Abstract
Aim:
Baicalin, one of the major flavonoids in Scutellaria baicalensis, possesses antioxidant and anti-inflammatory properties. However, the effects of baicalin on metabolic disorders and hepatic steatosis have not been investigated.
Methods:
Body weight was examined in high-fat diet (HFD)-fed rats with or without baicalin treatment. At the end of the experiment, serum biochemical parameters, liver histology and lipid profile were analyzed to assess whether the animals were suffering from metabolic disorders or hepatic steatosis. In the liver, the phosphorylation of AMP activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) and the gene expression of some enzymes involved in lipogenesis were examined. The effects of baicalin on the phosphorylation of AMPK and lipid accumulation induced by high glucose in human hepatoma HepG2 cells were also examined.
Results:
Baicalin (80 mg/kg) administered ip for 16 weeks suppressed body weight gain in HFD-fed rats. Weight reduction was accompanied by the reduction of visceral fat mass. Baicalin significantly decreased the elevated serum cholesterol, free fatty acid and insulin concentrations caused by the HFD. Baicalin also suppressed systemic inflammation by reducing the serum level of tumor necrosis factor α. Baicalin reduced hepatic lipid accumulation, enhanced the phosphorylation of AMPK and ACC and down-regulated genes involved in lipogenesis, including fatty acid synthase and its upstream regulator SREBP-1c. In HepG2 cells, baicalin (5 and 10 μmol/L) increased the phosphorylation of AMPK and decreased lipid accumulation following the addition of high glucose.
Conclusion:
Our study suggests that baicalin might have beneficial effects on the development of hepatic steatosis and obesity-related disorders by targeting the hepatic AMPK.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Boden G . Obesity and free fatty acids. Endocrinol Metab Clin North Am 2008; 37: 635–46.
Festi D, Colecchia A, Sacco T, Bondi M, Roda E, Marchesini G . Hepatic steatosis in obese patients: clinical aspects and prognostic significance. Obes Rev 2004; 5: 27–42.
Akbar DH, Kawther AH . Non-alcoholic fatty liver disease and metabolic syndrome: what we know and what we don't know. Med Sci Monit 2006; 12: RA23–RA26.
Clark JM, Diehl AM . Nonalcoholic fatty liver disease: an underrecognized cause of cryptogenic cirrhosis. JAMA 2003; 289: 3000–4.
Wieckowska A, McCullough AJ, Feldstein AE . Noninvasive diagnosis and monitoring of nonalcoholic steatohepatitis: present and future. Hepatology 2007; 46: 582–9.
Adams LA, Angulo P, Lindor KD . Nonalcoholic fatty liver disease. CMAJ 2005; 172: 899–905.
Younossi ZM . Review article: current management of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Aliment Pharmacol Ther 2008; 28: 2–12.
Marcaurelle LA, Johannes CW . Application of natural product-inspired diversity-oriented synthesis to drug discovery. Prog Drug Res 2008; 66: 189–216.
Lin CL, Huang HC, Lin JK . Theaflavins attenuate hepatic lipid accumulation through activating AMPK in human HepG2 cells. J Lipid Res 2007; 48: 2334–43.
Zang M, Xu S, Maitland-Toolan KA, Zuccollo A, Hou X, Jiang B, et al. Polyphenols stimulate AMP-activated protein kinase, lower lipids, and inhibit accelerated atherosclerosis in diabetic LDL receptor-deficient mice. Diabetes 2006; 55: 2180–91.
Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature 2006; 444: 337–42.
Yu X, McCorkle S, Wang M, Lee Y, Li J, Saha AK, et al. Leptinomimetic effects of the AMP kinase activator AICAR in leptin-resistant rats: prevention of diabetes and ectopic lipid deposition. Diabetologia 2004; 47: 2012–21.
Song Z, Deaciuc I, Zhou Z, Song M, Chen T, Hill D, et al. Involvement of AMP-activated protein kinase in beneficial effects of betaine on high-sucrose diet-induced hepatic steatosis. Am J Physiol Gastrointest Liver Physiol 2007; 293: G894–G902.
Park KG, Min AK, Koh EH, Kim HS, Kim MO, Park HS, et al. Alpha-lipoic acid decreases hepatic lipogenesis through adenosine monophosphate-activated protein kinase (AMPK)-dependent and AMPK-independent pathways. Hepatology 2008; 48: 1477–86.
Yang J, Maika S, Craddock L, King JA, Liu ZM . Chronic activation of AMP-activated protein kinase-alpha1 in liver leads to decreased adiposity in mice. Biochem Biophys Res Commun 2008; 370: 248–53.
Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, et al. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 2001; 108: 1167–74.
Bajaj M, Suraamornkul S, Pratipanawatr T, Hardies LJ, Pratipanawatr W, Glass L, et al. Pioglitazone reduces hepatic fat content and augments splanchnic glucose uptake in patients with type 2 diabetes. Diabetes 2003; 52: 1364–70.
Huang WH, Lee AR, Yang CH . Antioxidative and anti-inflammatory activities of polyhydroxyflavonoids of Scutellaria baicalensis GEORGI. Biosci Biotechnol Biochem 2006; 70: 2371–80.
Waisundara VY, Hsu A, Huang D, Tan BK . Scutellaria baicalensis enhances the anti-diabetic activity of metformin in streptozotocin-induced diabetic Wistar rats. Am J Chin Med 2008; 36: 517–40.
Regulska-Ilow B, Biernat J, Grajeta H, Ilow R, Drzewicka M . Influence of bioflavonoids from the radix extract of Scutellaria baicalensis on the level of serum lipids, and the development of laboratory rats fed with fresh and oxidized fats. Nahrung 2004; 48: 123–8.
Sekiya N, Kogure T, Kita T, Kasahara Y, Sakakibara I, Goto H, et al. Reduction of plasma triglyceride level and enhancement of plasma albumin concentration by Oren-gedoku-to administration. Phytomedicine 2002; 9: 455–60.
Sekiya N, Kainuma M, Hikiami H, Nakagawa T, Kouta K, Shibahara N, et al. Oren-gedoku-to and Keishi-bukuryo-gan-ryo inhibit the progression of atherosclerosis in diet-induced hypercholesterolemic rabbits. Biol Pharm Bull 2005; 28: 294–8.
Fujimoto M, Tsuneyama K, Kainuma M, Sekiya N, Goto H, Takano Y, et al. Evidence-based efficacy of Kampo formulas in a model of non alcoholic fatty liver. Exp Biol Med (Maywood) 2008; 233: 328–37.
Heider JG, Boyett RL . The picomole determination of free and total cholesterol in cells in culture. J Lipid Res 1978; 19: 514–8.
Hardie DG . AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat Rev Mol Cell Biol 2007; 8: 774–85.
Caldwell SH, Argo CK, Al-Osaimi AM . Therapy of NAFLD: insulin sensitizing agents. J Clin Gastroenterol 2006; 40 Suppl 1: S61–S66.
Shimano H, Yahagi N, memiya-Kudo M, Hasty AH, Osuga J, Tamura Y, et al. Sterol regulatory element-binding protein-1 as a key transcription factor for nutritional induction of lipogenic enzyme genes. J Biol Chem 1999; 274: 35832–9.
Zang M, Zuccollo A, Hou X, Nagata D, Walsh K, Herscovitz H, et al. AMP-activated protein kinase is required for the lipid-lowering effect of metformin in insulin-resistant human HepG2 cells. J Biol Chem 2004; 279: 47898–905.
Chang CP, Huang WT, Cheng BC, Hsu CC, Lin MT . The flavonoid baicalin protects against cerebrovascular dysfunction and brain inflammation in experimental heatstroke. Neuropharmacology 2007; 52: 1024–33.
Kim DH, Kim HK, Park S, Kim JY, Zou Y, Cho KH, et al. Short-term feeding of baicalin inhibits age-associated NF-kappaB activation. Mech Ageing Dev 2006; 127: 719–25.
Stickel F, Schuppan D . Herbal medicine in the treatment of liver diseases. Dig Liver Dis 2007; 39: 293–304.
Viollet B, Foretz M, Guigas B, Horman S, Dentin R, Bertrand L, et al. Activation of AMP-activated protein kinase in the liver: a new strategy for the management of metabolic hepatic disorders. J Physiol 2006; 574: 41–53.
Misra P . AMP activated protein kinase: a next generation target for total metabolic control. Expert Opin Ther Targets 2008; 12: 91–100.
Hardie DG . The AMP-activated protein kinase pathway--new players upstream and downstream. J Cell Sci 2004; 117: 5479–87.
Ma KL, Ruan XZ, Powis SH, Chen Y, Moorhead JF, Varghese Z . Inflammatory stress exacerbates lipid accumulation in hepatic cells and fatty livers of apolipoprotein E knockout mice. Hepatology 2008; 48: 770–81.
Steinberg GR . Inflammation in obesity is the common link between defects in fatty acid metabolism and insulin resistance. Cell Cycle 2007; 6: 888–94.
Wan JY, Gong X, Zhang L, Li HZ, Zhou YF, Zhou QX . Protective effect of baicalin against lipopolysaccharide/D-galactosamine-induced liver injury in mice by up-regulation of heme oxygenase-1. Eur J Pharmacol 2008; 587: 302–8.
Acknowledgements
We thank Dr C AALKJAER for critically reading the manuscript. This study was supported by grants from the National Natural Science Foundation of China (No 30672467) and the Ministry of Science and Technology (No 2007AA02Z308).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Guo, Hx., Liu, Dh., Ma, Y. et al. Long-term baicalin administration ameliorates metabolic disorders and hepatic steatosis in rats given a high-fat diet. Acta Pharmacol Sin 30, 1505–1512 (2009). https://doi.org/10.1038/aps.2009.150
Received:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/aps.2009.150
Keywords
This article is cited by
-
Pharmacological properties of baicalin on liver diseases: a narrative review
Pharmacological Reports (2021)
-
Safety evaluation of root extract of Pueraria lobata and Scutellaria baicalensis in rats
BMC Complementary Medicine and Therapies (2020)
-
Baicalin and its aglycone: a novel approach for treatment of metabolic disorders
Pharmacological Reports (2020)
-
Scutellaria baicalensis regulates FFA metabolism to ameliorate NAFLD through the AMPK-mediated SREBP signaling pathway
Journal of Natural Medicines (2018)
-
A comprehensive overview of hepatoprotective natural compounds: mechanism of action and clinical perspectives
Archives of Toxicology (2016)
