Flavonoids as chemopreventive agents: metabolism, apoptosis, and oxidative stress modulation

Authors

  • Faruk Alam Faculty of Pharmaceutical Science, Assam down town University, Panikhaiti, Guwahati, Assam, 781026, India
  • Surabhi Mandal Department of Pharmaceutical Analysis, Himalayan Pharmacy Institute, Majhitar, Rangpo, East Sikkim, 737136, India
  • Bhupendra Shrestha Department of Pharmaceutical Analysis, Himalayan Pharmacy Institute, Majhitar, Rangpo, East Sikkim, 737136, India
  • Barasha Bharadwaj Department of Pharmaceutical Analysis, Himalayan Pharmacy Institute, Majhitar, Rangpo, East Sikkim, 737136, India
  • Bramhajit Chatterjee Department of Pharmaceutical Technology, Brainware University, Ramkrishnapur Rd, Barasat, Kolkata, WB, 700125, India

DOI:

https://doi.org/10.69857/joapr.v14i2.1486

Keywords:

Flavonoids, Anticancer properties, Gut microbiota, Metabolism

Abstract

Background: Liposomes are widely used as drug delivery systems because of their reduced systemic toxicity. Over the past few decades, numerous drug-loaded liposomes have been approved for clinical use in the treatment of cancer, viral, and fungal infections. Various liposomal formulations have progressed to later phases of clinical trials. Liposomes are spherical vesicles composed of a single or multiple phospholipid bilayers surrounding an aqueous core. Drug-loaded liposomes can exhibit controlled or targeted drug delivery, low immunogenicity, high biocompatibility, biodegradability, prolonged drug half-life, increased efficiency, reduced systemic toxicity, and enhanced pharmacokinetic properties. Methodology: This review article addresses the characteristics and types of liposomes; novel methods for their preparation, such as the Supercritical Anti-solvent Method and the Dual Asymmetric Centrifugation Method; lipid preferences; future directions for liposomes; marketed liposomal formulations; and associated patents. Results and Discussion: It has the potential to protect the drug against degradation. The aforementioned drug delivery system increases in vivo drug distribution toward target sites. PEGylated liposomes can prolong circulation time. It requires expertise in techniques, such as thin-film hydration and reverse-phase evaporation, for preparation. It has been utilized in nanomedicine. This particular delivery system requires characterizations like size, drug loading, drug release, etc. Conclusion: Liposome-embedded delivery systems advance nanotechnology and biopharmaceutics. The role of modern medicine has continued to expand, particularly in the management of chronic diseases.

Downloads

Download data is not yet available.

References

Elshafie HS, Camele I, Mohamed AA. A Comprehensive Review on the Biological, Agricultural and Pharmaceutical Properties of Secondary Metabolites Based-Plant Origin. Int. J. Mol. Sci., 24, (2023) https://doi.org/10.3390/ijms24043266.

Reshi ZA, Ahmad W, Lukatkin AS, Javed S Bin. From Nature to Lab: A Review of Secondary Metabolite Biosynthetic Pathways, Environmental Influences, and In Vitro Approaches. Metabolites, 13, (2023) https://doi.org/10.3390/metabo13080895.

Seigler DS, Friesen JB, Bisson J, Graham JG, Bedran-Russo A, McAlpine JB, Pauli GF. Do Certain Flavonoid IMPS Have a Vital Function? Front. Nutr., 8, 1–16 (2021) https://doi.org/10.3389/fnut.2021.762753.

Kumar GA, Kumar S, Bhardwaj R, Swapnil P, Meena M, Seth CS, Yadav A. Recent advancements in multifaceted roles of flavonoids in plant–rhizomicrobiome interactions. Front. Plant Sci., 14, 1–14 (2023) https://doi.org/10.3389/fpls.2023.1297706.

Zeng Q, Feng X, Hu Y, Su S. The human gut microbiota is associated with host lifestyle: a comprehensive narrative review. Front. Microbiol., 16, 1–11 (2025) https://doi.org/10.3389/fmicb.2025.1549160.

Wang H, Zhao T, Liu Z, Danzengquzhen, Cisangzhuoma, Ma J, Li X, Huang X, Li B. The neuromodulatory effects of flavonoids and gut Microbiota through the gut-brain axis. Front. Cell. Infect. Microbiol., 13, 1–11 (2023) https://doi.org/10.3389/fcimb.2023.1197646.

Li X, Xie E, Sun S, Shen J, Ding Y, Wang J, Peng X, Zheng R, Farag MA, Xiao J. Flavonoids for gastrointestinal tract local and associated systemic effects: A review of clinical trials and future perspectives. J. Adv. Res., 77, 15–41 (2025) https://doi.org/10.1016/j.jare.2025.01.014.

Jomova K, Alomar SY, Valko R, Liska J, Nepovimova E, Kuca K, Valko M. Flavonoids and their role in oxidative stress, inflammation, and human diseases. Chem. Biol. Interact., 413, 111489 (2025) https://doi.org/10.1016/j.cbi.2025.111489.

Pyo Y, Kwon KH, Jung YJ. Anticancer Potential of Flavonoids: Their Role in Cancer Prevention and Health Benefits. Foods, 13, 1–16 (2024) https://doi.org/10.3390/foods13142253.

Khan J, Deb PK, Priya S, Medina KD, Devi R, Walode SG, Rudrapal M. Dietary flavonoids: Cardioprotective potential with antioxidant effects and their pharmacokinetic, toxicological and therapeutic concerns. Molecules, 26, 1–24 (2021) https://doi.org/10.3390/molecules26134021.

Safe S, Jayaraman A, Chapkin RS, Howard M, Mohankumar K, Shrestha R. Flavonoids: structure–function and mechanisms of action and opportunities for drug development. Toxicol. Res., 37, 147–62 (2021) https://doi.org/10.1007/s43188-020-00080-z.

Chen S, Wang X, Cheng Y, Gao H, Chen X. A Review of Classification, Biosynthesis, Biological Activities and Potential Applications of Flavonoids. Molecules, 28, 1–27 (2023) https://doi.org/10.3390/molecules28134982.

Paul JK, Azmal M, Haque ASNB, Meem M, Talukder OF, Ghosh A. Unlocking the secrets of the human gut microbiota: Comprehensive review on its role in different diseases. World J. Gastroenterol., 31, 1–20 (2025) https://doi.org/10.3748/wjg.v31.i5.99913.

Al-Ishaq RK, Liskova A, Kubatka P, Büsselberg D. Enzymatic metabolism of flavonoids by gut microbiota and its impact on gastrointestinal cancer. Cancers (Basel)., 13, (2021) https://doi.org/10.3390/cancers13163934.

Pateriya D, Prasoodanan P. K. V, Scaria J, Sharma VK. Landscape of flavonoid metabolism in human gut microbiome and its association with health and disease. Gut Microbes Reports, 2, (2025) https://doi.org/10.1080/29933935.2025.2520788.

Dias MC, Pinto DCGA, Silva AMS. Plant flavonoids: Chemical characteristics and biological activity. Molecules, 26, 1–16 (2021) https://doi.org/10.3390/molecules26175377.

Zhao Y, Zhong X, Yan J, Sun C, Zhao X, Wang X. Potential roles of gut microbes in biotransformation of natural products: An overview. Front. Microbiol., 13, (2022) https://doi.org/10.3389/fmicb.2022.956378.

Wada K, Suda W, Ueno T, Masuoka H, Yamakawa M, Nakashima Y, Sugino M, Mori T, Uchiyama S, Sumoto Y, Kiguchi Y, Hattori M, Nagata C. Gut microbiota associated with equol production in school-age children. Eur. J. Nutr., 64, 1–11 (2025) https://doi.org/10.1007/s00394-025-03625-w.

Xiong HH, Lin SY, Chen LL, Ouyang KH, Wang WJ. The Interaction between Flavonoids and Intestinal Microbes: A Review. Foods, 12, 1–34 (2023) https://doi.org/10.3390/foods12020320.

Hai Y, Zhang Y, Liang Y, Ma X, Qi X, Xiao J, Xue W, Luo Y, Yue T. Advance on the absorption, metabolism, and efficacy exertion of quercetin and its important derivatives: Absorption, metabolism and function of quercetin. Food Front., 1, 420–34 (2020) https://doi.org/10.1002/fft2.50.

Li E, Wang T, Zhou R, Zhou Z, Zhang C, Wu W, He K. Myricetin and myricetrin alleviate liver and colon damage in a chronic colitis mice model: Effects on tight junction and intestinal microbiota. J. Funct. Foods, 87, 104790 (2021) https://doi.org/10.1016/j.jff.2021.104790.

Fossatelli L, Maroccia Z, Fiorentini C, Bonucci M. Resources for Human Health from the Plant Kingdom: The Potential Role of the Flavonoid Apigenin in Cancer Counteraction. Int. J. Mol. Sci., 25, (2024) https://doi.org/10.3390/ijms25010251.

Xu H, Lan Y, Xing J, Li Y, Liu L, Wang Y. AfCHIL, a Type IV Chalcone Isomerase, Enhances the Biosynthesis of Naringenin in Metabolic Engineering. Front. Plant Sci., 13, (2022) https://doi.org/10.3389/fpls.2022.891066.

Tang Z. Cyanidin-3-glucoside: targeting atherosclerosis through gut microbiota and anti-inflammation. Front. Nutr., 12, 1–12 (2025) https://doi.org/10.3389/fnut.2025.1627868.

Zhou M, Ma J, Kang M, Tang W, Xia S, Yin J, Yin Y. Flavonoids, gut microbiota, and host lipid metabolism. Eng. Life Sci., 24, 1–19 (2024) https://doi.org/10.1002/elsc.202300065.

Pandey P, Lakhanpal S, Mahmood D, Kang HN, Kim B, Kang S, Choi J, Choi M, Pandey S, Bhat M, Sharma S, Khan F, Park MN, Kim B. An updated review summarizing the anticancer potential of flavonoids via targeting NF-kB pathway. Front. Pharmacol., 15, 1–18 (2024) https://doi.org/10.3389/fphar.2024.1513422.

Silva-Pinto PA, de Pontes JTC, Aguilar-Morón B, Canales CSC, Pavan FR, Roque-Borda CA. Phytochemical insights into flavonoids in cancer: Mechanisms, therapeutic potential, and the case of quercetin. Heliyon, 11, (2025) https://doi.org/10.1016/j.heliyon.2025.e42682.

Wei J, Xiao Y, Feng Q, Liu H, Zou K, Li L. The association between fruit and vegetable intake and gastrointestinal cancers risk from Mendelian randomization analysis. Sci. Rep., 14, 1–10 (2024) https://doi.org/10.1038/s41598-024-79650-2.

Gupta D, Guliani E. Flavonoids: Molecular mechanism behind natural chemoprotective behavior-a mini review. Biointerface Res. Appl. Chem., 12, 5983–95 (2022) https://doi.org/10.33263/BRIAC125.59835995.

Mir SA, Dar A, Hamid L, Nisar N, Malik JA, Ali T, Bader GN. Flavonoids as promising molecules in the cancer therapy: An insight. Curr. Res. Pharmacol. Drug Discov., 6, 100167 (2024) https://doi.org/10.1016/j.crphar.2023.100167.

Bai R, Cui J. Regulation of fatty acid synthase on tumor and progress in the development of related therapies. Chin. Med. J. (Engl)., 137, 1894–902 (2024) https://doi.org/10.1097/CM9.0000000000002880.

Azizi E, Fouladdel S, Movahhed TK, Modaresi F, Barzegar E, Ghahremani MH, Ostad SN, Atashpour S. Quercetin Effects on Cell Cycle Arrest and Apoptosis and Doxorubicin Activity in T47D Cancer Stem Cells. Asian Pacific J. Cancer Prev., 23, 4145–54 (2022) https://doi.org/10.31557/APJCP.2022.23.12.4145.

Wu ZY, Qiu KY, Gai YJ, Wu JH, Zhou BX, Shi QF. Quercetin: A Natural Ally in Combating Breast Cancer. Int. J. Nanomedicine, 20, 9155–77 (2025) https://doi.org/10.2147/IJN.S518174.

Li X, Wu Z, Yuan L, Chen X, Huang H, Cheng F, Shen W. Hesperidin inhibits colon cancer progression by downregulating SLC5A1 to suppress EGFR phosphorylation. J. Cancer, 16, 876–87 (2025) https://doi.org/10.7150/jca.104867.

Qiu M, Wei W, Zhang J, Wang H, Bai Y, Guo DA. A Scientometric Study to a Critical Review on Promising Anticancer and Neuroprotective Compounds: Citrus Flavonoids. Antioxidants, 12, (2023) https://doi.org/10.3390/antiox12030669.

Cirmi S, Maugeri A, Ferlazzo N, Gangemi S, Calapai G, Schumacher U, Navarra M. Anticancer potential of Citrus juices and their extracts: A systematic review of both preclinical and clinical studies. Front. Pharmacol., 8, (2017) https://doi.org/10.3389/fphar.2017.00420.

Farhan M, Rizvi A, Aatif M, Ahmad A. Current Understanding of Flavonoids in Cancer Therapy and Prevention. Metabolites, 13, (2023) https://doi.org/10.3390/metabo13040481.

Lotfi N, Yousefi Z, Golabi M, Khalilian P, Ghezelbash B, Montazeri M, Shams MH, Baghbadorani PZ, Eskandari N. The potential anti-cancer effects of quercetin on blood, prostate and lung cancers: An update. Front. Immunol., 14, 1–21 (2023) https://doi.org/10.3389/fimmu.2023.1077531.

Elsori D, Pandey P, Verma M, Vadia N, Roopashree R, Vyas M, Lakshmi L, Maharana L, Nathiya D, Saeed M, Obaidur Rab S, Khan F. Recent advancement in the anticancer efficacy of the natural flavonoid scutellarin: a comprehensive review. Front. Pharmacol., 16, 1–15 (2025) https://doi.org/10.3389/fphar.2025.1579609.

Arshad Husain Rahmani, Ali Yousif Babiker SA. Hesperidin a Bioflavonoid in Cancer Therapy. Molecules, 28, 5152 (2023) 10.3390/molecules28135152.

Zhou J, Li H, Wu B, Zhu L, Huang Q, Guo Z, He Q, Wang L, Peng X, Guo T. Network pharmacology combined with experimental verification to explore the potential mechanism of naringenin in the treatment of cervical cancer. Sci. Rep., 14, 1–12 (2024) https://doi.org/10.1038/s41598-024-52413-9.

Tsouh Fokou PV, Kamdem Pone B, Appiah-Oppong R, Ngouana V, Bakarnga-Via I, Ntieche Woutouoba D, Flore Donfack Donkeng V, Tchokouaha Yamthe LR, Fekam Boyom F, Arslan Ateşşahin D, Sharifi-Rad J, Calina D. An Update on Antitumor Efficacy of Catechins: From Molecular Mechanisms to Clinical Applications. Food Sci. Nutr., 13, 1–16 (2025) https://doi.org/10.1002/fsn3.70169.

Asiri A, Bokahri BT, Sadaf, Eisa AA, Aljohani HM, Nofal W, Kausar T, Najm MZ. Curcumin, EGCG and apigenin in cervical cancer: mechanistic insights and therapeutic potential. Front. Pharmacol., 16, 1–17 (2025) https://doi.org/10.3389/fphar.2025.1592395.

Xie X, Wei Y. A review on anti-cancer properties of quercetin in gastric cancer. Front. Pharmacol., 16, 1–7 (2025) https://doi.org/10.3389/fphar.2025.1563229.

Hao X, Ding M, Chi C, Xu X, Zhang X, Hu M. The potential of kaempferol in digestive system tumors: recent advances and mechanistic insights. Discov. Oncol., 15, (2024) https://doi.org/10.1007/s12672-024-01510-2.

Han SH, Lee JH, Woo JS, Jung GH, Jung SH, Han EJ, Park YS, Kim BS, Kim SK, Park BK, Choi C, Jung JY. Myricetin induces apoptosis through the MAPK pathway and regulates JNK-mediated autophagy in SK-BR-3 cells. Int. J. Mol. Med., 49, 1–11 (2022) https://doi.org/10.3892/ijmm.2022.5110.

Posadino AM, Giordo R, Ramli I, Zayed H, Nasrallah GK, Wehbe Z, Eid AH, Gürer ES, Kennedy JF, Aldahish AA, Calina D, Razis AFA, Modu B, Habtemariam S, Sharifi-Rad J, Pintus G, Cho WC. An updated overview of cyanidins for chemoprevention and cancer therapy. Biomed. Pharmacother., 163, (2023) https://doi.org/10.1016/j.biopha.2023.114783.

Rudrapal M, Khairnar SJ, Khan J, Dukhyil A Bin, Ansari MA, Alomary MN, Alshabrmi FM, Palai S, Deb PK, Devi R. Dietary Polyphenols and Their Role in Oxidative Stress-Induced Human Diseases: Insights Into Protective Effects, Antioxidant Potentials and Mechanism(s) of Action. Front. Pharmacol., 13, 1–15 (2022) https://doi.org/10.3389/fphar.2022.806470.

De Almeida AJPO, De Oliveira JCPL, Da Silva Pontes LV, De Souza Júnior JF, Gonçalves TAF, Dantas SH, De Almeida Feitosa MS, Silva AO, De Medeiros IA. ROS: Basic Concepts, Sources, Cellular Signaling, and its Implications in Aging Pathways. Oxid. Med. Cell. Longev., 2022, (2022) https://doi.org/10.1155/2022/1225578.

Reis JF, Monteiro VVS, Souza Gomes R, Carmo MM, Costa GV, Ribera PC, Monteiro MC. Action mechanism and cardiovascular effect of anthocyanins: A systematic review of animal and human studies. J. Transl. Med., 14, 1–16 (2016) https://doi.org/10.1186/s12967-016-1076-5.

Sheng Y, Sun Y, Tang Y, Yu Y, Wang J, Zheng F, Li Y, Sun Y. Catechins: Protective mechanism of antioxidant stress in atherosclerosis. Front. Pharmacol., 14, 1–15 (2023) https://doi.org/10.3389/fphar.2023.1144878.

Tuo Y, Lu X, Tao F, Tukhvatshin M, Xiang F, Wang X, Shi Y, Lin J, Hu Y. The Potential Mechanisms of Catechins in Tea for Anti-Hypertension: An Integration of Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation. Foods, 13, (2024) https://doi.org/10.3390/foods13172685.

Jia Y, Wang H, Fan W, Lv J, Niu Q, Zhu R, Zhang Q. Effects of polyphenol-rich seed foods on lipid and inflammatory markers in patients with coronary heart disease: a systematic review. Front. Nutr., 11, (2024) https://doi.org/10.3389/fnut.2024.1493410.

Hedayati N, Yaghoobi A, Salami M, Gholinezhad Y, Aghadavood F, Eshraghi R, Aarabi MH, Homayoonfal M, Asemi Z, Mirzaei H, Hajijafari M, Mafi A, Rezaee M. Impact of polyphenols on heart failure and cardiac hypertrophy: clinical effects and molecular mechanisms. Front. Cardiovasc. Med., 10, (2023) https://doi.org/10.3389/fcvm.2023.1174816.

Michno A, Grużewska K, Ronowska A, Gul-Hinc S, Zyśk M, Jankowska-Kulawy A. Resveratrol Inhibits Metabolism and Affects Blood Platelet Function in Type 2 Diabetes. Nutrients, 14, 1–12 (2022) https://doi.org/10.3390/nu14081633.

Liang ZF, Xu YM, Song JJ, Gao ZH, Qian H, Xu XZ. Interventional effect of hesperetin on N-methyl-N’-nitro-N-nitrosoguanidine-induced exosomal circ008274 in affecting normal cells to promote gastric carcinogenesis. World J. Gastroenterol., 31, 104920 (2025) https://doi.org/10.3748/wjg.v31.i16.104920.

Stabrauskiene J, Kopustinskiene DM, Lazauskas R, Bernatoniene J. Naringin and Naringenin: Their Mechanisms of Action and the Potential Anticancer Activities. Biomedicines, 10, 1–16 (2022) https://doi.org/10.3390/biomedicines10071686.

Rahmani AH, Almatroudi A, Allemailem KS, Alharbi HOA, Alwanian WM, Alhunayhani BA, Algahtani M, Theyab A, Almansour NM, Algefary AN, Aldeghaim SSA, Khan AA. Role of Mangiferin in Management of Cancers through Modulation of Signal Transduction Pathways. Biomedicines, 11, (2023) https://doi.org/10.3390/biomedicines11123205.

Kaewmanee M, Limpaiboon T, Ngernyuang N. Apigenin Induces Apoptosis and Inhibits Migration in Human Cholangiocarcinoma Cells. Toxics, 13, (2025) https://doi.org/10.3390/toxics13020112.

Ghasemi-Pirbaluti M, Pourgheysari B, Shirzad H, Sourani Z, Beshkar P. The Inhibitory Effect of Epigallocatechin Gallate on the Viability of T Lymphoblastic Leukemia Cells is Associated with Increase of Caspase-3 Level and Fas Expression. Indian J. Hematol. Blood Transfus., 34, 253–60 (2018) https://doi.org/10.1007/s12288-017-0854-4.

Kciuk M, Alam M, Ali N, Rashid S, Głowacka P, Sundaraj R, Celik I, Yahya EB, Dubey A, Zerroug E, Kontek R. Epigallocatechin-3-Gallate Therapeutic Potential in Cancer: Mechanism of Action and Clinical Implications. Molecules, 28, 1–44 (2023) https://doi.org/10.3390/molecules28135246.

Shahriari Felordi M, Alikhani M, Farzaneh Z, Alipour Choshali M, Ebrahimi M, Aboulkheyr Es H, Piryaei A, Najimi M, Vosough M. (-)-Epigallocatechin-3-gallate induced apoptosis by dissociation of c-FLIP/Ku70 complex in gastric cancer cells. J. Cell. Mol. Med., 27, 2572–82 (2023) https://doi.org/10.1111/jcmm.17873.

Ouyang J, Zhu K, Liu Z, Huang J. Prooxidant Effects of Epigallocatechin-3-Gallate in Health Benefits and Potential Adverse Effect. Oxid. Med. Cell. Longev., 2020, (2020) https://doi.org/10.1155/2020/9723686.

Randisi F, Perletti G, Marras E, Gariboldi MB. Green Tea Components: In Vitro and In Vivo Evidence for Their Anticancer Potential in Colon Cancer. Cancers (Basel)., 17, (2025) https://doi.org/10.3390/cancers17040623.

Talib WH, Awajan D, Alqudah A, Alsawwaf R, Althunibat R, Abu AlRoos M, Al Safadi A, Abu Asab S, Hadi RW, Al Kury LT. Targeting Cancer Hallmarks with Epigallocatechin Gallate (EGCG): Mechanistic Basis and Therapeutic Targets. Molecules, 29, 1–25 (2024) https://doi.org/10.3390/molecules29061373.

Wang M, Yu F, Zhang Y, Chang W, Zhou M. The Effects and Mechanisms of Flavonoids on Cancer Prevention and Therapy: Focus on Gut Microbiota. Int. J. Biol. Sci., 18, 1451–75 (2022) https://doi.org/10.7150/ijbs.68170.

Rodrigues K, Nadaf S, Rarokar N, Gurav N, Jagtap P, Mali P, Ayyanar M, Kalaskar M, Gurav S. QBD approach for the development of hesperetin loaded colloidal nanosponges for sustained delivery: In-vitro, ex-vivo, and in-vivo assessment. OpenNano, 7, 100045 (2022) https://doi.org/10.1016/j.onano.2022.100045.

Al-Shalabi E, Abusulieh S, Hammad AM, Sunoqrot S. Rhoifolin loaded in PLGA nanoparticles alleviates oxidative stress and inflammation in vitro and in vivo. Biomater. Sci., 10, 5504–19 (2022) https://doi.org/10.1039/d2bm00309k.

He Z, Liu Y, Wang H, Li P, Chen Y, Wang C, Zhou C, Song S, Chen S, Huang G, Yang Z. Dual-grafted dextran based nanomicelles: Higher antioxidant, anti-inflammatory and cellular uptake efficiency for quercetin. Int. J. Biol. Macromol., 224, 1361–72 (2023) https://doi.org/10.1016/j.ijbiomac.2022.10.222.

Published

2026-03-15

How to Cite

Alam, F. ., Mandal, S. ., Shrestha, B. ., Bharadwaj, B. ., & Chatterjee, B. . (2026). Flavonoids as chemopreventive agents: metabolism, apoptosis, and oxidative stress modulation. Journal of Applied Pharmaceutical Research, 14(2), 1-12. https://doi.org/10.69857/joapr.v14i2.1486

Issue

Section

Articles