Houttuynia cordata Facilitates Metformin on Ameliorating Insulin Resistance Associated with Gut Microbiota Alteration in OLETF Rats
Abstract
:1. Introduction
2. Materials and Methods
2.1. Preparation of Houttuynia cordata Extract
2.2. Ultra-Performance Liquid Chromatography Based Fingerprinting
2.3. Determination of Total Phenolic and Flavonoid Contents of HCE
2.4. Animals and Experimental Schedule
2.5. Oral Glucose Tolerance Test and Intraperitoneal Insulin Tolerance Test
2.6. Serum and Liver Biochemical Analyses
2.7. Analysis of Serum and Fecal Endotoxin Levels
2.8. Measurement of Serum Pro-Inflammatory Cytokines
2.9. Histopathological Analysis
2.10. Quantification of Fecal Short Chain Fatty Acid
2.11. Western Blot Analysis
2.12. Fecal Microbial Analysis Using Denaturing Gradient Gel Electrophoresis and Real-Time PCR
2.13. Statistical Analysis
3. Results
3.1. Composition of Houttuynia cordata Extract
3.2. Amelioration of Insulin and Glucose-Related Parameters
3.3. Improvement of Serum Lipid Profile and Hepatic Triglycerides
3.4. Suppression of Systemic Endotoxin and Inflammation
3.5. Activation of adenosine monophosphate-activated protein kinase
3.6. Histopathological Analysis
3.7. Modification of Gut Microbiota Distribution and Profile of SCFAs
4. Discussion
5. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
- World Health Organization (WHO). Global Status Report on Noncommunicable Diseases 2014; World Health Organization: Geneva, Switzerland, 2012. [Google Scholar]
- World Health Organization (WHO). Global Health Estimates: Deaths by Cause, Age, Sex and Country, 2000–2012; World Health Organization: Geneva, Switzerland, 2014. [Google Scholar]
- Holman, R. Metformin as first choice in oral diabetes treatment: The UKPDS experience. Journ. Annu. Diabetol. Hotel Dieu 2007, 13–20. [Google Scholar]
- Kumar, M.; Prasad, S.K.; Hemalatha, S. A current update on the phytopharmacological aspects of Houttuynia cordata Thunb. Pharmacogn. Rev. 2014, 8, 22–35. [Google Scholar] [PubMed]
- Chen, W.T.; Yang, C.L.; Yin, M.C. Protective effects from Houttuynia cordata aqueous extract against acetaminophen-induced liver injury. Biomedicine 2014, 4, 5. [Google Scholar] [CrossRef] [PubMed]
- Chen, Y.F.; Yang, J.S.; Chang, W.S.; Tsai, S.C.; Peng, S.F.; Zhou, Y.R. Houttuynia cordata Thunb extract modulates G0/G1 arrest and Fas/CD95-mediated death receptor apoptotic cell death in human lung cancer A549 cells. J. Biomed. Sci. 2013, 20, 18. [Google Scholar] [CrossRef] [PubMed]
- Miyata, M.; Koyama, T.; Yazawa, K. Water extract of Houttuynia cordata Thunb. leaves exerts anti-obesity effects by inhibiting fatty acid and glycerol absorption. J. Nutr. Sci. Vitaminol. 2010, 56, 150–156. [Google Scholar] [CrossRef] [PubMed]
- Kim, G.S.; Kim, D.H.; Lim, J.J.; Lee, J.J.; Han, D.Y.; Lee, W.M.; Jung, W.C.; Min, W.G.; Won, C.G.; Rhee, M.H.; et al. Biological and antibacterial activities of the natural herb Houttuynia cordata water extract against the intracellular bacterial pathogen salmonella within the RAW 264.7 macrophage. Biol. Pharm. Bull. 2008, 31, 2012–2017. [Google Scholar] [CrossRef] [PubMed]
- Lau, K.M.; Lee, K.M.; Koon, C.M.; Cheung, C.S.; Lau, C.P.; Ho, H.M.; Lee, M.Y.; Au, S.W.; Cheng, C.H.; Lau, C.B.; et al. Immunomodulatory and anti-SARS activities of Houttuynia cordata. J. Ethnopharmacol. 2008, 118, 79–85. [Google Scholar] [CrossRef] [PubMed]
- Lee, J.H.; Ahn, J.; Kim, J.W.; Lee, S.G.; Kim, H.P. Flavonoids from the aerial parts of Houttuynia cordata attenuate lung inflammation in mice. Arch. Pharm. Res. 2015, 38, 1304–1311. [Google Scholar] [CrossRef] [PubMed]
- Tremaroli, V.; Backhed, F. Functional interactions between the gut microbiota and host metabolism. Nature 2012, 489, 242–249. [Google Scholar] [CrossRef] [PubMed]
- Wang, J.H.; Bose, S.; Kim, G.C.; Hong, S.U.; Kim, J.H.; Kim, J.E.; Kim, H. Flos Lonicera ameliorates obesity and associated endotoxemia in rats through modulation of gut permeability and intestinal microbiota. PLoS ONE 2014, 9, e86117. [Google Scholar] [CrossRef] [PubMed]
- Hussain, A.; Bose, S.; Wang, J.-H.; Yadav, M.K.; Mahajan, G.B.; Kim, H. Fermentation, a feasible strategy for enhancing bioactivity of herbal medicines. Food Res. Int. 2016, 81, 1–16. [Google Scholar] [CrossRef]
- Wang, J.H.; Bose, S.; Kim, H.G.; Han, K.S.; Kim, H. Fermented Rhizoma Atractylodis Macrocephalae alleviates high fat diet-induced obesity in association with regulation of intestinal permeability and microbiota in rats. Sci. Rep. 2015, 5, 8391. [Google Scholar] [CrossRef] [PubMed]
- Hussain, A.; Yadav, M.K.; Bose, S.; Wang, J.H.; Lim, D.; Song, Y.K.; Ko, S.G.; Kim, H. Daesiho-Tang is an effective herbal formulation in attenuation of obesity in mice through alteration of gene expression and modulation of intestinal microbiota. PLoS ONE 2016, 11, e0165483. [Google Scholar] [CrossRef] [PubMed]
- Shin, N.R.; Lee, J.-C.; Lee, H.-Y.; Kim, M.-S.; Whon, T.W.; Lee, M.-S.; Bae, J.-W. An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut 2013. [Google Scholar]
- Kawano, K.; Hirashima, T.; Mori, S.; Saitoh, Y.; Kurosumi, M.; Natori, T. Spontaneous long-term hyperglycemic rat with diabetic complications. Otsuka Long-Evans Tokushima Fatty (OLETF) strain. Diabetes 1992, 41, 1422–1428. [Google Scholar] [CrossRef] [PubMed]
- Moran, T.H.; Bi, S. Hyperphagia and obesity in OLETF rats lacking CCK-1 receptors. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2006, 361, 1211–1218. [Google Scholar] [CrossRef] [PubMed]
- Singleton, V.L.; Orthofer, R.; Lamuela-Raventós, R.M. Analysis of total phenols and other oxidation substrates and antioxidants by means of folin-ciocalteu reagent. Methods Enzymol. 1999, 299, 152–178. [Google Scholar]
- Kumar, M.; Prasad, S.K.; Krishnamurthy, S.; Hemalatha, S. Antihyperglycemic Activity of Houttuynia cordata Thunb. in Streptozotocin-Induced Diabetic Rats. Adv. Pharmacol. Sci. 2014, 2014, 809438. [Google Scholar] [PubMed]
- Patcharee, P.; Wilawan, P.; Chusri, T. Anti-hyperglycemic and Anti-hyperlipidemic Effects of Extract from Houttuynia cordata Thumb. in Streptozotocin-Induced Diabetic Rats. Pharmacogn. J. 2017, 9, 382–387. [Google Scholar]
- Shaw, R.J. Metformin trims fats to restore insulin sensitivity. Nat. Med. 2013, 19, 1570–1572. [Google Scholar] [CrossRef] [PubMed]
- Wang, H.Y.; Lu, M.; Xiu, Y.F. Houttuynia cordata modulates connective tissue growth factor and insulin resistance in rats with diabetes mellitus. Chin. J. New Drug 2009, 16, 1540–1544. [Google Scholar]
- Zhang, Y.; An, H.; Pan, S.Y.; Zhao, D.D.; Zuo, J.C.; Li, X.K.; Gao, Y.; Mu, Q.Q.; Yu, N.; Ma, Y.; et al. Jiang Tang Xiao Ke Granule, a Classic Chinese Herbal Formula, Improves the Effect of Metformin on Lipid and Glucose Metabolism in Diabetic Mice. Evid. Based Complement. Altern. Med. 2016, 2016, 1592731. [Google Scholar] [CrossRef] [PubMed]
- Lian, F.; Tian, J.; Chen, X.; Li, Z.; Piao, C.; Guo, J.; Ma, L.; Zhao, L.; Xia, C.; Wang, C.Z.; et al. The efficacy and safety of chinese herbal medicine jinlida as add-on medication in type 2 diabetes patients ineffectively managed by metformin monotherapy: A double-blind, randomized, placebo-controlled, multicenter trial. PLoS ONE 2015, 10, e0130550. [Google Scholar] [CrossRef] [PubMed]
- Waisundara, V.Y.; Hsu, A.; Huang, D.; Tan, B.K. Scutellaria baicalensis enhances the anti-diabetic activity of metformin in streptozotocin-induced diabetic Wistar rats. Am. J. Chin. Med. 2008, 36, 517–540. [Google Scholar] [CrossRef] [PubMed]
- Mooradian, A.D. Dyslipidemia in type 2 diabetes mellitus. Nat. Clin. Pract. Endocrinol. Metab. 2009, 5, 150–159. [Google Scholar] [CrossRef] [PubMed]
- Haffner, S.M. American diabetes association dyslipidemia management in adults with diabetes. Diabetes Care 2004, 27 (Suppl. 1), s68–s71. [Google Scholar] [PubMed]
- Murguia-Romero, M.; Jimenez-Flores, J.R.; Sigrist-Flores, S.C.; Espinoza-Camacho, M.A.; Jimenez-Morales, M.; Pina, E.; Mendez-Cruz, A.R.; Villalobos-Molina, R.; Reaven, G.M. Plasma triglyceride/HDL-cholesterol ratio, insulin resistance, and cardiometabolic risk in young adults. J. Lipid Res. 2013, 54, 2795–2799. [Google Scholar] [CrossRef] [PubMed]
- Vega, G.L.; Barlow, C.E.; Grundy, S.M.; Leonard, D.; DeFina, L.F. Triglyceride-to-high-density-lipoprotein-cholesterol ratio is an index of heart disease mortality and of incidence of type 2 diabetes mellitus in men. J. Investig. Med. 2014, 62, 345–349. [Google Scholar] [CrossRef] [PubMed]
- Gonzalez-Chavez, A.; Simental-Mendia, L.E.; Elizondo-Argueta, S. Elevated triglycerides/HDL-cholesterol ratio associated with insulin resistance. Cir. Cir. 2011, 79, 126–131. [Google Scholar] [PubMed]
- Robinson, A.C.; Burke, J.; Robinson, S.; Johnston, D.G.; Elkeles, R.S. The effects of metformin on glycemic control and serum lipids in insulin-treated NIDDM patients with suboptimal metabolic control. Diabetes Care 1998, 21, 701–705. [Google Scholar] [CrossRef] [PubMed]
- Esser, N.; Legrand-Poels, S.; Piette, J.; Scheen, A.J.; Paquot, N. Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes Res. Clin. Pract. 2014, 105, 141–150. [Google Scholar] [CrossRef] [PubMed]
- Donath, M.Y. Targeting inflammation in the treatment of type 2 diabetes: Time to start. Nat. Rev. Drug Discov. 2014, 13, 465–476. [Google Scholar] [CrossRef] [PubMed]
- Cani, P.D.; Amar, J.; Iglesias, M.A.; Poggi, M.; Knauf, C.; Bastelica, D.; Neyrinck, A.M.; Fava, F.; Tuohy, K.M.; Chabo, C.; et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 2007, 56, 1761–1772. [Google Scholar] [CrossRef] [PubMed]
- Decker, K. Biologically active products of stimulated liver macrophages (Kupffer cells). Eur. J. Biochem. 1990, 192, 245–261. [Google Scholar] [CrossRef] [PubMed]
- Jaeschke, H.; Smith, C.W.; Clemens, M.G.; Ganey, P.E.; Roth, R.A. Mechanisms of inflammatory liver injury: Adhesion molecules and cytotoxicity of neutrophils. Toxicol. Appl. Pharmacol. 1996, 139, 213–226. [Google Scholar] [CrossRef] [PubMed]
- Tsutsui, H.; Adachi, K.; Seki, E.; Nakanishi, K. Cytokine-induced inflammatory liver injuries. Curr. Mol. Med. 2003, 3, 545–559. [Google Scholar] [CrossRef] [PubMed]
- Bergheim, I.; Luyendyk, J.P.; Steele, C.; Russell, G.K.; Guo, L.; Roth, R.A.; Arteel, G.E. Metformin prevents endotoxin-induced liver injury after partial hepatectomy. J. Pharmacol. Exp. Ther. 2006, 316, 1053–1061. [Google Scholar] [CrossRef] [PubMed]
- Kalariya, N.M.; Shoeb, M.; Ansari, N.H.; Srivastava, S.K.; Ramana, K.V. Antidiabetic drug metformin suppresses endotoxin-induced uveitis in rats. Investig. Ophthalmol. Vis. Sci. 2012, 53, 3431–3440. [Google Scholar] [CrossRef] [PubMed]
- Koh, S.J.; Kim, J.M.; Kim, I.K.; Ko, S.H.; Kim, J.S. Anti-inflammatory mechanism of metformin and its effects in intestinal inflammation and colitis-associated colon cancer. J. Gastroenterol. Hepatol. 2014, 29, 502–510. [Google Scholar] [CrossRef] [PubMed]
- Li, J.; Zhao, F. Anti-inflammatory functions of Houttuynia cordata Thunb. and its compounds: A perspective on its potential role in rheumatoid arthritis. Exp. Ther. Med. 2015, 10, 3–6. [Google Scholar] [CrossRef] [PubMed]
- Chun, J.M.; Nho, K.J.; Kim, H.S.; Lee, A.Y.; Moon, B.C.; Kim, H.K. An ethyl acetate fraction derived from Houttuynia cordata extract inhibits the production of inflammatory markers by suppressing NF-small ka, CyrillicB and MAPK activation in lipopolysaccharide-stimulated RAW 264.7 macrophages. BMC Complement. Altern. Med. 2014, 14, 234. [Google Scholar] [CrossRef] [PubMed]
- Sanz, Y.; Santacruz, A.; Gauffin, P. Gut microbiota in obesity and metabolic disorders. Proc. Nutr. Soc. 2010, 69, 434–441. [Google Scholar] [CrossRef] [PubMed]
- Sartor, R.B. Therapeutic correction of bacterial dysbiosis discovered by molecular techniques. Proc. Natl. Acad. Sci. USA 2008, 105, 16413–16414. [Google Scholar] [CrossRef] [PubMed]
- Mata, N.; Alonso, R.; Badimon, L.; Padró, T.; Fuentes, F.; Muniz, O.; Perez-Jiménez, F.; López-Miranda, J.; Díaz, J.L.; Vidal, J.I.; et al. Clinical characteristics and evaluation of LDL-cholesterol treatment of the Spanish Familial Hypercholesterolemia Longitudinal Cohort Study (SAFEHEART). Lipids Health Dis. 2011, 10, 94. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Cabreiro, F. Metformin Joins Forces with Microbes. Cell Host Microbe 2016, 19, 1–3. [Google Scholar] [CrossRef] [PubMed]
- Zhang, X.; Zhao, Y.; Xu, J.; Xue, Z.; Zhang, M.; Pang, X.; Zhao, L. Modulation of gut microbiota by berberine and metformin during the treatment of high-fat diet-induced obesity in rats. Sci. Rep. 2015, 5, 14405. [Google Scholar] [CrossRef] [PubMed]
- Larsen, N.; Vogensen, F.K.; van den Berg, F.W.J.; Nielsen, D.S.; Andreasen, A.S.; Pedersen, B.K.; Al-Soud, W.A.; Sørensen, S.J.; Hansen, L.H.; Jakobsen, M. Gut Microbiota in Human Adults with Type 2 Diabetes Differs from Non-Diabetic Adults. PLoS ONE 2010, 5, e9085. [Google Scholar] [CrossRef] [PubMed]
- Ryan, K.K.; Tremaroli, V.; Clemmensen, C.; Kovatcheva-Datchary, P.; Myronovych, A.; Karns, R.; Wilson-Perez, H.E.; Sandoval, D.A.; Kohli, R.; Backhed, F.; et al. FXR is a molecular target for the effects of vertical sleeve gastrectomy. Nature 2014, 509, 183–188. [Google Scholar] [CrossRef] [PubMed]
- Ley, R.E. Gut microbiota in 2015: Prevotella in the gut: Choose carefully. Nat. Rev. Gastroenterol. Hepatol. 2016, 13, 69–70. [Google Scholar] [CrossRef] [PubMed]
- De la Cuesta-Zuluaga, J.; Mueller, N.T.; Corrales-Agudelo, V.; Velásquez-Mejía, E.P.; Carmona, J.A.; Abad, J.M.; Escobar, J.S. Metformin is associated with higher relative abundance of mucin-degrading Akkermansia muciniphila and several short-chain fatty acid–producing microbiota in the gut. Diabetes Care 2016. [Google Scholar] [CrossRef]
- Schneeberger, M.; Everard, A.; Gomez-Valades, A.G.; Matamoros, S.; Ramirez, S.; Delzenne, N.M.; Gomis, R.; Claret, M.; Cani, P.D. Akkermansia muciniphila inversely correlates with the onset of inflammation, altered adipose tissue metabolism and metabolic disorders during obesity in mice. Sci. Rep. 2015, 5, 16643. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Dao, M.C.; Everard, A.; Aron-Wisnewsky, J.; Sokolovska, N.; Prifti, E.; Verger, E.O.; Kayser, B.D.; Levenez, F.; Chilloux, J.; Hoyles, L.; et al. Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: Relationship with gut microbiome richness and ecology. Gut 2016, 65, 426–436. [Google Scholar] [CrossRef] [PubMed]
- Forslund, K.; Hildebrand, F.; Nielsen, T.; Falony, G.; Le Chatelier, E.; Sunagawa, S.; Prifti, E.; Vieira-Silva, S.; Gudmundsdottir, V.; Pedersen, H.K.; et al. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature 2015, 528, 262–266. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Noriega, B.S.; Sanchez-Gonzalez, M.A.; Salyakina, D.; Coffman, J. Understanding the impact of omega-3 rich diet on the gut microbiota. Case Rep. Med. 2016, 2016, 3089303. [Google Scholar] [CrossRef] [PubMed]
- Murri, M.; Leiva, I.; Gomez-Zumaquero, J.M.; Tinahones, F.J.; Cardona, F.; Soriguer, F.; Queipo-Ortuno, M.I. Gut microbiota in children with type 1 diabetes differs from that in healthy children: A case-control study. BMC Med. 2013, 11, 46. [Google Scholar] [CrossRef] [PubMed]
- Pedersen, H.K.; Gudmundsdottir, V.; Nielsen, H.B.; Hyotylainen, T.; Nielsen, T.; Jensen, B.A.; Forslund, K.; Hildebrand, F.; Prifti, E.; Falony, G.; et al. Human gut microbes impact host serum metabolome and insulin sensitivity. Nature 2016, 535, 376–381. [Google Scholar] [CrossRef] [PubMed]
- Suri, R.S.; Mahon, J.L.; Clark, W.F.; Moist, L.M.; Salvadori, M.; Garg, A.X. Relationship between Escherichia coli O157:H7 and diabetes mellitus. Kidney Int. Suppl. 2009, 112, S44–S46. [Google Scholar] [CrossRef] [PubMed]
- Everard, A.; Belzer, C.; Geurts, L.; Ouwerkerk, J.P.; Druart, C.; Bindels, L.B.; Guiot, Y.; Derrien, M.; Muccioli, G.G.; Delzenne, N.M.; et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc. Natl. Acad. Sci. USA 2013, 110, 9066–9071. [Google Scholar] [CrossRef] [PubMed]
- Cani, P.D.; Bibiloni, R.; Knauf, C.; Waget, A.; Neyrinck, A.M.; Delzenne, N.M.; Burcelin, R. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 2008, 57, 1470–1481. [Google Scholar] [CrossRef] [PubMed]
- Cani, P.D.; Knauf, C. How gut microbes talk to organs: The role of endocrine and nervous routes. Mol. Metab. 2016, 5, 743–752. [Google Scholar] [CrossRef] [PubMed]
- Canfora, E.E.; Jocken, J.W.; Blaak, E.E. Short-chain fatty acids in control of body weight and insulin sensitivity. Nat. Rev. Endocrinol. 2015, 11, 577–591. [Google Scholar] [CrossRef] [PubMed]
- Gao, Z.; Yin, J.; Zhang, J.; Ward, R.E.; Martin, R.J.; Lefevre, M.; Cefalu, W.T.; Ye, J. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes 2009, 58, 1509–1517. [Google Scholar] [CrossRef] [PubMed]
- Lin, H.V.; Frassetto, A.; Kowalik, E.J., Jr.; Nawrocki, A.R.; Lu, M.M.; Kosinski, J.R.; Hubert, J.A.; Szeto, D.; Yao, X.; Forrest, G.; et al. Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLoS ONE 2012, 7, e35240. [Google Scholar] [CrossRef] [PubMed]
- Den Besten, G.; van Eunen, K.; Groen, A.K.; Venema, K.; Reijngoud, D.J.; Bakker, B.M. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J. Lipid Res. 2013, 54, 2325–2340. [Google Scholar] [CrossRef] [PubMed]
- Long, Y.C.; Zierath, J.R. AMP-activated protein kinase signaling in metabolic regulation. J. Clin. Investig. 2006, 116, 1776–1783. [Google Scholar] [CrossRef] [PubMed]
- Hawley, S.A.; Gadalla, A.E.; Olsen, G.S.; Hardie, D.G. The antidiabetic drug metformin activates the AMP-activated protein kinase cascade via an adenine nucleotide-independent mechanism. Diabetes 2002, 51, 2420–2425. [Google Scholar] [CrossRef] [PubMed]
- Kang, H.; Koppula, S. Houttuynia cordata attenuates lipid accumulation via activation of AMP-activated protein kinase signaling pathway in HepG2 cells. Am. J. Chin. Med. 2014, 42, 651–664. [Google Scholar] [CrossRef] [PubMed]
- Kawser Hossain, M.; Abdal Dayem, A.; Han, J.; Yin, Y.; Kim, K.; Kumar Saha, S.; Yang, G.M.; Choi, H.Y.; Cho, S.G. Molecular mechanisms of the anti-obesity and anti-diabetic properties of flavonoids. Int. J. Mol. Sci. 2016, 17, 569. [Google Scholar] [CrossRef] [PubMed]
- Shin, N.R.; Moon, J.S.; Shin, S.Y.; Li, L.; Lee, Y.B.; Kim, T.J.; Han, N.S. Isolation and characterization of human intestinal Enterococcus avium EFEL009 converting rutin to quercetin. Lett. Appl. Microbiol. 2016, 62, 68–74. [Google Scholar] [CrossRef] [PubMed]
Groups | LETO | OLETF | Metformin | Metformin + HCE |
---|---|---|---|---|
TG (mg/dL) | 35.2 ± 17.8 a | 118.0 ± 32.7 b | 113.9 ± 41.4 bc | 79.5 ± 35.3 c |
TC (mg/dL) | 122.5 ± 15.1 a | 169.9 ± 21.2 b | 150.6 ± 40.4 ab | 132.8 ± 31.1 a |
HTG (mg/g tissue) | 50.3 ± 6.0 a | 98.6 ± 13.8 b | 75.2 ± 5.3 c | 79.4 ± 6.5 c |
HDL (mg/dL) | 16.1 ± 1.7 a | 12.2 ± 1.6 b | 14.9 ± 2.8 ab | 15.6 ± 3.5 a |
TG/HDL ratio | 2.2 ± 1.1 a | 9.7 ± 2.7 b | 8.5 ± 3.9 ab | 5.8 ± 3.3 a |
© 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Wang, J.-H.; Bose, S.; Lim, S.-K.; Ansari, A.; Chin, Y.-W.; Choi, H.S.; Kim, H. Houttuynia cordata Facilitates Metformin on Ameliorating Insulin Resistance Associated with Gut Microbiota Alteration in OLETF Rats. Genes 2017, 8, 239. https://doi.org/10.3390/genes8100239
Wang J-H, Bose S, Lim S-K, Ansari A, Chin Y-W, Choi HS, Kim H. Houttuynia cordata Facilitates Metformin on Ameliorating Insulin Resistance Associated with Gut Microbiota Alteration in OLETF Rats. Genes. 2017; 8(10):239. https://doi.org/10.3390/genes8100239
Chicago/Turabian StyleWang, Jing-Hua, Shambhunath Bose, Soo-Kyoung Lim, AbuZar Ansari, Young-Won Chin, Han Seok Choi, and Hojun Kim. 2017. "Houttuynia cordata Facilitates Metformin on Ameliorating Insulin Resistance Associated with Gut Microbiota Alteration in OLETF Rats" Genes 8, no. 10: 239. https://doi.org/10.3390/genes8100239