Protective effect of ginsenoside against acute renal failure via reduction of renal oxidative stress and enhanced expression of ChAT in the proximal convoluted tubule and ERK1/2 in the paraventricular nuclei.

Generation of reactive oxygen species significantly contributes to the pathogenesis of acute renal failure (ARF) induced by myoglobin release. Ginsenosides (GS), the principal active ingredients of ginseng, is considered as an extremely good antioxidative composition of Chinese traditional and herbal drugs. The purpose of the present study was to investigate the protective effect of ginsenoside in rats with ARF on the changes of cholinergic nervous system in the kidney as well as on the involvement of mitogen-activated protein kinases (MAPK) in the hypothalamic paraventricular nuclei (PVN). In our assay, glycerol-induced acute renal failure in rats was employed to study the protective effects of ginsenoside. Our results indicated that the treatment of ARF rats with ginsenosides for 48 h significantly reduced lipid peroxidation, restored the superoxide dismutase (SOD) level. Meanwhile, the obvious increase of choline acetyltransferase-immunoreactivity (ChAT-IR) in the proximal convoluted tubular cells (PCT) was observed by immunohistochemistry in ARF+GS group. The same effect was also observed in the changes of p-ERK1/2-IR in the hypothalamic paraventricular nuclei. Our results suggest that ginsenoside administered orally may have a strong renal protective effect against glycerol-induced ARF, reduce the renal oxidative stress, and ginsenoside can also activate the cholinergic system in PCT, simultaneously MAPK signal pathway in the PVN was also activated.

Protective effect of ginsenoside against acute renal failure and expression of tyrosine hydroxylase in the locus coeruleus.

Acute renal failure (ARF) is mainly characterized by acute tubular necrosis. No significant change was found for mortality rates over the past few decades despite significant advances in supportive care. In recent years, great effort has been focused on traditional and herbal medicine, which is much less toxic than those agents conventionally used and which is nowadays considered as a novel therapeutic agent for ARF. However, the effect of ginsenosides (GS) administered orally on ARF has not been reported yet and little is known about its cellular and molecular mechanism. The purpose of the study is to investigate the protective effect of ginsenoside in rats with ARF on the changes of tyrosine hydroxylase immunoreactivity (TH-IR) as well as on the involvement of mitogen-activated protein kinases (MAPK) in the locus coeruleus. In our assay, glycerol-induced acute renal failure in rats was employed to study the protective effects of ginsenoside. Our results indicated that the treatment of ARF rats with ginsenosides for 48 h significantly reduced the serum blood urea nitrogen, creatinine level, and lipid peroxidation, restored the GSH level and the normal renal morphology. Immunohistochemistry showed that an obvious increase of TH-IR was further enhanced in ARF+GS group. The same effect was also observed in the changes of p-ERK1/2-IR in the locus coeruleus. Our results suggest that ginsenoside administered orally may have a strong renal protective effect against glycerol-induced ARF, and ginsenoside can also activate the brain catecholaminergic neurons in the locus coeruleus. Our future attention will be focused to the question whether there is a correlation between the renal protective effect of ginsenosides against acute renal failure and the activation of tyrosine hydroxylase in the locus coeruleus.

Antitumour and antimicrobial activities of endophytic streptomycetes from pharmaceutical plants in rainforest.

AIMS: The aim of this study was to screen antitumour and antimicrobial activities of endophytic actinomycetes isolated from pharmaceutical plants in rainforest in Yunnan province, China. METHODS AND RESULTS: Antitumour activity was studied by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and antimicrobial activity was determined by agar well diffusion method. The high bioactive endophytic isolates were identified and further investigated for the presence of polyketide synthases (PKS-I, PKS-II) and nonribosomal peptide synthetases (NRPS) sequences by specific amplification. The molecular identification confirmed that the 41 isolates showed significant activities were members of the genus Streptomyces. Among them, 31.7% of endophytic streptomycete cultures were cytotoxic against A549 cells, 29.3% against HL-60 cells, 85.4% against BEL-7404 cells, 90.2% against P388D1 cells, 65.9% were active against Escherichia coli, 24.4% against Staphylococcus aureus, 31.7% against Staphylococcus epidermidis, 12.2% against Candida albicans and no strain displayed antagonistic activity against Klebsiella pneumoniae. High frequencies of positive PCR amplification were obtained for PKS-I (34.1%), PKS-II (63.4%) and NRPS (61.0%) biosynthetic systems. CONCLUSIONS: Many endophytic streptomycetes isolated from pharmaceutical plants in rainforest possess remarkable and diverse antitumour and antimicrobial bioactivities. SIGNIFICANCE AND IMPACT OF THE STUDY: These endophytic streptomycetes are precious resources obtained from rainforests, and they could be a promising source for bioactive agents.

Analgesic effect of interferon-alpha via mu opioid receptor in the rat.

Using the tail-flick induced by electro-stimulation as a pain marker, it was found that pain threshold (PT) was significantly increased after injecting interferon-alpha (IFN alpha) into the lateral ventricle of rats. This effect was dosage-dependent and abolished by monoclonal antibody (McAb) to IFN alpha. Naloxone could inhibit the analgesic effect of IFN alpha, suggesting that the analgesic effect of IFN alpha be related to the opioid receptors. Beta-funaltrexamine (beta-FNA), the mu specific receptor antagonist could completely block the analgesic effect of IFN alpha. The selective delta-opioid receptor antagonist, ICI174,864 and the kappa-opioid receptor antagonist, nor-BNI both failed to prevent the analgesic effect of IFN alpha. IFN alpha could significantly inhibit the production of the cAMP stimulated by forskolin in SK-N-SH cells expressing the mu-opioid receptor, not in NG108-15 cells expressing the delta-opioid receptor uniformly. The results obtained provide further evidence for opioid activity of IFN alpha and suggest that this effect is mediated by central opioid receptors of the mu subtype. The evidence is consistent with the hypothesis that multiple actions of cytokines, such as immunoregulatory and neuroregulatory effects, might be mediated by distinct domains of cytokines interacting with different receptors.