The beneficial effect of glycerophosphocholine to local fat accumulation: a comparative study with phosphatidylcholine and aminophylline.

Injection lipolysis or mesotherapy gained popularity for local fat dissolve as an alternative to surgical liposuction. Phosphatidylcholine (PPC) and aminophylline (AMPL) are commonly used compounds for mesotherapy, but their efficacy and safety as lipolytic agents have been controversial. Glycerophosphocholine (GPC) is a choline precursor structurally similar to PPC, and thus introduced in aesthetics as an alternative for PPC. This study aimed to evaluate the effects of GPC on adipocytes differentiation and lipolysis and compared those effects with PPC and AMPL using in vitro and in vivo models. Adipogenesis in 3T3-L1 was measured by Oil Red O staining. Lipolysis was assessed by measuring the amount of glycerol released in the culture media. To evaluate the lipolytic activity of GPC on a physiological condition, GPC was subcutaneously injected to one side of inguinal fat pads for 3 days. Lipolytic activity of GPC was assessed by hematoxylin and eosin staining in adipose tissue. GPC significantly suppressed adipocyte differentiation of 3T3-L1 in a concentration-dependent manner (22.3% inhibition at 4 mM of GPC compared to control). Moreover, when lipolysis was assessed by glycerol release in 3T3-L1 adipocytes, 6 mM of GPC stimulated glycerol release by two-fold over control. Subcutaneous injection of GPC into the inguinal fat pad of mice significantly reduced the mass of fat pad and the size of adipocytes of injected site, and these effects of GPC were more prominent over PPC and AMPL. Taken together, these results suggest that GPC is the potential therapeutic agent as a local fat reducer.

Eugenol ameliorates hepatic steatosis and fibrosis by down-regulating SREBP1 gene expression via AMPK-mTOR-p70S6K signaling pathway.

Beneficial effect of eugenol on fatty liver was examined in hepatocytes and liver tissue of high fat diet (HFD)-fed C57BL/6J mice. To induce a fatty liver, palmitic acid or isolated hepatocytes from HFD-fed Sprague-Dawley (SD) rats were used in vitro studies, and C57BL/6J mice were fed HFD for 10 weeks. Lipid contents were markedly decreased when hepatocytes were treated with eugenol for up to 24 h. Gene expressions of sterol regulatory element binding protein 1 (SREBP1) and its target enzymes were suppressed but those of lipolysis-related proteins were increased. As a regulatory kinase for lipogenic transcriptional factors, the AMP-activated protein kinase (AMPK) signaling pathway was examined. Protein expressions of phosphorylated Ca(2+)-calmodulin dependent protein kinase kinase (CAMKK), AMPK and acetyl-CoA carboxylase (ACC) were significantly increased and those of phosphorylated mammalian target of rapamycin (mTOR) and p70S6K were suppressed when the hepatocytes were treated with eugenol at up to 100 µM. These effects were all reversed in the presence of specific inhibitors of CAMKK, AMPK or mTOR. In vivo studies, hepatic triglyceride (TG) levels and steatosis score were decreased by 45% and 72%, respectively, in eugenol-treated mice. Gene expressions of fibrosis marker protein such as α-smooth muscle actin (α-SMA), collagen type I (Col-I) and plasminogen activator inhibitor-1 (PAI-1) were also significantly reduced by 36%, 63% and 40% in eugenol-treated mice. In summary, eugenol may represent a potential intervention in populations at high risk for fatty liver.

Nectandrin A Enhances the BMP-Induced Osteoblastic Differentiation and Mineralization by Activation of p38 MAPK-Smad Signaling Pathway.

Osteoblastic activity of nectandrin A was examined in C2C12 cells. Nectandrin A enhances the BMP-induced osteoblastic differentiation and mineralization, manifested by the up-regulation of differentiation markers (alkaline phosphatase and osteogenic genes) and increased calcium contents. In C2C12 cells co-transfected with expression vector encoding Smad4 and Id1-Luc reporter, nectandrin A increased Id1 luciferase activity in a concentration-dependent manner, when compared to that in BMP-2 treated cells, indicating that Smad signaling pathway is associated with nectandrin A-enhanced osteoblastic differentiation in C2C12 cells. In addition, nectandrin A activated p38 mitogen-activated protein kinase (MAPK) in time- and concentration-dependent manners, and phosphorylated form of pSmad1/5/8 and alkaline phosphatase activity were both decreased when the cells were pretreated with SB203580, a p38 MAPK inhibitor, suggesting that p38 MAPK might be an upstream kinase for Smad signaling pathway. Taken together, nectandrin A enhances the BMP-induced osteoblastic differentiation and mineralization of C2C12 cells via activation of p38 MAPK-Smad signaling pathway, and it has a therapeutic potential for osteoporosis by promoting bone formation.

Quercetin enhances hypoxia-mediated apoptosis via direct inhibition of AMPK activity in HCT116 colon cancer.

Tumor hypoxia is considered the best validated target in clinical oncology because of its significant contribution to chemotherapy failure and drug resistance. As an approach to target hypoxia, we assessed the potential of quercetin, a flavonoid widely distributed in plants, as a anticancer agent under hypoxic conditions and examined its pharmacological mechanisms by primarily focusing on the role of AMP-activated protein kinase (AMPK). Quercetin significantly attenuated tumor growth in an HCT116 cancer xenograft in vivo model with a substantial reduction of AMPK activity. In a cell culture system, quercetin more dramatically induced apoptosis of HCT116 cancer cells under hypoxic conditions than normoxic conditions, and this was tightly associated with inhibition of hypoxia-induced AMPK activity. An in vitro kinase assay demonstrated that quercetin directly inhibits AMPK activity. Inhibition of AMPK by expressing a dominant-negative form resulted in an increase of apoptosis under hypoxia, and a constitutively active form of AMPK effectively blocked quercetin-induced apoptosis under hypoxia. Collectively, our data suggest that quercetin directly inhibits hypoxia-induced AMPK, which plays a protective role against hypoxia. Quercetin also reduced the activity of hypoxia-inducible factor-1 (HIF-1), a major transcription factor for adaptive cellular response to hypoxia. Moreover, quercetin sensitized HCT116 cancer cells to the anticancer drugs cisplatin and etoposide under hypoxic conditions. Our findings suggest that AMPK may serve as a novel target for overcoming tumor hypoxia-associated negative aspects.

Erratum: Lee et al. Ginseng Extracts, GS-KG9 and GS-E3D, Prevent Blood-Brain Barrier Disruption and Thereby Inhibit Apoptotic Cell Death of Hippocampal Neurons in Streptozotocin-Induced Diabetic Rats. Nutrients 2020, 12, 2383.

The authors have requested that the following changes be made to their paper [...].

Ginsenoside Rg1 suppresses hepatic glucose production via AMP-activated protein kinase in HepG2 cells.

Panax ginseng is known to have anti-diabetic activity, but the active ingredients are not yet fully identified. In this study, we found the inhibitory effect of Rg(1) on hepatic glucose production through AMP-activated protein kinase (AMPK) activation in HepG2 cells. Rg(1) significantly inhibited hepatic glucose production in a concentration-dependent manner, and this effect was reversed in the presence of compound C, a selective AMPK inhibitor. In addition, Rg(1) markedly induced the phosphorylations of liver kinase B1 (LKB1), AMPK and forkhead box class O1 (FoxO1), a key transcription factor for gluconeogenic enzymes, in time- and concentration-dependent manners. Glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) activities were inhibited by 24% and 21%, respectively, when the cells were exposed to 40 microM of Rg(1), resulting from phosphorylation of FoxO1 and inhibition of gluconeogenic gene expression. Taken together, our results demonstrated the suppressive effect of Rg(1) on hepatic glucose production via LKB1-AMPK-FoxO1 pathway in HepG2 human hepatoma cells.

An active part of Artemisia sacrorum Ledeb. attenuates hepatic lipid accumulation through activating AMP-activated protein kinase in human HepG2 cells.

Artemisia sacrorum Ledeb. (Compositae) (ASL) is a traditional Chinese medicine used to treat different hepatic diseases. However, a hypolipidemic effect of ASL on fatty liver disease has not been reported. Therefore, we investigated whether 95% ethanol eluate (EE), an active part of ASL, would attenuate hepatic lipid accumulation in human HepG2 cells by activating AMP-activated protein kinase (AMPK). Significant decreases in triglyceride levels and increases in AMPK and acetyl-CoA carboxylase (ACC) phosphorylation were observed when the cells were treated with 95% EE. EE down-regulated the lipogenesis gene expression of sterol regulatory element-binding protein 1c (SREBP1c) and its target genes, such as fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD1), in a time- and dose-dependent manner. In contrast, the lipolytic gene expression of peroxisome proliferator-activated receptor alpha (PPAR-alpha) and CD36 increased in a time- and dose-dependent manner. These effects were abolished by pretreatment with compound C, an AMPK inhibitor. However, there were no differences in the gene expression of SREBP2, low density lipoprotein receptor (LDLR), hydroxymethyl glutaryl CoA reductase (HMG-CoA), or glucose transporter 2 (GLUT2). At the same time, 95% EE significantly increased the gene expression of acyl CoA oxidase (ACOX) in a time- and dose-dependent manner. Thus, AMPK mediated 95% EE induced suppression of SREBP1c and activation of PPAR-alpha respectively. These finding indicate that 95% EE attenuates hepatic lipid accumulation through AMPK activation and may be active in the prevention of serious diseases such as fatty liver, obesity, and type-2 diabetic mellitus.

Fermented ginseng protects streptozotocin-induced damage in rat pancreas by inhibiting nuclear factor-kappaB.

In this study, we investigated the protective effects of fermented ginseng (FG) on hyperglycemia induced by streptozotocin (STZ) in Sprague Dawley rats. FG was administered orally at dose of 250 (FGL) or 500 mg/kg (FGH) for 20 days starting one week before STZ injection. FG restored the plasma insulin levels by 266% and 334% in FGL and FGH, respectively, and resulting in reduction of plasma glucose concentration. Histological observation indicated that STZ-induced destruction of pancreatic islets was protected by FG. Consistent with this observation, FG reduced protein and mRNA levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), as determined by Western blotting and RT-PCR, respectively. The molecular mechanism of FG's inhibition of iNOS and COX-2 gene expressions appeared to involve the inhibition of nuclear factor-kappaB (NF-kappaB) activation via prevention of inhibitor kappaB (IkappaB) phosphorylation and degradation. The cytoprotective effects of FG were also mediated through suppression of extracelluar signal-regulated kinase (ERK) and c-JUN N-terminal kinase (JNK) pathways. Collectively, these results suggest that FG might be used to preserve functional beta-cell mass.

Pectin lyase-modified red ginseng extract improves glucose homeostasis in high fat diet-fed mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Red ginseng has long been used as a traditional folk medicine for various diseases including diabetes. Recently, a preparation of red ginseng extract by pectin lyase modification has been developed and named as GS-E3D. AIM OF THE STUDY: The aim of this study is to evaluate the preventive effect of GS-E3D on hyperglycemia induced by feeding a high fat diet (HFD) in mice. MATERIALS AND METHODS: GS-E3D was orally administered to C57BL/6J mice at different doses (250, 500, or 1000 mg/kg/day) for 6 weeks while on a HFD. Body weight and blood glucose were monitored weekly, and oral glucose tolerance test (OGTT) was performed at 5th week of the experiment. Glycemic indications and metabolic parameters were further measured in serum. RESULTS: Six weeks of GS-E3D treatment to mice significantly inhibited HFD-induced body weight gain, hyperglycemia, hyperinsulinemia and hypertriglyceridemia. Notably, GS-E3D treated mice at doses of 250, 500 and 1000 mg/kg showed 41.8%, 45.0% and 55.1% reduction in insulin resistance index, respectively, compared to HFD control mice. OGTT revealed that GS-E3D markedly prevented steep rise of blood glucose and insulin levels after glucose challenge and ameliorated HFD-induced glucose and insulin intolerance. The histological analysis showed enlarged adipocytes in HFD-fed mice whereas the adipocyte hypertrophy was prevented in GS-E3D treated mice in a dose-dependent manner. Furthermore, when peripheral glucose uptake level was assessed by total and membranous glucose transporter type 4 (GLUT4) protein contents, GS-E3D restored GLUT4 protein expression to the levels of regular diet fed mice, and dose-dependently translocated them to the plasma membrane. CONCLUSION: The results collectively show that GS-E3D ameliorates obesity-related impaired glucose tolerance by improving insulin sensitivity in the epidydimal adipose tissue.

Targets of monoclonal antibodies for immunological diseases.

Immunological disorders such as allergy, autoimmune diseases, auto-inflammatory syndromes and immunological deficiency syndromes are difficult to treat with chemical drugs. Recently, many monoclonal antibodies targeting various molecules including interleukin, tumor necrosis factor-α, cluster of differentiation, integrins, complement C5 and B lymphocyte stimulator are clinically available and give a hope to patients suffering from these intractable diseases. Here, we selected twenty-seven monoclonal antibodies approved by US FDA since 1997 and they are classified according to their target molecules. Although these biomedicines possessed some restrictions such as high cost and susceptible to infectious disease, these drawbacks can be overcome through cost-cutting innovations including biosimilars and careful monitoring. New targets are emerging rapidly and more effective biomedicines with acceptable side effects are in the pipeline for next decade.

GS-KG9 ameliorates diabetic neuropathic pain induced by streptozotocin in rats.

BACKGROUND: Diabetic neuropathy is one of the most devastating ailments of the peripheral nervous system. Neuropathic pain develops in ∼30% of diabetics. Here, we examined the suppressive effect of GS-KG9 on neuropathic pain induced by streptozotocin (STZ). METHODS: Hyperglycemia was induced by intraperitoneal injection of STZ. Rats showing blood glucose level > 250 mg/dL were divided into five groups, and treatment groups received oral saline containing GS-KG9 (50 mg/kg, 150 mg/kg, or 300 mg/kg) twice daily for 4 wk. The effects of GS-KG9 on pain behavior, microglia activation in the lumbar spinal cord and ventral posterolateral (VPL) nucleus of the thalamus, and c-Fos expression in the dorsal horn of the lumbar spinal cord were examined. RESULTS: The development of neuropathic pain began at Day 5 and peaked at Week 4 after STZ injection. Mechanical and thermal pains were both significantly attenuated in GS-KG9-treated groups from 10 d after STZ injection as compared to those in the STZ control. GS-KG9 also repressed microglia activation in L4 dorsal horn and VPL region of the thalamus. In addition, increase in c-Fos-positive cells within L4 dorsal horn lamina I and II of the STZ control group was markedly alleviated by GS-KG9. CONCLUSION: These results suggest that GS-KG9 effectively relieves STZ-induced neuropathic pain by inhibiting microglial activation in the spinal cord dorsal horn and VPL region of the thalamus.

Design and synthesis of 4-quinolinone 2-carboxamides as calpain inhibitors.

Calpains are involved in a variety of calcium-regulated cellular processes, such as signal transduction, cell proliferation, differentiation, and apoptosis. Excessive calpain activation contributes to serious cellular damage and has been reported in many pathological conditions. 4-Quinolinone 2-carboxamide derivatives were prepared and evaluated for mu-calpain inhibitory activities. Of the compounds synthesized, 3a and 3k, which possess a primary amide and 4-methoxyphenethyl amide at P1' region, were found to most potently inhibit mu-calpain with IC50 values of 0.71+/-0.07 and 0.73+/-0.23 microM, respectively. On the other hand, the incorporation of pyridine-containing amides decreased inhibitory activity.

Ginseng seed oil ameliorates hepatic lipid accumulation in vitro and in vivo.

BACKGROUND: Despite the large number of studies on ginseng, pharmacological activities of ginseng seed oil (GSO) have not been established. GSO is rich in unsaturated fatty acids, mostly oleic and linoleic acids. Unsaturated fatty acids are known to exert a therapeutic effect in nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the protective effect and underlying mechanisms of GSO against NAFLD using in vitro and in vivo models. METHODS: In vitro lipid accumulation was induced by free fatty acid mixture in HepG2 cells and by 3 wk of high fat diet (HFD)-feeding in Sprague-Dawley rats prior to hepatocyte isolation. The effects of GSO against diet-induced hepatic steatosis were further examined in C57BL/6J mice fed a HFD for 12 wk. RESULTS: Oil Red O staining and intracellular triglyceride levels showed marked accumulation of lipid droplets in both HepG2 cells and rat hepatocytes, and these were attenuated by GSO treatment. In HFD-fed mice, GSO improved HFD-induced dyslipidemia and hepatic insulin resistance. Increased hepatic lipid contents were observed in HFD-fed mice and it was lowered in GSO (500 mg/kg)-treated mice by 26.4% which was evident in histological analysis. Pathway analysis of hepatic global gene expression indicated that GSO increased the expression of genes associated with ß-oxidation (Ppara, Ppargc1a, Sirt1, and Cpt1a) and decreased the expression of lipogenic genes (Srebf1 and Mlxipl), and these were confirmed with reverse transcription and quantitative polymerase-chain reaction. CONCLUSION: These findings suggest that GSO has a beneficial effect on NAFLD through the suppression of lipogenesis and stimulation of fatty acid degradation pathway.

Meta- and cross-species analyses of insulin resistance based on gene expression datasets in human white adipose tissues.

Ample evidence indicates that insulin resistance (IR) is closely related to white adipose tissue (WAT), but the underlying mechanisms of IR pathogenesis are still unclear. Using 352 microarray datasets from seven independent studies, we identified a meta-signature which comprised of 1,413 genes. Our meta-signature was also enriched in overall WAT in in vitro and in vivo IR models. Only 12 core enrichment genes were consistently enriched across all IR models. Among the meta-signature, we identified a drug signature made up of 211 genes with expression levels that were co-regulated by thiazolidinediones and metformin using cross-species analysis. To confirm the clinical relevance of our drug signature, we found that the expression levels of 195 genes in the drug signature were significantly correlated with both homeostasis model assessment 2-IR score and body mass index. Finally, 18 genes from the drug signature were identified by protein-protein interaction network cluster. Four core enrichment genes were included in 18 genes and the expression levels of selected 8 genes were validated by quantitative PCR. These findings suggest that our signatures provide a robust set of genetic markers which can be used to provide a starting point for developing potential therapeutic targets in improving IR in WAT.

Compound K attenuates glucose intolerance and hepatic steatosis through AMPK-dependent pathways in type 2 diabetic OLETF rats.

BACKGROUND/AIMS: Non-alcoholic fatty liver disease is associated with insulin resistance. Compound K (CK) is the final metabolite of panaxadiol ginsenosides that have been shown to exert antidiabetic effects. However, the molecular mechanism of the antidiabetic effects in the liver have not been elucidated; further, whether CK has beneficial effects in hepatosteatosis remains unclear. Therefore, we evaluated the effect of CK on hepatosteatosis as well as its mechanism in high-fat diet (HFD)-fed type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. METHODS: Twenty-four-week-old male OLETF rats were assigned to four groups: control (saline), CK 10 mg/kg, CK 25 mg/kg, or metformin 300 mg/kg (positive control); all treatments were administered orally for 12 weeks. RESULTS: Fasting glucose levels of the CK25 group were significantly lower than those of the control group during the 12 weeks. The results of the oral glucose tolerance test showed that both the glucose concentration after glucose loading and the fasting insulin levels of the CK25 group were significantly lower than those of the control. Hepatosteatosis was significantly improved by CK25. CK25 and metformin significantly increased the phosphorylation of hepatic adenosine monophosphate-activated protein kinase (AMPK). CK25 significantly inhibited the expression of sterol regulatory element-binding protein-1c and fatty acid synthase, while upregulating that of peroxisome proliferator-activated receptor-α and carnitine palmitoyltransferase-1. CONCLUSIONS: CK improved glucose intolerance and hepatosteatosis in HFD-fed OLETF rats through AMPK activation, which has dual mode of action that involves decreasing the synthesis of fatty acids and increasing fatty acid oxidation.

Compound K enhances insulin secretion with beneficial metabolic effects in db/db mice.

Compound K (CK) is a final metabolite of panaxadiol ginsenosides. Although Panax ginseng is known to have antidiabetic activity, the active ingredient is not yet fully identified. In our preliminary studies, panaxadiol ginsenosides showed insulin secretion stimulating activity. Therefore, it would be interesting to know whether and how CK has antidiabetic activity. In in vitro studies using HIT-T15 cells and primary cultured islets, CK enhanced the insulin secretion in a concentration-dependent manner. This effect, however, was completely abolished in the presence of diazoxide (K+ channel opener) or nifedipine (Ca2+ channel blocker). Insulin secretion stimulating activity of a single oral CK administration was also confirmed with an oral glucose tolerance test (OGTT) using ICR mice. From these studies, we may conclude that CK lowered the plasma glucose level by stimulating insulin secretion and this action was presumably associated with an ATP-sensitive K+ channel. In a long-term study using C57BL/KsJ db/ db mice, CK treatment significantly decreased the fasting blood glucose levels in a dose-dependent fashion. OGTT revealed that CK improved glucose tolerance with increased insulin levels 30 min after the glucose challenge. Concurrently, CK treatment prevented the destruction of islets and preserved more insulin. Next, to gain insight into the extra-pancreatic molecular mechanism of CK, we performed a global gene expression profiling study in the liver and adipose tissues. According to DNA microarray analysis, CK shifted glucose metabolism from hepatic glucose production to hepatic glucose utilization in the liver and improved insulin sensitivity through enhancing plasma adiponectin levels, resulting in overexpression of genes for adipogenesis and glucose transporter in the adipose tissue. Taken together, we may suggest that CK could be developed as a therapeutic tool in type 2 diabetic patients with disability of insulin secretion and/or insulin resistance.

In vivo and in vitro anti-inflammatory activities of alpha-linolenic acid isolated from Actinidia polygama fruits.

The fruit of Actinidia polygama (AP) has long been used as a folk medicine in Korea for the treatment of pain, rheumatoid arthritis and inflammation. In the present study, bioassay-guided fractionation of AP led to the separation and identification of a polyunsaturated fatty acid, alpha-linolenic acid (ALA), which was found to show anti-inflammatory activity. The anti-inflammatory effects of ALA, using acetic acid or carrageenan-induced inflammation models, were investi gated in mice or rats, respectively. ALA significantly inhibited the acetic acid-induced vascular permeability in a dose dependent manner (34.2 and 37.7% inhibition at doses of 5 and 10 mg/ kg, respectively). ALA also significantly reduced a rat paw edema induced by a single treatment of carrageenan. To investigate the mechanism of the anti-inflammatory action of ALA, the effects of ALA on lipopolysaccharide (LPS)-induced responses in the murine mac rophages cell line, RAW 264.7, were examined. Exposure of LPS-stimulated cells to ALA inhibited the accumulation of nitrite and prostaglandin E2 (PGE2) in the culture medium. Consistent with these observations, the protein and mRNA expression levels of iNOS and COX-2 enzyme were markedly inhibited by ALA in a dose dependent manner. These results suggest that the anti-inflammatory activity of ALA might be due to the suppression of the expressions of iNOS and COX-2 mRNA.

Vinegar-processed ginseng radix improves metabolic syndrome induced by a high fat diet in ICR mice.

Ginseng has made a successful transition from the world of traditional tonic remedies to conventional medicine, and since the 1920s ginseng root has been documented to be effective in diabetes, hypertension, dyslipidemia and obesity. Based on this wide spectrum of activity we wondered whether ginseng root extract might also be effective in metabolic syndrome (MetSyn). In a series of investigations to develop a potential anti-MetSyn agent, we prepared a vinegar-processed form of ginseng radix (ginsam, GS) and compared its anti-MetSyn effects to those of non-processed ginseng radix (GR) in an ICR mouse model of MetSyn induced by a high fat diet. GR- and GS-treated mice (500 mg/kg/day for 8 weeks) had an 81% and 90% decrease in insulin resistance respectively, compared to the high fat diet (HFD) control. White adipocyte size was dramatically reduced by 67% and 80% in GR- ahd GS-treated groups respectively, compared to the HFD fed control. This result was reflected by a marked inhibition of weight gain in GS-treated mice (GR vs. GS, 53% vs. 86%). Analysis of ginsenoside composition indicated that prosapogenin Rg3 might be responsible for the anti-MetSyn activity of GS. In conclusion, Vinegar-processed ginseng radix (GS) was found to have a significantly greater anti-MetSyn effect than ginseng radix, and we suggest that ginsam should be subjected to clinical trials in the future, and that the role of prosapogenin Rg3 in the anti-MetSyn effect of ginsam should be confirmed.

Acanthopanax senticosus reverses fatty liver disease and hyperglycemia in ob/ob mice.

Non-alcoholic fatty liver disease (NAFLD) is common in obesity. However, weight reduction alone does not prevent the progression of NAFLD to end-stage disease associated with the development of cirrhosis and liver disease. In a previous experiment, 50% ethanol extract of Acanthopanax senticosus stem bark (ASSB) was found to reduce body weight and insulin resistance in high fat diet-induced hyperglycemic and hyperlipidemic ICR mice. To evaluate the anti-steatosis action of ASSB, insulin-resistant ob/ob mice with fatty livers were treated with ASSB ethanol extract for an 8 week-period. ASSB ethanol extract reversed the hepatomegaly, as evident in reduction of % liver weight/body weight ratio. ASSB ethanol extract also specifically lowered circulating glucose and lipids, and enhanced insulin action in the liver. These changes culminated in inhibition of triglyceride synthesis in non-adipose tissues including liver and skeletal muscle. Gene expression studies confirmed reductions in glucose 6-phosphatase and lipogenic enzymes in the liver. These results demonstrate that ASSB ethanol extract is an effective treatment for insulin resistance and hepatic steatosis in ob/ob mice by decreasing hepatic lipid synthesis.

Salicornia herbacea prevents high fat diet-induced hyperglycemia and hyperlipidemia in ICR mice.

Salicornia herbacea L. (Chenopodiaceae) has been used as a seasoned vegetable by living in coastal areas. S. herbacea (SH) has been demonstrated to stimulate cytokine production, nitric oxide release, and to show anti-oxidative effect. In a series of investigations to develop potential anti-diabetic and/or anti-hyperlipidemic agents from Korean indigenous plants, 50% ethanol extract of Salicornia herbacea was found to prevent the onset of the hyperglycemia and hyperlipidemia induced by high fat diet in ICR mice. At 6 week old, the ICR mice were randomly divided into five groups; two control and three treatment groups. The control mice were to receive either a regular diet (RD) or high-fat diet (HFD), and the treatment groups were fed a high fat diet with either 350 mg/kg, 700 mg/kg of SH (SH350 and SH700) or 250 mg/kg of metformin (MT250) for a 10-week period. SH not only reduced body weight but also corrected associated hyperglycemia and hyperlipidemia in a dose dependent manner. SH exerted beneficial effects on the plasma glucose and lipid homeostasis possibly ascribed to its specific effects on lipogenesis related genes (SREBP1a, FAS, GAPT), and PEPCK, glucose 6-phosphatase gene expressions in liver. Ethanol extract of S. herbacea has potential as a preventive agent for type 2 diabetes (and possibly hyperlipidemia) and deserves future clinical trial.