandem mass spectroscopy（LC-MS/MS）. Compared with the TPG coarse suspension, TPG nanocrystals exhibited significant increase in AUC0–∞（approximately 1.85-fold）. Taken together, TPG nanocrystals could be used as a promising drug delivery system due to the enhanced oral bioavailability of TPG.
基金supported by the National Natural Science Foundation of China(82074036).
文摘Objective:To explore and validate the potential targets of Paeoniae Radix Alba(P.Radix,Bai Shao)in protecting against chemical liver injury through network pharmacology,molecular docking technology,and in vitro cell experiments.Methods:Network pharmacology was used to identify the common potential targets of P.Radix and chemical liver injury.Molecular docking was used to fit the components,which were subsequently verified in vitro.A cell model of hepatic fibrosis was established by activating hepatic stellate cell(HSC)-LX2 cells with 10 ng/mL transforming growth factor-β1.The cells were exposed to different concentrations of total glucosides of paeony(TGP),the active substance of P.Radix,and then evaluated using the cell counting kit-8 assay,enzyme-linked immunosorbent assay,and western blot.Results:Analysis through network pharmacology revealed 13 key compounds of P.Radix,and the potential targets for preventing chemical liver injury were IL-6,AKT serine/threonine kinase 1,jun protooncogene,heat shock protein 90 alpha family class A member 1(HSP90AA1),peroxisome proliferator activated receptor gamma(PPARG),PTGS2,and CASP3.Gene Ontology(GO)enrichment analysis indicated the involvement of response to drugs,membrane rafts,and peptide binding.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis revealed that the main pathways involved lipid and atherosclerosis and chemical carcinogenesis-receptor activation.Paeoniflorin and albiflorin exhibited strong affinity for HSP90AA1,PTGS2,PPARG,and CASP3.Different concentrations of TGP can inhibit the expression of COL-I,COL-III,IL-6,TNF-a,IL-1β,HSP-90a,and PTGS2 while increasing the expression of PPAR-γand CASP3 in activated HSC-LX2 cells.Conclusion:P.Radix primarily can regulate targets such as HSP90AA1,PTGS2,PPARG,CASP3.TGP,the main active compound of P.Radix,protects against chemical liver injury by reducing the inflammatory response,activating apoptotic proteins,and promoting the apoptosis of activated HSCs.
基金Supported by the Major State Basic Research Development Program of China(973 Program,No.2006CB504803)
文摘Objective： To investigate the effects and mechanism of the active components of Red Paeonia and Fthizoma chuanxiong （Xiongshao Capsule, 芎芍胶囊, XSC） on angiogenesis in atherosclerosis plaque in rabbits. Metbods： Fifty New Zealand rabbits were randomly divided into the normal group, the model group, and the three medicated groups treated respectively with Simvastatin （2.5 mg/kg per day）, low-dose （0.24 g/kg per day） and high-dose （0.48 g/kg per day） XSC, 10 in each group. Rabbits in the normal group were fed with regular diet. To those in the other four groups, high fat diet was given, and a balloon angioplasty was performed two weeks later to establish abdominal aortic atherosclerosis model. Then, the model rabbits were fed continuously with high fat diet, and to those in the medicated groups, the testing drugs were added in the forage correspondingly for 6 successive weeks. Levels of blood lipids were measured at the end of the experiment. Meantime, serum levels of high sensitivity C-reactive protein （hsCRP） and tumor necrosis factor α （TNF-α） were detected with enzyme-linked immunoassay; the plaque area （PA）, cross-sectional vascular area （CVA） and correcting plaque area （PNCVA） were determined quantitatively using imaging software; and the protein expression of vascular endothelial growth factor （VEGF） and factor Ⅷ related antigen （FⅧRAg） in plaque was detected using immunohistochemical method. Results： As compared with the model group, the content of total cholesterol （TC） in the three medicated groups, and contents of triglyceride （TG） and low-density lipoprotein cholesterol （LDL-C） in the Simvastatin group were lower to various extents （P〈0.05, P〈0.01）. The serum level of hsCRP in all modeled rabbits was higher than that in the normal group, but in the three treated groups it was significantly lower than that in the model group （P〈0.05, P〈0.01）. Expressions of VEGF and FⅧRAg, as well as PNCVA in the three medicated groups were significantly lower than those in the model control group （P〈0.05, P〈0.01）. Conclusion： The active components of Red Paeonia and Rhizoma chuanxiong have definite effects in delaying the genesis and development of atherosclerosis, its mechanism might be related with the inhibition on angiogenesis in plaque, and also with its actions of lipo-metabolism regulation and anti-inflammation.
