Hypouricemic effect of flaccidoside II in rodents.

To investigate the effect of flaccidoside II on the serum uric acid levels in hyperuricemic rodents. Both mice and rats were injected intraperitoneally with potassium oxonate to induce hyperuricemia. Different dosages of flaccidoside II were orally administrated to hyperuricemic and normal rodents for 7 days, respectively. Liver xanthine oxidase (XOD) activities in hyperuricemic mice were determined using the colorimetric method. Acute toxicity of flaccidoside II was also evaluated in mice. Allopurinol, as a positive control, was administered under the same treatment scheme. The results showed that flaccidoside II (32, 16 and 8 mg/kg) could significantly lower serum uric acid levels in hyperuricemic mice. Flaccidoside II (24, 12 and 6 mg/kg) could also markedly lower serum uric acid levels in hyperuricemic rats. However, unlike allopurinol, oral administration of flaccidoside II did not produce any observable hypouricemic effect in normal animals. Flaccidoside II at the dose of 32 mg/kg significantly suppressed XOD activities in the liver of hyperuricemic mice, while at doses of 16 and 8 mg/kg flaccidoside II did not show a significant effect on XOD activities. In addition, flaccidoside II (300 mg/kg) has no or less toxicity than allopurinol in mice. These findings demonstrate that flaccidoside II exhibits anti-hyperuricemic activity in hyperuricemic animals.

Protective effect of homonojirimycin from Commelina communis (dayflower) on influenza virus infection in mice.

The effects of homonojirimycin (HNJ), one of alkaloids from Commelina communis L., on protection against influenza virus infection in mice were investigated. HNJ was found to improve the survival rate, prolong the mean survival time and reduce virus yields in lungs on days 4 and 6 post-infection (p.i.), after the agent had been orally administered to the mice from 2 days before infection to 6 days p.i. Administration of HNJ (1 mg/kg) significantly increased interferon (IFN)-γ and interleukin (IL)-10 levels but decreased tumor necrosis factor (TNF)-α and IL-6 levels in serum and lungs of influenza-infected mice on days 2, 4 or 6 p.i. These results showed that HNJ exerted protection against influenza virus infection and produced effective immune responses in vivo.

Effect of total alkaloids from Commelina communis L. on lung damage by influenza virus infection.

Whether administration of total alkaloids from Commelina communis L. (TAC) reduces lung damage in influenza virus-infected mice was investigated. Compared with untreated mice, significantly less severe damage was found in the lungs of mice administered TAC at 8 mg/kg per day for 6 days. TAC significantly decreased viral loads in the lungs. The concentrations of IFN-γ in the serum of TAC-treated mice were significantly lower than those of virus control mice at 4 and 6 days post-infection. The results indicate that TAC imparted partial protection to the mice by reducing pulmonary viral loads and limiting lesions in the lungs.

Anti-influenza-virus activity of total alkaloids from Commelina communis L.

The antiviral activity of total alkaloids from Commelina communis L. (TAC) against influenza virus A/PR/8/34 (H1N1) was investigated in vitro and in vivo. TAC exhibited an inhibitory action on the growth of influenza virus in Madin-Darby canine kidney cells when added before or after viral infection. In mice infected with influenza virus, orally administered TAC at 8, 16 or 32 mg/kg per day for 6 days significantly increased the survival rate, prolonged the mean survival time and reduced the viral titers in the lung and the lung index, compared with that of the untreated virus control. The results obtained suggest that TAC has a pronounced protective effect against infection by influenza A virus.

Synthesis of oleanolic acid saponins mimicking components of Chinese folk medicine Di Wu.

3,28-Di-O-rhamnosylated oleanolic acid saponins, mimicking components of Chinese folk medicine Di Wu, have been designed and synthesized. One-pot glycosylation and 'inverse procedure' technologies have been applied thus significantly simplifying the preparation of desired saponins. The cytotoxic activity of compounds 3-O-[alpha-L-rhamnopyranosyl-(1-->2)-beta-D-xylopyranosyl]oleanolic acid 28-O-[alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl] ester (3), 3-O-[alpha-L-rhamnopyranosyl]oleanolic acid 28-O-[alpha-L-rhamnopyranosyl- (1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl] ester (4), 3-O-[alpha-L-rhamnopyranosyl]oleanolic acid 28-O-[alpha-L-rhamnopyranosyl] ester (5), and 3-O-[alpha-L-rhamnopyranosyl]oleanolic acid 28-O-[6-O-(alpha-L-rhamnopyranosyl)hexyl] ester (6) was preliminarily evaluated against HL-60 human promyelocytic leukemia cells. The natural saponin 3 and designed saponin 4 exhibited comparable moderate cytotoxic activity under our testing conditions.

Synthesis of flaccidoside II, a bidesmosidic triterpene saponin isolated from Chinese folk medicine Di Wu.

A total synthesis of flaccidoside II, 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-xylopyranosyloleanolic acid 28-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside, isolated from Chinese folk medicine Di Wu, has been accomplished from building blocks isopropyl 2-O-acetyl-3,4-di-O-benzoyl-1-thio-beta-D-xylopyranoside, 2,3,4-tri-O-benzoyl-alpha-L-rhamnopyranosyl trichloroacetimidate, oleanolic acid trityl ester, ethyl 2,3-di-O-acetyl-6-O-benzoyl-1-thio-beta-D-glucopyranoside and 4-methoxyphenyl 2,3,4-tri-O-acetyl-beta-D-glucopyranoside. The use of a partially protected thioglycosyl donor significantly simplified the synthesis of the target saponin.

Involvement of protein kinase C in 5-HT-evoked thermal hyperalgesia and spinal fos protein expression in the rat.

The present study was designed to characterize nociceptive response induced by 5-hydroxytryptamine (5-HT) and to investigate effects of inhibition of protein kinase C (PKC) in the periphery on noxious stimulus-evoked activity of the secondary neurons in the spinal cord. Subcutaneous injection of 5-HT (50 microg) and alpha-methylserotonin (alpha-m-5-HT, 5-HT2A receptor agonist, 50 microg) into the unilateral hindpaw evoked significant decreases in paw withdrawal latency (PWL). The 5-HT-induced hyperalgesia was abolished by ketanserin (5-HT2A antagonist, 10 microg, intraplantarly or i.pl.), but not by WAY100635 (5-HT1A antagonist, 100 microg, i.pl.). 5-HT and alpha-m-5-HT also evoked numerous expressions of c-Fos-like immunoreactivity (c-fos-LI) in the ipsilateral dorsal horn (predominantly laminae I-II) of the lumbar spinal cord. However, treatment with 8-OH-DPAT (5-HT1A receptor agonist, 100 microg, i.pl.) elicited only moderate thermal hyperalgesia and very limited expression of spinal c-fos-LI. Intraplantar chelerythrine (2, 6 or 10 microg), a PKC inhibitor, dose-dependently attenuated the hyperalgesia evoked by alpha-m-5-HT. Chelerythrine (10 microg, i.pl.) also completely prevented the development of hyperalgesia evoked by 5-HT but not by 8-OH-DPAT. Furthermore, pretreatment with chelerythrine significantly inhibited the expressions of c-fos-LI evoked by alpha-m-5-HT in laminae I-VI and by 5-HT in laminae I-II. These results demonstrate that PKC activation was involved in the development of nociceptive responses elicited by 5-HT and activation of peripheral 5-HT2A, but not 5-HT1A, receptors. The study also provides evidence at a cellular level that inhibition of PKC in the periphery suppresses the 5-HT-evoked neuronal activity in the central nervous system.

Therapeutic effect of Zijin capsule in liver fibrosis in rats.

AIM:To confirm the therapeutic effect of Zijin capsule on liver fibrosis in rat model.METHODS:Model group: Bovine serum albumin (BSA) Freund's incomplete adjuvant 0.5ml was injected subdermally at d(1) d(15) d(22) d(29) and d(36) for primary sensitization. Seven days after the fifth injection, BSA antibody in the serum was detected by double agar diffusion method. Normal saline of 0.4ml was injected through cauda vein to BSA antibody-positive rat twice a week for fifteen times. Traditional Chinese medicine (TCM) decoction group and Zijin capsule group: In the attack injection period, Chinese medicinal decoction or Zijin capsule was given ig, the others were the same as in the model group. NS was used in the control group. The collagen content of rat liver was determined by Bergman's method and expressed as x-±s.The liver pathological changes were divided into four grades and expressed as the avarage of the total rank sum.RESULTS:The collagen content (mg/g) of the liver in the control group (7.2± 1.9) was significantly lower than that in the other groups; it was higher in the model group (31.7± 16.6) than that in the two therapeutic groups; and lower in Zijin capsule group (9.7 ± 2.8) than that in the TCM decoction group (11.5± 5.3). The pathological changes were more aggravated in the model group (37.4) than those in the two therapeutic groups; and more severe in the TCM decoction group (30.2) than in the Zijin capsule group (22.9).CONCLUSION: The therapeutic effect of Zijin capsule on the model was confirmed.