Phenolic Compounds for Drug Discovery: Potent Candidates for Anti-cancer, Anti-diabetes, Anti-inflammatory and Anti-microbial.

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Authors

  • Elisha Apatewen Akanbong Kirikkale University
  • Ali Senol
  • Alparslan Kadir Devrim

Keywords:

Anti-cancer, Anti-diabetes, Anti-inflammatory, Anti-microbial and Phenolic compounds

Abstract

Due to the ubiquitous nature of phenolics and their well-documented health benefits, they have great potentials for drug development. Thus, this review sought to add to existing literature regarding the anti-cancer, anti-diabetic, anti-inflammatory and anti-microbial potentials of phenolic compounds mainly, phenolic acids and flavonoids. Hence, ensuring a good balance between reactive species; reactive oxygen species and reactive nitrogen species (ROS and RNS respectively) and anti-oxidants via the consumption of diets rich in phenolic compounds is crucial for the prevention of oxidative stress-related diseases. Aside from that, consuming phenolics reduces one’s risk of contracting microbial-borne diseases as they possess an anti-microbial potential. Consequently, phenolic compounds are potent candidates for drug development. However, further studies should be conducted to elucidate their anti-cancer, anti-diabetic, anti-inflammatory and anti-microbial mechanisms. Also, studies should be carried to ascertain the efficacies of phenolic compounds-metal complexes in anti-cancer, anti-diabetic, anti-inflammatory and anti-microbial.

References

Abdel Rahman GAN, El-Azab SM, El Bolok AH, El- Gayar SF, Mohamed AF. 2020. Antioxidant and Apoptotic Activity of Free and NanoSinapic Acid on HEp-2 Cell Line. Indian Journal of Public Health Research and Development, 11(4): 953-958.

Abotaleb M, Liskova A, Kubatka P, Büsselberg D. 2020. Therapeutic Potential of Plant Phenolic Acids in the Treatment of Cancer. Biomolecules, 10(2): 221.

Afonso AF, Pereira OR, Cardoso SM. 2020. Health- Promoting Effects of Thymus PhenolicRich Extracts: Antioxidant, Anti-inflammatory and Antitumoral Properties. Antioxidants, 9(9): 814.

Aguirre MO, López LT, Pottosin I, Dobrovinskaya

O. 2021. Phenolic Compounds Cannabidiol, Curcumin and Quercetin Cause Mitochondrial Dysfunction and Suppress Acute Lymphoblastic Leukemia Cells. Int. J. Mol. Sci., 22(1): 204.

Akanbong EA, Senol A, Sudağıdan M, Devrim AK. 2021. Unraveling Microbiome: The Role of Microbiota in Patients’ Response to Oncological Treatment and Its Influence on Hostbiochemistry. IJVAR, 4(2): 69-77.

Akgul H, Aslan A, Akata I, Gunal S, Bal C, Baba H.

Phenolic Content and Biological Activities of Trametes Hirsuta. Fresenıus Env. Bulletin, 30: 4130-4135.

Almeida IV, Cavalcante FML, Vicentini VEP. 2016.

Different responses of vanillic acid, a phenolic compound, in HTC cells: cytotoxicity, antiproliferative activity, and protection from DNA induced damage.

Genet. Mol. Res., 15(4), PMID: 28002613.

Amin AR, Kucuk O, Khuri FR, Shin DM. 2009. Perspectives for cancer prevention with natural compounds. J. Clin. Oncol., 27(16): 2712-25.

Anantharaju PG, Gowda PC, Vimalambike MG, Madhunapantula SV. 2016. An overview on the role of dietary phenolics for the treatment of cancers. Nutrition journal, 15(1): 1-16.

Anbalagan V, Raju K, Shanmugam M. 2017. Assessment of Lipid Peroxidation and Antioxidant Status in Vanillic Acid Treated 7,12-Dimethylbenz[a]anthracene Induced Hamster Buccal Pouch Carcinogenesis. J. Clin.

Diagn. Res. 11(3): BF01-BF04.

Azab A, Nassar A, Azab AN. 2016. Antiinflammatory activity of natural products. Molecules, 21(10): 1321.

Azeem AA, Mounir AM, El-Shahat AN. 2021.

Studying the Anti-Diabetic Effect of GammaIrradiated Pumpkin Seeds. Pakıstan J. Zool, 1-7.

Badr DA, Amer ME, Abd-Elhay WM, Nasr MS, Abuamara TM, Ali H, Fazary AE. 2019. Histopathological and genetic changes proved the anticancer potential of free and nano-capsulated sinapic acid. Applied Biological Chemistry, 62(1): 1-10.

Bhavani P, Subramania P, Kanimozhi S. 2017. Preventive Efficacy of Vanillic Acid on Regulation of Redox Homeostasis, Matrix Metalloproteinases and Cyclin D1 in Rats Bearing Endometrial Carcinoma. Ind J Clin Biochem, 32(4): 429-436.

Borquaye LS, Saah SA, Adu-Poku D, AduGyamfi L, Bitian K, Bambil W. 2020. Antiinflammatory, antioxidant and total phenolic content of the ethanolic extracts of Celtis africana Burm. f. Current Science, 6(3): 43-49.

Bors W, Heller W, Michel C, Saran M. 1990. [36] Flavonoids as antioxidants: determination of radical- scavenging efficiencies. Methods in enzymology, 186: 343-355.

Bouzaiene NN, Jaziri SK, Kovacic H, ChekirGhedira

L. 2015. The effects of caffeic, coumaric and ferulic acids on proliferation, superoxide production, adhesion and migration of human tumor cells in vitro, European Journal of Pharmacology, 766: 99-105.

Catarino MD, Talhi O, Rabahi A, Silva AMS, Cardoso SM. 2016. The anti-inflammatory potential of flavonoids: Mechanistic aspects. In Studies in Natural Products Chemistry, 48: 65-99.

Chen Y, Xu J, Yu H, Qing C. 2008. Cytotoxic phenolics from Bulbophyllum odoratissimum. Food Chem. 107: 169-173.

Cheng S, Gao N, Zhang Z, Chen G. (2010). Quercetin Induces Tumor-Selective Apoptosis through Downregulation of Mcl-1 and Activation of Bax. Clinical Cancer Research, 16(23): 5679-5691.

Chou TH, Ding HY, Hung WJ, Liang CH. 2010. Antioxidative characteristics and inhibition of α- melanocyte stimulating hormone-stimulated melanogenesis of vanillin and vanillic acid from Origanum vulgare. Exp. Dermatol. 19(8): 742-750.

Chiang EPI, Tsai SY, Kuo YH, Pai MH, Chiu HL, Rodriguez RL. 2014. Caffeic Acid Derivatives Inhibit the Growth of Colon Cancer: Involvement of the PI3-K/Akt and AMPK Signaling Pathways. PLoS ONE 9(6): e99631.

Clifford MN. 1999. Chlorogenic acids and other cinnamates - nature, occurrence, and dietary burden, J. Sci. Food Agric. 79(3): 362–372.

Craig WJ. 1999. Health-promoting properties of common herbs. The American Journal of Clinical Nutrition, 70(3): 491s-499s.

Debnath T, Kim DH, Lim BO. 2013. Natural products as a source of anti-inflammatory agents associated with inflammatory bowel disease. Molecules, 18(6): 7253-7270.

Demiroglu-Zergeroglu A, Basara-Cigerim B, Kilic ESER, Yanikkaya-Demirel G. 2010. The investigation of effects of quercetin and its combination with cisplatin on malignant mesothelioma cells in vitro. Journal of biomedicine and biotechnology, 2010: 851589.

Dewick PM. 2001. Front Matter and Index. Medicinal Natural Products: A Biosynthetic Approach, Second Edition, John Wiley & Sons, Ltd, Chichester, UK. DOI: 10.1002/9780470742761.

Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, Shimomura I. 2017. Increased oxidative stress in obesity and its impact on metabolic syndrome. The Journal of clinical investigation, 114(12): 1752-1761.

Ganugapati J, Mukkavalli S, Sahithi A. 2011. Docking studies of green tea flavonoids as insulin mimetics. Int J Comput Appl, 30(4): 48-52.

Gong J, Zhou S, Yang S. 2019. Vanillic Acid Suppresses HIF-1α Expression via Inhibition of mTOR/p70S6K/4E-BP1 and Raf/MEK/ERK Pathways in Human Colon Cancer HCT116 Cells. Int. J. Mol. Sci. 20(3):465.

Griesbach RJ. 2005. Biochemistry and genetics of flower color. Plant Breed Rev, 25: 89-114. DOI:10.1002/9780470650301

Haghiac M, Walle T. 2009. Quercetin Induces Necrosis and Apoptosis in SCC-9 Oral Cancer Cells. Nutrition and Cancer, 53(2): 220-231.

Hanhineva K, Törrönen R, Bondia-Pons I, Pekkinen J, Kolehmainen M, Mykkänen H, Poutanen K. 2010. Impact of dietary polyphenols on carbohydrate metabolism. International journal of molecular sciences, 11(4): 1365-1402.

Hatamie S, Nouri M, Karandikar SK, Kulkarni A, Dhole SD, Phase DM, Kale SN. 2012. Complexes of cobalt nanoparticles and polyfunctional curcumin as antimicrobial agents. Materials Science and Engineering: C, 32(2): 92-97.

Havsteen BH. 2002. The biochemistry and medical significance of the flavonoids. Pharmacology & therapeutics, 96(2-3): 67-202.

Hayashi T, Sawa K, Kawasaki M, Arisawa M, Shimizu M, Morita N. 1988. Inhibition of cow's milk xanthine oxidase by flavonoids. Journal of natural products, 51(2): 345-348.

Heleno SA, Martins A, Queiroz MJR, Ferreira IC. 2015. Bioactivity of phenolic acids: Metabolites versus parent compounds: A review. Food chemistry, 173: 501- 513.

Hernández A, Ruiz-Moyano S, Galván AI, Merchán AV, Nevado FP, Aranda E, Martín A. 2021. Anti-fungal activity of phenolic sweet orange peel extract for controlling fungi responsible for post-harvest fruit decay. Fungal Biology, 125(2): 143-152.

Ho HH, Chang CS, Ho WC, Liao SY, Wu CH, Wang CJ. 2010. Anti-metastasis effects of gallic acid on gastric cancer cells involves inhibition of NF-κB activity and downregulation of PI3K/AKT/small GTPase signals.

Food and Chemical Toxicology, 48(8-9): 2508-2516.

Hong S, Pangloli P, Perumal R, Cox S, Noronha LE, Dia VP, Smolensky D. 2020. A Comparative Study on Phenolic Content, Antioxidant Activity and Anti- Inflammatory Capacity of Aqueous and Ethanolic Extracts of Sorghum in LipopolysaccharideInduced RAW 264.7 Macrophages. Antioxidants, 9(12): 1297.

Janakiraman K, Kathiresan S, Mariadoss AV. 2014. Influence of sinapic acid on induction of apoptosis in human laryngeal carcinoma cell line. Int J Modern Res Rev, 2(5): 165-170.

Jiang S, Zhao X, Li u C, Dong Q, Mei L, Chen C, Yue H. 2021. Identification of phenolic compounds in fruits of Ribes stenocarpum Maxim. By UHPLC-QTOF/MS and their hypoglycemic effects in vitro and in vivo. Food Chemistry, 344: 128568.

Jorgensen RA. 1995. Cosuppression, flower color patterns, and metastable gene expression states. Science, 268(5211): 686-691. DOI: 10.1126/science.268.5211.686

Jung EH, Ran-Kim S, Hwang IK, Youl Ha T. 2007. Hypoglycemic effects of a phenolic acid fraction of rice bran and ferulic acid in C57BL/KsJ-db/db mice. Journal of Agricultural and Food Chemistry, 55(24): 9800-9804.

Kampa M, Alexaki VI, Notas G. 2004. Antiproliferative and apoptotic effects of selective phenolic acids on T47D human breast cancer cells: potential mechanisms of action. Breast Cancer Res 6(2): R63-R74.

Kanski J, Aksenova M, Stoyanova A, Butterfield DA. 2002. Ferulic acid antioxidant protection against hydroxyl and peroxyl radical oxidation in synaptosomal and neuronal cell culture systems in vitro: structure-activity studies. J. Nutr. Biochem., 13: 273- 281.

Kim JK, Diel JA. 2009. Nuclear cyclin D1: an oncogenic driver in human cancer. J Cell Physiol., 220(2): 292–296.

Kumar N, Gupta S, Yadav TC, Pruthi V. 2019. Extrapolation of phenolic compounds as multitarget agents against cancer and inflammation, J. Biomol. Struct. Dyn., 37(9): 2355–2369.

Kumar N, Goelb N. 2019. Phenolic acids: Natural versatile molecules with promising therapeutic applications. Biotech.Reports, 24: e00370.

Kumar S, Pandey AK. 2013. Chemistry and biological activities of flavonoids: an overview. The scientific world journal, 2013: 162750.

Lee CS, Baek J, Han SY. 2017. The role of kinase modulators in cellular senescence for use in cancer treatment. Molecules, 22(9):1411.

Leyva-López N, Gutierrez-Grijalva EP, AmbrizPerez DL, Heredia JB. 2016. Flavonoids as cytokine modulators: a possible therapy for inflammationrelated diseases. International journal of molecular sciences, 17(6): 921.

Liu Z, Li D, Yu L, Niu F. 2012. Gallic Acid as a Cancer-Selective Agent Induces Apoptosis in Pancreatic Cancer Cells. Chemotherapy, 58:185194.

López-Lázaro M. 2009. Distribution and biological activities of the flavonoid luteolin. Mini reviews in medicinal chemistry, 9(1): 31-59.

Lu SJ, Chong FC. 2012. Combining molecular docking and molecular dynamics to predict the binding modes of flavonoid derivatives with the neuraminidase of the 2009 H1N1 influenza A virus. International journal of molecular sciences, 13(4): 44964507.

Mihanfar A, Darband SG, Sadighparvar S, Kaviani M, Mirza-Aghazadeh-Attari M, Yousefi B, Majidinia M. 2021. In vitro and in vivo anticancer effects of syringic acid on colorectal cancer: Possible mechanistic view.

Chemico-Biological Interactions, 337: 109337.

Mouria M, Gukovskaya AS, Jung Y, Buechler P. 2002. Food-Derived Polyphenols Inhibit Pancreatic Cancer Growth Through Mitochondrial Cytochrome C Release And Apoptosis. Int. J. Cancer, 98(5): 761-769.

Nwosu F, Morris J, Lund VA, Stewart D, Ross HA, McDougall GJ. 2011. Anti-proliferative and potential anti-diabetic effects of phenolic-rich extracts from edible marine algae. Food chemistry, 126(3): 10061012.

Oubihi A, Hosni H, Nounah I, Ettouil A, Harhar H, Alaoui K, Guessous Z. 2020. Phenolic Content, Antioxidant Activity, Anti-Inflammatory Potential, and Acute Toxicity Study of Thymus leptobotrys Murb. Extracts. Biochemistry Research International, 2020: Article ID: 8823209.

Oyeyinka SA, Abdulsalam AO, El-Imam AMA, Oyeyinka AT, Olagunju OF, Kolawole FL, Njobeh PB. 2021. Total phenolic content, antioxidant, anti- inflammatory and anti-microbial potentials of Bambara groundnut (Vigna subterranea L.) seed extract. British Food Journal, 123(11): 3421-25.

Panche AN, Diwan AD, Chandra SR. 2016. Flavonoids: an overview. Journal of nutritional science, 5: e47.

Pereira DM, Valentão P, Pereira JA, Andrade PB. 2009. Phenolics: from chemistry to biology. Molecules, 14(6):2202-2211.

Prasad CV, Anjana T, Banerji A, Gopalakrishnapillai

A. 2010. Gallic acid induces GLUT4 translocation and glucose uptake activity in 3T3L1 cells. FEBS letters, 584(3): 531-536.

Pudziuvelyte L, Liaudanskas M, Jekabsone A, Sadauskiene I, Bernatoniene J. 2020. Elsholtzia ciliata (Thunb.) Hyl. Extracts from Different Plant Parts: Phenolic Composition, Antioxidant, and Anti-Inflammatory Activities. Molecules, 25(5): 1153.

Rahman GANA, El-Azab SM, El Bolok AH, El- Gayar SF, Mohamed AF. 2019. Chemopreventive Effect of Sinapic Acid on Head and Neck Squamous Cell Carcinoma, 1(1): 12-15.

Rosa LDS, Silva NJA, Soares NCP, Monteiro MC, Teodoro AJ. 2016. Anticancer properties of phenolic acids in colon cancer–a review. J Nutr Food Sci, 6(2): 1-7.

Sakurai H, Yoshikawa Y, Yasui H. 2008. Current state for the development of metallopharmaceutics and anti-diabetic metal complexes. Chemical Society Reviews, 37(11): 2383-2392.

Samanta A, Das G, Das SK. 2011. Roles of flavonoids in plants. Carbon, 100(6): 12-35.

Senthilkumar K, Elumalai P, Arunkumar R, Banudevi S. 2010. Quercetin regulates insulin like growth factor signaling and induces intrinsic and extrinsic pathway mediated apoptosis in androgen independent prostate cancer cells (PC-3). Mol Cell Biochem., 344: 173-184.

Shakeri A, Panahi Y, Johnston T.P, Sahebkar A. 2019. Biological properties of metal complexes of curcumin. BioFactors, 45(3): 304-317.

Subhan MA, Alam K, Rahaman MS, Rahman MA, and Awal R. 2014. Synthesis and characterization of metal complexes containing curcumin (C 21 H 20 O 6) and study of their anti-microbial activities and DNAbinding properties. Journal of Scientific research, 6(1): 97109.

Takahashi A, Ohnishi T. 2004. The significance of the study about the biological effects of solar ultraviolet radiation using the exposed facility on the international space station. Biol Sci Space, 18: 255–260.

Taner G, Vardar DÖ, Aydin S, Aytaç Z. 2016. Use of in vitro assays to assess the potential cytotoxic, genotoxic and antigenotoxic effects of vanillic and cinnamic acid. Drug Chem. Toxicol. 16: 1-8.

Tkacz K, Wojdyło A, Turkiewicz IP, Nowicka P. 2021. Anti-diabetic, anti-cholinesterase, and antioxidant potential, chemical composition and sensory evaluation of novel sea buckthorn-based smoothies. Food Chemistry, 338: 128105.

Tsao R, Deng Z. 2004. Separation procedures for naturally occurring antioxidant hytochemicals, J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 812(1-2): 85–99.

Van Erk MJ, Roepman P, Van der Lende TR, Stierum RH. 2005. Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr, 44(3): 143-156. DOI 10.1007/s00394-004-0503-1

Velli SK, Sundaram J, Murugan M, Balaraman G. 2019. Protective effect of vanillic acid against benzo(a)pyrene induced lung cancer in Swiss albino mice. J. Biochem. Mol. Toxicol, 33(10): e22382.

Wahle KWJ, Brown I, Rotondo D, Heys SD. 2010.

Plant Phenolics in the Prevention and Treatment of Cancer. In: Giardi MT, Rea G, Berra B. (eds) Bio-Farms for Nutraceuticals. Advances in Experimental Medicine and Biology, vol 698. Springer, Boston, MA.

Walker EH, Pacold ME, Perisic O, Stephens L, Hawkins PT, Wymann MP, Williams RL. 2000. Structural determinants of phosphoinositide 3kinase inhibition by wortmannin, LY294002, quercetin, myricetin, and staurosporine. Molecular cell, 6(4): 909919.

Wang P, Zhang K, Zhang Q, Mei J. 2012. Effects of quercetin on the apoptosis of the human gastric carcinoma cells. Toxicology in Vitro, 26(2):221-228.

Wang H, Cao G, Prior RL. 1996. Total antioxidant capacity of fruits. Journal of agricultural and food chemistry, 44(3): 701-705.

Wang T, Gong X, Jiang R, Li H, Du W, Kuang G. 2016. Ferulic acid inhibits proliferation and promotes apoptosis via blockage of PI3K/Akt pathway in osteosarcoma cell. American journal of translational research, 8(2): 968.

Wu Y, Ding Y, Tanaka Y, Zhang W. 2014. Risk factors contributing to type 2 diabetes and recent advances in the treatment and prevention. International journal of medical sciences, 11(11): 1185.

Vaquero MJR, Alberto MR, de Nadra MCM. 2007. Influence of phenolic compounds from wines on the growth of Listeria monocytogenes. Food Control, 18(5): 587-593.

Wang H, Cao G, Prior RL. 1996. Total Antioxidant Capacity of Fruits. J. Agric. Food Chem., 44(3): 701.

Zhang X, Wu Q, Yang S. 2017. Ferulic acid promoting apoptosis in human osteosarcoma cell lines. Pak J Med Sci., 33(1): 127-131.

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Published

2021-12-14

How to Cite

Akanbong, E. A., Senol, A., & Devrim, A. K. (2021). Phenolic Compounds for Drug Discovery: Potent Candidates for Anti-cancer, Anti-diabetes, Anti-inflammatory and Anti-microbial. International Journal of Veterinary and Animal Research (IJVAR), 4(3), 115–121. Retrieved from https://ijvar.org/index.php/ijvar/article/view/497

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Review Article