Comprehensive Review on Mechanistic Insights, Optimal Dosages, and Safety Prospective of Natural Products in Anticancer Therapeutics

Authors

  • Gul-e-Saba Chaudhry * Institute of Climate Adaptation and Marine Biotechnology, Universiti Malaysia Terengganu, Kuala Terengganu, 21030, Malaysia
  • Zeenia Institute of Climate Adaptation and Marine Biotechnology, Universiti Malaysia Terengganu, Kuala Terengganu, 21030, Malaysia
  • Abdah Md Akim Department of Biomedical Sciences, Universiti Putra Malaysia, Seri Kembangan, Selangor, 43300, Malaysia
  • Yeong Yik Sung Institute of Climate Adaptation and Marine Biotechnology, Universiti Malaysia Terengganu, Kuala Terengganu, 21030, Malaysia
  • Tengku Sifzizul Institute of Climate Adaptation and Marine Biotechnology, Universiti Malaysia Terengganu, Kuala Terengganu, 21030, Malaysia

DOI:

https://doi.org/10.55121/fds.v1i1.137

Keywords:

Anthocyanin, Cancer, Apoptosis, Drug safety, Curcumin, Genistein gossypol, Hispidulin, Resveratrol

Abstract

Cancer remains a formidable global health challenge, necessitating sustained research efforts to develop innovative and efficacious therapeutic modalities. The exploration of alternative cancer therapies has gained prominence, given the adverse side effects associated with conventional treatments like chemotherapy. Natural medicines, particularly those derived from botanical sources, emerge as a potentially more viable option for cancer treatment within the confines of therapeutic and safe dosage parameters. This comprehensive review elucidates the effective mechanisms and safety profiles related to the dosage of these natural compounds. The literature under consideration spans and has been meticulously curated from reputable databases, including PubMed, Scopus, and Google Scholar. Noteworthy natural substances encompassed in this scrutiny include gossypol, curcumin, resveratrol, genistein, anthocyanin, and hispidulin. The review outlines their respective mechanisms, therapeutic dosages, and safety perspectives within the context of cancer treatment. These compounds manifest diverse anticancer effects, ranging from the induction of apoptosis and inhibition of cell proliferation to the modulation of crucial signaling pathways. These natural compounds exhibit promising anticancer potential by targeting key facets of cancer progression, notably by i) instigating apoptosis and ii) intervening in cell cycle checkpoints. However, a more strategic and nuanced investigation is imperative to fully elucidate their optimal dosages, modes of action, and potential synergies with existing cancer treatment modalities. This critical gap in our understanding underscores the necessity for further in-depth research to optimize the therapeutic potential of these plant-derived chemicals.

References

[1] World Health Organization, Public Health Agency of Canada, 2005. Preventing chronic diseases: A vital investment. World Health Organization: Geneva.

[2] Mathers, C.D., Loncar, D., 2006. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Medicine. 3(11), e442. DOI: https://doi.org/10.1371/journal.pmed.0030442

[3] Lopez, A.D., Mathers, C.D., Ezzati, M., et al., 2006. Global and regional burden of disease and risk factors, 2001: Systematic analysis of population health data. The Lancet. 367(9524), 1747-1757. DOI: https://doi.org/10.1016/S0140-6736(06)68770-9

[4] Deaths: Final Data for 2003 [Internet]. Centers for Disease Control and Prevention. Available from: https://www.cdc.gov/nchs/data/hestat/finaldeaths03/finaldeaths03.htm

[5] Desai, A.G., Qazi, G.N., Ganju, R.K., et al., 2008. Medicinal plants and cancer chemoprevention. Current Drug Metabolism. 9(7), 581-591. DOI: https://doi.org/10.2174/138920008785821657

[6] Arbiser, J.L., Bonner, M.Y., Gilbert, L.C., 2017. Targeting the duality of cancer. NPJ Precision Oncology. 1(1), 23. DOI: https://doi.org/10.1038/s41698-017-0026-x

[7] Xu, W., Jing, L., Wang, Q., et al., 2015. Bax-PGAM5L-Drp1 complex is required for intrinsic apoptosis execution. Oncotarget. 6(30), 30017. DOI: https://doi.org/10.18632/oncotarget.5013

[8] Lopez, J., Tait, S.W.G., 2015. Mitochondrial apoptosis: Killing cancer using the enemy within. British Journal of Cancer. 112(6), 957-962. DOI: https://doi.org/10.1038/bjc.2015.85

[9] Pfeffer, C.M., Singh, A.T., 2018. Apoptosis: A target for anticancer therapy. International Journal of Molecular Sciences. 19(2), 448. DOI: https://doi.org/10.3390/ijms19020448

[10] Peng, W., Wu, J.G., Jiang, Y.B., et al., 2015. Antitumor activity of 4-O-(2”-O-acetyl-6”-O-p-coumaroyl-β-D-glucopyranosyl)-p-coumaric acid against lung cancers via mitochondrial-mediated apoptosis. Chemico-biological Interactions. 233, 8-13. DOI: https://doi.org/10.1016/j.cbi.2015.03.014

[11] Khalil, A.M., 2021. Apoptosis, guardian of the genome. World Journal of Biology Pharmacy and Health Sciences. 5(1), 37-54. DOI: https://doi.org/10.30574/wjbphs.2021.5.1.0003

[12] Li, M., Tang, D., Yang, T., et al., 2022. Apoptosis triggering, an important way for natural products from herbal medicines to treat pancreatic cancers. Frontiers in Pharmacology. 12, 796300. DOI: https://doi.org/10.3389/fphar.2021.796300

[13] Ahmad, R., Ahmad, N., Naqvi, A.A., et al., 2017. Role of traditional Islamic and Arabic plants in cancer therapy. Journal of Traditional and Complementary Medicine. 7(2), 195-204. DOI: https://doi.org/10.1016/j.jtcme.2016.05.002

[14] Zaid, H., Silbermann, M., Ben-Arye, E., et al., 2012. Greco-Arab and Islamic herbal-derived anticancer modalities: From tradition to molecular mechanisms. Evidence-Based Complementary and Alternative Medicine. 349040. DOI: https://doi.org/10.1155/2012/349040

[15] Seca, A.M., Pinto, D.C., 2018. Plant secondary metabolites as anticancer agents: Successes in clinical trials and therapeutic application. International Journal of Molecular Sciences. 19(1), 263. DOI: https://doi.org/10.3390/ijms19010263

[16] Lichota, A., Gwozdzinski, K., 2018. Anticancer activity of natural compounds from plant and marine environment. International Journal of Molecular Sciences. 19(11), 3533. DOI: https://doi.org/10.3390/ijms19113533

[17] Hassan, B., 2020. Plants and cancer treatment. Medicinal plants: Use in prevention and treatment of diseases. Intech Open: London. DOI: https://doi.org/10.5772/intechopen.90568

[18] van Wyk, A.S., Prinsloo, G., 2020. Health, safety and quality concerns of plant-based traditional medicines and herbal remedies. South African Journal of Botany. 133, 54-62. DOI: https://doi.org/10.1016/j.sajb.2020.06.031

[19] Akim, A., Zafar, M.N., Abdullah, M.A., et al., 2020. Induction of apoptosis and role of paclitaxel-loaded hyaluronic acid-crosslinked nanoparticles in the regulation of AKT and RhoA. Journal of Advanced Pharmaceutical Technology & Research. 11(3), 101-106.

[20] Jan, R., Zafar, M.N., Mohammad, H., et al., 2019. Vitex rotundifolia fractions induced apoptosis in human breast cancer T-47D cell line via activation of extrinsic and intrinsic pathway. Asian Pacific Journal of Cancer Prevention. 20(12), 3555. DOI: https://doi.org/10.31557/APJCP.2019.20.12.3555

[21] Nithya, M., Ambikapathy, V., Panneerselvam, A., et al., 2014. Anti-tumour activity of different extracts of Ganoderma lucidum (curt.: fr.) p. karst. World Journal of Pharmaceutical Research. 3(4), 2204-2214.

[22] Mou, X., Kesari, S., Wen, P.Y., et al., 2011. Crude drugs as anticancer agents. International Journal of Clinical and Experimental Medicine. 4(1), 17-25.

[23] Chaudhry, G.E.S., Sohimi, N.K.A., Mohamad, H., et al., 2021. Xylocarpus moluccensis induces cytotoxicity in human hepatocellular carcinoma HepG2 cell line via activation of the extrinsic pathway. Asian Pacific Journal of Cancer Prevention. 22(S1), 17-24. DOI: https://doi.org/10.31557/APJCP.2021.22.S1.17

[24] Siegel, R.L., Miller, K.D., Wagle, N.S., et al., 2023. Cancer statistics, 2023. CA: A Cancer Journal for Clinicians. 73(1), 17-48. DOI: https://doi.org/10.3322/caac.21763

[25] de Melo, F.H.M., Oliveira, J.S., Sartorelli, V.O.B., et al., 2018. Cancer chemoprevention: Classic and epigenetic mechanisms inhibiting tumorigenesis. What have we learned so far?. Frontiers in Oncology. 8, 644. DOI: https://doi.org/10.3389/fonc.2018.00644

[26] Kotecha, R., Takami, A., Espinoza, J.L., 2016. Dietary phytochemicals and cancer chemoprevention: A review of the clinical evidence. Oncotarget. 7, 52517-52529. DOI: https://doi.org/10.18632/oncotarget.9593

[27] Dehelean, C.A., Marcovici, I., Soica, C., et al., 2021. Plant-derived anticancer compounds as new perspectives in drug discovery and alternative therapy. Molecules. 26(4), 1109. DOI: https://doi.org/10.3390/molecules26041109

[28] Senapati, S., Mahanta, A.K., Kumar, S., et al., 2018. Controlled drug delivery vehicles for cancer treatment and their performance. Signal Transduction and Targeted Therapy. 3, 7. DOI: https://doi.org/10.1038/s41392-017-0004-3

[29] Hasumi, K., Aoki, Y., Watanabe, R., et al., 2011. Therapeutic response in patients with advanced malignancies treated with combined dendritic cell-activated T cell-based immunotherapy and intensity-modulated radiotherapy. Cancers. 3(2), 2223-2242. DOI: https://doi.org/10.3390/cancers3022223

[30] Wang, X., Wang, Y., Chen, Z.G., et al., 2009. Advances of cancer therapy by nanotechnology. Cancer Research and Treatment. 41(1). DOI: https://doi.org/10.4143/crt.2009.41.1.1

[31] Chaudhry, G.E., Islamiah, M., Ismail, N., et al., 2018. Induction of apoptosis by Aaptos sp., fractions in human breast cancer cell line, MCF-7. International Journal of Research in Pharmaceutical Science. 9(2), 328-337.

[32] Garcia-Oliveira, P., Otero, P., Pereira, A.G., et al., 2021. Status and challenges of plant-anticancer compounds in cancer treatment. Pharmaceuticals. 14(2), 157. DOI: https://doi.org/10.3390/ph14020157

[33] Chaudhry, G.E., Akim, A.M., Sung, Y.Y., et al., 2022. Cancer and apoptosis. Methods in molecular biology. 2543, 191-210. DOI: https://doi.org/10.1007/978-1-0716-2553-8_16

[34] Song, Y.H., Sun, H., Zhang, A.H., et al., 2014. Plant-derived natural products as leads to anti-cancer drugs. Journal of Medicinal Plant and Herbal Therapy Research. 2, 6-15.

[35] Nabeelah Bibi, S., Fawzi, M.M., Gokhan, Z., et al., 2019. Ethnopharmacology, phytochemistry, and global distribution of Mangroves—A comprehensive review. Marine Drugs. 17(4), 231. DOI: https://doi.org/10.3390/md17040231

[36] Chaudhry, G.E., Rahman, N.H., Sevakumaran, V., et al., 2020. Induction of cytotoxicity by Bruguiera gymnorrhiza in human breast carcinoma (MCF-7) cell line via activation of the intrinsic pathway. Journal of Advanced Pharmaceutical Technology & Research. 11(4), 233-237.

[37] Chaudhry, G.E., Jan, R., Mohamad, H., et al., 2019. Vitex rotundifolia fractions induce apoptosis in human breast cancer cell line, MCF-7, via extrinsic and intrinsic pathways. Research in Pharmaceutical Sciences. 14(3), 273-285. DOI: https://doi.org/10.4103/1735-5362.258496

[38] Sithranga Boopathy, N., Kathiresan, K., 2010. Anticancer drugs from marine flora: An overview. Journal of Oncology. 214186. DOI: https://doi.org/10.1155/2010/214186

[39] Jan, R., Zafar, M.N., Sung, Y.Y., et al., 2020. Phytochemistry and biological activity of Vitex rotundifolia L. Research Journal of Pharmacy and Technology. 13(11), 5534-5538.

[40] Barnes, J., Heinrich, M., 2004. Fundamentals of pharmacognosy and phytotherapy. Churchill Livingstone: London.

[41] Tag, H., Kalita, P., Dwivedi, P., et al., 2012. Herbal medicines used in the treatment of diabetes mellitus in Arunachal Himalaya, northeast, India. Journal of Ethnopharmacology. 141(3), 786-795. DOI: https://doi.org/10.1016/j.jep.2012.03.007

[42] Twilley, D., Lall, N., 2018. The role of natural products from plants in the development of anticancer agents. Natural products and drug discovery. Elsevier: Amsterdam. pp 139-178.DOI: https://doi.org/10.1016/B978-0-08-102081-4.00007-1

[43] Choudhari, A.S., Mandave, P.C., Deshpande, M., et al., 2020. Phytochemicals in cancer treatment: From preclinical studies to clinical practice. Frontiers in Pharmacology. 10, 1614. DOI: https://doi.org/10.3389/fphar.2019.01614

[44] Gaston, T.E., Mendrick, D.L., Paine, M.F., et al., 2020. “Natural” is not synonymous with “Safe”: Toxicity of natural products alone and in combination with pharmaceutical agents. Regulatory Toxicology and Pharmacology. 113, 104642. DOI: https://doi.org/10.1016/j.yrtph.2020.104642

[45] Haq, I., 2004. Safety of medicinal plants. Pakistan Journal of Medical Research. 43(4), 203-210.

[46] Bent, S., 2008. Herbal medicine in the United States: Review of efficacy, safety, and regulation. Journal of General Internal Medicine. 23, 854-859. DOI: https://doi.org/10.1007/s11606-008-0632-y

[47] Capasso, F., Gaginella, T.S., Grandolini, G., et al., 2003. The complexity of herbal medicines. Phytotherapy. Springer: Berlin, Heidelberg. pp. 11-12. DOI: https://doi.org/10.1007/978-3-642-55528-2_4

[48] Ghosh, N., Ghosh, R.C., Kundu, A., et al., 2018. Herb and drug interaction. Natural products and drug discovery. Elsevier: Amsterdam. pp. 467-490. DOI: https://doi.org/10.1016/B978-0-08-102081-4.00017-4

[49] Raoufinejad, K., Gholami, K., Javadi, M., et al., 2020. A retrospective cohort study of herbal medicines use during pregnancy: Prevalence, adverse reactions, and newborn outcomes. Traditional Integrative Medicine. DOI: https://doi.org/10.18502/tim.v5i2.3627

[50] Heydari, M., Rauf, A., Thiruvengadam, M., et al., 2022. Editorial: Clinical safety of natural products, an evidence-based approach. Frontiers in Pharmacology. 13, 960556. DOI: https://doi.org/10.3389/fphar.2022.960556

[51] Gadelha, I.C., Fonseca, N.B., Oloris, S.C., et al., 2014. Gossypol toxicity from cottonseed products. The Scientific World Journal. 231635. DOI: https://doi.org/10.1155/2014/231635

[52] Kenar, J.A., 2006. Reaction chemistry of gossypol and its derivatives. Journal of the American Oil Chemists’ Society. 83(4), 269-302. DOI: https://doi.org/10.1007/s11746-006-1203-1

[53] Renner, O., Mayer, M., Leischner, C., et al., 2022. Systematic review of Gossypol/AT-101 in cancer clinical trials. Pharmaceuticals. 15(2), 144. DOI: https://doi.org/10.3390/ph15020144

[54] Abou-Donia, M.B., 1976. Physiological effects and metabolism of gossypol. Residue Reviews. 61, 125-160. DOI: https://doi.org/10.1007/978-1-4613-9401-3_5

[55] Rogers, G.M., Poore, M.H., Paschal, J.C., 2002. Feeding cotton products to cattle. Veterinary Clinics: Food Animal Practice. 18(2), 267-294. DOI: https://doi.org/10.1016/s0749-0720(02)00020-8

[56] PubChem Compound Summary for CID 3503, Gossypol [Internet]. National Center for Biotechnology Information; 2023. [cited 2023 Sep 19]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Gossypol

[57] Zeng, Y., Ma, J., Xu, L., et al., 2019. Natural product gossypol and its derivatives in precision cancer medicine. Current Medicinal Chemistry. 26(10), 1849-1873. DOI: https://doi.org/10.2174/0929867324666170523123655

[58] Volate, S.R., Kawasaki, B.T., Hurt, E.M., et al., 2010. Gossypol induces apoptosis by activating p53 in prostate cancer cells and prostate tumor—initiating cells. Molecular Cancer Therapeutics. 9(2), 461-470. DOI: https://doi.org/10.1158/1535-7163.MCT-09-0507

[59] Moon, D.O., Choi, Y.H., Moon, S.K., et al., 2011. Gossypol decreases tumor necrosis factor-α-induced intercellular adhesion molecule-1 expression via suppression of NF-κB activity. Food and Chemical Toxicology. 49(4), 999-1005. DOI: https://doi.org/10.1016/j.fct.2011.01.006

[60] Xiong, J., Li, J., Yang, Q., et al., 2017. Gossypol has anti-cancer effects by dual-targeting MDM2 and VEGF in human breast cancer. Breast Cancer Research. 19(1), 27. DOI: https://doi.org/10.1186/s13058-017-0818-5

[61] Huang, Y.W., Wang, L.S., Dowd, M.K., et al., 2009. (-)-Gossypol reduces invasiveness in metastatic prostate cancer cells. Anticancer Research. 29(6), 2179-2188.

[62] Lee, S., Hong, E., Jo, E., et al., 2022. Gossypol induces apoptosis of human pancreatic cancer cells via CHOP/endoplasmic reticulum stress signaling pathway. Journal of Microbiology and Biotechnology. 32(5), 645-656. DOI: https://doi.org/10.4014/jmb.2110.10019

[63] Jiang, J., Sugimoto, Y., Liu, S., et al., 2004. The inhibitory effects of gossypol on human prostate cancer cells-PC3 are associated with transforming growth factor beta1 (TGFβ1) signal transduction pathway. Anticancer Research. 24(1), 91-100.

[64] Clément, M.O., 2017. Gossypol: A potential promising anticancer agent. Scholar Academic Journal of Pharmacy. 6(6), 236-244. DOI: https://doi.org/10.21276/sajp

[65] Qian, S., Wang, Z., 1984. Gossypol: A potential antifertility agent for males. Annual Review of Pharmacology and Toxicology. 24(1), 329-360. DOI: https://doi.org/10.1146/annurev.pa.24.040184.001553

[66] Van Poznak, C., Seidman, A.D., Reidenberg, M.M., et al., 2001. Oral gossypol in the treatment of patients with refractory metastatic breast cancer: A phase I/II clinical trial. Breast Cancer Research and Treatment. 66, 239-248. DOI: https://doi.org/10.1023/A:1010686204736

[67] Stein, M.N., Goodin, S., Gounder, M., et al., 2020. A phase I study of AT-101, a BH3 mimetic, in combination with paclitaxel and carboplatin in solid tumors. Investigational New Drugs. 38, 855-865. DOI: https://doi.org/10.1007/s10637-019-00807-2

[68] Xie, H., Yin, J., Shah, M.H., et al., 2019. A phase II study of the orally administered negative enantiomer of gossypol (AT-101), a BH3 mimetic, in patients with advanced adrenal cortical carcinoma. Investigational New Drugs. 37, 755-762. DOI: https://doi.org/10.1007/s10637-019-00797-1

[69] Baggstrom, M.Q., Qi, Y., Koczywas, M., et al., 2011. A phase II study of AT-101 (Gossypol) in chemotherapy-sensitive recurrent extensive-stage small cell lung cancer. Journal of Thoracic Oncology. 6(10), 1757-1760. DOI: https://doi.org/10.1097/JTO.0b013e31822e2941

[70] Bushunow, P., Reidenberg, M.M., Wasenko, J., et al., 1999. Gossypol treatment of recurrent adult malignant gliomas. Journal of Neuro-oncology. 43, 79-86. DOI: https://doi.org/10.1023/A:1006267902186

[71] Wang, Y., Li, X., Zhang, L., et al., 2020. A randomized, double-blind, placebo-controlled study of B-cell lymphoma 2 homology 3 mimetic gossypol combined with docetaxel and cisplatin for advanced non-small cell lung cancer with high expression of apurinic/apyrimidinic endonuclease 1. Investigational New Drugs. 38, 1862-1871. DOI: https://doi.org/10.1007/s10637-020-00927-0

[72] Swiecicki, P.L., Bellile, E., Sacco, A.G., et al., 2016. A phase II trial of the BCL-2 homolog domain 3 mimetic AT-101 in combination with docetaxel for recurrent, locally advanced, or metastatic head and neck cancer. Investigational New Drugs. 34, 481-489. DOI: https://doi.org/10.1007/s10637-016-0364-5

[73] Stein, M.N., Hussain, M., Stadler, W.M., et al., 2016. A Phase II study of AT-101 to overcome Bcl-2 mediated resistance to androgen deprivation therapy in patients with newly diagnosed castration-sensitive metastatic prostate cancer. Clinical Genitourinary Cancer. 14(1), 22-27. DOI: https://doi.org/10.1016/j.clgc.2015.09.010

[74] Schelman, W.R., Mohammed, T.A., Traynor, A.M., et al., 2014. A phase I study of AT-101 with cisplatin and etoposide in patients with advanced solid tumors with an expanded cohort in extensive-stage small cell lung cancer. Investigational New Drugs. 32, 295-302. DOI: https://doi.org/10.1007/s10637-013-9999-7

[75] Sonpavde, G., Matveev, V., Burke, J.M., et al., 2012. Randomized phase II trial of docetaxel plus prednisone in combination with placebo or AT-101, an oral small molecule Bcl-2 family antagonist, as first-line therapy for metastatic castration-resistant prostate cancer. Annals of Oncology. 23(7), 1803-1808. DOI: https://doi.org/10.1093/annonc/mdr555

[76] Ready, N., Karaseva, N.A., Orlov, S.V., et al., 2011. Double-blind, placebo-controlled, randomized phase 2 study of the proapoptotic agent AT-101 plus docetaxel, in second-line non-small cell lung cancer. Journal of Thoracic Oncology. 6(4), 781-785. DOI: https://doi.org/10.1097/JTO.0b013e31820a0ea6

[77] Heist, R.S., Fain, J., Chinnasami, B., et al., 2010. Phase I/II study of AT-101 with topotecan in relapsed and refractory small cell lung cancer. Journal of Thoracic Oncology. 5(10), 1637-1643. DOI: https://doi.org/10.1097/JTO.0b013e3181e8f4dc

[78] de Peyster, A., Wang, Y.Y., 1993. Genetic toxicity studies of gossypol. Mutation Research. 297(3), 293-312. DOI: https://doi.org/10.1016/0165-1110(93)90021-e

[79] Waites, G.M., Wang, C., Griffin, P.D., 1998. Gossypol: Reasons for its failure to be accepted as a safe, reversible male antifertility drug. International Journal of Andrology. 21(1), 8-12. DOI: https://doi.org/10.1046/j.1365-2605.1998.00092.x

[80] Quintana, P.J., de Peyster, A., Klatzke, S., et al., 2000. Gossypol-induced DNA breaks in rat lymphocytes are secondary to cytotoxicity. Toxicology Letters. 117(1-2), 85-94. DOI: https://doi.org/10.1016/s0378-4274(00)00244-7

[81] Pal, D., Sahu, P., Sethi, G., et al., 2022. Gossypol and its natural derivatives: Multitargeted phytochemicals as potential drug candidates for oncologic diseases. Pharmaceutics. 14(12), 2624. DOI: https://doi.org/10.3390/pharmaceutics14122624

[82] Giordano, A., Tommonaro, G., 2019. Curcumin and cancer. Nutrients. 11(10), 2376. DOI: https://doi.org/10.3390/nu11102376

[83] PubChem Compound Summary for CID 969516, Curcumin [Internet]. National Center for Biotechnology Information; 2023. [cited 2023 Sep 19]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Curcumin

[84] Pulido-Moran, M., Moreno-Fernandez, J., Ramirez-Tortosa, C., et al., 2016. Curcumin and health. Molecules. 21(3), 264. DOI: https://doi.org/10.3390/molecules21030264

[85] Barchitta, M., Maugeri, A., Favara, G., et al., 2019. Nutrition and wound healing: An overview focusing on the beneficial effects of curcumin. International Journal of Molecular Sciences. 20(5), 1119. DOI: https://doi.org/10.3390/ijms20051119

[86] Mantzorou, M., Pavlidou, E., Vasios, G., et al., 2018. Effects of curcumin consumption on human chronic diseases: A narrative review of the most recent clinical data. Phytotherapy Research. 32(6), 957-975. DOI: https://doi.org/10.1002/ptr.6037

[87] Tan, R.Z., Liu, J., Zhang, Y.Y., et al., 2019. Curcumin relieved cisplatin-induced kidney inflammation through inhibiting Mincle-maintained M1 macrophage phenotype. Phytomedicine. 52, 284-294. DOI: https://doi.org/10.1016/j.phymed.2018.09.210

[88] Tan, B.L., Norhaizan, M.E., 2019. Curcumin combination chemotherapy: The implication and efficacy in cancer. Molecules. 24(14), 2527. DOI: https://doi.org/10.3390/molecules24142527

[89] Kunnumakkara, A.B., Bordoloi, D., Padmavathi, G., et al., 2017. Curcumin, the golden nutraceutical: Multitargeting for multiple chronic diseases. British Journal of Pharmacology. 174(11), 1325-1348. DOI: https://doi.org/10.1111/bph.13621

[90] Anand, P., Sundaram, C., Jhurani, S., et al., 2008. Curcumin and cancer: An “old-age” disease with an “age-old” solution. Cancer Letters. 267(1), 133-164. DOI: https://doi.org/10.1016/j.canlet.2008.03.025

[91] Tomeh, M.A., Hadianamrei, R., Zhao, X., 2019. A review of curcumin and its derivatives as anticancer agents. International Journal of Molecular Sciences. 20(5), 1033. DOI: https://doi.org/10.3390/ijms20051033

[92] Watson, J.L., Greenshields, A., Hill, R., et al., 2010. Curcumin-induced apoptosis in ovarian carcinoma cells is p53-independent and involves p38 mitogen-activated protein kinase activation and downregulation of Bcl-2 and survivin expression and Akt signaling. Molecular Carcinogenesis. 49(1), 13-24. DOI: https://doi.org/10.1002/mc.20571

[93] Pourhanifeh, M.H., Darvish, M., Tabatabaeian, J., et al., 2020. Therapeutic role of curcumin and its novel formulations in gynecological cancers. Journal of Ovarian Research. 13, 130. DOI: https://doi.org/10.1186/s13048-020-00731-7

[94] Hewlings, S.J., Kalman, D.S., 2017. Curcumin: A review of its effects on human health. Foods. 6(10), 92. DOI: https://doi.org/10.3390/foods6100092

[95] Nelson, K.M., Dahlin, J.L., Bisson, J., et al., 2017. The essential medicinal chemistry of curcumin. Journal of Medicinal Chemistry. 60(5), 1620-1637. DOI: https://doi.org/10.1021/acs.jmedchem.6b00975

[96] Walker, B.C., Mittal, S., 2020. Antitumor activity of curcumin in glioblastoma. International Journal of Molecular Sciences. 21(24), 9435. DOI: https://doi.org/10.3390/ijms21249435

[97] Chan, E.W.C., Wong, C.W., Tan, Y.H., et al., 2019. Resveratrol and pterostilbene: A comparative overview of their chemistry, biosynthesis, plant sources and pharmacological properties. Journal of Applied Pharmaceutical Science. 9(7), 124-129.DOI: https://doi.org/10.7324/JAPS.2019.90717

[98] Intagliata, S., Modica, M.N., Santagati, L.M., et al., 2019. Strategies to improve resveratrol systemic and topical bioavailability: An update. Antioxidants. 8(8), 244. DOI: https://doi.org/10.3390/antiox8080244

[99] Ahmadi, R., Ebrahimzadeh, M.A., 2020. Resveratrol—A comprehensive review of recent advances in anticancer drug design and development. European Journal of Medicinal Chemistry. 200, 112356. DOI: https://doi.org/10.1016/j.ejmech.2020.112356

[100] PubChem Compound Summary for CID 445154, Resveratrol [Internet]. National Center for Biotechnology Information; 2023. [cited 2023 Sep 19]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Resveratrol

[101] Jang, M., Cai, L., Udeani, G.O., et al., 1997. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science. 275(5297), 218-220. DOI: https://doi.org/10.1126/science.275.5297.218

[102] Baur, J.A., Sinclair, D.A., 2006. Therapeutic potential of resveratrol: The in vivo evidence. Nature Reviews Drug Discovery. 5, 493-506. DOI: https://doi.org/10.1038/nrd2060

[103] Athar, M., Back, J.H., Tang, X., et al., 2007. Resveratrol: A review of preclinical studies for human cancer prevention. Toxicology and Applied Pharmacology. 224(3), 274-283. DOI: https://doi.org/10.1016/j.taap.2006.12.025

[104] Shukla, Y., Singh, R., 2011. Resveratrol and cellular mechanisms of cancer prevention. Annals of the New York Academy of Sciences. 1215(1), 1-8. DOI: https://doi.org/10.1111/j.1749-6632.2010.05870.x

[105] Nakagawa, H., Kiyozuka, Y., Uemura, Y., et al., 2001. Resveratrol inhibits human breast cancer cell growth and may mitigate the effect of linoleic acid, a potent breast cancer cell stimulator. Journal of Cancer Research and Clinical Oncology. 127, 258-264. DOI: https://doi.org/10.1007/s004320000190

[106] Joe, A.K., Liu, H., Suzui, M., et al., 2002. Resveratrol induces growth inhibition, S-phase arrest, apoptosis, and changes in biomarker expression in several human cancer cell lines. Clinical Cancer Research. 8(3), 893-903.

[107] Shih, A., Davis, F.B., Lin, H.Y., et al., 2002. Resveratrol induces apoptosis in thyroid cancer cell lines via a MAPK-and p53-dependent mechanism. The Journal of Clinical Endocrinology & Metabolism. 87(3), 1223-1232. DOI: https://doi.org/10.1210/jcem.87.3.8345

[108] Roman, V., Billard, C., Kern, C., et al., 2002. Analysis of resveratrol‐induced apoptosis in human B‐cell chronic leukaemia. British Journal of Haematology. 117(4), 842-851. DOI: https://doi.org/10.1046/j.1365-2141.2002.03520.x

[109] Liang, Y.C., Tsai, S.H., Chen, L., et al., 2003. Resveratrol-induced G2 arrest through the inhibition of CDK7 and p34CDC2 kinases in colon carcinoma HT29 cells. Biochemical Pharmacology. 65(7), 1053-1060. DOI: https://doi.org/10.1016/s0006-2952(03)00011-x

[110] Liao, P.C., Ng, L.T., Lin, L.T., et al., 2010. Resveratrol arrests cell cycle and induces apoptosis in human hepatocellular carcinoma Huh-7 cells. Journal of Medicinal Food. 13(6), 1415-1423. DOI: https://doi.org/10.1089/jmf.2010.1126

[111] Park, J.W., Choi, Y.J., Suh, S.I., et al., 2001. Bcl-2 overexpression attenuates resveratrol-induced apoptosis in U937 cells by inhibition of caspase-3 activity. Carcinogenesis. 22(10), 1633-1639. DOI: https://doi.org/10.1093/carcin/22.10.1633

[112] Wolter, F., Akoglu, B., Clausnitzer, A., et al., 2001. Downregulation of the cyclin D1/Cdk4 complex occurs during resveratrol-induced cell cycle arrest in colon cancer cell lines. The Journal of Nutrition. 131(8), 2197-2203. DOI: https://doi.org/10.1093/jn/131.8.2197

[113] Gao, X., Xu, Y.X., Divine, G., et al., 2002. Disparate in vitro and in vivo antileukemic effects of resveratrol, a natural polyphenolic compound found in grapes. The Journal of Nutrition. 132(7), 2076-2081. DOI: https://doi.org/10.1093/jn/132.7.2076

[114] Mouria, M., Gukovskaya, A.S., Jung, Y., et al., 2002. Food‐derived polyphenols inhibit pancreatic cancer growth through mitochondrial cytochrome C release and apoptosis. International Journal of Cancer. 98(5), 761-769. DOI: https://doi.org/10.1002/ijc.10202

[115] Mahyar-Roemer, M., Katsen, A., Mestres, P., et al., 2001. Resveratrol induces colon tumor cell apoptosis independently of p53 and precede by epithelial differentiation, mitochondrial proliferation and membrane potential collapse. International Journal of Cancer. 94(5), 615-622. DOI: https://doi.org/10.1002/ijc.1516

[116] Huang, C., Ma, W.Y., Goranson, A., et al., 1999. Resveratrol suppresses cell transformation and induces apoptosis through a p53-dependent pathway. Carcinogenesis. 20(2), 237-242. DOI: https://doi.org/10.1093/carcin/20.2.237

[117] Kuo, P.L., Chiang, L.C., Lin, C.C., 2002. Resveratrol-induced apoptosis is mediated by p53-dependent pathway in Hep G2 cells. Life Sciences. 72(1), 23-34. DOI: https://doi.org/10.1016/s0024-3205(02)02177-x

[118] Takashina, M., Inoue, S., Tomihara, K., et al., 2017. Different effect of resveratrol to induction of apoptosis depending on the type of human cancer cells. International Journal of Oncology. 50(3), 787-797. DOI: https://doi.org/10.3892/ijo.2017.3859

[119] Cottart, C.H., Nivet‐Antoine, V., Laguillier‐Morizot, C., et al., 2010. Resveratrol bioavailability and toxicity in humans. Molecular nutrition & Food Research. 54(1), 7-16. DOI: https://doi.org/10.1002/mnfr.200900437

[120] Crowell, J.A., Korytko, P.J., Morrissey, R.L., et al., 2004. Resveratrol-associated renal toxicity. Toxicological Sciences. 82(2), 614-619. DOI: https://doi.org/10.1093/toxsci/kfh263

[121] Juan, M.E., Vinardell, M.P., Planas, J.M., 2002. The daily oral administration of high doses of trans-resveratrol to rats for 28 days is not harmful. The Journal of Nutrition. 132(2), 257-260. DOI: https://doi.org/10.1093/jn/132.2.257

[122] Williams, L.D., Burdock, G.A., Edwards, J.A., et al., 2009. Safety studies conducted on high-purity trans-resveratrol in experimental animals. Food and Chemical Toxicology. 47(9), 2170-2182. DOI: https://doi.org/10.1016/j.fct.2009.06.002

[123] Boocock, D.J., Faust, G.E., Patel, K.R., et al., 2007. Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent. Cancer Epidemiology Biomarkers & Prevention. 16(6), 1246-1252. DOI: https://doi.org/10.1158/1055-9965.EPI-07-0022

[124] Vaz-da-Silva, M., Loureiro, A.I., Falcao, A., et al., 2008. Effect of food on the pharmacokinetic profile of trans-resveratrol. International Journal of Clinical Pharmacology and Therapeutics. 46(11), 564-570. DOI: https://doi.org/10.5414/cpp46564

[125] Almeida, L., Vaz‐da‐Silva, M., Falcão, A., et al., 2009. Pharmacokinetic and safety profile of trans‐resveratrol in a rising multiple‐dose study in healthy volunteers. Molecular Nutrition & Food Research. 53(S1), S7-S15. DOI: https://doi.org/10.1002/mnfr.200800177

[126] Ashrafizadeh, M., Najafi, M., Orouei, S., et al., 2020. Resveratrol modulates transforming growth factor-beta (tgf-β) signaling pathway for disease therapy: A new insight into its pharmacological activities. Biomedicines. 8(8), 261. DOI: https://doi.org/10.3390/biomedicines8080261

[127] Patel, K.R., Scott, E., Brown, V.A., et al., 2011. Clinical trials of resveratrol. Annals of the New York Academy of Sciences. 1215(1), 161-169. DOI: https://doi.org/10.1111/j.1749-6632.2010.05853.x

[128] Salehi, B., Mishra, A.P., Nigam, M., et al., 2018. Resveratrol: A double-edged sword in health benefits. Biomedicines. 6(3), 91. DOI: https://doi.org/10.3390/biomedicines6030091

[129] PubChem Compound Summary for CID 5281628, Hispidulin [Internet]. National Center for Biotechnology Information; 2023. [cited 2023 Sep 19]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Hispidulin

[130] Cui, B., Lee, Y.H., Chai, H., et al., 1999. Cytotoxic sesquiterpenoids from Ratibida columnifera. Journal of Natural Products. 62(11), 1545-1550. DOI: https://doi.org/10.1021/np990260y

[131] Flamini, G., Antognoli, E., Morelli, I., 2001. Two flavonoids and other compounds from the aerial parts of Centaurea bracteata from Italy. Phytochemistry. 57(4), 559-564. DOI: https://doi.org/10.1016/s0031-9422(01)00066-8

[132] Fullas, F., Hussain, R.A., Chai, H.B., et al., 1994. Cytotoxic constituents of Baccharis gaudichaudiana. Journal of Natural Products. 57(6), 801-807. DOI: https://doi.org/10.1021/np50108a017

[133] Kavvadias, D., Monschein, V., Sand, P., et al., 2003. Constituents of sage (Salvia officinalis) with in vitro affinity to human brain benzodiazepine receptor. Planta Medica. 69(2), 113-117. DOI: https://doi.org/10.1055/s-2003-37712

[134] Chao, S.W., Su, M.Y., Chiou, L.C., et al., 2015. Total synthesis of hispidulin and the structural basis for its inhibition of proto-oncogene kinase Pim-1. Journal of Natural Products. 78(8), 1969-1976. DOI: https://doi.org/10.1021/acs.jnatprod.5b00324

[135] Liu, K., Zhao, F., Yan, J., et al., 2020. Hispidulin: A promising flavonoid with diverse anti-cancer properties. Life Sciences. 259, 118395. DOI: https://doi.org/10.1016/j.lfs.2020.118395

[136] Chaudhry, G.E., Zeenia, Sharifi-Rad, J., Calina, D., 2023. Hispidulin: A promising anticancer agent and mechanistic breakthrough for targeted cancer therapy. Naunyn-Schmiedeberg’s Archives of Pharmacology. DOI: https://doi.org/10.1007/s00210-023-02645-9

[137] Lv, L., Zhang, W., Li, T., et al., 2020. Hispidulin exhibits potent anticancer activity in vitro and in vivo through activating ER stress in non‑small‑cell lung cancer cells. Oncology Reports. 43(6), 1995-2003. DOI: https://doi.org/10.3892/or.2020.7568

[138] Yadav, A.K., Thakur, J., Prakash, O.M., et al., 2013. Screening of flavonoids for antitubercular activity and their structure—activity relationships. Medicinal Chemistry Research. 22, 2706-2716. DOI: https://doi.org/10.1007/s00044-012-0268-7

[139] Atif, M., Ali, I., Hussain, A., et al., 2015. Pharmacological assessment of hispidulin—a natural bioactive flavone. Acta Poloniae Pharmaceutica. 72(5), 829-842.

[140] Zhai, K., Mazurakova, A., Koklesova, L., et al., 2021. Flavonoids synergistically enhance the anti-glioblastoma effects of chemotherapeutic drugs. Biomolecules. 11(12), 1841. DOI: https://doi.org/10.3390/biom11121841

[141] Tuli, H.S., Tuorkey, M.J., Thakral, F., et al., 2019. Molecular mechanisms of action of genistein in cancer: Recent advances. Frontiers in Pharmacology. 10, 1336. DOI: https://doi.org/10.3389/fphar.2019.01336

[142] Goh, Y.X., Jalil, J., Lam, K.W., et al., 2022. Genistein: A review on its anti-inflammatory properties. Frontiers in Pharmacology. 13, 820969. DOI: https://doi.org/10.3389/fphar.2022.820969

[143] PubChem Compound Summary for CID 5280961, Genistein [Internet]. National Center for Biotechnology Information; 2023. [cited 2023 Sep 19]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Genistein

[144] Sharifi-Rad, J., Quispe, C., Imran, M., et al., 2021. Genistein: An integrative overview of its mode of action, pharmacological properties, and health benefits. Oxidative Medicine and Cellular Longevity. 3268136. DOI: https://doi.org/10.1155/2021/3268136

[145] Peterson, G., Barnes, S., 1996. Genistein inhibits both estrogen and growth factor-stimulated proliferation of human breast cancer cells. Cell Growth and Differentiation-Publication American Association for Cancer Research. 7(10), 1345-1352.

[146] Matsukawa, Y., Marui, N., Sakai, T., et al., 1993. Genistein arrests cell cycle progression at G2-M. Cancer Research. 53(6), 1328-1331.

[147] Farina, H.G., Pomies, M., Alonso, D.F., et al., 2006. Antitumor and antiangiogenic activity of soy isoflavone genistein in mouse models of melanoma and breast cancer. Oncology Reports. 16(4), 885-891. DOI: https://doi.org/10.3892/or.16.4.885

[148] Sarkar, F.H., Adsule, S., Padhye, S., et al., 2006. The role of genistein and synthetic derivatives of isoflavone in cancer prevention and therapy. Mini Reviews in Medicinal Chemistry. 6(4), 401-407. DOI: https://doi.org/10.2174/138955706776361439

[149] Huang, W., Wan, C., Luo, Q., et al., 2014. Genistein-inhibited cancer stem cell-like properties and reduced chemoresistance of gastric cancer. International Journal of Molecular Sciences. 15(3), 3432-3443. DOI: https://doi.org/10.3390/ijms15033432

[150] Bloedon, L.T., Jeffcoat, A.R., Lopaczynski, W., et al., 2002. Safety and pharmacokinetics of purified soy isoflavones: Single-dose administration to postmenopausal women. The American Journal of Clinical Nutrition. 76(5), 1126-1137. DOI: https://doi.org/10.1093/ajcn/76.5.1126

[151] Huang, Z.R., Hung, C.F., Lin, Y.K., et al., 2008. In vitro and in vivo evaluation of topical delivery and potential dermal use of soy isoflavones genistein and daidzein. International Journal of Pharmaceutics. 364(1), 36-44. DOI: https://doi.org/10.1016/j.ijpharm.2008.08.002

[152] Bocheńska, K., Moskot, M., Smolińska-Fijołek, E., et al., 2021. Impact of isoflavone genistein on psoriasis in in vivo and in vitro investigations. Scientific Reports. 11(1), 18297. DOI: https://doi.org/10.1038/s41598-021-97793-4

[153] Serebrenik, A.A., Verduyn, C.W., Kaytor, M.D., 2023. Safety, pharmacokinetics, and biomarkers of an amorphous solid dispersion of genistein, a radioprotectant, in healthy volunteers. Clinical Pharmacology in Drug Development. 12(2), 190-201. DOI: https://doi.org/10.1002/cpdd.1188

[154] Cooper-Driver, G.A., 2001. Contributions of Jeffrey Harborne and co-workers to the study of anthocyanins. Phytochemistry. 56(3), 229-236. DOI: https://doi.org/10.1016/s0031-9422(00)00455-6

[155] Sarma, A.D., Sreelakshmi, Y., Sharma, R., 1997. Antioxidant ability of anthocyanins against ascorbic acid oxidation. Phytochemistry. 45(4), 671-674. DOI: https://doi.org/10.1016/S0031-9422(97)00057-5

[156] Lin, B.W., Gong, C.C., Song, H.F., et al., 2017. Effects of anthocyanins on the prevention and treatment of cancer. British Journal of Pharmacology. 174(11), 1226-1243. DOI: https://doi.org/10.1111/bph.13627

[157] PubChem Compound Summary for CID 101115386 [Internet]. National Center for Biotechnology Information; 2023. [cited 2023 Sep 19]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/101115386

[158] Panchal, S.K., John, O.D., Mathai, M.L., et al., 2022. Anthocyanins in chronic diseases: The power of purple. Nutrients. 14(10), 2161. DOI: https://doi.org/10.3390/nu14102161

[159] Burton-Freeman, B., Brzeziński, M., Park, E., et al., 2019. A selective role of dietary anthocyanins and flavan-3-ols in reducing the risk of type 2 diabetes mellitus: A review of recent evidence. Nutrients. 11(4), 841. DOI: https://doi.org/10.3390/nu11040841

[160] Grosso, G., 2018. Effects of polyphenol-rich foods on human health. Nutrients. 10(8), 1089. DOI: https://doi.org/10.3390/nu10081089

[161] Ho, M.L., Chen, P.N., Chu, S.C., et al., 2010. Peonidin 3-glucoside inhibits lung cancer metastasis by downregulation of proteinases activities and MAPK pathway. Nutrition and Cancer. 62(4), 505-516. DOI: https://doi.org/10.1080/01635580903441261

[162] Afaq, F., Malik, A., Syed, D., et al., 2005. Pomegranate fruit extract modulates UV‐B-mediated phosphorylation of mitogen‐activated protein kinases and activation of nuclear factor kappa B in normal human epidermal keratinocytes. Photochemistry and Photobiology. 81(1), 38-45. DOI: https://doi.org/10.1562/2004-08-06-RA-264

[163] Shin, D.Y., Lee, W.S., Lu, J.N., et al., 2009. Induction of apoptosis in human colon cancer HCT-116 cells by anthocyanins through suppression of Akt and activation of p38-MAPK. International Journal of Oncology. 35(6), 1499-1504. DOI: https://doi.org/10.3892/ijo_00000469

[164] Giampieri, F., Cianciosi, D., Alvarez-Suarez, J.M., et al., 2023. Anthocyanins: What do we know until now?. Journal of Berry Research. 1-6. DOI: https://doi.org/10.3233/JBR-220087

[165] Benot-Dominguez, R., Cimini, A., Barone, D., et al., 2022. The emerging role of cyclin-dependent kinase inhibitors in treating diet-induced obesity: New opportunities for breast and ovarian cancers?. Cancers. 14(11), 2709. DOI: https://doi.org/10.3390/cancers14112709

[166] Ashwin, P.P., Sutar, N.G., Vishnu, A.S., et al., 2023. Anticancer activity of anthocyanins: A comprehensive review. Journal of Survey in Fisheries Sciences. 10(1S), 5993-6007.

[167] Forester, S.C., Waterhouse, A.L., 2010. Gut metabolites of anthocyanins, gallic acid, 3-O-methylgallic acid, and 2, 4, 6-trihydroxybenzaldehyde, inhibit cell proliferation of Caco-2 cells. Journal of Agricultural and Food Chemistry. 58(9), 5320-5327. DOI: https://doi.org/10.1021/jf9040172

[168] Sehitoglu, M.H., Farooqi, A.A., Qureshi, M.Z., et al., 2014. Anthocyanins: Targeting of signaling networks in cancer cells. Asian Pacific Journal of Cancer Prevention. 15(5), 2379-2381. DOI: https://doi.org/10.7314/apjcp.2014.15.5.2379

[169] Malik, M., Zhao, C., Schoene, N., et al., 2003. Anthocyanin-rich extract from aronia meloncarpa E. Induces a cell cycle block in colon cancer but not normal colonic cells. Nutrition & Cancer. 46(2), 186-196. DOI: https://doi.org/10.1207/S15327914NC4602_12

[170] Wang, L.S., Stoner, G.D., 2008. Anthocyanins and their role in cancer prevention. Cancer Letters. 269(2), 281-290. DOI: https://doi.org/10.1016/j.canlet.2008.05.020

[171] Reddivari, L., Vanamala, J., Chintharlapalli, S., et al., 2007. Anthocyanin fraction from potato extracts is cytotoxic to prostate cancer cells through activation of caspase-dependent and caspase-independent pathways. Carcinogenesis. 28(10), 2227-2235. DOI: https://doi.org/10.1093/carcin/bgm117

[172] Chang, Y.C., Huang, H.P., Hsu, J.D., et al., 2005. Hibiscus anthocyanins rich extract-induced apoptotic cell death in human promyelocytic leukemia cells. Toxicology and Applied Pharmacology. 205(3), 201-212. DOI: https://doi.org/10.1016/j.taap.2004.10.014

[173] Hientz, K., Mohr, A., Bhakta-Guha, D., et al., 2017. The role of p53 in cancer drug resistance and targeted chemotherapy. Oncotarget. 8(5), 8921. DOI: https://doi.org/10.18632/oncotarget.13475

[174] Diaconeasa, Z.M., Frond, A.D., Ştirbu, I., et al., 2018. Anthocyanins—smart molecules for cancer prevention. Phytochemicals—Source of Antioxidants and Role in Disease Prevention. IntechOpen: London. DOI: https://doi.org/10.5772/intechopen.79613

[175] Gull, A., Sheikh, M.A., Kour, J., et al., 2022. Anthocyanins. Nutraceuticals and health care. Academic Press: Cambridge. pp. 317-329. DOI: https://doi.org/10.1016/B978-0-323-89779-2.00018-1

[176] Wallace, T.C., Giusti, M.M., 2015. Anthocyanins. Advances in Nutrition. 6(5), 620-622. DOI: https://doi.org/10.3945/an.115.009233

[177] Morazzoni, P., Bombardelli, E., 1996. Vaccinium myrtillus L. Fitoterapia. 67, 3-29.

[178] He, J., Giusti, M.M., 2010. Anthocyanins: Natural colorants with health-promoting properties. Annual Review of Food Science and Technology. 1, 163-187. DOI: https://doi.org/10.1146/annurev.food.080708.100754

[179] Gonçalves, A.C., Nunes, A.R., Falcão, A., et al., 2021. Dietary effects of anthocyanins in human health: A comprehensive review. Pharmaceuticals. 14(7), 690. DOI: https://doi.org/10.3390/ph14070690

Downloads

Published

2024-08-09

Issue

Section

Articles