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Improving cobalt catalysts Tethering molecular catalysts together is a tried and trusted method for making them easier to purify and reuse. Lin et al. now show that the assembly of a covalent organic framework (COF) structure can also improve fundamental catalytic performance. They used cobalt porphyrin complexes as building blocks for a COF. The resulting material showed greatly enhanced activity for the aqueous electrochemical reduction of CO 2 to CO. Science , this issue p. 1208

The objective of this study was to investigate the effects of various concentrations and incubation times of water extract of clam (WEC) on glutathione, its antioxidant and the detoxification defense systems in normal and CCl4-induced oxidative damaged primary rat hepatocytes. This study showed that when the hepatocytes were treated with WEC(0.14 ~ 1.68 mg/ml), the intracellular glutathione (GSH) levels, GSH/GSSG ratio, and the activities of GSH-related enzymes (GPx, GRd, and GST) were higher than those in the control at 24 or 48 hour treatments. However, the lactate dehydrogenase (LDH) leakage and microscopic observations did not differ from those of the control. Yet, when the hepatocytes were pretreated with various concentrations of WEC for 24 hours and then exposed to 5 mM carbon tetrachloride (CCl4) for 1 hour, at concentrations of WEC between 0.42 ~ 1.68 mg/ml, the viabilities, intracellular GSH level, and activities of GST and GPx were significantly increased compared to those of the CCl4-treated control group ( p < 0.05). In conclusion, WEC could improve the viability and the capabilities of detoxification and antioxidation in hepatocytes by increasing the GSH level and the activities of GSH-related enzymes.

We examined the anti-angiogenic effects of Ganoderma tsugae methanol extract (GTME) on human epidermoid carcinoma A-431 cells. Our data indicate that GTME inhibits the expression of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) in vitro and in vivo, and also inhibits the capillary tube formation of human umbilical vein endothelial cells (HUVECs). We also show that the suppression of VEGF expression by GTME can be restored by treatment with EGF. These results suggest that GTME inhibits VEGF expression via the suppression of EGFR expression, resulting in the downregulation of VEGF secretion from epidermoid carcinoma A-431 cells. These findings reveal a novel role for G. tsugae in inhibiting EGFR and VEGF expression, which are important for tumor angiogenesis and growth. Thus, GTME may provide a potential therapeutic approach for anti-tumor treatment.

In this study, we investigated the possible pathophysiological mechanisms in primary dysmenorrhea. The study was undertaken to determine the effect of homocysteine on the nitric oxide (NO) pathway in primary dysmenorrheal women. A total of 94 students from a local nursing college participated. Group 1 consisted of 51 normal subjects with no dysmenorrhea. Group 2 had 43 subjects with dysmenorrheal symptoms. Our results show that serum NO levels in group 2 are higher than those in group 1. However, the serum homocysteine level was lower in group 2. These observations indicate that the NO pathway is involved in the pathophysiological mechanism responsible for the damaging effects of homocysteine on dysmenorrheal women.

The study objective of this research is in order to investigate the hepatoprotective and therapeutic effects of propolis ethanol extract (PEE) on acute econazole-induced liver injury. Positive control of various concentrations of PEE on liver function and the dose-response relationship of liver injury induced by various doses of econazole were firstly observed from biochemical assay of serum level of aspartate transaminase (SGOT) and serum alanine transaminase (SGPT) and histopathological microscopic examination. The hepatoprotective effects of various concentration of PEE on liver damage induced by hepatotoxic dose (300 mg/kg) of econazole were observed by the obvious decrement of SGOT and SGPT level and further confirmed by hepatohistological microscopic examination. The inhibitory effects of PEE on FeCl2-induced (in vitro) or econazole-induced (in vivo) lipid peroxidation were investigated from the measurement of the formed malonic dialdehyde (MDA) level in the rat liver homogenate. The IC50 (μM) of various concentrations of PEE in the superoxide scavenging activity in econazole (300 mg/kg)-damaged rat liver homogenate were assessed by cytochrome c reduction method and compared with that of (+)-alpha-tocopherol. It could be postulated that the hepatoprotective effect of PEE may be, at least in part, due to their inhibitory ability on membrane lipid peroxidation and free radical formation or due to their free radical scavenging ability.

Acute oral administration of absolute ethanol (1.0 ml/kg) to fasting rats produced extensive necrosis of the gastric mucosa within 1 h. Pretreatment 30 min before administration of ethanol with oral tetramethylpyrazine (TMP) prevented this necrosis. Gross examination of the gastric mucosa of rats that received TMP showed fewer gastric lesions than that of rats who did not receive TMP. TMP pretreatment in rats exhibited superoxide scavenging activity in absolute ethanol-induced lipid peroxidation in gastric mucosal homogenates. TMP added in vitro to gastric homogenates made from control rats also showed scavenging activity. We conclude that the gastric protective mechanism of TMP could be attributed, at least in part, to its ability to inhibit lipid peroxidation and hence indirectly protect the gastric mucosa from oxidative stress.

Arctium lappa Linne (burdock) is a perennial herb which is popularly cultivated as a vegetable. In order to evaluate its hepatoprotective effects, a group of rats (n = 10) was fed a liquid ethanol diet (4 g of absolute ethanol/ 80 ml of liquid basal diet) for 28 days and another group (n = 10) received a single intraperitoneal injection of 0.5 ml/kg carbon tetrachloride (CCl(4)) in order to potentiate the liver damage on the 21st day (1 day before the beginning of A. lappa treatment). Control group rats were given a liquid basal diet which did not contain absolute ethanol. When 300 mg/kg A. lappa was administered orally 3 times per day in both the 1-day and 7-day treatment groups, some biochemical and histopathological parameters were significantly altered, both in the ethanol group and the groups receiving ethanol supplemented with CCl(4). A. lappa significantly improved various pathological and biochemical parameters which were worsened by ethanol plus CCl(4)-induced liver damage, such as the ethanol plus CCl(4)-induced decreases in total cytochrome P-450 content and NADPH-cytochrome c reductase activity, increases in serum triglyceride levels and lipid peroxidation (the deleterious peroxidative and toxic malondialdehyde metabolite may be produced in quantity) and elevation of serum transaminase levels. It could even restore the glutathione content and affect the histopathological lesions. These results tended to imply that the hepatotoxicity induced by ethanol and potentiated by CCl(4) could be alleviated with 1 and 7 days of A. lappa treatment. The hepatoprotective mechanism of A. lappa could be attributed, at least in part, to its antioxidative activity, which decreases the oxidative stress of hepatocytes, or to other unknown protective mechanism(s).

To investigate whether combination treatment with Taohong Siwu Decoction (桃红四物汤, TSD) and recombinant tissue-type plasminogen activator (rt-PA) potentiate in reducing infarct volume and alleviate thromboembolic stroke in an in vivo rat model. Adult male Wistar rats were subjected to embolic middle cerebral artery occlusion (MCAO) and treated with rt-PA (4 and 8 mg/kg) alone (n=5), TSD [0.7 g/(kg·day)] alone (n=5), combination of rt-PA and TSD, 24 h after stroke. Rats were sacrificed at 14 days after treatment and lesion volumes were measured. To investigate the underlying mechanism of neuroprotective effect of the combination treatment, cleaved caspase-3, tumor necrosis factor alpha (TNF-α), hypoxia-inducible factor (HIF)-1α, and inducible nitric oxide synthase (iNOS) immunostaining were performed. Combination treatment significantly reduced infarct volume of cerebral ischemic regions compared with treatment of rt-PA and TSD alone and that of the saline control group (P

The antioxidative effect of hot water extract of the mushroom Ganoderma lucidum on ethanol-induced free radical generation had been studied. In order to further investigate the hepatic and renal protective mechanism of Ganoderma lucidum, rates of lipid peroxidation were determined. The hot water extract of Ganoderma lucidum dose-dependently exhibited antioxidative effect on mouse liver and kidney lipid peroxidation; our results indicated that hepatic and renal homogenates have a higher malonic dialdehyde level in an ethanol administered group than in the Ganoderma lucidum treated group. It was concluded that the hepatic and renal protective mechanism of Ganoderma lucidum, might be due at least in part to its prominent superoxide scavenging effect. Ganoderma extract could protect the liver and kidney from superoxide induced hepatic and renal damages.

Solanum alatum Moench. has been shown to have a protective effect against carbon tetrachloride (CCI4)-induced liver injury. Solanum alatum treatment (100 mg/kg, p.o) decreased the elevation of serum alanine aminotransferase (ALT; GPT) and aspartate aminotransferase (AST; GOT) induced by acetaminophen (paracetamol) (600 mg/kg, i.p.) administration. It also decreased the extent of visible necrosis in liver tissue. In addition, Solanum alatum treatment restored hepatic glutathione (GSH) depletion induced by acetaminophen (600 mg/kg, i.p.) administration. Microsomal enzyme levels such as P-450, reductas and aniline hydroxylation enzyme were also restored to normal levels after Solanum alatum administration. The hepatoprotective mechanism may function through direct binding with acetaminophen toxic metabolites, decreasing the attraction of acetaminophen metabolites for other cellular GSH or thiol protein. Additionally, Solanum alatum treatment increased the concentration of hepatic GSH and maintained a high level activity of GSTase, which led to acceleration of the excretion of toxic acetaminophen metabolites.

Propolis designates a series of gums, resins and balms of viscous consistency, which are gathered by honeybees from certain parts, mainly the buds and barks of plants, especially those found on coniferous trees. Bees bring propolis back to the hive, where it is modified and mixed with other substances including the bees' own wax and salivary secretions. In this study, the influences of propolis ethanol extract on chronic alcohol induced liver microsomal enzyme changes were investigated. Three grams of alcohol was added to rats' daily diet for four weeks to induce chronic alcohol liver injuries, and two different doses of propolis ethanol extract were p.o. administrated three times per day on the 28th, 29th, and 30th day. During the period of propolis administration, the ethanol diet was continued. After sacrifice, the rat livers were excised for assay of microsomal enzymes activity, glutathione (GSH) concentration, glutathione-S-transferase (GSTase) and γ-glutamylcysteine synthetase (γ-GCSase) activity. It was found that 30 mg/kg of propolis ethanol extract significantly prevented the elevations of total cytochrome P-450 enzymes, NADPH-dependent cytochrome C reductase, aniline hydroxylation, 7-ethoxyresorufin hydroxylation (7-ERH), 7-penthoxyresorufin hydroxylation (7-PRH), and lipid peroxidation induced by chronic ethanol administration. Additionally, propolis ethanol extract (100 mg/kg) also induced GSTase and γ-GCSase activities and decreased glutathione levels in the liver.

Propolis designates a mixture of gums, resins and balms, of viscous consistency, which are gathered on certain parts (buds and bark, mainly) of vegetables (especially coniferous trees) by honeybees. They bring this back to the hive, where it is modified and mixed with other substances (essentially their own wax and salivary secretions). In this study, the hepatoprotective and therapeutic effects of propolis ethanol extract on chronic alcohol-induced liver injuries were investigated in rats. 3.125 ml of 99.5% alcohol was added to animal's daily diet for four weeks to induce chronic alcohol liver injuries. After sacrifice, serum transaminases (GOT, GPT), triacylglyceride and hepatic triacylglyceride (HTG) concentration were assayed to observe liver injuries induced by chronic alcohol abuse. In addition, the phenomenon of alcohol induced fatty liver were also observed by histopathological changes. Different doses of propolis ethanol extract were p.o. administered three times per day for three days, after four weeks' alcohol administration. It was found that 10 mg/kg of propolis ethanol extract significantly decreased the elevations of serum GOT, GPT, TG and HTG. In histopathological examination, 30 mg/kg of propolis ethanol extract also remarkably decreased the hepatocellular fatty degeneration, apparent as vacuolization, induced by chronic alcohol abuse.

The hepatoprotective effects of Eclipta prostrata (Linn.) were studied on acute hepatitis induced in mice by a single dose of carbon tetrachloride (31.25 μ/kg, i.P.) or acetaminophen (600 mg/kg, i.p.) and in rats by a single dose of β-D-galactosamine (188 mg/kg, i.p.). The hepatoprotective activity was monitored by estimating the serum transaminases (SGOT and SGPT) levels and histopathological changes in the liver of experimental animals. The Eclipta prostrata extracts significantly inhibited the acute elevation of serum transaminases induced by carbon tetrachloride in mice and by β-D-GaLN in rats. However, in the experimental model of acetaminophen, although an inhibiting tendency was noticed, no statistical significance was observed. Histopathologically, the crude E. prostrata extract significantly ameliorates either CCl 4 or GaLN-induced histopathological changes in the liver of experimental animals but no statistically significant improvement could be observed in acetaminophen induced liver damage. All serological and histopathological effects of Eclipta prostrata were compared with that of Bupleurum chinense DC., which has been previously reported and used as a treatment criteria for hepatitis (Chiu et al., 1988; 1989; Lin et al., 1990a, b).

The present study was carried out to investigate the hepatoprotective effects of a dose of C. xanthorrhiza on acute hepatotoxicity induced in rats by a single dose of β-D-galactosamine (288 mg/kg, i.p.), and its mechanism of action. C. xanthorrhiza (100 mg/kg) was administered p.o. to experimental animals according to the protocol followed by the i.p. administration of a single dose of hepatotoxin. Hepatoprotective activity was monitored by estimating serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) levels and histopathological changes in the livers of C. xanthorrhiza -treated and untreated groups of animals. The results clearly indicated that the extract of C. xanthorrhiza significantly reduced the acute elevation of serum transaminases induced by hepatotoxin, and alleviated the degree of liver damage at 24 h after the intraperitoneal administration of the hepatotoxins.

The hepatoprotective effect of Alstonia scholaris R. Br. on liver injuries induced by carbon tetrachloride (CCl4), ß-D-galactosamine, acetaminophen and ethanol were investigated by means of serum-biochemical and histopathological examinations. Post treatment of A scholaris reduced dose-dependently the elevation of serum transaminases level and histopathological changes such as cell necrosis, inflammatory cell infiltration, which were caused by the single administration of 32 μl/kg CCl4 or 600 mg/kg acetaminophen in mice. A. scholaris significantly lowered 288 mg/kg ß-D-galactosamine induced serum transaminases elevation in the serum-biochemical analysis in rats. A tendency was also shown to inhibit cell necrosis and inflammatory cell infiltration caused by ß-D-galactosamine in histopathological examination. All serological and histopathological effects of A. scholaris were compared with those of Bupleurum chinense, which has been reported previously as a treatment criteria of hepatitis.

The hepatoprotective effects of the Taiwanese herb ‘Horngtyan-wu’ (Alternanthera sessilis (L.) DC.) were investigated in three kinds of experimental animal model. Acute hepatitis was induced by various chemicals such as carbon tetrachloride (31.25 μL/kg, i.p.) or acetaminophen (paracetamol; 600 mg/kg, i.p.) in mice and D(+)-galactosamine (188 mg/kg, i.p.) in rats. When treated with A. sessilis (300 mg/kg, p.o.) at 2, 6 and 10 h, a reduction in elevation of serum glutamate oxaloacetic transaminase (SGOT) and glutamate pyruvic transaminase (SGPT) levels could be observed at 24 h after administration of the three hepatotoxins. These serological observations were also confirmed by histopathological examinations including centrilobular necrosis, eosinophilic bodies, pyknotic nuclei, microvesicular degeneration of hepatocytes and others. The liver microscopic examination showed a noted improvement in groups receiving A. sessilis. All pharmacological and histopathological effects were compared with observations using the hepatoprotective Chinese herb, Bupleurum chinense (Family Umbelliferae). It was confirmed that A. sessilis has hepatoprotective effects against liver injuries induced by hepatotoxins with different mechanisms.

To examine the inhibitory actions of the immunoregulator platonin against proliferation of rat vascular smooth muscle cells (VSMCs).VSMCs were prepared from the thoracic aortas of male Wistar rats. Cell proliferation was examined using MTT assays. Cell cycles were analyzed using flow cytometry. c-Jun N-terminal kinase (JNK)1/2, extracellular signal-regulated kinase (ERK)1/2, AKT, and c-Jun phosphorylation or p27 expression were detected using immunoblotting.Pretreatment with platonin (1-5 μmol/L) significantly suppressed VSMC proliferation stimulated by PDGF-BB (10 ng/mL) or 10% fetal bovine serum (FBS), and arrested cell cycle progression in the S and G(2)/M phases. The same concentrations of platonin significantly inhibited the phosphorylation of JNK1/2 but not ERK1/2 or AKT in VSMCs stimulated by PDGF-BB. Furthermore, platonin also attenuated c-Jun phosphorylation and markedly reversed the down-regulation of p27 expression after PDGF-BB stimulation.Platonin inhibited VSMC proliferation, possibly via inhibiting phosphorylation of JNK1/2 and c-Jun, and reversal of p27 down-regulation, thereby leading to cell cycle arrest at the S and G(2)/M phases. Thus, platonin may represent a novel approach for lowering the risk of abnormal VSMC proliferation and related vascular diseases.

Background Platelet activation is relevant to a variety of coronary heart diseases. Our previous studies revealed that sesamol possesses potent antiplatelet activity through increasing cyclic AMP formation. Although platelets are anucleated cells, they also express the transcription factor, NF-κB, that may exert non-genomic functions in platelet activation. Therefore, we further investigated the inhibitory roles of sesamol in NF-κB-mediated platelet function. Methods Platelet aggregation, Fura 2-AM fluorescence, and immunoblotting analysis were used in this study. Results NF-κB signaling events, including IKKβ phosphorylation, IκBα degradation, and p65 phosphorylation, were markedly activated by collagen (1 μg/ml) in washed human platelets, and these signaling events were attenuated by sesamol (2.5~25 μM). Furthermore, SQ22536 and ODQ, inhibitors of adenylate cyclase and guanylate cyclase, respectively, strongly reversed the sesamol (25 μM)-mediated inhibitory effects of IKKβ phosphorylation, IκBα degradation, and p65 phosphorylation stimulated by collagen. The protein kinase A (PKA) inhibitor, H89, also reversed sesamol-mediated inhibition of IκBα degradation. Moreover, BAY11-7082, an NF-κB inhibitor, abolished IκBα degradation, phospholipase C (PLC)γ2 phosphorylation, protein kinase C (PKC) activation, [Ca2+]i mobilization, and platelet aggregation stimulated by collagen. Preincubation of platelets with the inhibitors, SQ22536 and H89, both strongly reversed sesamol-mediated inhibition of platelet aggregation and [Ca2+]i mobilization. Conclusions Sesamol activates cAMP-PKA signaling, followed by inhibition of the NF-κB-PLC-PKC cascade, thereby leading to inhibition of [Ca2+]i mobilization and platelet aggregation. Because platelet activation is not only linked to hemostasis, but also has a relevant role in inflammation and metastasis, our data demonstrating that inhibition of NF-κB interferes with platelet function may have a great impact when these types of drugs are considered for the treatment of cancer and various inflammatory diseases.

Ethnopharmacological relevance Ganoderma, known as Lingzhi or Reishi, has been traditionally administered throughout Asia for centuries as a cancer treatment and for other medicinal purposes. Aim of the study To investigate the inhibitory activity and explore the molecular mechanisms of anti-tumor effect on colorectal cancer cells in vitro and in vivo as well as to test the side effects of Ganoderma tsugae. Materials and methods Methanol fraction was obtained from dried fruiting bodies of Ganoderma. TLC and HPLC were performed to differentiate and confirm the identification of different species as well as to quantify the bioactive molecules in methanol extracts of Ganoderma species. MTT and Trypan blue exclusion assay as well as tumorigenesis study were used to assess the anti-tumor effect in vitro and in vivo. Using flow cytometry and Western Blots, we examined further the molecular mechanisms of anti-tumor effect. Finally, biochemical and hematological profiles and pathological examinations were used to evaluate the safety. Results The Ganoderma tsugae extracts inhibit colorectal cancer cell proliferation caused by accumulating cells in G2/M phase, and it may be through downregulation of cyclin A and B1 and upregulation of p21 and p27. Tumorigenesis study in nude mice revealed the extracts caused tumor shrinkage. Additionally, safety assay showed Ganoderma tsugae extracts caused no significant side effects in an animal model. Conclusions This study provides molecular evidence that Ganoderma tsugae extracts exert anti-tumor effects both in vitro and in vivo on colorectal adenocarcinoma cells by inducing G2/M cell cycle arrest. More importantly, no significant physiological changes resulting from treatment with Ganoderma tsugae extracts were observed in the animal model. Therefore, these data provide new insights into the possible therapeutic use of Ganoderma tsugae for treating colorectal cancer.

Free radicals and lipid peroxides, both of which are easily formed in the diabetic state, play an important role in the development of diabetic complications. Antioxidative therapy may help prevent diabetic complications caused by lipoperoxidation and free-radical formation in diabetes mellitus (DM). A number of findings suggest that oxidative stress exists in persons with high-risk DM. Auricular pellet acupressure has reportedly been an effective treatment method for a variety of medical conditions, including anxiety, juvenile myopia, essential hypertension, and senile vascular dementia. However, its effects on antioxidative enzymes have not been elucidated. We therefore evaluated the impact of auricular pellet acupressure on antioxidative status in persons with high-risk DM.Our study involved 69 persons with high-risk DM, who were allocated either to undergo acupressure as active treatment for the experimental group or to a control group.The experimental group in the study received auricular pellet acupressure three times daily for 5 consecutive days. After a 2-day rest period, the procedure was performed on the contralateral ear. Acupressure was performed twice on each ear, with each application followed by its application to the contralateral ear, over a total treatment period of 20 days. The control groups did not undergo auricular pellet acupressure.At the end of the 20-day period of treatment of the experimental group, blood was collected from all of the study participants for assay of serum superoxide dismutase (SOD) and catalase concentrations, as was also done for the control group.Serum concentrations of SOD (p0.05) and catalase (p0.0001) were significantly higher in the experimental group than in the control group.Our findings suggest that auricular pellet acupressure can increase the concentration of antioxidative enzymes in persons with high-risk DM.

Acute p.o. administration of 99.5% ethanol (0.1 ml) to fasted mice produced heart toxicity. Pretreatment with p.o. administration of tetramethylpyrazine (TMP) could prevent such toxicity effectively and dose-dependently. The maximal antioxidative effect against 99.5% ethanol-induced heart toxicity could be observed at 1 hour after TMP administration. In order to further investigate the heart protective mechanism of TMP, both lipid peroxidation level in vivo and superoxide scavenging activity were conducted. TMP exhibited a dose-dependently anti-lipid peroxidation effect in mice heart homogenate, and results indicated that 99.5% ethanol-induced intoxicated mice hearts have higher malonic dialdehyde (MDA) levels compared with those in TMP administrated mice hearts. These results suggest that the potentially heart protective mechanism of TMP could be contributed, at least in part, to its prominent anti-lipid peroxidation and anti-free radical formation effects, hence it could protect the heart from lipid peroxidation-induced heart toxicity.

Acute p.o. administration of absolute ethanol (10 ml/kg) to fasted mice would produce extensive renal failure. Pretreatment with p.o. administration of propolis ethanol extract (PEE) could prevent such renal failure effectively and dose dependently. This renal protective effect of PEE may be contributed, at least in part, to its antioxidative activity. The maximal antioxidative effect against absolute ethanol (AE)-induced renal failure could be observed 1 hour after PEE administration. In order to further investigate the renal protective mechanism of PEE, lipid peroxidation and superoxide scavenging activity were conducted in vivo. PEE exhibited dose-dependent antioxidative effects on lipid peroxidation in mice renal homogenate. Results indicated that mice with acute renal failure have higher malonic dialdehyde (MDA) levels compared with those in PEE administered mice. It was concluded that the renal protective mechanism of PEE could be contributed, at least in part, to its prominent superoxide scavenging effect; hence, it could protect, indirectly, the kidney from superoxide-induced renal damages.

Acute p.o. administration of absolute ethanol (1.0 ml/kg) to fasted rats produced extensive necrosis of gastric mucosa. Pretreatment with p.o. administration of propolis ethanol extract (PEE) could effectively and dose-dependently prevent such necrosis. This protective effect is called "cytoprotection." The maximal cytoprotective effect against absolute ethanol (AE)-induced gastric mucosal lesion was observed 1 hour after PEE administration. A gross examination of the gastric mucosa showed a marked improvement in groups receiving PEE. In order to further investigate the gastric protective mechanism of PEE, lipid peroxidation (LPO) levels in vivo and in vitro were estimated. PEE exhibited dose-dependent superoxide scavenging activity and antioxidant effects on AE-induced LPO in rat gastric mucosal homogenates. It was concluded that the gastric protective mechanism of PEE was due, at least in part, to its ability to inhibit LPO, and hence indirectly protect the gastric mucosa from oxidative stress.

Acute administration of absolute ethanol (10 ml/kg) per os to fasted mice produced extensive renal failure as measured by a rise in blood urea nitrogen and creatinine. Pretreatment with oral administration of tetramethylpyrazine (TMP) prevented such failure. The maximal effect against absolute ethanol-induced renal failure could be observed 1 h after TMP administration. In order to further investigate the renal protective mechanism of TMP, experiments on lipid peroxidation and superoxide scavenging activity were conducted. Renal homogenates made from mice treated with ethanol showed that TMP pretreatment had an antioxidant effect. Mice in acute renal failure had higher malonic dialdehyde concentrations than those pretreated with TMP. The renal protective mechanism of TMP was attributed, in part, to its prominent superoxide scavenging effect, which protects the kidney from superoxide-induced renal damage.

2,3,5,6-Tetramethylpyrazine (TMP) is well known as a true calcium antagonist. The aim of this study was to investigate the hepatoprotective and therapeutic effects of TMP on acute econazole-induced liver injury. The hepatological effect of various concentrations of TMP was first assessed by the biochemical assays of SGOT and SGPT and then by hepatohistological microscopic examination. The dose-response relationship of liver injury induced by various doses of econazole was observed simultaneously from serum biochemical assay of SGOT and SGPT, and also from hepatohistological microscopic examination, by determination of the hepatoprotective effects of various concentrations of TMP on SGOT and SGPT elevation induced by a hepatotoxic dose of econazole (300 mg/kg). The inhibitory effect of various concentrations of TMP or vitamin E (positive control, 0.5 mM in vitro, 0.69 mM in vivo) on FeCl 2 -induced (in vitro) or econazole-induced (in vivo) lipid peroxidation was also investigated. The superoxide scavenging activity of various concentrations of TMP in econazole-damaged rat liver homogenate was assessed by the cytochrome C reduction method. Results showed that the hepatoprotective effect of TMP might be, at least in part, due to its inhibitory ability on membrane lipid peroxidation and free radical formation, or due to its free radical scavenging ability. Improvement of serum transaminases and MDA levels in rat liver homogenate, hepatohistological microscopic examination, and assessment of free radical scavenging activity by the cytochrome C reduction method were used to detect hepatoprotective and therapeutic effects of TMP on acute econazole-induced liver injury.

In order to elucidate possible male/female differences in emesis, the effects of various emetogenic drugs (cisplatin, copper sulfate, veratrine, nicotine, serotonin) and motion stimulus were compared between male and female Suncus murinus. Cisplatin (IP), nicotine (SC), veratrine (SC) and copper sulfate (PO) induced dose-dependent emesis in either sex, and there was no apparent difference in estimated ED50 values. However, male animals tended to be more susceptible to serotonin-induced emesis. The ID50 values for tropisetron, a 5-HT3 receptor antagonist, to block serotonin-induced emesis were also similar between male and female animals. However, tropisetron was less effective against cisplatin-induced emesis in females. Therefore, cisplatin may release more serotonin to induce emesis in females. Reciprocal shaking (horizontal oscillation 40 mm, frequency 0.5 to 2.0 Hz, duration 5 min) induced more frequent emesis in male animals, and the latency to the first vomit was shorter in males than in females. These results suggest that there is substantial sex-dependent difference in the emetic responses and male animals are in general more susceptible. These results are discussed in the light of similar studies in man.

The hepatoprotective effect of Huanglian-Jie-Du-Tang (HLJDT), a Chinese medicinal prescription, was investigated in three kinds of experimental models. The animals were treated with HLJDT (300 mg/kg, p.o.) thrice at 2, 4 and 10 hours after administration with carbon tetrachloride (32 μl/kg, i.p.), acetaminophen (600 mg/kg, i.p.) and β-D-galactosamine (188 mg/kg, i.p.). Significant hepatoprotective effects on carbon tetrachloride and actaminophen induced liver injuries were noted, but no significant effect on β-D-galactosamine induced liver injury was observed. These hepatoprotective effects were evidenced by comparing the serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) levels in HLJDT treated and untreated groups. Serum enzyme activities in the carbon tetrachloride and acetaminophen experiments were significantly lower in the treated groups while the herbal prescription has no effect on the β-D-galactosamine experiment. These results demonstrated that Huanglian-Jie-Du-Tang has a hepatoprotective effect against experimental liver injuries induced by specific hepatotoxins, and therefore may be useful in treating some, but not all, liver injuries.

Curcuma xanthorrhiza Roxb. (Zingiberaceae family, commonly known as temu lawak or Javanese turmeric in Indonesia), which is found both wild and cultivated in Indonesia, has been traditionally used for medicinal purposes. C. xanthorrhiza is also used as a tonic in Indonesia. The aim of the present study is to clarify whether C. xanthorrhiza treatment may prevent acute liver damage induced by acetaminophen and carbon tetrachloride in mice. The results clearly indicated that extract of C. xanthorrhiza could reduce significantly the acute elevation of serum transaminases levels induced by the two kinds of hepatotoxins, and alleviated the degree of liver damage at 24 hours after the intraperitoneal administration of two hepatotoxins. It may be concluded that C. xanthorrhiza can protect the liver from various hepatotoxins, hence C. xanthorrhiza could be useful in the treatment of liver injuries and has promise as a kind of broad spectrum hepatoprotective agent.

The hepatoprotective effects of a Taiwanese crude herb, Hwang-hua-mih-tsay (Wedelia chinensis (Osbeck) Merr.), were investigated. Acute hepatitis was induced by three hepatotoxins: carbon tetrachloride and acetaminophen in mice, and D(+)-galactosamine in rats. After treatment with W. chinensis (300 mg/kg, p.o.) at 2,6 and 10 hours, a reduction in the elevation of serum glutamate oxaloacetic transaminase (SGOT) and glutamate pyruvic transaminase (SGPT) levels was observed at 24 hrs after hepatotoxins were administered. These serological observations were confirmed by histopathological examinations. A microscopic examination of the liver showed a marked improvement in groups receiving W. chinensis. In order to further confirm the hepatoprotective effect of W. chinensis, all pharmacological and histopathological effects were compared with Bupleurum chinense DC. (family Umbelliferae), a well documented antihepatotoxicity herb. It was concluded that W. chinensis has a definite hepatoprotective effect against liver injuries.

Alpha- and beta-fibrinogenases prepared from Trimeresurus mucrosquamatus venom digested specifically the alpha(A) and beta(B) chains of the fibrinogen molecule, respectively. alpha-Fibrinogenase digested bovine fibrinogen more markedly than human fibrinogen, while beta-fibrinogenase digested human fibrinogen more markedly than bovine fibrinogen. Human fibrin was also digested by both enzymes. Plasma fibrinogens of 4 animal species were digested by alpha-fibrinogenase to the same degree, while those by beta-fibrinogenase in the following order: human greater than dog greater than guinea-pig greater than rabbit. The fibrinogenolytic effects of alpha-fibrinogenase on human fibrinogen were strongly inhibited by sera of the 4 animal species, while those of beta-fibrinogenase were inhibited in the following order: rabbit greater than guinea-pig greater than dog greater than human. It was concluded that the different activities of the protease inhibitors in the plasma of animal species are mainly responsible for the sensitivity differences.

Blood samples were collected by cardiac puncture from nine-week-old suncus, mice and rats those had been fasted for 16 hours, and the serum was assayed for the levels of corticosterone, cortisol, and other constituents. The following results were obtained: The serum levels of corticosterone and cortisol and corticosterone/cortisol ratio of suncus were about the same as those of human. The SGPT, gamma-GT, ALP, LDH, Ca and K values in suncus were all within the normal range of the respective values in human. SGOT, amylase, BUN, Na, Cl, Fe and inorganic phosphate values were higher, and total cholesterol, triglyceride, phospholipid, creatinine, urea, total protein, albumin and bilirubin levels were lower in suncus than the respective normal values in human. The values of SGOT, amylase, ZTT, and K were higher in female than in male suncus, while the values of gamma-GT and ALP were higher in the male. Feeding the animals individually in the individual cages for a week increased the values of direct bilirubin, total cholesterol, ZTT, Na, K and Cl and lowered the value of urea. The values of SGPT, ALP and triglyceride of suncus obtained in 1984 were higher, the value of albumin was lower, than the respective values obtained in 1983. The value of cholinesterase in suncus was very small.

A vAlt>srY of animal venoms, mostly of snake origin, modify blood coagulation (HOUSSAY, 1930; L~ et al., 1955 ; OUYANG, 1957 ; BoQusr, 1964 ; MF,AiJME, 1966 ; ROSENFELD et al., 1968 ; JI z-PO1tRAS, 1970; LEE, 1975 ; Tu, 1977) . JOSHUA and I3HAY (1975) demonstrated that an extract from the venom sac of the oriental hornet (Vespa orientalis) had an anticoagulant effect on blood coagulation. HABERMANN (1954) reported that honey bee (Apia mellifera) venom inhibited blood coagulation through inactivation of tissue thromboplastin probably by its phospholipase A component . Since the effect of this venom on other clotting factors is not well known, it was of interest to investigate the anticoagulant action of this venom and elucidate its mode of action . Apis mellifera venom, crude cephalin (chloroform extract of acetone-dried rabbit brain) and Russell's viper venom in crude cephalin were obtained from Sigma Chem. Co . Thrombin (bovine) was purchased from Parke-Davis Co. and dissolved in 50~ glycerolsaline to give a stock solution of 1000 N.LH . p/ml (S~GGI~ts and SMrrH, 1942) . Fibrinogen (bovine) was purchased from Pentex Co. and dissolved in imidazole-saline (pH 7"4j and the stock solution of 20 mg/ml was stored at -70°C before use . Rabbit brain thromboplastin was prepared according to the method of BIGGS and MACi?A1tLAN13 (1962) . Plateletpoor plasma was obtained from citrated blood (1 :9, v/v) after centrifugation for 20 min at 3000 rpm and 4°C . Blood collected from the rabbit marginal ear vein through a 19-gauge needle was mixed with 0'1 M Na9EDTA (1 :14, v/v) as anticoagulant and centrifuged for 10 min at 800 g and at room temperature . The platelet pellet was washed with Tris-buffered saline (pH 7"4) containing NaEEDTA (3 mM), apyrase (ADPase activity, 0~5 U/ml) and bovine serum albumin (1 mg/ml) and recentrifuged (modification of the methods of MUSTARD et al., 1972 and ARDIJE et al., 1971) . This wash procedure was repeated two times and the washed platelets were suspended in Tris-buffered saline, ruptured with a stirrer and then frozen and thawed three times before use . Whole blood clotting time was determined by the method of LEe and WFnre (1913) . Calcium clotting time of plasma was carried out as described by BIGGS and MACFARLANE (1962). The one-stage method of Qulcx (1938) was used to measure the plasma prothrombin time . Partial thromboplastin time was measured by the method of NYS et al. (1962) .

Serum constituents and liver of the wild male suncus as well as of those bred and fed in our laboratory were examined serologically and histologically. The following results were obtained: The serum glutamic-oxaloacetic transaminase, gamma-glutamyl transaminase, inorganic phosphate, blood urea nitrogen, creatinine, uric acid, and zinc turbidity test levels of wild suncus were higher than those of 4 and 8 week old fed suncus. The total cholesterol level of wild suncus was lower than those of 4 and 8 week old fed suncus. In wild suncus, the total bilirubin and direct bilirubin levels were higher, and the Ca and albumin levels were lower than those of 4 week old fed suncus. However, no significant differences were observed between the wild and the 8 week old fed suncus. Although the alkaline phosphatese and thymol turbidity test levels of wild suncus were larger than those of 8 week old fed suncus, no significant differences were observed between the wild and the 4 week old fed suncus. The histological study revealed the presence of fatty droplets in only 2 of the 67 wild suncus examined while fatty droplets (grade +) were observed in almost all the fed suncus. In one case of the wild suncus, moderate round cell infiltration in interlobular connective tissue was found.

A comparative study was conducted to contrast the hepatotoxicity of several chemicals in the musk shrew (Suncus murinus) versus other common laboratory species (mouse or rat), and the following results were obtained from serum enzymes (SGOT and SGPT) and histopathological findings of liver specimens. The sensitivity of Suncus liver to CCl4 was different from that of mouse liver. The sensitivity of Suncus liver to beta-D-galactosamine was weaker than that of rat liver. The sensitivity of Suncus liver to ethanol was stronger than that of mouse liver. After a single oral administration of ethanol (99.5% v/v, 0.1 ml/50 g body weight), the gallbladder of Suncus became enlarged and dark blue in color. A striking fatty degeneration was seen 24 h after a single ip administration of amethopterin at 50 mg/kg in Suncus liver.

Background We previously identified two hydrolyzable tannins, chebulagic acid (CHLA) and punicalagin (PUG) that blocked herpes simplex virus type 1 (HSV-1) entry and spread. These compounds inhibited viral glycoprotein interactions with cell surface glycosaminoglycans (GAGs). Based on this property, we evaluated their antiviral efficacy against several different viruses known to employ GAGs for host cell entry. Results Extensive analysis of the tannins’ mechanism of action was performed on a panel of viruses during the attachment and entry steps of infection. Virus-specific binding assays and the analysis of viral spread during treatment with these compounds were also conducted. CHLA and PUG were effective in abrogating infection by human cytomegalovirus (HCMV), hepatitis C virus (HCV), dengue virus (DENV), measles virus (MV), and respiratory syncytial virus (RSV), at μM concentrations and in dose-dependent manners without significant cytotoxicity. Moreover, the natural compounds inhibited viral attachment, penetration, and spread, to different degrees for each virus. Specifically, the tannins blocked all these steps of infection for HCMV, HCV, and MV, but had little effect on the post-fusion spread of DENV and RSV, which could suggest intriguing differences in the roles of GAG-interactions for these viruses. Conclusions CHLA and PUG may be of value as broad-spectrum antivirals for limiting emerging/recurring viruses known to engage host cell GAGs for entry. Further studies testing the efficacy of these tannins in vivo against certain viruses are justified.