Anti-hyperglycemic and hypolipidemic effects of black ginseng extract containing increased Rh4, Rg5, and Rk1 content in muscle and liver of type 2 diabetic db/db mice.
Ontology highlight
ABSTRACT:
SUBMITTER: Jeong YJ
PROVIDER: S-EPMC7347743 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Individual differences in ginsenoside pharmacokinetics following ginseng administration in humans are still unclear. We aimed to investigate the pharmacokinetic properties of various ginsenosides, including Rb1, Rg3, Rg5, Rk1, F2, and compound K (CK), after a single oral administration of red ginseng (RG) and bioconverted red ginseng extract (BRG). This was a randomized, open-label, single-dose, single-sequence crossover study with washout every 1 week, and 14 healthy Korean men were enrolled. All subjects were equally assigned to two groups and given RG or BRG capsules. The pharmacokinetic parameters of ginsenosides were measured from the plasma drug concentration-time curve of individual subjects. Ginsenosides Rg3, Rk1 + Rg5, F2, and CK in the BRG group showed a higher C max, AUC(0-t), and AUC(0-∞) and shorter T max (for CK) than those in the RG group. These results suggest that BRG may lead to a higher absorption rate of bioactive ginsenosides. This study provides valuable information on the pharmacokinetics of various bioactive ginsenosides, which is needed to enhance the therapeutic efficacy and pharmacological activity of ginseng.
| S-EPMC8803428 | biostudies-literature
Project description:Stauntonia chinensis DC. has been utilised as a traditional herbal medicine for its anti-hyperglycemic characteristic, which has been associated with triterpene saponins. The goal of the current evaluation was to examine hypoglycemic activity and affiliated mechanism of total saponins from S. chinensis. The chemical composition was analysed by HPLC-ESI-MS/MS. The fasting blood glucose, oral glucose tolerance test, insulin tolerance test, insulin and glycogen levels of type 2 diabetic db/db mice administered total saponins were quantified to determine the hypoglycemic effects. The serum lipid profiles were assessed to determine the hypolipidemic effects. Western blotting was used to quantify the protein levels of insulin receptor substrates (IRS)-1/PI3K/AKT, AMPK/ACC and GLUT4. Twenty triterpene saponins were identified from the total saponins, which exhibited hypoglycemic activities and modulated hyperlipidemia that was associated with type 2 diabetes. The hypoglycemic effects were partly due to the activation of GLUT4, which is regulated by IRS-1/PI3K/AKT. The activation of the AMPK/ACC signalling pathway may be responsible for the hypolipidemic activity. This study revealed that total saponins from S. chinensis have significant hypoglycemic and hypolipidemic activity in diabetic db/db mice, indicating that these may be utilised in the development of saponins based on S. chinensis for the treatment of type 2 diabetes.
| S-EPMC6237556 | biostudies-literature
Project description:Cell-free fat extract (CEFFE), the liquid fraction derived from fat tissues, is enriched with a variety of growth factors and possesses pro-angiogenic, anti-apoptotic, and anti-oxidative properties. The aim of this study was to determine if CEFFE could accelerate chronic wound healing in mice with diabetes and investigate its underlying mechanisms. A model of circular full-thickness wound (6 mm diameter) was produced in the central dorsal region of spontaneous type 2 diabetes mellitus db/db mice. The mice were divided to three groups depending on dosage of CEFFE administered for the study; high dose CEFFE group (CEFFEhigh; administered 2.5 ml/kg/day via subcutaneous injection for six days), low dose CEFFE group (CEFFElow; administered 2.5 ml/kg/day via subcutaneous injection for three days), and a control group receiving phosphate buffer solution. Wound closure was evaluated on day 3, 7, 10, and 14 post-operation. Histological analyses, including hematoxylin-eosin staining and Masson's trichrome staining and immunohistological staining of anti-CD31 and anti-CD68, were also performed. Moreover, the effects of CEFFE on proliferation, migration, and tube formation of human immortal keratinocyte cells (HaCaT) and human vascular endothelial cells (HUVEC) were tested in vitro. The results showed that the local injection of CEFFE significantly accelerated wound healing in mice with diabetes. CEFFE improved re-epithelization and collagen secretion, promoted angiogenesis, and inhibited inflammatory macrophage infiltration in vivo. CEFFE also promoted HaCaT proliferation and migration and enhanced tubular formation in cultured HUVEC. It was concluded that CEFFE accelerates wound healing through pro-angiogenic and anti-inflammatory activities.
| S-EPMC7476113 | biostudies-literature
Project description:Black ginseng, a new type of processed ginseng that has a unique ginsenoside profile, has been shown to display potent pharmacological activities in in vitro and in vivo models. Although red ginseng is considered beneficial for the prevention of diabetes, the relationship between black ginseng and diabetes is unknown. Therefore, this study was designed to evaluate the anti-diabetic potential of black ginseng extract (BGE) in streptozotocin (STZ)-induced insulin-deficient diabetic mice, in comparison with red ginseng extract (RGE). HPLC analyses showed that BGE has a different ginsenoside composition to RGE; BGE contains Rg5 and compound k as the major ginsenosides. BGE at 200 mg/kg reduced hyperglycemia, increased the insulin/glucose ratio and improved islet architecture and β-cell function in STZ-treated mice. The inhibition of β-cell apoptosis by BGE was associated with suppression of the cytokine-induced nuclear factor-κB-mediated signaling pathway in the pancreas. Moreover, these anti-diabetic effects of BGE were more potent than those of RGE. Collectively, our data indicate that BGE, in part by suppressing cytokine-induced apoptotic signaling, protects β-cells from oxidative injury and counteracts diabetes in mice.
| S-EPMC4709037 | biostudies-literature
Project description:Ginsenoside Rk1 and Rg5 are minor ginseng saponins that have received more attention recently because of their high oral bioavailability. Each of them can effectively inhibit the survival and proliferation of human liver cancer cells, but the underlying mechanism remains largely unknown. Network pharmacology and bioinformatics analysis demonstrated that G-Rk1 and G-Rg5 yielded 142 potential targets, and shared 44 putative targets associated with hepatocellular carcinoma. Enrichment analysis of the overlapped genes showed that G-Rk1 and G-Rg5 may induce apoptosis of liver cancer cells through inhibition of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signal pathways. Methyl thiazolyl tetrazolium (MTT) assay was used to confirm the inhibition of cell viability with G-Rk1 or G-Rg5 in highly metastatic human cancer MHCC-97H cells. We evaluated the apoptosis of MHCC-97H cells by using flow cytometry and 4',6-diamidino-2-phenylindole (DAPI) staining. The translocation of Bax/Bak led to the depolarization of mitochondrial membrane potential and release of cytochrome c and Smac. A sequential activation of caspase-9 and caspase-3 and the cleavage of poly(ADP-ribose) polymerase (PARP) were observed after that. The levels of anti-apoptotic proteins were decreased after treatment of G-Rk1 or G-Rg5 in MHCC-97H cells. Taken together, G-Rk1 and G-Rg5 promoted the endogenous apoptotic pathway in MHCC-97H cells by targeting and regulating some critical liver cancer related genes that are involved in the signal pathways associated with cell survival and proliferation.
| S-EPMC8271777 | biostudies-literature
Project description:Oral therapeutics used to treat type 2 diabetes and cardiovascular disease often fail to prevent the progression of disease and their comorbidities. Rooibos (Aspalathus linearis), an endemic South African plant used as an herbal tea, has demonstrated positive effects on glycemia and hypercholesterolemia. However, the treatment efficacy of rooibos extract in combination with conventional hypoglycemic and hypolipidemic medications on blood glucose and lipid profiles has not been established. This study aimed to investigate the effects of combining an aspalathin-rich green rooibos extract (Afriplex GRT™) with pioglitazone and atorvastatin, on blood glucose and lipid levels in obese diabetic (db/db) mice. Six-week-old male db/db mice and their nondiabetic lean littermate controls (db+) were divided into 8 experimental groups (n = 6/group). Db/db mice were treated daily either with pioglitazone (25 mg/kg), atorvastatin (80 mg/kg) and GRT (100 mg/kg), a combination of either drug with GRT or a combination of GRT-pioglitazone and atorvastatin for 5 weeks. Untreated vehicle controls were given dimethyl sulfoxide (0.1%) and phosphate buffered saline solution. At termination, serum and liver tissue were collected for lipid and gene expression analysis. Treatment with GRT, pioglitazone and atorvastatin combination effectively lowered fasting plasma glucose (FPG) levels in db/db mice (p = 0.02), whilst increasing body weight, liver weight, and reducing retroperitoneal fat weight. Atorvastatin monotherapy was effective at reducing cholesterol (from 4.00 ± 0.12 to 2.93 ± 0.13, p = 0.0003), LDL-C (from 0.58 ± 0.04 to 0.50 ± 0.00, p = 0.04), HDL-C (from 2.86 ± 0.05 to 2.50 ± 0.04, p = 0.0003) and TG (from 2.77 ± 0.50 to 1.48 ± 0.23, p = 0.04), compared to the untreated diabetic control. The hypotriglyceridemic effect of atorvastatin was enhanced when used in combination with both GRT and pioglitazone. The addition of pioglitazone to GRT significantly lowered FPG and TG. In db/db mice, Apoa1 was significantly downregulated in the liver, whilst Pparγ was significantly upregulated compared to their db+ counterparts. GRT monotherapy downregulated Apoa1 expression (p = 0.02). Atorvastatin combined with GRT significantly downregulated mRNA expression of Apoa1 (p = 0.03), whilst upregulating the expression of Pparγ (p = 0.03), Pparα (p = 0.002), Srebp1 (p = 0.002), and Fasn (p = 0.04). The GRT-pioglitazone-atorvastatin combination therapy downregulated Apoa1 (p = 0.006), whilst upregulating Fasn (p = 0.005), Pparα (p = 0.041), and Srebp1 (p = 0.03). Natural products can improve the efficacy of current drugs to prevent diabetes-associated complications. GRT in combination with pioglitazone enhanced the reduction of FPG, whilst the addition of atorvastatin to the combination, significantly lowered triglyceride levels. However, when GRT was used in combination with atorvastatin only cholesterol levels were affected. Although these results confirm both glucose- and lipoprotein-lowering biological effects of GRT in combination with pioglitazone and atorvastatin, increased expression of genes involved in lipogenesis, cholesterol, and fatty acid transport, β-oxidation, and synthesis and storage of fatty acids, may exacerbate the hepatotoxic effects of atorvastatin.
| S-EPMC8118332 | biostudies-literature
Project description:The excessive release of reactive oxygen species (ROS) can result in the development of chronic inflammation. The mechanisms involved in inflammation are various, with endoplasmic reticulum (ER) stress known to be among them. We have previously shown that black ginseng (BG) reduced lipid accumulation in and enhanced the antioxidant function of the liver in vitro and in vivo mostly due to ginsenoside Rb1, Rg3 and Rk1 components. Therefore, this study investigated the antioxidant effect of BG on the intestines and its possible mechanistic pathway through ER stress. The results showed that BG extract decreased ROS and nitric oxide (NO) production and reduced inducible nitric oxide synthase (iNOS) expression levels in vitro, and these results were confirmed by zebrafish embryos in vivo. However, this phenotype was abolished in the absence of inositol-requiring enzyme 1 (IRE1α) but not in the absence of protein kinase RNA (PKR)-like ER-resistant kinase (PERK) or X-box-binding protein 1 (XBP1) in the mouse embryo fibroblast (MEF) knockout (KO) cells, suggesting that BG elicits an antioxidant effect in an IRE1α-dependent manner. Antioxidant and anti-inflammatory effects were assessed in the liver and intestines of the mouse model affected by nonalcoholic fatty liver disease (NAFLD), which was induced by a high-fat/high-fructose diet. In the liver, BG treatment rescued NAFLD-induced glutathione (GSH), catalase (CAT), tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 expression. In the intestines, BG also rescued NAFLD-induced shortened villi, inflammatory immune cell infiltration, upregulated IL-6, cytosine-cytosine-adenosine-adenosine-thymidine (CCAAT)/enhancer-binding homologous protein (CHOP) and binding immunoglobulin protein (BiP) expression. In conclusion, our results show that BG reduces ROS and NO production followed by inflammation in an IRE1α-dependent and XBP1-independent manner. The results suggest that BG provides antioxidant and anti-inflammatory effects through an ER stress mechanism.
| S-EPMC7825445 | biostudies-literature
Project description:Cigarette smoke (CS) is a risk factor that can induce airway enlargement, airway obstruction, and airway mucus hypersecretion. Although studies have shown that Korean black ginseng extract (BGE) has potent anti-inflammatory and antioxidant activities, the CS-induced inflammatory responses and molecular mechanisms are yet to be examined. The aim of this study was to examine the effect of BGE on the airway inflammatory response and its molecular mechanisms, using CS/lipopolysaccharides (LPS)-exposed animals and PMA-stimulated human airway epithelial NCI-H292 cells. The results show that BGE inhibited the recruitment of immune cells and the release of inflammatory mediators, such as tumor necrosis factor (TNF)-α and interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, elastase, and reactive oxygen species (ROS) in the airways of CS/LPS-exposed animals. BGE inhibited mucus secretion and the expression of Mucin 5AC (MUC5AC). Furthermore, BGE exhibited an anti-inflammatory effect by downregulating a signaling pathway mediated by transforming growth factor-β-activated kinase (TAK) 1, an important protein that accelerates inflammation by cigarette smoke (CS). Overall, the findings show that BGE inhibits lung inflammation and mucus secretion by decreasing the activation of TAK1 both in human epithelial cells and in CS/LPS-exposed animals, and could be a potential adjuvant in the treatment and prevention of airway inflammatory diseases caused by airway irritants such as CS.
| S-EPMC9025275 | biostudies-literature
Project description:diabetes, mouse models, diabetic nephropathy, streptozotocin db/db Keywords: other
2004-01-20 | GSE710 | GEO
Project description:Dendrobium is a traditional Chinese herb with anti-diabetic effects and has diverse bibenzyls as well as phenanthrenes. Little is known about Dendrobium polyphenols anti-diabetic activities, so, a rich-polyphenols extract of D. loddigesii (DJP) was used for treatment of diabetic db/db mice; the serum biochemical index and tissue appearance were evaluated. In order to gain an insight into the anti-diabetic mechanism, the oxidative stress index, tumor necrosis factor-? (TNF-?), interleukin-6 (IL-6) and gut microbiota modulation were determined by ELISA, immunohistochemistry or high throughput sequencing 16S rRNA gene. The results revealed that DJP had the effects to decrease the blood glucose, body weight, low density lipoprotein cholesterol (LDL-C) levels and increase insulin (INS) level in the mice. DJP improved the mice fatty liver and diabetic nephropathy. DJP showed the anti-oxidative abilities to reduce the malondialdehyde (MDA) level and increase the contents of superoxide dismutase (SOD), catalase (CAT) as well as glutathione (GSH). DJP exerted the anti-inflammatory effects of decreasing expression of IL-6 and TNF-?. After treatment of DJP, the intestinal flora balance of the mice was ameliorated, increasing Bacteroidetes to Firmicutes ratios as well as the relative abundance of Prevotella/Akkermansia and reducing the relative abundance of S24-7/Rikenella/Escherichia coli. The function's prediction of gut microbiota indicated that the microbial compositions involved carbohydrate metabolism or lipid metabolism were changed. This study revealed for the first time that DJP improves the mice symptoms of diabetes and complications, which might be due to the effects that DJP induced the decrease of inflammation as well as oxidative stress and improvement of intestinal flora balance.
| S-EPMC6320866 | biostudies-other