Flavonoids as Antiobesity Agents: A Review

Rufino, Ana T.; Costa, Vera M.; Carvalho, Félix; Fernandes, Eduarda

doi:10.1002/med.21740

Cited by 174Phytochemicals and Antioxidant ActivitiesFlavonoids in Medical ResearchNatural Antidiabetic Agents Studies

Flavonoids as Antiobesity Agents: A Review

Rufino, Ana T., Costa, Vera M., Carvalho, Félix, Fernandes, Eduarda·2021·Medicinal Research Reviews

DOI 10.1002/med.21740

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Abstract

Obesity is a global health problem that affects all age groups in both developing and developed countries. In recent years, the prevalence of overweight and obesity has reached pandemic levels, resulting in a dramatic increase in the incidence of various comorbidities, such as cardiovascular diseases, type 2 diabetes, and cancer, consequently leading to massive health and socioeconomic burdens. Together with lifestyle changes, antiobesity pharmacotherapy is gaining momentum as an adjunctive treatment. However, the available pharmacological approaches have limited use owing to either significant adverse effects or low efficacy. Over the years, natural products have been an important source of lead compounds for drug discovery. Among these, flavonoids are associated with important biological effects and health‐promoting activities. In this review, we discuss the modulatory effects of flavonoids on obesity and their potential mechanisms of action. The literature strongly suggests that most common flavonoids demonstrate a pronounced effect on obesity as shown by their ability to lower body weight, fat mass, and plasma triglycerides/cholesterol, both in in vitro and in vivo models. The impact of flavonoids on obesity can be observed through different mechanisms: reducing food intake and fat absorption, increasing energy expenditure, modulating lipid metabolism, or regulating gut microbiota profile. A better understanding of the known antiobesity mechanisms of flavonoids will enable their potential use to treat this medical condition. Therefore, this review focuses on the putative biological mechanisms through which flavonoids may prevent or treat obesity and highlights new perspectives on future pharmacological use.

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Beside antioxidant activity, flavonoids have anti-inflammatory, vasodilator, anticoagulant, cardioprotective, anti-diabetic, neuroprotective, and anti-obesity activities, making them of interest as anti-aging compounds.
“Beside the antioxidant activity, flavonoids have anti-inflammatory, vasodilator, anticoagulant, cardioprotective, anti-diabetic, neuroprotective, and anti-obesity activities, which make them of great interest as anti-aging compounds (Table 3) [228,229,230,231,232,233,234,235,236,237,238,239,240,241,242,243,244,245,246,247,248,249,250,251,252,253,254,255,256,257].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [228]

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“For instance, rutin increased the expression of genes responsible for energy expenditure in BAT, including PGC1α and Dio2,(171) and increased muscle mitochondrial biogenesis through AMPK activation.(172) Additionally, epicatechin decreased the rate of weight gain through modulation of mitochondrial function related pr…”
Background
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The Interaction between Flavonoids and Intestinal Microbes: A Review
Xiong, H.-H., Lin, S.-Y., Chen, L., Ouyang, K., & Wang, W. (2023) · Foods · doi:10.3390/foods12020320 · Cited by 222 · see citing works
The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence
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Flavonoids—Natural Gifts to Promote Health and Longevity
Fan, X., Fan, Z., Yang, Z., Huang, T., Tong, Y., Yang, D., Mao, X., & Yang, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23042176 · Cited by 127 · see citing works
Advanced application of nanotechnology in active constituents of Traditional Chinese Medicines
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Effects and mechanisms of tea on obesity
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Flavonoids: Food associations, therapeutic mechanisms, metabolism and nanoformulations
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Clinical development and informatics analysis of natural and semi-synthetic flavonoid drugs: A critical review
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Dietary flavonoids intake contributes to delay biological aging process: analysis from NHANES dataset
Xing, W., Gao, W., Zhao, Z., Xu, X., Bu, H., Su, H., Mao, G., & Chen, J. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04321-1 · Cited by 70 · see citing works
Polyphenol Extraction from Food (by) Products by Pulsed Electric Field: A Review
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Inhibitory effects of fermented Ougan ( Citrus reticulata cv. Suavissima ) juice on high-fat diet-induced obesity associated with white adipose tissue browning and gut microbiota modulation in mice
Guo, X., Cao, X., Fang, X., Guo, A., & Li, E. (2021) · Food & Function · doi:10.1039/d0fo03423a · Cited by 67 · see citing works
The Biphasic Effect of Flavonoids on Oxidative Stress and Cell Proliferation in Breast Cancer Cells
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Effects of the Treatment with Flavonoids on Metabolic Syndrome Components in Humans: A Systematic Review Focusing on Mechanisms of Action
Gouveia, H. J. C. B., Urquiza-Martínez, M. V., Manhães‐de‐Castro, R., de Santana, B. J. R. C., Villarreal, J. P., Mercado-Camargo, R., Torner, L., Aquino, J. D. S., Toscano, A. E., & Guzmán‐Quevedo, O. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23158344 · Cited by 64 · see citing works
High-Crystallinity Covalent Organic Framework Synthesized in Deep Eutectic Solvent: Potentially Effective Adsorbents Alternative to Macroporous Resin for Flavonoids
Gao, M., Wang, D., Deng, L., Liu, S., Zhang, K., Quan, T., Yang, L., Kang, X., Xia, Z., & Gao, D. (2021) · Chemistry of Materials · doi:10.1021/acs.chemmater.1c02344 · Cited by 61 · see citing works
Immunomodulatory potential of flavonoids for the treatment of autoimmune diseases and tumour
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A comprehensive review of the metabolism of citrus flavonoids and their binding to bitter taste receptors
Li, L., Yan, X., Chen, F., Zheng, L., Hu, Y., He, F., Ni, H., Chen, F., & Li, Q. (2023) · Comprehensive Reviews in Food Science and Food Safety · doi:10.1111/1541-4337.13129 · Cited by 50 · see citing works
Improving the Health-Benefits of Kales (Brassica oleracea L. var. acephala DC) through the Application of Controlled Abiotic Stresses: A Review
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Role of Phytonutrients in the Prevention and Treatment of Chronic Diseases: A Concrete Review
Tufail, T., Fatima, S., Ain, H. B. U., Ikram, A., Noreen, S., Ребезов, М. Б., AL-Farga, A. M., Saleh, R. A., & Shariati, M. A. (2025) · ACS Omega · doi:10.1021/acsomega.4c02927 · Cited by 49 · see citing works
Hawk Tea Flavonoids as Natural Hepatoprotective Agents Alleviate Acute Liver Damage by Reshaping the Intestinal Microbiota and Modulating the Nrf2 and NF-κB Signaling Pathways
Xu, T., Hu, S., Liu, Y., Sun, K., Luo, L., & Zeng, L. (2022) · Nutrients · doi:10.3390/nu14173662 · Cited by 45 · see citing works
Pharmacological Activity of Flavonoid Quercetin and Its Therapeutic Potential in Testicular Injury
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Intestinal Flora Mediates Antiobesity Effect of Rutin in High‐Fat‐Diet Mice
Yan, X., Zhai, Y., Zhou, W., Qiao, Y., Guan, L., Liu, H., Jiang, J., & Peng, L. (2022) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.202100948 · Cited by 42 · see citing works
EGCG Inhibits Adipose-Derived Mesenchymal Stem Cells Differentiation into Adipocytes and Prevents a STAT3-Mediated Paracrine Oncogenic Control of Triple-Negative Breast Cancer Cell Invasive Phenotype
Suárez, N. G., Torres, S. R., Ouanouki, A., Cheikh-Hussein, L. E., & Annabi, B. (2021) · Molecules · doi:10.3390/molecules26061506 · Cited by 42 · see citing works
Phloretin and phlorizin mitigates inflammatory stress and alleviate adipose and hepatic insulin resistance by abrogating PPARγ S273-Cdk5 interaction in type 2 diabetic mice
Kumar, S., Chhimwal, J., Kumar, S., Singh, R., Patial, V., Purohit, R., & Padwad, Y. S. (2023) · Life Sciences · doi:10.1016/j.lfs.2023.121668 · Cited by 40 · see citing works
Simultaneous extraction of natural organic acid and flavonoid antioxidants from Hibiscus manihot L. flower by tailor-made deep eutectic solvent
Liu, J.-Z., Lyu, H.-C., Fu, Y., Jiang, J.-C., & Cui, Q. (2022) · LWT · doi:10.1016/j.lwt.2022.113533 · Cited by 40 · see citing works
Modulation of the gut microbiota and lipidomic profiles by black chokeberry (Aronia melanocarpa L.) polyphenols via the glycerophospholipid metabolism signaling pathway
Zhu, Y., Wei, Y., Karras, I., Cai, P.-J., Xiao, Y., Jia, C., Qian, X.-L., Zhu, S.-Y., Zheng, L.-J., Hu, X., et al. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.913729 · Cited by 37 · see citing works
Antioxidant, Anti-Obesity, and Hypolipidemic Effects of Polyphenol Rich Star Anise (Illicium verum) Tea in High-Fat-Sugar Diet-Induced Obesity Rat Model
Iftikhar, N., Hussain, A. I., Kamal, G. M., Manzoor, S., Fatima, T., Alswailmi, F. K., Ahmad, A., Alsuwayt, B., & Alnasser, S. M. (2022) · Antioxidants · doi:10.3390/antiox11112240 · Cited by 37 · see citing works
Inflammation and Obesity: The Pharmacological Role of Flavonoids in the Zebrafish Model
Russo, C., Maugeri, A., Musumeci, L., Sarro, G. D., Cirmi, S., & Navarra, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032899 · Cited by 39 · see citing works
Success stories of natural product-derived compounds from plants as multidrug resistance modulators in microorganisms
Zhai, X., Wu, G., Tao, X., Yang, S., Lv, L., Zhu, Y., Dong, D., & Xiang, H. (2023) · RSC Advances · doi:10.1039/d3ra00184a · Cited by 36 · see citing works
Natural Sympathomimetic Drugs: From Pharmacology to Toxicology
Costa, V. M., Rossato‐Grando, L. G., Milandri, E., Nardi, J., Teixeira, P., Mladěnka, P., Remião, F., & OEMONOM, O. B. O. T. (2022) · Biomolecules · doi:10.3390/biom12121793 · Cited by 36 · see citing works
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Targeting mitochondria with natural polyphenols for treating Neurodegenerative Diseases: a comprehensive scoping review from oxidative stress perspective
Guan, Y., Li, L., Yang, R., Lü, Y., & Tang, J. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-06605-0 · Cited by 35 · see citing works
Anti-Inflammatory Mechanisms of Dietary Flavones: Tapping into Nature to Control Chronic Inflammation in Obesity and Cancer
Kariagina, A., & Doseff, A. I. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232415753 · Cited by 34 · see citing works
Preventive Effects of Anthocyanins from Lyciumruthenicum Murray in High-Fat Diet-Induced Obese Mice Are Related to the Regulation of Intestinal Microbiota and Inhibition of Pancreatic Lipase Activity
Li, N., Liu, X., Zhang, J., Lang, Y.-Z., Lu, L., Mi, J., Cao, Y., Yan, Y., & Ran, L. (2022) · Molecules · doi:10.3390/molecules27072141 · Cited by 29 · see citing works
Proanthocyanidins as the main pancreatic lipase inhibitors in chokeberry fruits
Sosnowska, D., Podsędek, A., & Kucharska, A. Z. (2022) · Food & Function · doi:10.1039/d1fo04429j · Cited by 29 · see citing works
A White Grape Juice Extract Reduces Fat Accumulation through the Modulation of Ghrelin and Leptin Expression in an In Vivo Model of Overfed Zebrafish
Montalbano, G., Maugeri, A., Guerrera, M. C., Miceli, N., Navarra, M., Barreca, D., Cirmi, S., & Germanà, A. (2021) · Molecules · doi:10.3390/molecules26041119 · Cited by 25 · see citing works
Rheumatoid arthritis molecular targets and their importance to flavonoid‐based therapy
Rufino, A. T., Freitas, M., Proença, C., de Oliveira, J. M. P. F., Fernandes, E. G. R., & Ribeiro, D. (2023) · Medicinal Research Reviews · doi:10.1002/med.21990 · Cited by 28 · see citing works
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Translational Research on Bee Pollen as a Source of Nutrients: A Scoping Review from Bench to Real World
Kacemi, R., & Campos, M. G. (2023) · Nutrients · doi:10.3390/nu15102413 · Cited by 27 · see citing works
Baicalin attenuate diet-induced metabolic syndrome by improving abnormal metabolism and gut microbiota
Lin, Y., Wang, Z., Wang, M., Jiang, Z., Qin, Y.-Q., Huang, T., Song, Y., Liang, H.-T., & Liu, E. (2022) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2022.174996 · Cited by 26 · see citing works
Effects of natural products on macrophage immunometabolism: A new frontier in the treatment of metabolic diseases
Li, J., Guo, C., Yang, X., Xie, W., Mi, W., Hua, C., Tang, C. C., & Wang, H. (2025) · Pharmacological Research · doi:10.1016/j.phrs.2025.107634 · Cited by 23 · see citing works
Unveiling the Power of Flavonoids: A Dynamic Exploration of Their Impact on Cancer through Matrix Metalloproteinases Regulation
Rajendran, P. (2024) · Biomedicine · doi:10.37796/2211-8039.1447 · Cited by 22 · see citing works
A review of the lipolytic effects and the reduction of abdominal fat from bioactive compounds and moro orange extracts
de Lima, L. P., & Barbosa, A. D. P. (2021) · Heliyon · doi:10.1016/j.heliyon.2021.e07695 · Cited by 22 · see citing works
Regulatory Roles of Flavonoids in Caspase-11 Non-Canonical Inflammasome-Mediated Inflammatory Responses and Diseases
Yi, Y. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241210402 · Cited by 21 · see citing works
Dietary flavonoids in health and diseases: A concise review of their role in homeostasis and therapeutics
Mohan, A., Mahadevan, G. D., Iyer, V. A., Mukherjee, T. K., Patel, V. H., Kumar, R., Siddiqui, N. M., Nayak, M., Maurya, P. K., & Kumar, P. (2025) · Food Chemistry · doi:10.1016/j.foodchem.2025.144674 · Cited by 20 · see citing works
Comparison Study on Wild and Cultivated Opuntia sp.: Chemical, Taxonomic, and Antioxidant Evaluations
Boudjouan, F., Zeghbib, W., Carneiro, J., Silva, R., Morais, J., Vasconcelos, V. M., & Lopes, G. (2022) · Agriculture · doi:10.3390/agriculture12111755 · Cited by 20 · see citing works
The cellular and molecular targets of natural products against metabolic disorders: a translational approach to reach the bedside
Shen, X., Yang, H., Yang, Y., Zhu, X., & Sun, Q. (2024) · MedComm · doi:10.1002/mco2.664 · Cited by 20 · see citing works
Morin inhibits the activity of pancreatic lipase and adipogenesis
Vp, V., Sundarraj, R., & Perumal, M. K. (2024) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2024.176705 · Cited by 19 · see citing works
The Amorphous Solid Dispersion of Chrysin in Plasdone® S630 Demonstrates Improved Oral Bioavailability and Antihyperlipidemic Performance in Rats
Wang, C., Liu, X., Zhao, R., Yang, M., Liu, W., Dai, Q., Bao, X., Chen, Y., & Ma, J. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15102378 · Cited by 18 · see citing works
Natural Flavonoid-Derived Enzyme Mimics DHKNase Balance the Two-Edged Reactive Oxygen Species Function for Wound Healing and Inflammatory Bowel Disease Therapy
Feng, G., Zhang, H., Liu, H., Zhang, X., Jiang, H., Liao, S., Luo, X., Yao, H., Xiang, B., Liu, S., et al. (2024) · Research · doi:10.34133/research.0464 · Cited by 18 · see citing works
Targeted Antimicrobial Agents as Potential Tools for Modulating the Gut Microbiome
Chou, S., Zhang, S., Guo, H., Chang, Y., Zhao, W., & Mou, X. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.879207 · Cited by 18 · see citing works
Effects of dietary inflammatory index, blood lead levels, and flavonoid intake on stroke risk in older Americans: A cross-sectional study
Zhuo, S., Zhang, B., Zhang, J., Yang, M., & Zheng, Y. (2023) · Journal of Stroke and Cerebrovascular Diseases · doi:10.1016/j.jstrokecerebrovasdis.2023.107336 · Cited by 17 · see citing works
Covalent Interactions of Anthocyanins with Proteins: Activity-Based Protein Profiling of Cyanidin-3- O -glucoside
Hu, J., Yu, T., Huang, K., Liang, C., Li, Y., Li, X., Sun, J., & Bai, W. (2024) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.4c03869 · Cited by 17 · see citing works
Synthesis of phenylboronic acid-functionalized covalent organic framework via thiol-ene “click” reaction for highly efficient adsorption of cis-diol containing flavonoids
Li, Z., Jiang, M., Hu, Z., & Chen, Z. (2023) · Microporous and Mesoporous Materials · doi:10.1016/j.micromeso.2023.112798 · Cited by 16 · see citing works
Plant-Based Inhibitors of Protein Aggregation
Zhytniakivska, O. A., Chaturvedi, T., & Thomsen, M. H. (2025) · Biomolecules · doi:10.3390/biom15040481 · Cited by 18 · see citing works
Understanding risk and causal mechanisms for developing obesity in infants and young children: A National Institutes of Health workshop
Aagaard, K. M., Barkin, S. L., Burant, C., Carnell, S., Demerath, E. W., Donovan, S. M., Eneli, I., Francis, L. A., Gilbert‐Diamond, D., Hivert, M., et al. (2024) · Obesity Reviews · doi:10.1111/obr.13690 · Cited by 18 · see citing works
Critical review on the intervention effects of flavonoids from cereal grains and food legumes on lipid metabolism
Huang, Y., & Xu, B. (2024) · Food Chemistry · doi:10.1016/j.foodchem.2024.141790 · Cited by 16 · see citing works
The novel intervention effect of cold green tea beverage on high-fat diet induced obesity in mice
Ma, H., Zhang, B., Hu, Y., Li, X., Wang, J., Yang, F., Ji, X., & Wang, S. (2020) · Journal of Functional Foods · doi:10.1016/j.jff.2020.104279 · Cited by 17 · see citing works
Astragalus polysaccharide regulates brown adipogenic differentiation through miR-1258-5p-modulated cut-like homeobox 1 expression
Cao, Y., Deng, B., Zhang, S., Gao, H., Song, P., Zhang, J., & Zhao, J. (2021) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmab151 · Cited by 16 · see citing works
Current Updates on Potential Role of Flavonoids in Hypoxia/Reoxygenation Cardiac Injury Model
Ali, S. S., Noordin, L., Bakar, R. A., Zainalabidin, S., Jubri, Z., & Ahmad, W. A. N. W. (2021) · Cardiovascular Toxicology · doi:10.1007/s12012-021-09666-x · Cited by 15 · see citing works
Effects of Lingonberry (Vaccinium vitis-idaea L.) Supplementation on Hepatic Gene Expression in High-Fat Diet Fed Mice
Ryyti, R., Pemmari, A., Peltola, R., Hämäläinen, M., & Moilanen, E. (2021) · Nutrients · doi:10.3390/nu13113693 · Cited by 15 · see citing works
Integrated metabolomics and transcriptomics insights on flavonoid biosynthesis of a medicinal functional forage, Agriophyllum squarrosum (L.), based on a common garden trial covering six ecotypes
Fang, T., Zhou, S., Qian, C., Xia, Y., Yin, X., Fan, X., Zhao, P., Liao, Y., Shi, L., Chang, Y., et al. (2022) · Frontiers in Plant Science · doi:10.3389/fpls.2022.985572 · Cited by 15 · see citing works
Flavonoids and cardiovascular risk factors: a review
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Authors: Rufino, A. T., Costa, V. M., Carvalho, F., & Fernandes, E.
Affiliations: Universidade do Porto (PT)
Corresponding author: Rufino, Ana T.
Fernandes, Eduarda
ORCID: Rufino, Ana T.
Costa, Vera M.
Carvalho, Félix
Fernandes, Eduarda
Venue: Medicinal Research Reviews
Publisher: Wiley
Published: 2020-10-20
Volume: 41
Issue: 1
Pages: 556-585
ISSN: 0198-6325 (ISSN-L)
1098-1128
DOI: 10.1002/med.21740
OpenAlex: W3094242363
Cited by: 174
References: 225
Citations by year: 2026: 12 · 2025: 33 · 2024: 38 · 2023: 41 · 2022: 32 · 2021: 17 · 2020: 1
FWCI: 1.99
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Medicinal Research Reviews (publishedVersion)
PubMed (publishedVersion)
Funders: European Regional Development Fund (POCI‐01‐0145‐FEDER‐029241)
Fundação para a Ciência e a Tecnologia (PTDC/MED‐QUI/29241/2017, SFRH/BHD/110001/2015)
Topics: Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
Health Sciences › Medicine › Pharmacology › Flavonoids in Medical Research
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
Keywords: flavonoids, obesity, anti-obesity, mechanism of action, lipid metabolism, energy expenditure, dietary intake, fat absorption, gut microbiota, plasma triglycerides, cholesterol, type 2 diabetes, cardiovascular disease, natural products, drug discovery
MeSH terms: Gastrointestinal Microbiome, Diabetes Mellitus, Type 2, Flavonoids, Humans, Obesity, Anti-Obesity Agents

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Flavonoids as Antiobesity Agents: A Review

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