Blue honeysuckle rich in cyanidin-3-O-glucoside inhibited adipogenic differentiation by modulation of the adipogenesis pathway in 3T3-L1 adipocytes

  • Hyun Jeong Lee Department of Food Science and Biotechnology, Sejong University, Seoul, Republic of Korea
  • Eun-Hye Choi Department of Food Science and Biotechnology, Sejong University, Seoul, Republic of Korea
  • Yoon-Seok Chun Ari B&C Co., Giheung-gu, Yongin-si, Jyunggi-do, Republic of Korea
  • Jong-Kyu Kim Ari B&C Co., Giheung-gu, Yongin-si, Jyunggi-do, Republic of Korea
  • Jung-Ok Lee Aribio H&B Co., Guseong-ro, Giheung-gu, Gyeonggi-do, Republic of Korea
  • Jin-Seol Rhee Pharmacology Team, Aribio Co., Ltd., Bundang-gu, Seongnam-si, Republic of Korea
  • Youn-Bi Jang Pharmacology Team, Aribio Co., Ltd., Bundang-gu, Seongnam-si, Republic of Korea
  • Tae-Gyu Lim Department of Food Science and Biotechnology, Sejong University, Seoul, Republic of Korea
  • Soon-Mi Shim Department of Food Science and Biotechnology, Sejong University, Seoul, Republic of Korea
Keywords: Blue honeysuckle; cyanidin-3-O-glucoside; 3T3-L1 cell; Adipogenesis; Anti-adipogenic.


Background: Blue honeysuckle (BH; Lonicera caerulea L.), which is a traditional medicinal plant, is known to be a rich source of anthocyanins and phenolic acids due to its strong antioxidant and anti-inflammatory activities. Its anti-obesity effects, which are a result of attenuating abnormal lipid and glucose metabolisms, have also been reported.

Aim: The purpose of this study is to investigate the effect of BH on genes and proteins that are involved in the adipocyte differentiation using 3T3-L1 cells.

Methods: The effects of the water extracts of the BH were examined on adipogenesis and lipolysis using a biochemical and molecular analysis of the 3T3-L1 cells.

Results: Cyanidin-3-O-glucoside (C3G) from the BH extract was determined in order to contain 1.67 mg/g by the high-performance liquid chromatography analysis. The lipid accumulation in the adipocytes was reduced, which ranged from 58 to 26% in the BH (500 and 1,000 µg/mL) compared to the control group. The lipolysis that was measured by the glycerol content was not affected by the BH at 1,000 μg/mL. The BH downregulated the expression of the main transcription factors of the adipogenesis pathway, such as peroxisome proliferator-activated receptor γ, 1, 2, adipose differentiation-related protein, CCAAT/enhancer binding protein α, and acetyl CoA carboxylase, while increasing the expression of the Adenosine monophosphate (AMP)-activated protein kinase α.

Conclusion: These findings suggest that the BH is a good source of C3G, and it could be effective in regard to inhibiting the adipogenesis as opposed to the lipolysis, which indicates the potential for natural anti-obesity ingredients.


Download data is not yet available.


Ng CY, Amini F, Ahmad Bustami N, Tan ESS, Tan PY, Mitra SR. Association of DNA damage with vitamin D and hair heavy metals of obese women. Mol Cell Toxicol 2021; 17(4): 429–38. doi: 10.1007/s13273-021-00149-2

Zimmet P. The burden of type 2 diabetes: are we doing enough? Diabetes Metab 2003; 29(4): 6S9–18. doi: 10.1016/S1262-3636(03)72783-9

Inzucchi SE. Oral antihyperglycemic therapy for type 2 diabetes: scientific review. JAMA 2002; 287(3): 360–72. doi: 10.1001/jama.287.3.360

Ku SK, Sung SH, Choung JJ, Choi JS, Shin YK, Kim JW. Anti-obesity and anti-diabetic effects of a standardized potato extract in ob/ob mice. Exp Ther Med 2016; 12(1): 354–64. doi: 10.3892/etm.2016.3256

Yuan G-F, Chen X-E, Li D. Conjugated linolenic acids and their bioactivities: a review. Food Funct 2014; 5(7):1360–8. doi: 10.1039/C4FO00037D

Clément L, Poirier H, Niot I, Bocher V, Guerre-Millo M, Krief S, et al. Dietary trans-10, cis-12 conjugated linoleic acid induces hyperinsulinemia and fatty liver in the mouse. J Lipid Res 2002; 43(9): 1400–9. doi: 10.1194/jlr.M20008-JLR200

Wendel AA, Purushotham A, Liu L-F, Belury MA. Conjugated linoleic acid fails to worsen insulin resistance but induces hepatic steatosis in the presence of leptin in ob/ob mice. J Lipid Res 2008; 49(1): 98–106. doi: 10.1194/jlr.M700195-JLR200

Choi E-H, Chun Y-S, Kim J, Ku S-K, Jeon S, Park T-S, et al. Modulating lipid and glucose metabolism by glycosylated kaempferol rich roasted leaves of Lycium chinense via upregulating adiponectin and AMPK activation in obese mice-induced type 2 diabetes. J Funct Foods 2020; 72(72): 104072. doi: 10.1016/j.jff.2020.104072

Jin X-H, Ohgami K, Shiratori K, Suzuki Y, Koyama Y, Yoshida K, et al. Effects of blue honeysuckle (Lonicera caerulea L.) extract on lipopolysaccharide-induced inflammation in vitro and in vivo. Exp Eye Res 2006; 82(5): 860–7. doi: 10.1016/j.exer.2005.10.024

Chaovanalikit A, Thompson MM, Wrolstad RE. Characterization and quantification of anthocyanins and polyphenolics in blue honeysuckle (Lonicera caerulea L.). J Agric Food Chem 2004; 52(4): 848–52. doi: 10.1021/jf030509o

Kaczmarska E, Gawronski J, Dyduch-Sieminska M, Najda A, Marecki W, Zebrowska J. Genetic diversity and chemical characterization of selected Polish and Russian cultivars and clones of blue honeysuckle (Lonicera caerulea). Turk J Agric For 2015; 39(3): 394–402. doi: 10.3906/tar-1404-149

Halliwell B, Murcia MA, Chirico S, Aruoma OI. Free radicals and antioxidants in food and in vivo: what they do and how they work. Crit Rev Food Sci Nutr 1995; 35(1–2): 7–20. doi: 10.1080/10408399509527682

Pietta P-G. Flavonoids as antioxidants. J Nat Prod 2000; 63(7): 1035–42. doi: 10.1021/np9904509

Jurgoński A, Juśkiewicz J, Zduńczyk Z. An anthocyanin-rich extract from Kamchatka honeysuckle increases enzymatic activity within the gut and ameliorates abnormal lipid and glucose metabolism in rats. Nutrition 2013; 29(6): 898–902. doi: 10.1016/j.nut.2012.11.006

Liu M, Tan J, He Z, He X, Hou D-X, He J, et al. Inhibitory effect of blue honeysuckle extract on high-fat-diet-induced fatty liver in mice. Anim Nutr 2018; 4(3): 288–93. doi: 10.1016/j.aninu.2018.06.001

Kim JW, Lee YS, Seol DJ, Cho IJ, Ku SK, Choi JS, et al. Anti-obesity and fatty liver-preventing activities of Lonicera caerulea in high-fat diet-fed mice. Int J Mol Med 2018; 42(6): 3047–64. doi: 10.3892/ijmm.2018.3879

Moseti D, Regassa A, Kim W-K. Molecular regulation of adipogenesis and potential anti-adipogenic bioactive molecules. Int J Mol Sci 2016; 17(1): 124. doi: 10.3390/ijms17010124

Oszmiański J, Wojdyło A, Lachowicz S. Effect of dried powder preparation process on polyphenolic content and antioxidant activity of blue honeysuckle berries (Lonicera caerulea L. var. kamtschatica). LWT-Food Sci Technol 2016; 67: 214–22. doi: 10.1016/j.lwt.2015.11.051

Park M, Lee C, Lee H-J. Effects of Lonicera caerulea extract on adipocyte differentiation and adipogenesis in 3T3-L1 cells and mouse adipose-derived stem cells (MADSCs). J Nutr Health 2019; 52(1): 17–25. doi: 10.4163/jnh.2019.52.1.17

Chun Y-S, Ku S-K, Kim J-K, Park S, Cho I-H, Lee N-J. Hepatoprotective and anti-obesity effects of Korean blue honeysuckle extracts in high fat diet-fed mice. J Exerc Nutrition Biochem 2018; 22(4): 39. doi: 10.20463/jenb.2018.0029

Guo H, Guo J, Jiang X, Li Z, Ling W. Cyanidin-3-O-β-glucoside, a typical anthocyanin, exhibits antilipolytic effects in 3T3-L1 adipocytes during hyperglycemia: involvement of FoxO1-mediated transcription of adipose triglyceride lipase. Food Chem Toxicol 2012; 50(9): 3040–7. doi: 10.1016/j.fct.2012.06.015

Cristancho AG, Lazar MA. Forming functional fat: a growing understanding of adipocyte differentiation. Nat Rev Mol Cell Biol 2011; 12(11): 722–34. doi: 10.1038/nrm3198

Rosen ED, MacDougald OA. Adipocyte differentiation from the inside out. Nat Rev Mol Cell Biol 2006; 7(12): 885–96. doi: 10.1038/nrm2066

Chen D, Wang Y, Wu K, Wang X. Dual effects of metformin on adipogenic differentiation of 3T3-L1 preadipocyte in AMPK-dependent and independent manners. Int J Mol Sci 2018; 19(6): 1547. doi: 10.3390/ijms19061547

Schupp M, Cristancho AG, Lefterova MI, Hanniman EA, Briggs ER, Steger DJ, et al. Re-expression of GATA2 cooperates with peroxisome proliferator-activated receptor-γ depletion to revert the adipocyte phenotype. J Biol Chem 2009; 284(14): 9458–64. doi: 10.1074/jbc.M809498200

Rosen ED, Walkey CJ, Puigserver P, Spiegelman BM. Transcriptional regulation of adipogenesis. Genes Dev 2000; 14(11): 1293–307. doi: 10.1101/gad.14.11.1293

Jang J, Jung Y, Seo SJ, Kim SM, Shim YJ, Cho SH, et al. Berberine activates AMPK to suppress proteolytic processing, nuclear translocation and target DNA binding of SREBP-1c in 3T3-L1 adipocytes. Mol Med Rep 2017; 15(6): 4139–47. doi: 10.3892/mmr.2017.6513

Listenberger LL, Ostermeyer-Fay AG, Goldberg EB, Brown WJ, Brown DA. Adipocyte differentiation-related protein reduces the lipid droplet association of adipose triglyceride lipase and slows triacylglycerol turnover. J Lipid Res 2007; 48(12): 2751–61. doi: 10.1194/jlr.M700359-JLR200

Bijland S, Mancini SJ, Salt IP. Role of AMP-activated protein kinase in adipose tissue metabolism and inflammation. Clin Sci 2013; 124(8): 491–507. doi: 10.1042/CS20120536

Han MH, Kim HJ, Jeong J-W, Park C, Kim BW, Choi YH. Inhibition of adipocyte differentiation by anthocyanins isolated from the fruit of Vitis coignetiae pulliat is associated with the activation of AMPK signaling pathway. Toxicol Res 2018; 34(1): 13–21. doi: 10.5487/TR.2018.34.1.013

Liao W, Nguyen MA, Yoshizaki T, Favelyukis S, Patsouris D, Imamura T, et al. Suppression of PPAR-γ attenuates insulin-stimulated glucose uptake by affecting both GLUT1 and GLUT4 in 3T3-L1 adipocytes. Am J Physiol Endocrinol Metab 2007; 293(1):E219–27. doi: 10.1152/ajpendo.00695.2006

Chang BH-J, Li L, Paul A, Taniguchi S, Nannegari V, Heird WC, et al. Protection against fatty liver but normal adipogenesis in mice lacking adipose differentiation-related protein. Mol Cell Biol 2006; 26(3): 1063–76. doi: 10.1128/MCB.26.3.1063-1076.2006

Cao Z, Umek RM, McKnight SL. Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells. Genes Dev 1991; 5(9): 1538–52. doi: 10.1101/gad.5.9.1538

Lee YS, Kim WS, Kim KH, Yoon MJ, Cho HJ, Shen Y, et al. Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states. Diabetes 2006; 55(8): 2256–64. doi: 10.2337/db06-0006

Sun Q, Qi W, Yang JJ, Yoon KS, Clark JM, Park Y. Fipronil promotes adipogenesis via AMPKα-mediated pathway in 3T3-L1 adipocytes. Food Chem Toxicol 2016; 92: 217–23. doi: 10.1016/j.fct.2016.04.011
How to Cite
Lee H. J., Choi E.-H., Chun Y.-S., Kim J.-K., Lee J.-O., Rhee J.-S., Jang Y.-B., Lim T.-G., & Shim S.-M. (2022). Blue honeysuckle rich in cyanidin-3-O-glucoside inhibited adipogenic differentiation by modulation of the adipogenesis pathway in 3T3-L1 adipocytes. Food & Nutrition Research, 66.
Original Articles