ABSTRACT
OBJECTIVES: The aim of this study was to determine the protective mechanisms of wild ginseng cambial meristematic cells (CMCs) on non-alcoholic fatty liver disease in high-fat diet (HFD)-fed mice. METHODS: Male C57BL/6 mice received either normal-fat diet or HFD for 10 weeks along with wild ginseng CMCs (75, 150 and 300 mg/kg) or vehicle (0.5% carboxyl methyl cellulose) by oral administration once a day. Triglyceride and total cholesterol contents were measured in liver and serum samples. Parameters for hepatic lipid metabolism and mitochondria biogenesis were assessed. KEY FINDINGS: Treatment with wild ginseng CMCs markedly attenuated body weight, serum and hepatic lipid contents, and serum aminotransferase activity. While wild ginseng CMCs attenuated the increases in sterol regulatory element-binding transcription factor 1 (SREBP-1) and carbohydrate-responsive element-binding protein (ChREBP) expression, it enhanced the increases in carnitine palmitoyltransferase 1A (CPT1A) and peroxisome proliferator-activated receptor alpha (PPAR-α) expression. HFD decreased glutamate dehydrogenase activity and glutathione content, and increased lipid peroxidation, which were all attenuated by wild ginseng CMCs. Furthermore, wild ginseng CMCs enhanced mitochondrial biogenesis-related factors, including peroxisome proliferator-activated receptor-γ co activator 1α (PGC1α), nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM). CONCLUSIONS: Wild ginseng CMCs protect against HFD-induced liver injury, which prevents lipid accumulation and mitochondrial oxidative stress, and enhances mitochondrial biogenesis.
Subject(s)
Diet, High-Fat/adverse effects , Fatty Liver/drug therapy , Mitochondrial Diseases/drug therapy , Panax/chemistry , Animals , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors , Body Weight/drug effects , Carnitine O-Palmitoyltransferase/metabolism , Cholesterol/blood , Cholesterol/metabolism , DNA-Binding Proteins/metabolism , Fatty Liver/blood , Fatty Liver/metabolism , Glutathione/metabolism , High Mobility Group Proteins/metabolism , Lipid Metabolism/drug effects , Lipid Peroxidation/drug effects , Male , Mice , Mice, Inbred C57BL , Mitochondrial Diseases/blood , Mitochondrial Diseases/metabolism , Non-alcoholic Fatty Liver Disease/blood , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism , Nuclear Proteins/metabolism , Nuclear Respiratory Factor 1/metabolism , Organelle Biogenesis , PPAR alpha/metabolism , RNA-Binding Proteins/metabolism , Sterol Regulatory Element Binding Protein 1/metabolism , Transaminases/metabolism , Transcription Factors/metabolism , Triglycerides/bloodABSTRACT
AIMS: As an alternative strategy to obtain large amounts of ginseng extract with high yield of ginsenosides, we have utilized culture of cambial meristematic cells (CMCs) from wild ginseng. The anti-tumor effects of methanol extract of ginseng CMCs (MEGC) and their action mechanisms were investigated. MAIN METHODS: Mice were intraperitoneally administered with MEGC, and we explored NK cell activity, suppression of in vivo growth of tumor cells and relevant molecule expression. KEY FINDINGS: MEGC significantly potentiated NK cell activity and suppressed in vivo growth of B16 melanoma cells. However, we observed no increase in NK cell number and unaltered expression of NK cell-activating (NKG2D) and inhibitory (Ly49, CD94/NKG2A) receptors as well as NK cell activation markers (CD25, CD69, CD119, and CD212) in MEGC-treated group compared to the controls. Instead, MEGC significantly enhanced IL-2 responsiveness in the early effector phase and the constitutive expression of granzyme B. SIGNIFICANCE: Our data indicate that culture of CMCs is an attractive alternative method for sustainable production of ginseng extracts and clinical use. In addition, we have unraveled a novel mechanism underlying the potentiation of NK cell activity and antitumor effect of ginseng extract, in which it upregulates the constitutive expression of cytotoxic mediator(s) and IL-2 responsiveness.
Subject(s)
Adjuvants, Immunologic/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Cambium/chemistry , Killer Cells, Natural/immunology , Neoplasms, Experimental/drug therapy , Panax/chemistry , Plant Cells/chemistry , Plant Extracts/pharmacology , Adjuvants, Immunologic/chemistry , Animals , Antigens, Differentiation/immunology , Antineoplastic Agents, Phytogenic/chemistry , Immunity, Cellular/drug effects , Killer Cells, Natural/pathology , Male , Methanol/chemistry , Mice , Neoplasms, Experimental/immunology , Plant Extracts/chemistryABSTRACT
BACKGROUND: Panax ginseng has a wide range of biological activities including anti-inflammatory, antioxidant, and immunomodulatory functions. Wild ginseng cambial meristematic cells (CMCs) were obtained from P. ginseng cambium. This study examined the protective mechanism of wild ginseng CMCs against d-galactosamine (GalN)-induced liver injury. GalN, a well-known hepatotoxicant, causes severe hepatocellular inflammatory damage and clinical features similar to those of human viral hepatitis in experimental animals. METHODS: Hepatotoxicity was induced in rats using GalN (700 mg/kg, i.p.). Wild ginseng CMCs was administered orally once a day for 2 wks, and then 2 h prior to and 6 h after GalN injection. RESULTS: Wild ginseng CMCs attenuated the increase in serum aminotransferase activity that occurs 24 h after GalN injection. Wild ginseng CMCs also attenuated the GalN-induced increase in serum tumor necrosis factor-α, interleukin-6 level, and hepatic cyclooxygenase-2 protein and mRNA expression. Wild ginseng CMCs augmented the increase in serum interleukin -10 and hepatic heme oxygenase-1 protein and mRNA expression that was induced by GalN, inhibited the increase in the nuclear level of nuclear factor-kappa B, and enhanced the increase in NF-E2-related factor 2. CONCLUSION: Our findings suggest that wild ginseng CMCs protects liver against GalN-induced inflammation by suppressing proinflammatory mediators and enhancing production of anti-inflammatory mediators.
