Interaction of Veratrum nigrum with Panax ginseng against Obesity: A Sang-ban Relationship

Obesity has become a major health threat in developed countries. However, current medications for obesity are limited because of their adverse effects. Interest in natural products for the treatment of obesity is thus rapidly growing. Korean Medicine (KM) is characterized by the wide use of herbal formulas. However, the combination rule of herbal formulas in KM lacks experimental evidence. According to Shennong's Classic of Materia Medica, the earliest book of herbal medicine, Veratrum nigrum (VN) has antagonistic features against Panax ginseng (PG), and the PG-VN pair is strictly forbidden. In this study, we have shown the effects of PG, VN, and their combination on obesity in high-fat (HF) diet-induced obese mice and in 3T3-L1 cells. PG, VN, and PG-VN combination significantly reduced weight gain and the fat pad weight in HF diet-induced obese mice. They also significantly decreased lipid accumulation and the expressions of two major adipogenesis factors, PPARγ and C/EBPα, in 3T3-L1 cells. In addition, the PG-VN combination had synergistic effects compared with the mixture of extracts of PG and VN on inhibition of PPARγ and C/EBPα expressions at lower doses. These results indicate a new potential anti-obese pharmacotherapy and also provide scientific evidence supporting the usage of herbal combinations instead of mixtures in KM.

[1]  S. Su,et al.  Evaluation of the anti-inflammatory and analgesic properties of individual and combined extracts from Commiphora myrrha, and Boswellia carterii. , 2012, Journal of ethnopharmacology.

[2]  Kang Li,et al.  [Classification of 365 Chinese medicines in Shennong's Materia Medica Classic based on a semi-supervised incremental clustering method]. , 2011, Zhong xi yi jie he xue bao = Journal of Chinese integrative medicine.

[3]  Bo Zhang,et al.  Herb network construction and co-module analysis for uncovering the combination rule of traditional Chinese herbal formulae , 2010, BMC Bioinform..

[4]  Karin Aumayr,et al.  Drosophila Genome-wide Obesity Screen Reveals Hedgehog as a Determinant of Brown versus White Adipose Cell Fate , 2010, Cell.

[5]  Xin Zeng,et al.  A system for screening agonists targeting β2-adrenoceptor from chinese medicinal herbs , 2009, Journal of Zhejiang University SCIENCE B.

[6]  F. Thiesen,et al.  Rimonabant: an antagonist drug of the endocannabinoid system for the treatment of obesity , 2009, Pharmacological reports : PR.

[7]  H. Wagner,et al.  Synergy research: approaching a new generation of phytopharmaceuticals. , 2009, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[8]  H. Wagner Synergy Research: A New Approach to Evaluating the Efficacy of Herbal Mono-drug Extracts and Their Combinations , 2009, Natural product communications.

[9]  D. Barceloux Medical Toxicology of Natural Substances: Foods, Fungi, Medicinal Herbs, Plants, and Venomous Animals , 2008 .

[10]  Wei Guo-li,et al.  A survey of the studies on compatible law of ingredients in Chinese herbal prescriptions. , 2008 .

[11]  J. Um,et al.  Green tea seed oil reduces weight gain in C57BL/6J mice and influences adipocyte differentiation by suppressing peroxisome proliferator-activated receptor-γ , 2008, Pflügers Archiv - European Journal of Physiology.

[12]  Yonghong Liu,et al.  Hypotensive effect and toxicology of total alkaloids and veratramine from roots and rhizomes of Veratrum nigrum L. in spontaneously hypertensive rats. , 2008, Die Pharmazie.

[13]  Peter Tontonoz,et al.  Fat and beyond: the diverse biology of PPARgamma. , 2008, Annual review of biochemistry.

[14]  Yoshiji Yamada,et al.  Genetic factors for human obesity , 2008, Cellular and Molecular Life Sciences.

[15]  A. Johnson,et al.  Cisplatin-mediated sensitivity to TRAIL-induced cell death in human granulosa tumor cells. , 2008, Gynecologic oncology.

[16]  Xiao-feng Tian,et al.  Protection of Veratrum nigrum L. var. ussuriense Nakai alkaloids against ischemia-reperfusion injury of the rat liver. , 2007, World journal of gastroenterology.

[17]  H. Xiao,et al.  Temporal recruitment of CCAAT/enhancer-binding proteins to early and late adipogenic promoters in vivo. , 2006, Journal of molecular endocrinology.

[18]  A. Pandey,et al.  Sequential phosphorylation of CCAAT enhancer-binding protein β by MAPK and glycogen synthase kinase 3β is required for adipogenesis , 2005 .

[19]  V. Vuksan,et al.  Herbal remedies in the management of diabetes: lessons learned from the study of ginseng. , 2005, Nutrition, metabolism, and cardiovascular diseases : NMCD.

[20]  Amalia Waxman,et al.  Who Global Strategy on Diet, Physical Activity and Health * , 2004, Food and nutrition bulletin.

[21]  S. Ko,et al.  Wild ginseng prevents the onset of high-fat diet induced hyperglycemia and obesity in icr mice , 2004, Archives of pharmacal research.

[22]  Gösta Samuelson,et al.  Global strategy on diet, physical activity and health , 2004 .

[23]  Seung Hwan Kim,et al.  Effects of Panax ginseng extract on lipid metabolism in humans. , 2003, Pharmacological research.

[24]  L. Fajas Adipogenesis: a cross-talk between cell proliferation and cell differentiation , 2003, Annals of medicine.

[25]  Bruce M. Spiegelman,et al.  Obesity and the Regulation of Energy Balance , 2001, Cell.

[26]  P. Puigserver,et al.  Transcriptional regulation of adipogenesis. , 2000, Genes & development.

[27]  F. Paccaud,et al.  Dyslipidemia and abdominal obesity: an assessment in three general populations. , 2000, Journal of clinical epidemiology.

[28]  A. Heck,et al.  Orlistat, a New Lipase Inhibitor for the Management of Obesity , 2000, Pharmacotherapy.

[29]  C. Yuan,et al.  Ginseng pharmacology: multiple constituents and multiple actions. , 1999, Biochemical pharmacology.

[30]  J. Rey,et al.  Sibutramine: A Serotonin–Norepinephrine Reuptake-Inhibitor for the Treatment of Obesity , 1999, The Annals of pharmacotherapy.

[31]  B. Spiegelman,et al.  Cross-Regulation of C/EBPα and PPARγ Controls the Transcriptional Pathway of Adipogenesis and Insulin Sensitivity , 1999 .

[32]  K. Kemper,et al.  A review of 12 commonly used medicinal herbs. , 1998, Archives of family medicine.

[33]  A. Gotto,et al.  Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. , 1998, JAMA.

[34]  M. Lazar,et al.  Peroxisome Proliferator Activated Receptor γ, CCAAT/ Enhancer-binding Protein α, and Cell Cycle Status Regulate the Commitment to Adipocyte Differentiation* , 1997, The Journal of Biological Chemistry.

[35]  S. Ellis,et al.  Pravastatin limitation of atherosclerosis in the coronary arteries (PLAC I): reduction in atherosclerosis progression and clinical events. PLAC I investigation. , 1995, Journal of the American College of Cardiology.

[36]  A. Rautio,et al.  Ginseng Therapy in Non-Insulin-Dependent Diabetic Patients: Effects on psychophysical performance, glucose homeostasis, serum lipids, serum aminoterminalpropeptide concentration, and body weight , 1995, Diabetes Care.

[37]  J. L. Ramírez-Zacarías,et al.  Quantitation of adipose conversion and triglycerides by staining intracytoplasmic lipids with oil red O , 1992, Histochemistry.

[38]  R. Umek,et al.  Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells. , 1991, Genes & development.

[39]  A. Qureshi,et al.  Suppression of cholesterogenesis and reduction of LDL cholesterol by dietary ginseng and its fractions in chicken liver. , 1983, Atherosclerosis.

[40]  M. M. Bradford A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. , 1976, Analytical biochemistry.

[41]  R. Levy,et al.  Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. , 1972, Clinical chemistry.

[42]  D. A. Seaton,et al.  The Treatment of Obesity , 1963, The British journal of clinical practice.

[43]  Xue-rong Zheng,et al.  A survey of the studies on compatible law of ingredients in Chinese herbal prescriptions. , 2008, Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan.

[44]  G. Bray,et al.  Obesity , 2008, Annals of Internal Medicine.

[45]  A. Mokdad,et al.  Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. , 2003, JAMA.

[46]  E. Williamson,et al.  Synergy and other interactions in phytomedicines. , 2001, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[47]  Ames,et al.  PREVENTION OF CORONARY HEART DISEASE WITH PRAVASTATIN IN MEN WITH HYPERCHOLESTEROLEMIA , 2000 .

[48]  HOMAS,et al.  The Effect of Pravastatin on Coronary Events after Myocardial Infarction in Patients with Average Cholesterol Levels , 2000 .

[49]  B. Spiegelman,et al.  Cross-regulation of C/EBP alpha and PPAR gamma controls the transcriptional pathway of adipogenesis and insulin sensitivity. , 1999, Molecular cell.

[50]  Kazuo Nakamura,et al.  IN SPONTANEOUSLY HYPERTENSIVE RATS , 1985 .