Song-Chow Lin

Hepatoprotective Effects of Arctium lappa Linne on Liver Injuries Induced by Chronic Ethanol Consumption and Potentiated by Carbon Tetrachloride

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).

Hepatoprotective effects of arctium lappa on carbon tetrachloride- and acetaminophen-induced liver damage

The root of Arctium lappa Linne (A. lappa) (Compositae), a perennial herb, has been cultivated for a long time as a popular vegetable. In order to investigate the hepatoprotective effects of A. lappa, male ICR mice were injected with carbon tetrachloride (CCl4, 32 microl/kg, i.p.) or acetaminophen (600 mg/kg, i.p.). A. lappa suppressed the SGOT and SGPT elevations induced by CCl4 or acetaminophen in a dose-dependent manner and alleviated the severity of liver damage based on histopathological observations. In an attempt to elucidate the possible mechanism(s) of this hepatoprotective effect, glutathione (GSH), cytochrome P-450 (P-450) and malondialdehyde (MDA) contents were studied. A. lappa reversed the decrease in GSH and P-450 induced by CCl4 and acetaminophen. It was also found that A. lappa decreased the malondialdehyde (MDA) content in CCl4 or acetaminophen-intoxicated mice. From these results, it was suggested that A. lappa could protect the liver cells from CCl4 or acetaminophen-induced liver damages, perhaps by its antioxidative effect on hepatocytes, hence eliminating the deleterious effects of toxic metabolites from CCl4 or acetaminophen.

Protective and therapeutic effects of Curcuma xanthorrhiza on hepatotoxin-induced liver damage.

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.

A novel role of sesamol in inhibiting NF-κB-mediated signaling in platelet activation

BackgroundPlatelet 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.MethodsPlatelet aggregation, Fura 2-AM fluorescence, and immunoblotting analysis were used in this study.ResultsNF-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.ConclusionsSesamol 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.

Hepatoprotective activity of Taiwan folk medicine: Eclipta prostrata Linn. against various hepatotoxins induced acute hepatotoxicity

The hepatoprotective effects of Eclipta prostrata(Linn.) were studied on acute hepatitis induced in mice by a single dose of carbon tetrachloride (31.25 μL/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 CCl4 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).

Protective and therapeutic effects of Huanglian-Jie-Du-Tang on hepatotoxin-induced liver injuries

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 microliters/kg, i.p.), acetaminophen (600 mg/kg, i.p.) and beta-D-galactosamine (188 mg/kg, i.p.). Significant hepatoprotective effects on carbon tetrachloride and acetaminophen induced liver injuries were noted, but no significant effect on beta-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 beta-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.

The Hepatoprotective Effects of Solanum alatum Moench. on Acetaminophen-induced Hepatotoxicity in Mice

Solanum alatum Moench. has been shown to have a protective effect against carbon tetrachloride (CCl4)-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, reductase, 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.

Protective and therapeutic effect of the Indonesian medicinal herb Curcuma xanthorrhiza on β-D-galactosamine-induced liver damage

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.

Platonin inhibited PDGF-BB-induced proliferation of rat vascular smooth muscle cells via JNK1/2-dependent signaling

Aim:To examine the inhibitory actions of the immunoregulator platonin against proliferation of rat vascular smooth muscle cells (VSMCs).Methods: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.Results: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 G2/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.Conclusion: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 G2/M phases. Thus, platonin may represent a novel approach for lowering the risk of abnormal VSMC proliferation and related vascular diseases.

Protective effect of propolis ethanol extract on ethanol-induced renal toxicity: an in-vivo study.

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.