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Hovenia dulcis Thunb extract and its ingredient methyl vanillate activate Wnt/?-catenin pathway and increase bone mass in growing or ovariectomized mice.

ABSTRACT: The Wnt/?-catenin pathway is a potential target for development of anabolic agents to treat osteoporosis because of its role in osteoblast differentiation and bone formation. However, there is no clinically available anti-osteoporosis drug that targets this Wnt/?-catenin pathway. In this study, we screened a library of aqueous extracts of 350 plants and identified Hovenia dulcis Thunb (HDT) extract as a Wnt/?-catenin pathway activator. HDT extract induced osteogenic differentiation of calvarial osteoblasts without cytotoxicity. In addition, HDT extract increased femoral bone mass without inducing significant weight changes in normal mice. In addition, thickness and area of femoral cortical bone were also significantly increased by the HDT extract. Methyl vanillate (MV), one of the ingredients in HDT, also activated the Wnt/?-catenin pathway and induced osteoblast differentiation in vitro. MV rescued trabecular or cortical femoral bone loss in the ovariectomized mice without inducing any significant weight changes or abnormality in liver tissue when administrated orally. Thus, natural HDT extract and its ingredient MV are potential anabolic agents for treating osteoporosis.

SUBMITTER: Cha PH

PROVIDER: S-EPMC3899039 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Hovenia dulcis Thunb extract and its ingredient methyl vanillate activate Wnt/β-catenin pathway and increase bone mass in growing or ovariectomized mice.

Cha Pu-Hyeon PH Shin Wookjin W Zahoor Muhammad M Kim Hyun-Yi HY Min Do Sik do S Choi Kang-Yell KY

PloS one 20140122 1

The Wnt/β-catenin pathway is a potential target for development of anabolic agents to treat osteoporosis because of its role in osteoblast differentiation and bone formation. However, there is no clinically available anti-osteoporosis drug that targets this Wnt/β-catenin pathway. In this study, we screened a library of aqueous extracts of 350 plants and identified Hovenia dulcis Thunb (HDT) extract as a Wnt/β-catenin pathway activator. HDT extract induced osteogenic differentiation of calvarial ...[more]

PMID: 24465596

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Project description:BACKGROUND:Various extracts of Hovenia dulcis have been commonly used in Asia for cases of alcohol-related disorders. Fermentation is reported to enhance the level and biological activities of various bio-constituents of plant extracts. Therefore, this study was undertaken to evaluate the effects of fermented H. dulcis extract (FHDE) on ethanol-induced liver injury in mice. METHODS:FHDE was prepared using Bacillus subtilis and Lactobacillus plantarum. The effects of FHDE on ethanol-induced liver injury were evaluated in C57BL/6 N CrSlc mice. A mixed feed preparation containing the fermented extract with and without ethanol was given to mice for 29 days, according to its group. At the end of the experiment, blood and liver samples were collected from all mice in the group. Plasma biochemical analysis and histopathological investigation were performed to evaluate the impacts of treatment on the biomarkers of hepatic damage and inflammatory changes. Besides, the expression of genes that regulate the activities of enzymes associated with alcohol metabolism, antioxidant activity, and fatty acid oxidation was assessed using a quantitative real-time polymerase chain reaction. Moreover, the amino acid contents and the active ingredients of the extract were evaluated before and after fermentation. RESULTS:Fermentation resulted in a marked increase and decrease in the amount of Gamma-Amino-n-butyric acid (GABA) and glutamic acid, respectively. FHDE enhanced the body weight gain of mice compared to ethanol. Besides, plasma levels of triglyceride, low-density lipoprotein, the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were significantly (P < 0.05) reduced in the FHDE-treated groups relative to the ethanol-treated control. FHDE upregulated the expression of genes associated with enzymes involved in alcohol dehydrogenation (Adh1 and Aldh2), antioxidant activity (SOD and CAT), and fatty acid oxidation (PPAR-α and PGC-1α). However, the expressions of Cytochrome peroxidase Cyp2E1 and genes related to lipogenesis (SREBP-1c, FAS, SCD-1, and ACC) were significantly (P < 0.05) downregulated following treatment with the FHDE. Histopathological investigation demonstrated a slight degree of inflammatory cell infiltration and occasional fatty changes in the FHDE-treated groups. CONCLUSION:The GABA-enriched fermented H. dulcis extract prevented ethanol-induced hepatic damage by enhancing the antioxidant defense system, fatty acid oxidation, and reducing lipogenesis.

Project description:Garcinia spp. belongs to the family Clusiaceae has been traditionally used for the treatment of many ailments including the liver damage. Garcinia dulcis found in North Eastern region of Assam; India can be a potential candidature to combat different ailments. Objective: The present work has been designed in such a way to appraisal the antioxidant and hepatoprotective activity of fruit rind extract of this plant.The antioxidant activity was investigated through the various in vitro models, namely, 2,2-diphenyl-1-picrylhydrazine, 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid, nitrite oxide. Phytochemical investigation for total phenolic and flavonoids contents were carried out by standard protocol. For the evaluation of hepatoprotective activity, albino Wistar rats were divided into five groups, five animals per group and activity was determined by measuring the contents of liver function marker enzymes such as serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), serum alkaline phosphatase (ALP), and biochemical parameter, that is, Bilirubin and total protein. Histopathology observation of liver sections was conducted.Phytochemical investigation revealed the presence of both phenolic and flavonoid groups in the extract in a significant amount. Antioxidant activity of the plant extract was observed in all models and percentage of inhibition was dose-dependent. Intoxicated with carbon tetrachloride, elevated the liver function enzymes, bilirubin, and suppressed the production of total protein. Pretreatment with the extract decreased the SGOT, SGPT, ALP, and bilirubin level significantly and increased the production level of total protein in a dose-dependent manner. The histopathological observation supported the hepatoprotective potentiality of the extract.The results indicate that fruit rind part of G. dulcis is nontoxic and the plant can utilize as an antioxidant source. The plant has a protective agent for liver damages and other diseases caused by free radicals.In vitro antioxidant and in vivo hepatoprotective activity was evaluatedMethanolic extract was subjected to quantify the both phenolic and flavonoid contents. The extract showed the significant amount of both phenolic and flavonoids contents. The extract showed the free radical scavenging activity in 2,2-diphenyl-1-picrylhydrazine, 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid and nitrite oxide modelsThe extract was administrated against the carbon tetrachloride intoxicated animal models to evaluate the hepatoprotective activity by determining the level of liver marker enzymes such as serum glutamate pyruvate transaminase, SGOT, alkaline phosphatase and biochemical parameter such as protein and bilirubin. Pretreatment with the extract reversed the elevated level of the enzymes and increased the protein level in a dose-dependent mannerThe histopathological observations of the liver sections supported the hepatoprotective activity of the extractThe present study revealed that the Garcinia dulcis extract is a good candidature for preventing liver damage and other disease caused by free radicals. Abbreviations Used: DPPH: 2,2-diphenyl-1-picrylhydrazine, ABTS: 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid, SGOT: Serum glutamate oxaloacetate transaminase, SGPT: Serum glutamate pyruvate transaminase, ALP: Serum alkaline phosphatase.

Dataset Information

Hovenia dulcis Thunb extract and its ingredient methyl vanillate activate Wnt/?-catenin pathway and increase bone mass in growing or ovariectomized mice.

Publications

Hovenia dulcis Thunb extract and its ingredient methyl vanillate activate Wnt/β-catenin pathway and increase bone mass in growing or ovariectomized mice.

Similar Datasets

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