Ginsenoside Rf2, a new dammarane glycoside from Korean red ginseng (Panax ginseng)

A new dammarane glycoside named ginsenoside Rf₂ has been isolated from Korean red ginseng (Panax ginseng) and its chemical structure has been elucidated as 6-O-[α-L-rhamnopyranosyl (1→2) β-D-glucopyranosyl]dammarane-3β, 6α, 12β, 20(R), 25-pentol by chemical and spectral methods.     

Cytotoxicity of urushiols isolated from sap of Korean lacquer tree (Rhus vernicifera stokes)

Cytotoxicities of four urushiols, congeners isolated from the sap of Korean lacquer tree (Rhus vernicifera Stokes), to 29 human cancer cell lines originated from 9 organs were evaluated. Their values of 50% growth inhibition were below 4 microg/ml, and showed cell line specific cytotoxicity. The present result is the first report on the cytotoxicity of urushiols suggesting that they would have an anticancer activity to human cancer cells.     

Validation of the non-alcoholic fatty liver disease activity score

Aliment Pharmacol Ther 2011; 34: 214–218

Summary

Background The non‐alcoholic fatty liver disease (NAFLD) activity score (NAS) is a scoring system designed by the Nonalcoholic Steatohepatitis (NASH) Clinical Research Network (CRN) to encompass the spectrum of NAFLD and evaluate histological changes. However, the NAS and the correlation between the NAS and a diagnosis of NASH have not been validated outside the NASH CRN. Aim To validate the NAS outside the NASH CRN. Methods This study retrospectively examined liver biopsies from adults with NAFLD or steatohepatitis obtained from January 2003 to May 2010. Biopsy specimens were evaluated twice in a blinded manner by a single hepatopathologist, once to determine a diagnosis (steatohepatitis or steatosis/not‐steatohepatitis), and a second time to determine the NAS. Results A total of 386 liver biopsies were evaluated. Mean age of patients at time of biopsy was 49.9 ± 10.2 years. NASH was found in 51% of the patients. For NAS ≥5 as a diagnosis of steatohepatitis and NAS <5 for not‐steatohepatitis, the sensitivity was 57%, specificity: 95%, negative predictive value (NPV): 68% and positive predictive value (PPV): 93%. Lowering the NAS to ≥4 as a diagnosis of steatohepatitis increased the sensitivity to 85% with a decrease in specificity to 81%; NPV: 84%, PPV: 82% and Cohen’s kappa 0.658. Conclusions The NAFLD activity score is a valid scoring system encompassing the spectrum of NAFLD with an excellent level of agreement between the histological diagnosis and the NAFLD activity score. A NAFLD activity score ≥4 has optimal sensitivity and specificity for predicting steatohepatitis, and is the recommended value for admission into an interventional trial for NASH.     

Current treatment strategies for non-alcoholic fatty liver disease (NAFLD)

Nonalcoholic fatty liver disease (NAFLD) is recognized as the most common cause of chronic liver disease worldwide. NAFLD is a clinicopathologic syndrome ranging from simple steatosis, which is relatively benign, to the more severe form known as nonalcoholic steatohepatitis (NASH), which may progress to cirrhosis, liver failure, and hepatocellular carcinoma. NAFLD is associated with significant liver related morbidity and mortality, and its underlying pathophysiology is thought to result from a multiple hit process. The initial insult is the accumulation of hepatic fat secondary to insulin resistance. In the setting of hepatic steatosis, the second hit can be caused by reactive oxygen species, inflammatory cytokines, and adipokines. Several therapeutic modalities that target these mechanisms are under investigation, but no proven treatment has yet emerged. Insulin sensitizers such as thiazolidinediones and metformin show promise, and several studies have explored the role of lipid lowering agents, antioxidants, and cytoprotective agents. Novel agents such as anti-obesity drugs, selective cannabinoid-1 receptor blockers, and dual PPAR alpha and gamma agonists are also under investigation. Unfortunately, data on the long-term safety and efficacy of these agents and their impact on liver related histologic outcomes are currently lacking. NAFLD treatment currently focuses on reducing metabolic risk factors, with the mainstay of therapy focusing on life-style modifications such as gradual weight loss through diet and regular exercise.     

Pharmacological activity of sanchi ginseng (Panax notoginseng)

The pharmacological activity and constituents of the sanchi ginseng Panax notoginseng have been reviewed. The bulk of pharmacological findings have been based on the saponins or steryl glycosides, although polysaccharides with immunopotentiating activity, proteins with antifungal, ribonuclease and xylanase activity, and a triacylglycerol (trilinolein) with antioxidant activity have been reported. Protective actions against cerebral ischaemia, beneficial effects on the cardiovascular system, and haemostatic, antioxidant, hypolipidaemic, hepatoprotective, renoprotective and estrogen-like activities have been described. Various methods for authentication of P. notoginseng are available.     

非诺贝特在非酒精性脂肪性肝病大鼠中的作用探讨

目的高脂饮食构建NAFLD大鼠模型,观察非诺贝特对NFALD大鼠血清学肝功、血脂及肝脏病理的影响。方法将27只雄性SD大鼠随机分为正常组(N组)、病理组(B组)及非诺贝特组(F组),每组9只,分别予正常饮食及高脂饮食建立NAFLD模型。于4、8、12周后,每组各处死大鼠3只,称体重、肝湿重,计算肝指数;8周后测定血清天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、三酰甘油(TG)、总胆固醇(TC);肝脏病理切片行HE染色,观察病理改变。F组第5周开始药物干预。结果 8周时B组大鼠体重及肝指数高于N组,差异有统计学意义(P<0.05),F组肝指数低于B组,差异有统计学意义(P<0.05);12周时N组与F组大鼠肝指数组间比较差异无统计学意义(P>0.05),B组大鼠体重和肝指数大于N组,差异有统计学意义(P<0.05)。血清学指标:8周时N组与F组AST、ALT、TG、TC比较差异无统计学意义(P>0.05),B组AST、ALT、TG、TC明显高于N组,且差异有统计学意义(P<0.05)。12周时B组AST、ALT、TG、TC明显高于N组,差异有统计学意义(P<0.05),B组ALT、TG高于F组,差异有统计学意义(P<0.05),F组与N组AST、ALT、TC、TG差异无统计学意义(P>0.05)。结论改良法高脂饮食诱导SD大鼠非酒精性脂肪性肝病,造模成功;非诺贝特对NAFLD大鼠的肝脏酶学、血脂及病理学均有一定改善。     

非酒精性脂肪性肝病治疗药物的应用评价

非酒精性脂肪性肝病（NAFLD）是目前最常见的肝脏疾病之一,其药物治疗目的主要是减缓或减少肝硬化、肝癌及肝衰竭等终末期肝病的发生,降低病死率。本文综述近年来胰岛素增敏剂、降脂药、抗氧化剂和肝细胞保护剂等各种NAFLD药物治疗方案的临床应用评价。     

Rhus verniciflua Stokes glycoprotein (36kDa) has protective activity on carbon tetrachloride-induced liver injury in mice

This study was carried out to investigate the hepatoprotective effect of the glycoprotein isolated from Rhus verniciflua Stokes (RVS), which has traditionally been used for healing of inflammatory diseases. We evaluated the activities of alanine aminotransferase (ALT), lactate dehydrogenase (LDH), thiobarbituric acid-reactive substances (TBARS), and antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx)] activities in treatment with carbon tetrachloride (CCl(4)) in vivo. When mice were treated with CCl(4) in the absence of RVS glycoprotein, the activities of ALT, LDH, and TBARS were increased, while the antioxidant enzymes activities were decreased. However, when the mice were treated with CCl(4) in the presence of RVS glycoprotein, the activities of ALT, LDH, and TBARS were significantly reduced and SOD, CAT, and GPx activities were remarkably increased. In addition, RVS glycoprotein increased the nitric oxide (NO) production and decreased the nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1) activation in CCl(4)-treated mice. Collectively, these results pointed out that RVS glycoprotein can inhibit lipid peroxidation, enhance the activities of antioxidant enzymes, increase the NO production, and decrease the NF-κB and AP-1 activations. Therefore, we speculate that RVS glycoprotein protects from liver damage through its radical scavenging ability.     

Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults

Aliment Pharmacol Ther 2011; 34: 274–285

Summary

Background Non‐alcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease, and its worldwide prevalence continues to increase with the growing obesity epidemic. This study assesses the epidemiology of NAFLD in adults based on clinical literature published over the past 30 years. Aim To review epidemiology and natural history of non‐alcoholic fatty liver disease and non‐alcoholic steatohepatitis in adults based on clinical literature published over the past 30 years. Methods An in‐depth search of PubMed (1980–2010) was based on five search terms: ‘non‐alcoholic fatty liver disease’ OR ‘non‐alcoholic steatohepatitis’ OR ‘fatty liver’ OR ‘steatosis’ AND ‘incidence’ [MeSH Terms] OR ‘prevalence’ [MeSH Terms] OR ‘natural history’. Studies of paediatric cohorts were excluded. Articles were categorised by topic and summarised, noting generalisations concerning their content. Results Four study categories included NAFLD incidence, prevalence, risk factors and natural history. Studies related to NAFLD prevalence and incidence indicate that the diagnosis is heterogeneous and relies on a variety of assessment tools, including liver biopsy, radiological tests such as ultrasonography, and blood testing such as liver enzymes. The prevalence of NAFLD is highest in populations with pre‐existing metabolic conditions such as obesity and type II diabetes. Many studies investigating the natural history of NAFLD verify the progression from NASH to advanced fibrosis and hepatocellular carcinoma. Conclusions Non‐alcoholic fatty liver disease is the most common cause of elevated liver enzymes. Within the NAFLD spectrum, only NASH progresses to cirrhosis and hepatocellular carcinoma. With the growing epidemic of obesity, the prevalence and impact of NAFLD continues to increase, making NASH potentially the most common cause of advanced liver disease in coming decades.     

Korean red ginseng (Panax ginseng) prevents obesity by inhibiting angiogenesis in high fat diet-induced obese C57BL/6J mice

Adipose tissue growth and development are thought to be associated with angiogenesis and extracellular matrix remodeling. Because ginseng has been shown to inhibit angiogenesis and matrix metalloproteinase (MMP) activity, we hypothesized that adipose tissue growth and obesity can be regulated by Korean ginseng (Panax ginseng C.A. Meyer). Wild-type C57BL/6J mice were fed for 8 weeks with a low fat diet, a high fat diet (HFD), or HFD supplemented with 0.5% or 5% Korean red ginseng extract. We measured body weight, adipose tissue mass, food intake, MMP activity, and the expression of genes involved in angiogenesis and MMPs. Administering ginseng to HFD-induced obese mice produced reductions in body weight and adipose tissue mass compared with untreated counterparts. Ginseng treatment decreased blood vessel density and MMP activity in adipose tissues. Ginseng also reduced mRNA levels of angiogenic factors (e.g., VEGF-A and FGF-2) and MMPs (e.g., MMP-2 and MMP-9), whereas it increased mRNA levels of angiogenic inhibitors (e.g., TSP-1, TIMP-1, and TIMP-2) in adipose tissues. These results demonstrate that ginseng effectively reduces adipose tissue mass and prevents obesity in diet-induced obese mice and that this process may be mediated in part through the anti-angiogenic actions of ginseng.     

非酒精性脂肪性肝病的治疗进展

目前全球非酒精性脂肪性肝病的发病率增加,并与代谢综合征,尤其是肥胖及糖尿病密切相关.越来越多的证据表明,胰岛素抵抗是代谢综合征患者发生脂肪性肝炎的关键病因,其可增加脂肪变性及肝脏游离脂肪酸聚集,刺激氧化应激反应,促进脂质过氧化及炎症细胞因子产生.非酒精性脂肪性肝病的治疗以改善代谢综合征为主,尚缺乏已验证的疗效理想的治疗药物.近年来随着对其发病机制的深入理解,一些尚处于动物试验及前期临床研究的新药值得关注.     

The natural history and risk factors for progression of non-alcoholic fatty liver disease and steatohepatitis

Nonalcoholic fatty liver disease (NAFLD) is a condition of increasing incidence in western Countries seldom associated to other diseases of high prevalence in general population (i.e. diabetes and obesity). NAFLD ranges from simple fatty liver to steatohepatitis (NASH), which may lead to cryptogenic cirrhosis and in some cases hepatocellular carcinoma (HCC). Natural history of NAFLD in humans is poorly understood and progression of liver disease seems to be due to interaction between hosting (i.e. genetic, gut flora, insulin resistance) and environmental factors (social and eating behaviours) that should be responsible of increased oxidative stress within hepatocytes. Even if we need non-invasive markers able to describe the progression of liver disease, only meaning of liver biopsy is useful to characterize the stigmata of worsening such as inflammation and fibrosis.     

Simultaneous quantification of 14 ginsenosides in Panax ginseng C.A. Meyer (Korean red ginseng) by HPLC-ELSD and its application to quality control

A new method of high-performance liquid chromatography coupled with evaporative light scattering detection (HPLC-ELSD) was developed for the simultaneous quantification of 14 major ginsenosides, which are the marker compounds of Panax ginseng C.A. Meyer (Korean red ginseng). Various types of ginseng samples were extracted, and the amounts of the 14 ginsenosides (Rg1, Re, Rf, Rh1, Rg2, Rb1, Rc, Rb2, Rb3, Rd, Rg3, Rk1, Rg5, and Rh2) were determined by reverse-phase HPLC-ELSD using digoxin as an internal standard. The mobile phase consisted of a programmed gradient of aqueous acetonitrile. Calibration curves for each ginsenoside were determined for the quantification. The method was validated for linearity, precision, accuracy, limit of detection, and limit of quantification. This quantification method was applied to several finished ginseng products including white ginseng, red ginseng powder, and red ginseng concentrate. The amounts of the 14 ginsenosides in the various ginseng samples could be analyzed simultaneously. This validated HPLC method is expected to provide a new basis for the quality assessment of ginseng products.     

Decreased natural killer (NK) cell activity in zinc-deficient rats

• 1.1. In the study, the effect of zinc deficiency, a natural killer (NK), and lipopolysaccharide (LPS) activated NK cell activity were investigated.
• 2.2. Rats were fed with zinc-deficient and normal diet for 3 weeks.
• 3.3. NK and LPS activated NK cell activity was 7.2 ± 1.8%/10⁶ cells (n = 10) and 9.5 ± 4.3%/10⁶ cells (n = 10), respectively, in the zinc deficient group. In the control group fed with normal diet, NK and LPS activated NK cell activity was 22.2 ± 3.3%/10⁶ cells (n = 10) and 32.5 ± 3.5%/10⁶ cells (n = 10), respectively.
• 4.4. Plasma zinc concentration was 131.7 ± 8.8 μg/dl in the zinc-deficient group and 206 ± 17.7 μg/dl in the control group.
• 5.5. The results suggest that decreased NK and LPS activated NK cell activity is associated with zinc deficiency.

     

祛肝脂合剂治疗非酒精性脂肪肝大鼠的实验研究

目的 比较祛肝脂合剂和还原型谷胱甘肽(GSH)对实验性大鼠非酒精性脂肪性肝(NAFLD)的治疗效果,探讨其可能的机制.方法 将SD大鼠随机分为5组,除空白对照组外均饲以高脂饲料造模,连续喂养8周.用祛肝脂合剂给予治疗,并与阳性对照药还原型谷胱甘肽(GSH)组对比,用药.2周后取血,取肝,以备检测.观察肝脏组织学变化,检测血浆脂蛋白酶LPL及肝脂酶HL的活性和肝组织SOD、ATP含量变化.结果 ①随着NAFLD造模的进行,大鼠肝组织广泛脂肪变性,炎性细胞浸润、坏死,局部纤维组织增生.血清LPL、HL下降.肝组织SOD、ATP含量下降;②祛肝脂合剂组肝组织脂肪变性明显减轻,仅有轻微炎性细胞浸润,未见坏死灶及纤维组织增生,血清IJPL、HL升高,肝组织SOD、ATP含量升高(P<0.05);③GSH组肝组织广泛脂肪变性,炎症细胞浸润,点状坏死,但未见纤维组织增生;但血清[JPL、HL肝组织SOD、ATP含量均无明显变化(P>0.05).结论 祛肝脂合剂可以降低脂质在肝脏中的沉积,保护肝组织,对脂肪性肝炎有治疗作用.     

Review article: current management of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis

Background  Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome.
Aim  To assess the epidemiological impact and the current management of patients with NAFLD.
Methods  Published peer-reviewed literature and abstracts concerning NAFLD and non-alcoholic steatohepatitis (NASH) were reviewed. Articles specifically related to epidemiology, diagnosis and current treatment strategies for NAFLD and NASH are summarized.
Results  NAFLD is strongly associated with the epidemic of obesity and type-2 diabetes mellitus, and is estimated to affect about 20–30% of the population in the US. From the spectrum of NAFLD, only patients with biopsy-proven NASH (estimated prevalence in the US population is about 3–5%) have been convincingly shown to progress to cirrhosis, liver failure and hepatocellular carcinoma. The clinical manifestation of NAFLD is usually absent or subtle, with abnormal aminotransferases or incidental radiographic findings of fatty liver. The pathogenesis of NAFLD is attributed to a multi-hit process involving insulin resistance, oxidative stress, apoptotic pathways, and adipocytokines. In 2008, there is no established treatment for NAFLD. Weight loss and treatment for each component of metabolic syndrome. Nevertheless, a large number of agents are being considered in clinical trials of patients with NASH.
Conclusions  Awareness of the tremendous impact of NAFLD as an important cause of chronic liver disease is increasing along with a great deal of information about its pathogenesis. Future, well-designed clinical trials that target specific pathways involved in the pathogenesis of NASH are urgently needed.     

Hepatoprotective effects of Cassia semen ethanol extract on non-alcoholic fatty liver disease in experimental rat

Context: Cassia semen (Cs), a seed of Cassia obtusifolia L. (Leguminosae), is a popular functional beverage. Previous studies reported that Cs displayed antioxidant, antifungal and strong liver protective effects.

Objective: This study evaluates the hepatoprotective effects of Cs on non-alcoholic fatty liver disease (NAFLD).

Materials and methods: Seventy-two male Wistar rats raised with high-fat diet (HFD) were randomly allotted into model, metformin (0.2?g/kg) and Cs (0.5, 1, and 2?g/kg)-treated groups. Another 12 rats were raised with normal feed as control group; all the rats were orally administrated with drugs and vehicle for 6?weeks. Alanine transferase (ALT), aspartate transaminase (AST), triglycerides (TG), total cholesterol (TC), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8 and low density lipoprotein receptor (LDL-R) mRNA levels were measured at the end of the experiment.

Results: Twelve weeks of HFD administration significantly increased the levels of AST, ALT, TG, TC, TNF-α, IL-6, IL-8 and MDA, decreased SOD (199.42 vs. 137.70?U/mg protein) and GSH (9.76 vs. 4.55?mg/g protein) contents, compared to control group. Cs administration group significantly decreased the elevated biomarkers with the ED₅₀?=?1.2?g/kg for NAFLD rats. Cs treatment also prevents the decreased expression of LDL-R mRNA, and improved the histopathological changes compared to model group.

Conclusions: The hepatoprotective effect of Cs on NAFLD may possibly be due to its antioxidant effect. Cs may become a potent hepatoprotective agent in clinical therapy in the future.     

对非酒精性脂肪性肝病诊治中几个问题的思考

非酒精性脂肪性肝病（NAFLD）是指除外酒精和其他明确的肝损害因素所致的．以弥漫性肝细胞大泡性脂肪变为主要特征的临床病理综合征．包括单纯性脂肪肝以及由其演变的脂肪性肝炎（NASH）和肝硬化。