The roots of Panax ginseng has been widely used in foods and the prescriptions of traditional Chi... more The roots of Panax ginseng has been widely used in foods and the prescriptions of traditional Chinese medical care, especially in Asia. Alteration of liver microsomal cytochrome P450 activity is one of the primary factors causing herb-drug interaction. However, administration of a daily dose up to 50 mg ginsenoside Rd/kg to male C57BL/6JNarl mice for 7 consecutive days did not affect liver microsomal 7-ethoxyresorufin O-deethylation, pentoxyresorufin O-dealkylation, tolbutamide hydroxylation, nitrosodimethylamine N-demethylation, and nifedipine oxidation activities, which were marker activities of Cyp1a, Cyp2b, Cyp2c, Cyp2e1, and Cyp3a, respectively. Treatment with 50 mg/kg of ethanol extract of P. ginseng did not affect these activities either. These results indicate no evidence for the alteration of P450 activities by either ginsenoside Rd or P. ginseng extract under the treatment regimen in this study.
Aging is a natural human process. It is uniquely individual, taking into account experiences, lif... more Aging is a natural human process. It is uniquely individual, taking into account experiences, lifestyle habits and environmental factors. However, many disorders and syndromes, such as osteoporosis, neurodegenerative disorders, cognitive decline etc., often come with aging. The present study was designed to investigate the possible anti-aging effect of N6-(4-hydroxybenzyl)adenine riboside (T1-11), an adenosine analog isolated from Gastrodia elata, in a mouse model of aging created by D-galactose (D-gal) and the underlying mechanism, as well as explore the role of adenosine signaling in aging. T1-11 activated A2AR and suppressed D-gal- and BeSO4-induced cellular senescence in vitro. In vivo results in mice revealed that T1-11 abated D-gal-induced reactive oxygen species generation and ameliorated cognitive decline by inducing neurogenesis and lowering D-gal-caused neuron death. T1-11 could be a potent agent for postponing senility and preventing aging-related neuroinflammation and neurodegeneration.
Fibromyalgia (FM) is characterized by chronic widespread pain. The pathogenesis of FM remains unc... more Fibromyalgia (FM) is characterized by chronic widespread pain. The pathogenesis of FM remains unclear. No specific biomarkers are available. Animal models of FM may provide an opportunity to explore potential biomarkers in a relative homogenous disease condition. Here, we probed the metabolomics profiles of serum and urine in a mouse model of FM induced by intermittent cold stress (ICS). We focused on the role of acid-sensing ion channel 3 (ASIC3) in the metabolomics profiling because ICS treatment induced chronic widespread muscle pain lasting for 1 month in wild-type (Asic3+/+) but not Asic3-knockout (Asic3−/−) mice. Serum and urine samples were collected from both genotypes at different ICS stages, including before ICS (basal level) and post-ICS at days 10 (middle phase, P10) and 40 (recovery phase, P40). Control naïve mice and ICS-induced FM mice differed in 1H-NMR- and LC-MS-based metabolomics profiling. On pathway analysis, the leading regulated pathways in Asic3+/+ mice were ...
In liver injury, hepatic stellate cells (HSCs) acquire an activated phenotype, migrate to the inj... more In liver injury, hepatic stellate cells (HSCs) acquire an activated phenotype, migrate to the injured region in response to chemotactic factors and produce extracellular matrix (ECM) proteins including alpha-smooth muscle actin (alpha-SMA) and collagen in order to repair the damage. HSC-T6, a cell line of rat HSCs, was used in in vitro experiments. TGF-beta1 was used as a chemoattractant. The expression of alpha-SMA was used as a marker of activated hepatic stellate cells and cell migration was assayed with the Transwell method to investigate the active principles of the roots of Rheum palmatum L. (Dahuang), a well-known traditional Chinese herb used for treating liver diseases. Under cell activation and chemotaxis-directed fractionation and purification, four anthraquinones, rhein ( 1), emodin ( 2), chrysophanol ( 3) and physcion ( 4), and four phenylbutanoids, lindleyin ( 5), isolindleyin ( 7), 4-(4'-hydroxyphenyl)-2-butanone 4'- O-beta- D-glucopyranoside ( 8), and 4-(4'-hydroxyphenyl)-2-butanone ( 9), and a stilbene, 3,5,4'-trihydroxystilbene 4'- O-beta- D-glucopyranoside 6'- O-gallate ( 6) were isolated from the active fractions. Among them, compounds 1 and 2 inhibited alpha-SMA expression. However, compounds 3, 4, 6 and 8 attenuated chemotactic migration, but not alpha-SMA expression.
Anti-inflammation strategies are one of the proposed therapeutic approaches to hepatic fibrosis. ... more Anti-inflammation strategies are one of the proposed therapeutic approaches to hepatic fibrosis. Tetrandrine (C(38)H(42)O(8)N(2), molecular weight: 622; Tet), an alkaloid isolated from the Chinese medicinal herb Stephania tetrandra, has been shown to exert anti-inflammatory activity in pulmonary diseases. The purpose of the present study was to investigate the in vitro and in vivo effects of Tet on hepatic fibrosis. A cell line of rat hepatic stellate cells (HSC-T6) was stimulated with transforming growth factor-beta1 (TGF-beta1) or tumor necrosis factor-alpha (TNF-alpha). The inhibitory effects of Tet on the nuclear factor kappaB (NFkappaB) signaling cascade and molecular markers including intercellular adhesion molecule-1 (ICAM-1) and alpha-smooth muscle actin (alpha-SMA) secretion were assessed. Fibrosis was induced by dimethylnitrosamine (DMN) administration in rats for 4 weeks. Fibrotic rats were randomly assigned to one of the four groups: vehicle (0.7% carboxyl methyl cellulose, CMC), Tet (1 mg/kg), Tet (5 mg/kg), or silymarin (50 mg/kg), each given by gavage twice daily for 3 weeks starting after 1 week of DMN administration. At the end of the study, liver tissues were scored for fibrosis and analyzed for molecular markers of fibrosis. Tetrandrine (0.5-5.0 micromol/L) concentration-dependently inhibited NFkappaB transcriptional activity induced by TNF-alpha, including IkappaBalpha phosphorylation and mRNA expressions of ICAM-1 in HSC-T6 cells. In addition, Tet also inhibited TGF-beta1-induced alpha-SMA secretion and collagen deposition in HSC-T6 cells. Fibrosis scores of livers from DMN-treated rats with high-dose Tet (1.3 +/- 0.3) were significantly reduced in comparison with DMN-treated rats receiving saline (2.0 +/- 0.2). Hepatic collagen content of DMN rats was significantly reduced by either Tet or silymarin treatment. Double-staining results showed that alpha-SMA- and NFkappaB-positive cells were decreased in the fibrotic livers by Tet and silymarin treatment. In addition, mRNA expression of ICAM-1, alpha-SMA, and TGF-beta1 was attenuated by Tet treatment. Moreover, levels of plasma aspartate aminotransferase and alanine aminotransferase activities were reduced by Tet and silymarin treatment. Tetrandrine exerts antifibrotic effects in both HSC-T6 cells and in rats with DMN-induced fibrosis.
The roots of Panax ginseng has been widely used in foods and the prescriptions of traditional Chi... more The roots of Panax ginseng has been widely used in foods and the prescriptions of traditional Chinese medical care, especially in Asia. Alteration of liver microsomal cytochrome P450 activity is one of the primary factors causing herb-drug interaction. However, administration of a daily dose up to 50 mg ginsenoside Rd/kg to male C57BL/6JNarl mice for 7 consecutive days did not affect liver microsomal 7-ethoxyresorufin O-deethylation, pentoxyresorufin O-dealkylation, tolbutamide hydroxylation, nitrosodimethylamine N-demethylation, and nifedipine oxidation activities, which were marker activities of Cyp1a, Cyp2b, Cyp2c, Cyp2e1, and Cyp3a, respectively. Treatment with 50 mg/kg of ethanol extract of P. ginseng did not affect these activities either. These results indicate no evidence for the alteration of P450 activities by either ginsenoside Rd or P. ginseng extract under the treatment regimen in this study.
Aging is a natural human process. It is uniquely individual, taking into account experiences, lif... more Aging is a natural human process. It is uniquely individual, taking into account experiences, lifestyle habits and environmental factors. However, many disorders and syndromes, such as osteoporosis, neurodegenerative disorders, cognitive decline etc., often come with aging. The present study was designed to investigate the possible anti-aging effect of N6-(4-hydroxybenzyl)adenine riboside (T1-11), an adenosine analog isolated from Gastrodia elata, in a mouse model of aging created by D-galactose (D-gal) and the underlying mechanism, as well as explore the role of adenosine signaling in aging. T1-11 activated A2AR and suppressed D-gal- and BeSO4-induced cellular senescence in vitro. In vivo results in mice revealed that T1-11 abated D-gal-induced reactive oxygen species generation and ameliorated cognitive decline by inducing neurogenesis and lowering D-gal-caused neuron death. T1-11 could be a potent agent for postponing senility and preventing aging-related neuroinflammation and neurodegeneration.
Fibromyalgia (FM) is characterized by chronic widespread pain. The pathogenesis of FM remains unc... more Fibromyalgia (FM) is characterized by chronic widespread pain. The pathogenesis of FM remains unclear. No specific biomarkers are available. Animal models of FM may provide an opportunity to explore potential biomarkers in a relative homogenous disease condition. Here, we probed the metabolomics profiles of serum and urine in a mouse model of FM induced by intermittent cold stress (ICS). We focused on the role of acid-sensing ion channel 3 (ASIC3) in the metabolomics profiling because ICS treatment induced chronic widespread muscle pain lasting for 1 month in wild-type (Asic3+/+) but not Asic3-knockout (Asic3−/−) mice. Serum and urine samples were collected from both genotypes at different ICS stages, including before ICS (basal level) and post-ICS at days 10 (middle phase, P10) and 40 (recovery phase, P40). Control naïve mice and ICS-induced FM mice differed in 1H-NMR- and LC-MS-based metabolomics profiling. On pathway analysis, the leading regulated pathways in Asic3+/+ mice were ...
In liver injury, hepatic stellate cells (HSCs) acquire an activated phenotype, migrate to the inj... more In liver injury, hepatic stellate cells (HSCs) acquire an activated phenotype, migrate to the injured region in response to chemotactic factors and produce extracellular matrix (ECM) proteins including alpha-smooth muscle actin (alpha-SMA) and collagen in order to repair the damage. HSC-T6, a cell line of rat HSCs, was used in in vitro experiments. TGF-beta1 was used as a chemoattractant. The expression of alpha-SMA was used as a marker of activated hepatic stellate cells and cell migration was assayed with the Transwell method to investigate the active principles of the roots of Rheum palmatum L. (Dahuang), a well-known traditional Chinese herb used for treating liver diseases. Under cell activation and chemotaxis-directed fractionation and purification, four anthraquinones, rhein ( 1), emodin ( 2), chrysophanol ( 3) and physcion ( 4), and four phenylbutanoids, lindleyin ( 5), isolindleyin ( 7), 4-(4'-hydroxyphenyl)-2-butanone 4'- O-beta- D-glucopyranoside ( 8), and 4-(4'-hydroxyphenyl)-2-butanone ( 9), and a stilbene, 3,5,4'-trihydroxystilbene 4'- O-beta- D-glucopyranoside 6'- O-gallate ( 6) were isolated from the active fractions. Among them, compounds 1 and 2 inhibited alpha-SMA expression. However, compounds 3, 4, 6 and 8 attenuated chemotactic migration, but not alpha-SMA expression.
Anti-inflammation strategies are one of the proposed therapeutic approaches to hepatic fibrosis. ... more Anti-inflammation strategies are one of the proposed therapeutic approaches to hepatic fibrosis. Tetrandrine (C(38)H(42)O(8)N(2), molecular weight: 622; Tet), an alkaloid isolated from the Chinese medicinal herb Stephania tetrandra, has been shown to exert anti-inflammatory activity in pulmonary diseases. The purpose of the present study was to investigate the in vitro and in vivo effects of Tet on hepatic fibrosis. A cell line of rat hepatic stellate cells (HSC-T6) was stimulated with transforming growth factor-beta1 (TGF-beta1) or tumor necrosis factor-alpha (TNF-alpha). The inhibitory effects of Tet on the nuclear factor kappaB (NFkappaB) signaling cascade and molecular markers including intercellular adhesion molecule-1 (ICAM-1) and alpha-smooth muscle actin (alpha-SMA) secretion were assessed. Fibrosis was induced by dimethylnitrosamine (DMN) administration in rats for 4 weeks. Fibrotic rats were randomly assigned to one of the four groups: vehicle (0.7% carboxyl methyl cellulose, CMC), Tet (1 mg/kg), Tet (5 mg/kg), or silymarin (50 mg/kg), each given by gavage twice daily for 3 weeks starting after 1 week of DMN administration. At the end of the study, liver tissues were scored for fibrosis and analyzed for molecular markers of fibrosis. Tetrandrine (0.5-5.0 micromol/L) concentration-dependently inhibited NFkappaB transcriptional activity induced by TNF-alpha, including IkappaBalpha phosphorylation and mRNA expressions of ICAM-1 in HSC-T6 cells. In addition, Tet also inhibited TGF-beta1-induced alpha-SMA secretion and collagen deposition in HSC-T6 cells. Fibrosis scores of livers from DMN-treated rats with high-dose Tet (1.3 +/- 0.3) were significantly reduced in comparison with DMN-treated rats receiving saline (2.0 +/- 0.2). Hepatic collagen content of DMN rats was significantly reduced by either Tet or silymarin treatment. Double-staining results showed that alpha-SMA- and NFkappaB-positive cells were decreased in the fibrotic livers by Tet and silymarin treatment. In addition, mRNA expression of ICAM-1, alpha-SMA, and TGF-beta1 was attenuated by Tet treatment. Moreover, levels of plasma aspartate aminotransferase and alanine aminotransferase activities were reduced by Tet and silymarin treatment. Tetrandrine exerts antifibrotic effects in both HSC-T6 cells and in rats with DMN-induced fibrosis.
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