Tetrahydropalmatine Alleviates Hyperlipidemia by Regulating Lipid Peroxidation, Endoplasmic Reticulum Stress, and Inflammasome Activation by Inhibiting the TLR4-NF-κB Pathway.

Hyperlipidemia (HLP) is a lipid metabolism disorder that can induce a series of cardiovascular and cerebrovascular diseases, such as atherosclerosis, myocardial infarction, coronary heart disease, and stroke, which seriously threaten human health. Tetrahydropalmatine (THP) is a component of the plant Rhizoma corydalis and has been shown to exert hepatoprotective and anti-inflammatory effects in HLP. However, whether THP regulates lipid peroxidation in hyperlipidemia, endoplasmic reticulum (ER) stress and inflammasome activation and even the underlying protective mechanism against HLP remain unclear. An animal model of HLP was established by feeding a high-fat diet to golden hamsters. Our results showed that THP reduced the body weight and adipose index; decreased the serum content of ALT, AST, TC, TG, and LDL-C; decreased the free fatty acid hepatic lipid content (liver index, TC, TG, and free fatty acid); inhibited oxidative stress and lipid peroxidation; extenuated hepatic steatosis; and inhibited ER stress and inflammasome activation in high-fat diet-fed golden hamsters. In addition, for the first time, the potential mechanism by which THP protects against HLP through the TLR4-NF-κB signaling pathway was demonstrated. In conclusion, these data indicate that THP attenuates HLP through a variety of effects, including antioxidative stress, anti-ER stress, and anti-inflammatory effects. In addition, THP also inhibited the TLR4-NF-κB signaling pathway in golden hamsters.

Vitamin D receptor targets hepatocyte nuclear factor 4α and mediates protective effects of vitamin D in nonalcoholic fatty liver disease.

Epidemiological studies have suggested a link between vitamin D deficiency and increased risk for nonalcoholic fatty liver disease (NAFLD); however, the underlying mechanisms have remained unclear. Here, using both clinical samples and experimental rodent models along with several biochemical approaches, we explored the specific effects and mechanisms of vitamin D deficiency in NAFLD pathology. Serum vitamin D levels were significantly lower in individuals with NAFLD and in high-fat diet (HFD)-fed mice than in healthy controls and chow-fed mice, respectively. Vitamin D supplementation ameliorated HFD-induced hepatic steatosis and insulin resistance in mice. Hepatic expression of vitamin D receptor (VDR) was up-regulated in three models of NAFLD, including HFD-fed mice, methionine/choline-deficient diet (MCD)-fed mice, and genetically obese (ob/ob) mice. Liver-specific VDR deletion significantly exacerbated HFD- or MCD-induced hepatic steatosis and insulin resistance and also diminished the protective effect of vitamin D supplementation on NAFLD. Mechanistic experiments revealed that VDR interacted with hepatocyte nuclear factor 4 α (HNF4α) and that overexpression of HNF4α improved HFD-induced NAFLD and metabolic abnormalities in liver-specific VDR-knockout mice. These results suggest that vitamin D ameliorates NAFLD and metabolic abnormalities by activating hepatic VDR, leading to its interaction with HNF4α. Our findings highlight a potential value of using vitamin D for preventing and managing NAFLD by targeting VDR.

Pharmacokinetics of oral and intravenous cannabidiol and its antidepressant-like effects in chronic mild stress mouse model.

Cannabidiol (CBD) exhibits significant efficacy in mental and inflammatory diseases. Several studies have recently reported on the rapid antidepressant-like effects of CBD, suggesting that CBD is a potential anti-depressant or anti-stress drug. However, CBD is mainly administered orally or by inhalation with poor bioavailability, resulting in high costs. We aim to explore the efficacy of long-term periodic administration of CBD in chronic mild stress (CMS) via two routes and its pharmacokinetics. We treated ICR mice with CBD administered orally and intravenously and then determined the kinetic constants. A single bolus intravenous injection of CBD resulted in a half-life of 3.9 h, mean residence time of 3.3 h, and oral bioavailability of about 8.6%. The antidepressant-like effects of periodically administered CBD on the chronic mild stress mouse model are evaluated. Results demonstrated that such treatment at a high dose of 100 mg/kg CBD (p.o.) or a low dose of 10 mg/kg CBD (i.v.), elicited significant antidepressant-like behavioral effects in forced swim test, following increased mRNA expression of brain-derived neurotrophic factor (BDNF) and synaptophysin in the prefrontal cortex and the hippocampus. Our findings are expected to provide a reference for the development of intravenous antidepressant formulations of CBD.

Probiotic supplementation does not improve eradication rate of Helicobacter pylori infection compared to placebo based on standard therapy: a meta-analysis.

This meta-analysis included eligible randomized controlled trials (RCTs) with the aim of determining whether probiotic supplementation can improve H. pylori eradication rates. PUBMED, EBSCO, Web of Science, and Ovid databases were searched. We included RCTs that investigated the effect of combining probiotics, with or without a placebo, with standard therapy. A total of 21 RCTs that reported standard therapy plus probiotics were included. Compared to the placebo group, the probiotics group was 1.21(OR 1.21, 95% CI: 0.86, 1.69) and 1.28 (OR 1.28, 95% CI: 0.88, 1.86) times more likely to achieve eradication of H. pylori infection in intent-to-treat (ITT) analysis and per protocol (PP) analysis, respectively. Probiotics with triple therapy plus a 14-day course of treatment did not improve the eradication of H. pylori infection (OR 1.44, 95% CI: 0.87, 2.39) compared to the placebo. Moreover, the placebo plus standard therapy did not improve eradication rates compared to standard therapy alone (P = 0.816). However, probiotics did improve the adverse effects of diarrhea and nausea. These pooled data suggest that the use of probiotics plus standard therapy does not improve the eradication rate of H. pylori infection compared to the placebo.

ω-3 Fatty acids reverse lipotoxity through induction of autophagy in nonalcoholic fatty liver disease.

OBJECTIVE: The aim of this study was to evaluate the effect of ω-3 fatty acids on nonalcoholic fatty liver disease concerning hepatocyte lipid accumulation as well as apoptosis induced by free fatty acids (FFAs) and to explore the underlying mechanism involving autophagy. METHODS: Hepatocytes were incubated with a mixture of free fatty acids (FFAs) to mimic in vitro lipotoxicity in the pathogenesis of nonalcoholic fatty liver disease, presented by lipid accumulation and cellular apoptosis. Chemical inhibitor or inducer of autophagy and genetic deficit cells, as well as ω-3 fatty acids were used as intervention. The autophagic role of ω-3 fatty acids was investigated using Western blot and immunofluorescence. The underlying mechanism of ω-3 fatty acids involving autophagy was preliminarily explored by quantitative real-time polymerase chain reaction and Western blot. RESULTS: FFAs induce lipid accumulation and apoptosis in hepatocytes. Inhibition or genetic defect of autophagy increases lipid accumulation induced by FFA, whereas induction acts inversely. ω-3 Fatty acids reduced lipid accumulation and inhibited apoptosis induced by FFA. ω-3 Fatty acids induced autophagy by downregulating stearoyl-CoA desaturase 1 expression in hepatocytes. CONCLUSION: ω-3 Fatty acids exert protective effects on hepatocytes against lipotoxicity through induction of autophagy, as demonstrated by inhibition of lipid accumulation and apoptosis.

Traditional Chinese medicine for idiopathic precocious puberty: A hospital-based retrospective observational study.

OBJECTIVES: To characterize the application of traditional Chinese medicine (TCM) among children with idiopathic precocious puberty (IPP). DESIGN AND SETTING: This study examined data sets from patients diagnosed with IPP at Chang Gung Memorial Hospital between 2010 and 2012. The patients were allocated into three groups according their voluntary choice of treatment modalities: TCM users (received TCM treatment only), Western medicine (WM) users (received WM treatment only), and "no treatment" group (received no medical treatment at all). MAIN OUTCOME MEASURES: The demographic data of children with IPP were characterized. The prescription patterns and frequencies of TCM for IPP patients were analyzed. The patients' bone maturation rates and the change of predicted height after different approaches were measured as outcomes. RESULTS: There were 3390 patients enrolled in the study. Zhi-Bai-Di-Huang-Wan (70.62%) was the most common herbal formula and Mai-Ya (Hordei Fructus Germinatus) (51.58%) was the most common single herb prescribed for IPP in all of the 2784 prescriptions. The bone maturation rates of TCM users (0.95±0.20) and WM users (0.69±0.05) were both decelerated but the "no treatment" group had an accelerated bone maturation rate of 1.33±0.04. TCM and WM users also had higher predicted height after treatment (1.15±1.19cm versus 1.73±0.29cm), while the "no treatment" group had a decreased predicted height (-0.52±0.23cm). CONCLUSIONS: Our study revealed a comprehensive list of TCM prescriptions for IPP patients. Future well-designed, randomized, double-blinded, and placebo-controlled clinical trials are warranted to evaluate the efficacy and safety of TCM for precocity.

Effect of vitamins C and E supplementation on Helicobacter pylori eradication: a meta-analysis.

Vitamins C and E can act as potent antioxidants to reduce the damage caused by reactive oxygen species in gastric mucosa. Whether vitamin supplements for Helicobacter pylori eradication regimen could improve the rate of eradication remains uncertain. Therefore, we performed a meta-analysis to evaluate the efficacy of vitamins C and E supplementation for the eradication of H. pylori. Searches were conducted in the databases PubMed, EMBASE and Cochrane Library. Randomised controlled trials (RCT) that fulfilled the inclusion criteria and addressed the clinical questions of this analysis were further assessed. Of the six RCT included, five had a low methodological quality. Of the six RCT, three compared the efficacy of the eradication regimen v. eradication regimen plus vitamins C and E. The result of the meta-analysis showed a non-significant difference in the eradication rate of H. pylori between the two groups (risk ratio (RR) 0·93, P = 0·76). Another three RCT compared the eradication regimen v. eradication regimen plus vitamin C only, and there too there was no significant difference in the eradication rate (RR 0·83, P = 0·32). In conclusion, vitamins C and/or E supplements to the H. pylori eradication regimen could not improve the eradication rate. However, currently available data do not draw a definitive conclusion about the effectiveness of antioxidant vitamins on H. pylori eradication, owing to the small sample size and low-to-moderate methodological quality.

Hepatic veno-occlusive disease induced by Gymura segetum: report of two cases.

BACKGROUND: Hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome is associated with a high mortality because of its severity. Gymura segetum, a Chinese herbal medicine, is always used to cure injury and bleeding in rural areas in China. This study was undertaken to better understand VOD and its relations to the effect of Gymura segetum. METHODS: Between 2000 and 2002, two patients were admitted to our department because of VOD. Before admission, both of them had been injured and taken oral decoction of patent drug Gymura segetum. We analyzed the clinical manifestations, diagnosis and therapy of the two patients. RESULTS: Pyrrolizidine in Panax notginseng was proved to induce VOD. The diagnosis of VOD depended on hepatic biopsy. CONCLUSION: Gymura segetum can induce VOD. More attention should be paid to its unsuscepted side effects.

[Research on cytokines gene express of rats alcoholic liver disease affected by tea polyphenol].

OBJECTIVE: To evaluate the effect of tea polyphenol(TP) on the rat with alcoholic liver damage. METHOD: Rats were divided into 3 groups, in which 2 groups were stomach perfused with alcohol to result in ALD, and 1 group of them stomach perfused with TP simultaneously. Another group was normal control groups (stomach perfused with drinking water). In the end of 12 weeks, the liver specimen of each rat was observed by anglicizing its tissue damage, and all data collected was performed by statistical analysis in quantum and semi-quantum. Meanwhile cytokines gene express of each group is determined. RESULT: In the end of 12 weeks, alcoholic hepatitis appeared in rat liver. Hepatic injury in alcohol group and TP group were found, but could not be found in normal group. Compared with pure alcohol group, alcoholic liver damage mainly showing with steatosis in TP group were slight, in addition showing liver cellular swelling with small area, with less spot and focal necrosis, none bridging necrosis. Steatosis were slight relatively, mega-bubble steatosis were less found. Collagen deposition of TP group were less than those of pure alcohol group. Gene expression of. cytokine have diversity statistically such as IL-3, IL-4, IL-1R2, IL-6R, IL-7R2, IL-3Ra, IL-R1, IL-13, IL-1R1, IL-7R2, EPO-R, LIFR, IL-1R2, IL-5R2, CSF1, CD27, IL-6R. CONCLUSION: TP is able to attenuate alcoholic liver damage. It's mechanism is possibly due to modulating cytokines gene expression of cytokine.

[Effect of tea polyphenols on alcoholic liver injury].

OBJECTIVE: To reproduce an experimental model of alcoholic liver disease in rats and to investigate the preventive and treatment effects of tea polyphenols on alcoholic liver disease. METHODS: 68 male Sprague-Dawley rats were randomly divided into 3 groups: alcohol group (gastrically infused with 56% of ethanol once a day with a dose of 7 g/kg body weight for 4, 12 and 24 weeks), tea polyphenols group (gastric infusion with alcohol same as in the alcohol group and with tea polyphenols at 0.25 g/kg bw) and control group (gastric infusion with normal saline). At the end of 4, 12 and 24 weeks, blood samples were collected and then the rats were sacrificed. Liver samples were obtained for routine histological examination and the degree of hepatic steatosis and alcoholic hepatitis were examined. Blood specimens were used for evaluation of alanine transaminase (ALT) and aspartate aminotransferase (AST). RESULTS: (1) The levels of the two transaminases were elevated with the increase of the duration of ethanol feeding and the difference is significant. TP significantly mitigated the increase of ALT and AST activities induced by the alcohol. (2) Histological changes of the liver injury indicated that piecemeal or focal necrosis of hepatocytes was present in the centrilobular area. As fibrosis advanced, broader septa were formed with central-central and centra-portal bridging necrosis. In the TP infusion group, the severity of the pathological changes was significantly milder. CONCLUSION: The results of this study revealed that TP mitigated the development of alcoholic liver disease, and TP may be a potential drug for treatment of alcoholic liver disease.

Effects of tea polyphenols on hepatic fibrosis in rats with alcoholic liver disease.

BACKGROUND: As an anti-oxidation agent, tea polyphenols may have the effect of anti-fibrosis. This study was designed to observe the effect of tea polyphenols on hepatic fibrosis in rats with alcoholic liver disease and to explore the related mechanisms. METHODS: Sixty healthy Sprague-Dawley rats were divided randomly into normal control group, single alcohol group, and three alcohol groups given different doses of tea polyphenols. Alcohol or isovolumic normal saline and corresponding doses of tea polyphenols were given daily to the rats separately. The rats were sacrificed at the end of the 24th week. Masson staining was performed to observe liver fibrosis, serum endotoxin, and oxidant and anti-oxidant activity. RESULTS: Hepatic fibrosis was less severe in the rats of the alcohol groups given tea polyphenols than in the single alcohol group. Tea polyphenols increased the serum anti-oxidant capacity and decreased the endotoxin level. CONCLUSION: Tea polyphenols show anti-fibrosis effect in rats with alcoholic liver disease, and the mechanism may be related to the clearance of overall oxidant and decrease of the endotoxin level.

[Effect of tea polyphenol on liver fibrosis in rats and related mechanism].

OBJECTIVE: To investigate the effect of tea polyphenol (TP)'s on liver fibrosis in rats and its possible mechanism. METHOD: Rats were divided into 5 groups, 4 groups of which were stomach perfused with alcohol resulting in alcoholic liver fibrosis, and 3 groups of which were stomach perfused with TP simultaneously. Another group was normal control one. Histological change of rat liver was investigated and quantitative analysis was made in 24 weeks, and rat liver anti-oxidation index and serum endotoxin were determined at the same time. RESULT: Liver fibrosis in TP group was slight, and anti-oxidize index and endotoxin level were markedly improved in comparison with those of alcohol groups. CONCLUSION: Tea polyphenol can protect hepatocytes from fibrosis. Its mechanism is possibly due to cleaning up overfull lipid per-oxidation and reducing the level of endotoxin.