Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter May 10, 2021

The potential of immature poken (Citrus reticulata) extract in the weight management, lipid and glucose metabolism

  • Yung-Kai Lin , Yu-Ming Chung , Hui-Ting Yang , Yung-Hao Lin , Yung-Hsiang Lin , Wei-Chun Hu and Chi-Fu Chiang EMAIL logo

Abstract

Objectives

The prevalence of obesity was increasing globally, with nearly half a billion of the world’s population now considered to be overweight or obese. The immature poken (Citrus reticulata) was a good source of flavonoids and phenolic acids, which may exert an anti-obesity effect. However, the current efficacy in clinical trials was still unclear. Thus, the object of this study was to explore whether immature poken had an anti-obesity effect in the clinical trial.

Methods

In this study, we identified nine major compounds from immature poken extract (IPE), and most compounds significantly decreased the lipid accumulation in adipocytes. In addition, 20 subjects with body mass index (BMI) ≥ 24 or body fat > 30 were recruited and randomly allocated to placebo and experimental (IPE) groups for 6 week intervention and 2 week follow-up.

Results

In comparison with the baseline results (week 0), the body weight, body fat, and waist circumference at week 6 in the IPE group were significantly decreased by 1.49 kg, 0.33%, 2.1 cm. Moreover, in blood biochemical analysis, total cholesterol (TC), triglyceride (TG), fasting blood sugar (FBS), and insulin levels at week 6 in IPE group were also decreased by 3.6, 4.6, 2.1 (mg/dL), and 2.9 (μU/mL), respectively.

Conclusions

The finding showed that immature poken had important roles in fat metabolism by suppressing adipogenesis, and immature poken may provide new weight loss strategies for obese people.


Corresponding author: Chi-Fu Chiang, Research & Design Center, TCI CO., Ltd., 10F, No.187, Gangqian Rd., Neihu Dist., Taipei 114, Taiwan, Phone: +886 2 8797 7811 ext. 8827, E-mail:

  1. Research funding: None declared.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Not applicable.

  5. Ethical approval: Not applicable.

References

1. Trepanowski, JF, Kroeger, CM, Barnosky, A, Klempel, MC, Bhutani, S, Hoddy, KK, et al.. Effect of alternate-day fasting on weight loss, weight maintenance, and cardioprotection among metabolically healthy obese adults: a randomized clinical trial. JAMA Intern Med 2017;177:930–8. https://doi.org/10.1001/jamainternmed.2017.0936.Search in Google Scholar PubMed PubMed Central

2. Brown, L, Poudyal, H, Panchal, SK. Functional foods as potential therapeutic options for metabolic syndrome. Obes Rev 2015;16:914–41. https://doi.org/10.1111/obr.12313.Search in Google Scholar PubMed

3. Sagar, NA, Pareek, S, Sharma, S, Yahia, EM, Lobo, MG. Fruit and vegetable waste: bioactive compounds, their extraction, and possible utilization. Compr Rev Food Sci Food Saf 2018;17:512–31. https://doi.org/10.1111/1541-4337.12330.Search in Google Scholar PubMed

4. Hill, JO, Wyatt, HR, Peters, JC. Energy balance and obesity. Circulation 2012;126:126–32. https://doi.org/10.1161/circulationaha.111.087213.Search in Google Scholar

5. Li, H, Qi, J, Li, L. Phytochemicals as potential candidates to combat obesity via adipose non-shivering thermogenesis. Pharmacol Res 2019;147:104393. https://doi.org/10.1016/j.phrs.2019.104393.Search in Google Scholar PubMed

6. Velickovic, K, Wayne, D, Leija, HAL, Bloor, I, Morris, DE, Law, J, et al.. Caffeine exposure induces browning features in adipose tissue in vitro and in vivo. Sci Rep 2019;9:9104. https://doi.org/10.1038/s41598-019-45540-1.Search in Google Scholar PubMed PubMed Central

7. Salehi, B, Fokou, PVT, Sharifi-Rad, M, Zucca, P, Pezzani, R, Martins, N, et al.. The therapeutic potential of naringenin: a review of clinical trials. Pharmaceuticals 2019;12:11. https://doi.org/10.3390/ph12010011.Search in Google Scholar PubMed PubMed Central

8. He, D, Shan, Y, Wu, Y, Liu, G, Chen, B, Yao, S. Simultaneous determination of flavanones, hydroxycinnamic acids and alkaloids in citrus fruits by HPLC-DAD-ESI/MS. Food Chem 2011;127:880–5. https://doi.org/10.1016/j.foodchem.2010.12.109.Search in Google Scholar PubMed

9. Montalbano, G, Mania, M, Guerrera, MC, Laura, R, Abbate, F, Levanti, M, et al.. Effects of a flavonoid-rich extract from Citrus sinensis juice on a diet-induced obese zebrafish. Int J Mol Sci 2019;20. https://doi.org/10.3390/ijms20205116.Search in Google Scholar PubMed PubMed Central

10. Kim, GS, Park, HJ, Woo, JH, Kim, MK, Koh, PO, Min, W, et al.. Citrus aurantium flavonoids inhibit adipogenesis through the Akt signaling pathway in 3T3-L1 cells. BMC Compl Alternative Med 2012;12:31. https://doi.org/10.1186/1472-6882-12-31.Search in Google Scholar PubMed PubMed Central

11. Chou, YC, Ho, CT, Pan, MH. Immature Citrus reticulata extract promotes browning of beige adipocytes in high-fat diet-induced C57BL/6 mice. J Agric Food Chem 2018;66:9697–703. https://doi.org/10.1021/acs.jafc.8b02719.Search in Google Scholar PubMed

12. Sun, Y, Qiao, L, Shen, Y, Jiang, P, Chen, J, Ye, X. Phytochemical profile and antioxidant activity of physiological drop of citrus fruits. J Food Sci 2013;78:C37–42. https://doi.org/10.1111/j.1750-3841.2012.03002.x.Search in Google Scholar PubMed

13. Chang, HC, Yang, HC, Chang, HY, Yeh, CJ, Chen, HH, Huang, KC, et al.. Morbid obesity in Taiwan: prevalence, trends, associated social demographics, and lifestyle factors. PloS One 2017;12:e0169577. https://doi.org/10.1371/journal.pone.0169577.Search in Google Scholar PubMed PubMed Central

14. Kalsch, J, Bechmann, LP, Heider, D, Best, J, Manka, P, Kalsch, H, et al.. Normal liver enzymes are correlated with severity of metabolic syndrome in a large population based cohort. Sci Rep 2015;5:13058. https://doi.org/10.1038/srep13058.Search in Google Scholar PubMed PubMed Central

15. Depommier, C, Everard, A, Druart, C, Plovier, H, Van Hul, M, Vieira-Silva, S, et al.. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nat Med 2019;25:1096–103. https://doi.org/10.1038/s41591-019-0495-2.Search in Google Scholar PubMed PubMed Central

16. Pedersen, MH, Svart, MV, Lebeck, J, Bidlingmaier, M, Stodkilde-Jorgensen, H, Pedersen, SB, et al.. Substrate metabolism and insulin sensitivity during fasting in obese human subjects: impact of GH blockade. J Clin Endocrinol Metab 2017;102:1340–9. https://doi.org/10.1210/jc.2016-3835.Search in Google Scholar PubMed

17. Choi, Y, Kim, Y, Ham, H, Park, Y, Jeong, HS, Lee, J. Nobiletin suppresses adipogenesis by regulating the expression of adipogenic transcription factors and the activation of AMP-activated protein kinase (AMPK). J Agric Food Chem 2011;59:12843–9. https://doi.org/10.1021/jf2033208.Search in Google Scholar PubMed

18. He, YF, Liu, FY, Zhang, WX. Tangeritin inhibits adipogenesis by down-regulating C/EBPalpha, C/EBPbeta, and PPARgamma expression in 3T3-L1 fat cells. Genet Mol Res 2015;14:13642–8. https://doi.org/10.4238/2015.october.28.26.Search in Google Scholar PubMed

19. Lin, Y, Ren, N, Li, S, Chen, M, Pu, P. Novel anti-obesity effect of scutellarein and potential underlying mechanism of actions. Biomed Pharmacother 2019;117:109042. https://doi.org/10.1016/j.biopha.2019.109042.Search in Google Scholar PubMed

20. de Melo, TS, Lima, PR, Carvalho, KM, Fontenele, TM, Solon, FR, Tome, AR, et al.. Ferulic acid lowers body weight and visceral fat accumulation via modulation of enzymatic, hormonal and inflammatory changes in a mouse model of high-fat diet-induced obesity. Braz J Med Biol Res 2017;50:e5630. https://doi.org/10.1590/1414-431x20165630.Search in Google Scholar PubMed PubMed Central

21. Kang, SW, Kang, SI, Shin, HS, Yoon, SA, Kim, JH, Ko, HC, et al.. Sasa quelpaertensis Nakai extract and its constituent p-coumaric acid inhibit adipogenesis in 3T3-L1 cells through activation of the AMPK pathway. Food Chem Toxicol 2013;59:380–5. https://doi.org/10.1016/j.fct.2013.06.033.Search in Google Scholar PubMed

22. Yamamoto, N, Kanemoto, Y, Ueda, M, Kawasaki, K, Fukuda, I, Ashida, H. Anti-obesity and anti-diabetic effects of ethanol extract of Artemisia princeps in C57BL/6 mice fed a high-fat diet. Food Funct 2011;2:45–52. https://doi.org/10.1039/c0fo00129e.Search in Google Scholar PubMed

23. Hadrich, F, Sayadi, S. Apigetrin inhibits adipogenesis in 3T3-L1 cells by downregulating PPARgamma and CEBP-alpha. Lipids Health Dis 2018;17:95. https://doi.org/10.1186/s12944-018-0738-0.Search in Google Scholar PubMed PubMed Central

24. Oh, JH, Lee, JI, Karadeniz, F, Seo, Y, Kong, CS. 3,5-Dicaffeoyl-Epi-Quinic acid isolated from edible halophyte Atriplex gmelinii inhibits adipogenesis via AMPK/MAPK pathway in 3T3-L1 adipocytes. Evid base Compl Alternative Med 2018;2018:8572571. https://doi.org/10.1155/2018/8572571.Search in Google Scholar PubMed PubMed Central

25. Jung, UJ, Lee, MK, Park, YB, Kang, MA, Choi, MS. Effect of citrus flavonoids on lipid metabolism and glucose-regulating enzyme mRNA levels in type-2 diabetic mice. Int J Biochem Cell Biol 2006;38:1134–45. https://doi.org/10.1016/j.biocel.2005.12.002.Search in Google Scholar PubMed

26. Dallas, C, Gerbi, A, Elbez, Y, Caillard, P, Zamaria, N, Cloarec, M. Clinical study to assess the efficacy and safety of a citrus polyphenolic extract of red orange, grapefruit, and orange (Sinetrol-XPur) on weight management and metabolic parameters in healthy overweight individuals. Phytother Res 2014;28:212–8. https://doi.org/10.1002/ptr.4981.Search in Google Scholar PubMed

27. Lee, YS, Cha, BY, Choi, SS, Choi, BK, Yonezawa, T, Teruya, T, et al.. Nobiletin improves obesity and insulin resistance in high-fat diet-induced obese mice. J Nutr Biochem 2013;24:156–62. https://doi.org/10.1016/j.jnutbio.2012.03.014.Search in Google Scholar PubMed

28. Kim, MS, Hur, HJ, Kwon, DY, Hwang, JT. Tangeretin stimulates glucose uptake via regulation of AMPK signaling pathways in C2C12 myotubes and improves glucose tolerance in high-fat diet-induced obese mice. Mol Cell Endocrinol 2012;358:127–34. https://doi.org/10.1016/j.mce.2012.03.013.Search in Google Scholar PubMed

29. Malik, S, Bhatia, J, Suchal, K, Gamad, N, Dinda, AK, Gupta, YK, et al.. Nobiletin ameliorates cisplatin-induced acute kidney injury due to its anti-oxidant, anti-inflammatory and anti-apoptotic effects. Exp Toxicol Pathol 2015;67:427–33. https://doi.org/10.1016/j.etp.2015.04.008.Search in Google Scholar PubMed

30. Mulvihill, EE, Assini, JM, Lee, JK, Allister, EM, Sutherland, BG, Koppes, JB, et al.. Nobiletin attenuates VLDL overproduction, dyslipidemia, and atherosclerosis in mice with diet-induced insulin resistance. Diabetes 2011;60:1446–57. https://doi.org/10.2337/db10-0589.Search in Google Scholar PubMed PubMed Central

31. Wang, W, Pan, Y, Zhou, H, Wang, L, Chen, X, Song, G, et al.. Ferulic acid suppresses obesity and obesity-related metabolic syndromes in high fat diet-induced obese C57BL/6J mice. Food Agric Immunol 2018;29:1116–25. https://doi.org/10.1080/09540105.2018.1516739.Search in Google Scholar

Received: 2020-11-12
Accepted: 2021-03-23
Published Online: 2021-05-10

© 2021 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 28.3.2024 from https://www.degruyter.com/document/doi/10.1515/jcim-2020-0478/pdf
Scroll to top button