Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
권호 표지
DOI QR코드

DOI QR Code

Antioxidant and Anti-Obesity Effects of Juglans mandshurica in 3T3-L1 Cells and High-Fat Diet Obese Rats

  • Da-Hye Choi (Institute of Biological Resources, Chuncheon Bioindustry Foundation) ;
  • Min Hong (Institute of Biological Resources, Chuncheon Bioindustry Foundation) ;
  • Tae-Hyung, Kwon (Institute of Biological Resources, Chuncheon Bioindustry Foundation) ;
  • Soo-Ung Lee (Institute of Biological Resources, Chuncheon Bioindustry Foundation)
  • Received : 2023.11.22
  • Accepted : 2023.12.11
  • Published : 2024.03.28
Download PDF
⟨ Previous Next ⟩

Abstract

Juglans mandshurica Maxim. walnut (JMW) is well-known for the treatment of dermatosis, cancer, gastritis, diarrhea, and leukorrhea in Korea. However, the molecular mechanism underlying its antiobesity activity remains unknown. In the current study, we aimed to determine whether JMW can influence adipogenesis in 3T3-L1 preadipocytes and high-fat diet rats and determine the antioxidant activity. The 20% ethanol extract of JMW (JMWE) had a total polyphenol content of 133.33 ± 2.60 mg GAE/g. Considering the antioxidant capacity, the ABTS and DPPH values of 200 ㎍/ml of JMWE were 95.69 ± 0.94 and 79.38 ± 1.55%, respectively. To assess the anti-obesity activity of JMWE, we analyzed the cell viability, fat accumulation, and adipogenesis-related factors, including CCAAT-enhancer-binding protein alpha (C/EBPα), sterol regulatory element-binding protein-1c (SREBP1c), peroxisome proliferator-activated receptor-gamma (PPARγ), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC). We found that total lipid accumulation and triglyceride levels were reduced, and the fat accumulation rate decreased in a dose-dependent manner. Furthermore, JMWE suppressed adipogenesis-related factors C/EBPα, PPARγ, and SREBP1c, as well as FAS and ACC, both related to lipogenesis. Moreover, animal experiments revealed that JMWE could be employed to prevent and treat obesity-related diseases. Hence, JMWE could be developed as a healthy functional food and further explored as an anti-obesity drug.

Keywords

Acknowledgement

This work was supported by the Chuncheon Bio-industry Foundation

References

  1. Ntambi JM, Young-Cheul K. 2000. Adipocyte differentiation and gene expression. J. Nutr. 130: 122S-3126S.
  2. Zibaeenezhad MJ, Rezaiezadeh M, Ayatollahi SMT, Panjehshahin MR. 2003. Antihypertriglyceridemin effect of walnut oil. Angology 54: 411-414.
  3. Fruhbeck G, Gomez-Ambrosi J, Muruzabal FJ, Burrell MA. 2001. The adipocyte: a model for integration of endocrine and metabolic signaling in energy metabolism regulation. Am. J. Physiol. Endocrinol. Metab. 280: E827-E847.
  4. Darlington GJ, Ross SE, MacDouglad OA. 1998. The role of C/EBP genes in adipocyte differentiation. J. Biol. Chem. 273: 30057-30060.
  5. Morrison RF, Farmer SR. 2000. Hormonal signaling and transcriptional control of adipocyte differentiation. J. Nutr. 130: 3116S-3121S.
  6. Hietanen E, Greenwood MR. 1977. A comparison of lipoprotein lipase activity and adipocyte differentiation in growing male rats. J. Lipid Res. 18: 480-490.
  7. Wunderling K, Zurkovic J, Zink F, Kuerschner L, Thiele CL. 2023. Triglyceride cycling enables modification of stored fatty acids. Nat. Metab. 5: 699-709.
  8. Nielsen TS, Jessen N, Jorgensen JOL, Moller N, Lund S. 2014. Dissecting adipose tissue lipolysis: molecular regulation and implications for metabolic disease. J. Mol. Endocrinol. 52: R199-R222.
  9. Gaidhu MP, Anthony NM, Patel P, Hawke TJ, Ceddia RB. 2010. Dysregulation of lipolysis and lipid metabolism in visceral and subcutaneous adipocytes by high-fat diet: role of ATGL, HSL, and AMPK. Am. J. Physiol. Cell Physiol. 298: C961-C971.
  10. Ceddia RB. 2013. The role of AMP-activated protein kinase in regulating white adipose tissue metabolism. Mol. Cell. Endocrinol. 366: 194-203.
  11. Kohjima M, Higuchi N, Kato M, Kotoh K, Yoshimoto T, Fujino T, et al. 2008. SREBP-1c, regulated by insulin and AMPK signaling pathways, plays a role in nonalcoholic fatty liver disease. Int. J. Mol. Med. 21: 507-511.
  12. Cawley J, Meyerhoefer C. 2012. The medical care costs of obesity: an instrumental variables approach. J. Health Econ. 31: 219-230.
  13. Park GH, Oh MS. 2013. Inhibitory effects of Juglans mandshurica leaf on allergic dermatitis-like skin lesions-induced by 2,3- dinitrochlorobenzene in mice. Exp. Toxicol. Pathol. 66: 97-101.
  14. Zhao C, Qian X, Qin M, Sun X, Yu Q, Liu J, et al. 2023. Juglans mandshurica Maximowicz as a traditional medicine: review of its phytochemistry and pharmacological activity in East Asia. J. Pharm. Pharmacol. 75: 33-48.
  15. Makoto K, Susloparova E, Tsuyama I, Shimase T, Nakaba S, Takahashi N, et al. 2021. Influence of soil properties on the heartwood colour of Juglans mandshurica var. sachalinensis in a cool temperate forest. J. Wood Sci. 67. Article Number 49.
  16. Sun ZL, Dong JL, Wu J. 2017. Juglanin induces apoptosis and autophagy in human breast cancer progression via ROS/JNK promotion. Biomed. Pharmacother. 85: 303-312.
  17. Liu J, Meng M, Li C, Huang X, Di D. 2008. Simultaneous determination of three diarylheptanoids and an α-tetralone derivative in the green walnut husks (Juglans regia L.) by high-performance liquid chromatography with photodiode array detector. J. Choromatogr. A. 1190: 80-85.
  18. Yang H, Wang LB, Guo YP, Wang YL, Chen XX, Huang J, et al. 2021. Simultaneous quantification of diarylheptanoids and phenolic compounds in Juglans mandshurica Maxim. by UPLC-TQ-MS. Metabolites 8: 132.
  19. Xu H, Yu X, Qu S, Sui D. 2013. Juglone, isolated from Juglans mandshurica Maxim, induces apoptosis via down-regulation of AR expression in human prostate cancer LNCaP cells. Bioorg. Med. Chem. Lett. 23: 3631-3634.
  20. Folin O, Denis W. 1912. On phosphotungstic-phophomolybdic compounds as color reagents. J. Biol. Chem. 12: 239-243.
  21. Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C. 1999. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic. Biol. Med. 26: 1231-1237.
  22. Oyaizu M. 1986. Studies on products of browning reaction: antioxidant activities of products of browning reaction prepared from glucosamine. Jpn. J. Nutr. 44: 307-315.
  23. Olajide OA, Saker SD. 2020. Anti-inflammatory natural products. Annu. Rep. Med. Chem. 55: 153-177.
  24. Jennifer C, Stephie CM, Abhishri SB, Shalini BU. 2012. A review on skin whitening property of plant extracts. Int. J. Pharm. Bio Sci. 3: 322-347.
  25. Arya A, Nahar L, Khan HU, Saker SD. 2020. Anti-obesity natural products. Annu. Rep. Med. Chem. 55: 411-433.
  26. Cheng YH, Shen TF, Pang VF, Chen BJ. 2001. Effects of aflatoxin and carotenoids on growth performance and immune response in mule ducklings. Comp. Biochem. Physiol. Toxicol. Pharmacol. 128: 19-26.
  27. Demark-Wahnefried W, Price DT, Polascik TJ, Robertson CN, Anderson EE, Paulson DF, et al. 2001. Pilot study of dietary fat restriction and flaxseed supplementation in men with prostate cancer before surgery: exploring the effects on hormonal levels, prostate-specific antigen, and histopathologic features. Urology 58: 47-52.
  28. Demark-Wahnefried W, Robertson CN, Walther PJ, Polascik TJ, Paulson DF, Vollmer RT. 2004. Pilot study of dietary fat restriction and flaxseed supplementation in men with prostate cancer before surgery: exploring the effects on hormonal levels, prostate-specific antigen, and histopathologic features. Urology 63: 900-904.
  29. Giovannucci E. 1999. Tomatoes, tomato based products, lycopene and cancer: review of the epidermiological literature. J. Natl. Ancer Inst. 91: 317-331.
  30. Langset L. Oxidant, Antioxidants and disease prevention. ILSI Europe Concise Monograaph Series. Brussels, ILSI Europe/ILSI Press. ISBN 0-944398-52-9.
  31. Reddy L, Odhav B, Bhoola KD. 2003. Natural products for cancer prevention: a global perspective. Pharmacol. Ther. 99: 1-13.
  32. Zhao C, Qian X, Qin M, Sun X, Yu Q, Liu J, et al. 2023. Juglans mandshurica Maximowicz as a traditional medicine: review of its phytochemistry and pharmacological activity in east asia. J. Pharm. Pharmacol. 75: 33-48.
  33. Park S, Kim N, Yoo G, Kim SN, Kwon HJ, Jung K, et al. 2017. Phenolics and neolignans isolated from the fruits of Juglans mandshurica Maxim. and their effects on lipolysis in adipocytes. Phytochemistry 137: 87-93.
  34. Wang L, Wei Y, Ning C, Zhang M, Fan P, Lei D, et al. 2019. Ellagic acid promotes browning of white adipose tissues in high-fat dietinduced obesity in rats through suppressing white adipocyte maintaining genes. Endocrine 66: 923-936.
  35. Jou PC, Ho BY, Hsu YM, Pan TM. 2010. The effect of Monascus secondary polyketide metabolites, monascin and ankaflavin, on adipogenesis and lipogenesis activity in 3T3- L1. J. Agric. Food Chem. 58: 12703-12709.
  36. Sorisky A. 1999. From preadipocyte to adipocyte: differentiation-directed signals of insulin from the cell surface to the nucleus. Crit. Rev. Clin. Lab. Sci. 36: 1-34.
  37. Li KK, Liu CL, Shiu HT, Wong HL, Siu WS, Zhang C, et al. 2016. Cocoa tea (Camellia ptilophylla) water extract inhibits adipocyte differentiation in mouse 3T3-L1 preadipocytes. Sci. Rep. 1: 20172.
  38. Zhang T, Yamamoto N, Yamashita Y, Ashida H. 2014. The chalcones cardamonin and flavokawain B inhibit the differentiation of preadipocytes to adipocytes by activating ERK. Arch. Biochem. Biophys. 15: 44-54.
  39. Zhang C, Teng L, Shi Y, Jin J, Xue Y, Shang K, et al. 2002. Effect of emodin on proliferation and differentiation of 3T3- L1 preadipocyte and FAS activity. Chin. Med. J. 115: 1035-1038.
  40. Zebisch K, Voigt V, Wabitsch M, Brandsch M. 2012. Protocol for effective differentiation of 3T3-L1 cells to adipocytes. Anal. Biochem. 425: 88-90.
  41. Moseti D, Regassa A, Kim WK. 2016. Molecular regulation of adipogenesis and potential anti-adipogenic bioactive molecules. Int. J. Mol. Sci. 17: 124.
  42. Lefterova MI, Zhang Y, Steger DJ, Schupp M, Schug J, Cristancho A, et al. 2008. PPAR and C/EBP factors orchestrate adipocyte biology via adjacent binding on a genome-wide scale. Genes Dev. 22: 2941-2952.
  43. Wu Z, Rosen ED, Brun R, Hauser S, Adelmant G, Troy AE, et al. 1999. Cross-regulation of C/EBPα and PPARγ controls the transcriptional pathway of adipogenesis and insulin sensitivity. Mol. Cell. 3: 151-158.
  44. Tzeng TF, Lu HJ, Liou SS, Chang CJ, Liu IM. 2012. Emodin, a naturally occurring anthraquinone derivative, ameliorates dyslipidemia by activating AMP-activated protein kinase in high-fat-diet-fed-rats. Evid. Based Complement. Alternat. Med. 2012: 781812.
  45. Ho JN, Choi JW, Lim WC, Kim MK, Lee IY, Cho HY. 2012. Kefir inhibits 3T3-L1 adipocyte differentiation through down-regulation of adipogenic transcription factor expression. J. Sci. Food Agric. 93: 485-490.