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.

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.