Effects of intranasal administration of tripterygium glycoside-bearing liposomes on behavioral cognitive impairment of mice induced by central nervous system inflammation / 中国中药杂志

Tripterygium glycosides liposome(TPGL) were prepared by thin film-dispersion method, which were optimized accor-ding to their morphological structures, average particle size and encapsulation rate. The measured particle size was(137.39±2.28) nm, and the encapsulation rate was 88.33%±1.82%. The mouse model of central nervous system inflammation was established by stereotaxic injection of lipopolysaccharide(LPS). TPGL and tripterygium glycosides(TPG) were administered intranasally for 21 days. The effects of intranasal administration of TPG and TPGL on behavioral cognitive impairment of mice due to LPS-induced central ner-vous system inflammation were estimated by animal behavioral tests, hematoxylin-eosin(HE) staining of hippocampus, real-time quantitative polymerase chain reaction(RT-qPCR) and immunofluorescence. Compared with TPG, TPGL caused less damage to the nasal mucosa, olfactory bulb, liver and kidney of mice administered intranasally. The behavioral performance of treated mice was significantly improved in water maze, Y maze and nesting experiment. Neuronal cell damage was reduced, and the expression levels of inflammation and apoptosis related genes [tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), BCL2-associated X(Bax), etc.] and glial activation markers [ionized calcium binding adaptor molecule 1(IBA1) and glial fibrillary acidic protein(GFAP)] were decreased. These results indicated that liposome technique combined with nasal delivery alleviated the toxic side effects of TPG, and also significantly ameliorated the cognitive impairment of mice induced by central nervous system inflammation.

Benefit and risk of Tripterygium Glycosides Tablets in treatment of rheumatoid arthritis based on multi-criteria decision-making analysis / 中国中药杂志

Rheumatoid arthritis(RA) has a high disability rate and is highly harmful. It has a long course of treatment and is prone to adverse reactions or events(ADR/ADE). Selection of drugs in particular shall give consideration to both benefits and risk. Tripterygium Glycosides Tablets(TGT) is one of the important drugs for the treatment of RA. It has a remarkable efficacy, but a strong toxicity, which is controversial in clinical use. The study was oriented to patients, and quantitatively evaluated the efficacy and risk of TGT in treatment of RA, providing an intuitive basis for clinical safety and effective application of TGT. A multi-criteria decision-making analysis(MCDA) model of TGT was built in the treatment of RA, and then benefit and risk indicators were weighted by SWING method. Totally 53 random clinical trials(RCT) in accordance with the evaluation criteria were included by Meta-analysis method. The RCT results were merged by Meta-analysis, indicating that compared with the conventional therapy of chemical immunosuppressant(CISD), TGT could improve the curative effect whether it was used alone or in combination with CISD, but it would increase the incidence of reproductive system damage. The combined administration with CISD would also increase the incidence of liver and kidney damages. Treatment outcomes varied according to the different conditions of the combined administration with CISD. Based on MCDA model and clinical results, the benefit value, risk value and benefit-risk value of different doses, courses and combined administration of TGT in the treatment with RA were compared. The results showed that when the benefit and risk of the drug were equally important to the patient, the benefit-risk value of the single administration of TGT was 59, while that of the combined administration of TGT and CISD was 39. Therefore, the benefit-risk value of the single administration of TGT was 100% better than the combined administration. When the combined administration of TGT and CISD is unavoidable, the benefit-risk value of low-dose TGT(0.10-0.99 mg·kg~(-1)·d~(-1)) was 48, while that of high-dose TGT was 36. Therefore, low-dose TGT combined with CISD was more easily accepted by patients. The 2 to 3-month treatment course had a benefit-risk value of 40, while the long treatment course had a benefit-risk value of 38. Based on existing evidences, the single administration of TGT may be better than the combined administration with CISD. If the patients need to combine with CISD to treat RA, low dosage and 2 to 3-month course may be relatively optimal.

Meta-analysis of RCT studies on clinical efficacy of single administration of Tripterygium Glycosides Tablets or combined administration with methotrexate against rheumatoid arthritis / 中国中药杂志

To evaluate the clinical efficacy of single administration of Tripterygium Glycosides Tablets(TGT) or combined administration with methotrexate(MTX) against rheumatoid arthritis(RA) based on American College of Rheumatology(ACR) efficacy standard. Six databases, namely CNKI, WanFang, VIP, PubMed, Embase and Cochrane Library, were retrieved for randomized controlled trials(RCT), and clinical trials were screened out according to the preset inclusion and exclusion criteria. Then, the study quality was evaluated by the risk assessment tools. Data extraction and analysis were performed by using RevMan 5.3 software for Meta-analysis. Sensitivity analysis and publication bias analysis were made to test the stability and reliability of results. Until December 2018, a total of 1 709 articles were obtained, and finally 10 clinical RCT studies with a total of 1 184 patients were included. As a result, the single administration of TGT showed a significantly better ACR efficiency(RR=1.31, 95%CI[1.15, 1.49], P<0.000 1) than methotrexate(MTX). The combined administration of TGT and MTX showed a significantly better ACR efficiency(RR=1.28, 95%CI[1.20, 1.38], P<0.000 01) than the single administration of MTX. In conclusion, the single administration of TGT and the combined administration of TGT and MTX were more effective in achieving ACR20, ACR50, ACR70 compliance than the single administration of MTX. Further validations based on more RCT studies with high-quality are required.

Meta-analysis on safety of Tripterygium Glycosides Tablets in treatment of rheumatoid arthritis / 中国中药杂志

To systematically evaluate the adverse drug reaction(ADR) of Tripterygium Glycosides Tablets(TGT) in the treatment of rheumatoid arthritis(RA). Four Chinese databases(CNKI, VIP, WanFang, SinoMed) and three English databases(Cochrane Library, EMbase, PubMed), from the time of database establishing to August 2019, were systematically retrieved to collect literature on the treatment of all types of RA with TG. Screening literature and extracting data according to inclusion and exclusion criteria. All studies were assessed by using internationally recognized methodological quality assessment tools or reporting quality evaluation criteria, with data being extracted and Meta-analyzed. There were 79 studies included, randomized controlled trials(RCT) containing TGT in the treatment group, non-randomized controlled trials(non-RCT), case series, case reports, and RCT containing TGT only in the control group were covered. There were in the control group; 765 ADR of 2 214 patients in 30 RCT(treatment group given TGT), 11 non-RCT and 7 case reports. The results of Meta-analysis of these 48 literatures showed that the overall incidence of ADRs was 0.23(95%CI[0.22,0.24]); ADR mainly occured in the reproductive, gastrointestinal, skin and accessories, blood, hepatobiliary system damage and the incidence of ADR in systems mentioned about respectively were 0.14(95%CI[0.12,0.17]),0.07(95%CI[0.06,0.08]),0.06(95%CI[0.04,0.07]),0.04(95%CI[0.03,0.05]),0.04(95%CI[0.03,0.05]). Further subgroup analysis results showed that the incidence of total ADR, especially the gastrointestinal, reproductive and cutaneous ADR of patients with treatment alone was higher than that in those paients with MTX or MTX+LEF therapy; The incidence of ADR, especially the gastrointestinal ADR, was also positively correlated with daily dose and course of treatment, while the incidence of different systems ADR was also correlated with different drug manufacturers, for instance, damage on the female reproductive system occurs most frequently in Hunan manufacture TGT administration, same as the damage on skin and accessories induced by TGT from Jiangsu manufacture. Above all, The clinical treatment of TGT for RA will cause multi-system ADR, with the highest incidence in the reproductive system, followed by the gastrointestinal system, which is closely related to the way of medication(monotherapy), daily dose, course of medication and drug manufacturer. Therefore, it is recommended that, in the treatment of RA, using TGT in combination, low dose or short-course medication, take measures to protect the reproductive system, stomach and liver, and paying attention to the drug manufacturer as well response of patients during administration should be valued to avoid ADRs to the maximum possibility.

Systematic reviews of effects of Tripterygium Glycosides Tablets on pro-inflammatory factors in rheumatoid arthritis / 中国中药杂志

To systematically evaluate the effects of Tripterygium Glycosides Tablets alone or in combination with methotrexate(MTX) and leflunomide(LEF) on the levels of pro-inflammatory cytokines in patients or animal models with rheumatoid arthritis(RA), and to provide reference for clinical application and related basic research, this study systematically searched databases of CNKI, VIP, WanFang, PubMed, Embase and Cochrane Library, collected relevant clinical or animal experimental studies, used risk assessment tools to evaluate the quality of research, and used Revman 5.3 software to conduct Meta-analysis or descriptive analysis of the outcome indicators included in the literatures. Of the 1 709 papers retrieved, 3 clinical studies and 12 animal experiments were included. The results showed that compared with MTX alone, Tripterygium Glycosides Tablets combined with MTX could further reduce the expression levels of peripheral blood TNF-α(SMD=-8.88,95%CI[-10.77,-6.99],P<0.000 01),IL-1β(P<0.000 01) and IL-6(SMD=-8.63, 95%CI[-10.57,-6.69], P<0.000 01) in RA patients. Compared with LEF alone, the combination of Tripterygium Glycosides Tablets and LEF could not further reduce the expression levels of TNF-α(P=0.20), IL-1β(P=0.17), IL-6(P=0.31). In RA animal model, compared with model group, Tripterygium Glycosides Tablets could reduce the expression levels of peripheral blood IL-1β(SMD=-6.29,95%CI[-9.64,-2.93],P<0.000 2)in peripheral blood(SMD=-1.39,95%CI[-1.77,-1.02],P<0.000 01), joint fluid(P<0.000 01) and paw plasma(P=0.02), and also reduce the expression levels of TNF-α in RA animal model group. Compared with MTX alone, Tripterygium Glycosides Tablets alone reduced the same levels of TNF-α(P=0.42) and IL-6(P=0.08) in joint fluid, while Tripterygium Glycosides Tablets combined with MTX could further reduce the levels of IL-6(P=0.000 1) in joint fluid; compared with LEF alone, Tripterygium Glycosides Tablets have the similar effects on reducing the expression levels of peripheral blood TNF-α(P=0.16), IL-1β(P=0.32), IL-6(P=0.12), while Tripterygium Glycosides Tablets combined with LEF could further reduce the expression levels of TNF-α(P=0.008), IL-1β(P=0.02), IL-6(P<0.000 1) in peripheral blood. Therefore, Tripterygium Glycosides Tablets combined with MTX could further reduce the expression levels of pro-inflammatory cytokines in peripheral blood of RA patients. Tripterygium Glycosides Tablets alone could reduce the expression levels of pro-inflammatory cytokines in peripheral blood and local joint of RA animal models. Tripterygium Glycosides Tablets combined with MTX or LEF could further reduce the express levels of pro-inflammatory cytokines in peripheral blood of RA animal models. Due to the limitation of literature, this conclusion needs to be further validated.

Protective activity of picroliv on hepatic amoebiasis associated with carbon tetrachloride toxicity.

BACKGROUND AND OBJECTIVE: Picroliv, isolated from the root and rhizome of Picrorhiza kurroa, is known to have significant hepatoprotective activity. Its effects against Entamoeba histolytica induced liver damage are not studied. This study aims to evaluate the hepatoprotective action of picroliv against the hepatotoxic changes induced by carbon tetrachloride (CCl(4)) and E. histolytica infection in three animal models. METHODS: Mastomys, gerbils and albino Druckray rats were used in this study. A total of 30 animals were used for each model and divided into five groups of six animals each. Group I consisted of normal animals. The rest received six doses of CCl(4) intraperitoneally. Group II served as hepatotoxic control. The remaining animals were infected intraperitoneally with E. histolytica trophozoites, of which group III was the hepatotoxic plus amoeba infected control. The remaining animals were divided into two groups, one received hepatoprotective agent picroliv and the other silymarin. All animals were sacrificed seven days post amoeba infection. RESULTS: Increase in the enzyme levels induced by CCl(4) was further elevated after E. histolytica infection. Pinpoint abscesses were found to develop only in gerbils after E. histolytica infection. Picroliv was found to possess hepatoprotective activity against amoebic liver abscess. INTERPRETATION AND CONCLUSION: Significant recovery obtained in serum enzyme levels in all animal models and against amoebic liver abscess in gerbils on treatment with picroliv indicated that picroliv possesses therapeutic activity against E. histolytica induced hepatic damage.

Prevention of carbon tetrachloride-induced hepatic injury in mice by Picrorhiza kurrooa.

OBJECTIVE: Picrorhiza kurrooa (Pk) has been used in liver diseases in the Indian indigenous system of medicine. We undertook this study to determine whether Pk extract possesses hepatoprotective function and if so to determine its nature and mechanism. METHODS: Liver injury was induced in 16 mice by thrice-a-week injection of carbon tetrachloride (CCl4) for nine weeks. Eight of them were given daily feeding of Pk extract (12 mg/Kg) 10 days prior to CCl4 injection. Control mice (n = 6) were injected with olive oil for the same period. Serum markers of liver injury and histology of liver tissues were studied. Hepatic glutathione (GSH), total thiol (-SH), glucose 6-phosphate dehydrogenase (G6PD), catalase, lipid peroxidation and plasma membrane-bound Na+/K+ ATPase were also determined. RESULTS: CCl4 treatment resulted in significant elevation of serum ALT and AST. Liver GSH [6.3 (0.7) vs control 10.5 (1.1) micrograms/mg protein], -SH, G6PD, catalase and membrane-bound Na+/K+ AT-Pase [164.3 (23.2) vs control 358.4 (12.9) nmole pi released/min/mg protein] were significantly reduced. Significant increase of lipid peroxidation [3.0 (0.6) vs control 1.0 (0.3) nmole MDA/mg protein] and histologic changes characteristic of liver injury were also seen. Feeding of Pk extract in CCl4-treated mice caused significantly less alteration of serum ALT, AST, liver GSH [8.9 (0.7) micrograms/mg protein], -SH, G6PD, catalase and membrane-bound Na+/K+ ATPase [270.8 (21.3) nmole pi released/min/mg protein]. Histologic lesions of liver and lipid peroxidation [1.7 (0.4) nmole MDA/mg protein] were also significantly less in these animals. CONCLUSION: The extract of Pk appears to offer significant protection against liver damage by CCl4. It probably acts as free-radical scavenger and inhibitor of lipid peroxidation of liver plasma membrane.

Estudo da atividade antihistamínica da Kalanchoe Brasiliensis / Study of antihistamine activity o kalanchoe brasiliensis

O suco obtido por pressäo das folhas de Kalanchoe brasiliensis(Crassulaceae) apresentou atividade bloqueadora aos receptores histamínico. O suco contém compostos flavonóides, carboidratos e sais minerais. Uma fraçäo flavonóide: fraçäo B obtida através da participaçäo do suco entre n-butanol e água contém a substância responsável pela atividade anti-histamínica. Testando no íleo isolado de cobaia 50mg/mL de suco e 0,15 mg/mL de fraçäo B produziu-se deslocamento à direita dose-dependente da curva de concentraçäo resposta da histamina de modo competitivo. O antagonismo foi específico e reversível para histamina, näo modificou a resposta para a acetilcolina, Kcl e BaCl2. As respostas de permeabilidade vascular foram reduzidas em 20 a 25 por cento em animais pré-tratados com 4mL/Kg de suco ou com 12mg/Kg de fraçäo B. O suco e a fraçäo B näo foram efetivos em proteger a mucosa gástrica do ataque ácido gástrico. O suco(4mL/Kg) protegeu cobaias da morte por asfixia induzida por 5 mg de histamina, aproteçäo durou no mínimo 1h. concluimos que o efeito antihistamínico do suco e da fraçäo B foi produzido por bloqueio de receptores H1

Anticholestatic effect of picroliv, active hepatoprotective principle of Picrorhiza kurrooa, against carbon tetrachloride induced cholestasis.

Picroliv showed a dose (3-12 mg/kg, po for 7 days) dependent choleretic activity as evidenced by increase in bile flow and its contents (bile salts and bile acids). Significant anticholestatic activity was also observed against carbon tetrachloride induced cholestasis in conscious rat, anaesthetized guinea pig and cat. Picroliv was more active than the known hepatoprotective drug silymarin.

Bioactive glycosides from Chinese medicines

Glycosides are the bioactive components of many famous Chinese medicines. Here reported are some bioactive glycosides we discovered from Chinese medicines in recent years. (1) Pheolic glycosides from Chinese medicines: Gastrodia elata, acontium austroynanense and Helicia erratica, three bioactive phenolic glycosides were discovered and two of them have been developed into new drugs. (2) Terpenoidal glycosides: a) Monoterpenoid: the sweroside from Swertia mollensis has been developed intro an anti-hepatitis drug; b) Diterpenoid: Phlomis betonicoides contains sweet glycoides; c) Triterpenoid: many biologically active triterpenoid glycosides were isolated from Panax plants and Siraitia grosvenorii. (3) Steroidal glycosides: a) C21-steroid: Cynanchum otophyllum and C. atratrum contain anti-epilepsy and-tumor glycosides; b) C27-steroid Hemostatic saponins were found in Paris polyphylla.

In vitro studies on the effect of certain natural products against hepatitis B virus.

Picroliv (active principle from Picrorrhiza kurroa), its major components picroside I, catalpol, kutkoside I, kutkoside, andrographolide (active constituent of Andrographis paniculata), silymarin and Phyllanthus niruri extract were tested for the presence of anti hepatitis B virus surface antigen (anti HBs) like activity. HBsAg positive serum samples obtained from hepatitis B virus (HBV) associated acute and chronic liver diseases and healthy HBsAg carriers were used to evaluate the anti-HBs like activity of compounds/extract. The latter were mixed with serum samples and incubated at 37 degrees C overnight followed by HBsAg screening in the Elisa system. A promising anti-HBsAg like activity was noted in picroliv (and its major components) catalpol, P. niruri which differed from the classical viral neutralization. Picroliv also inhibited purified HBV antigens (HBsAg and HBsAg) prepared from healthy HBsAg carriers. The in vitro testing system appears to be a suitable model to identify an agent active against HBV, prior to undertaking detailed studies.

Evaluation of hepatoprotective activity of picroliv (from Picrorhiza kurroa) in Mastomys natalensis infected with Plasmodium berghei.

Administration of picroliv, a standardized fraction of alcoholic extent of Picrorhiza kurroa (3-12 mg/kg/day for two weeks) simultaneously with P. berghei infection showed significant protection against hepatic damage in Mastomys natalensis. The increased levels of serum glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), alkaline phosphatase, lipoprotein-X (LP-X) and bilirubin in the infected animals were marked reduced by different doses of picroliv. In the liver, picroliv decreased the levels of lipid peroxides and hydroperoxides and facilitated the recovery of superoxide dismutase and glycogen. Picroliv had no effect on the degree of parasitaemia.