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International Journal of Food Properties Volume 26, 2023 - Issue 1
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Review

Polymethoxyflavones: an updated review on pharmacological properties and underlying molecular mechanisms

Zarina Mushtaqa Department of Food Sciences, Government College University Faisalabad, Faisalabad, Pakistan
,
Mahwish Aslamb Faculty of Allied Health Sciences, University Institute of Diet and Nutritional Sciences, Lahore, Pakistan
,
Muhammad Imranc Department of Food Science and Technology, University of Narowal-Pakistan, Narowal, Pakistan
,
Mohamed A. Abdelgawadd Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka, Saudi Arabia
,
Farhan Saeeda Department of Food Sciences, Government College University Faisalabad, Faisalabad, PakistanORCID Iconhttps://orcid.org/0000-0001-5340-4015
ORCID Icon,
Tara Khursheede Department of Nutrition and Dietetics, National University of Medical Sciences (NUMS), Rawalpindi, Pakistan
,
Maryam Umara Department of Food Sciences, Government College University Faisalabad, Faisalabad, Pakistan
,
Waleed Al Abdulmonemf Department of Pathology, College of Medicine, Qassim University, Buraidah, Saudi Arabia
,
Ahmed H. Al Ghorabg Department of Chemistry, College of Science, Jouf University, Sakaka, Saudi Arabia
,
Suliman A. Alsagabyh Department of Medical Laboratory sciences, College of Applied Medical Sciences, Majmaah University, AI Majmaah, Saudi Arabia
,
Tabussam Tufaili University Institute of Diet & Nutritional Sciences, the University of Lahore, Lahore, PakistanCorrespondence[email protected]
ORCID Iconhttps://orcid.org/0000-0002-7632-5261
ORCID Icon,
Muhammad Ahtisham Razaa Department of Food Sciences, Government College University Faisalabad, Faisalabad, PakistanORCID Iconhttps://orcid.org/0000-0002-5648-2825
ORCID Icon,
Muzzamal Hussaina Department of Food Sciences, Government College University Faisalabad, Faisalabad, PakistanCorrespondence[email protected]
ORCID Iconhttps://orcid.org/0000-0001-6508-1962
ORCID Icon &
Entessar Al JBawij Agricultural Extension Directorate, MAAR, Damascus, SyriaCorrespondence[email protected]
ORCID Iconhttps://orcid.org/0000-0002-1804-1770
ORCID Icon show all
Pages 866-893 | Received 17 Oct 2022, Accepted 05 Feb 2023, Published online: 19 Mar 2023

References

  • Sharifi-Rad, J.; Cristina Cirone Silva, N.; Jantwal, A.; Bhatt, D.; Sharopov, I.; Cho, F. ;. C.; Martins, W. N. Therapeutic Potential of Allicin-Rich Garlic Preparations: Emphasis on Clinical Evidence Toward Upcoming Drugs Formulation. Appl. Sci. 2019, 9(24), 5555. DOI: 10.3390/app9245555.
  • Gao, Z.; Gao, W.; Zeng, S. L.; Li, P.; Liu, E. H. Chemical Structures, Bioactivities and Molecular Mechanisms of Citrus Polymethoxyflavones. J. Funct. Foods. 2018, 40, 498–509. DOI: 10.1016/j.jff.2017.11.036.
  • Md Idris, M. H.; Mohd Amin, S. N.; Mohd Amin, S. N.; Wibowo, A.; Zakaria, Z. A.; Shaameri, Z.; Hamzah, A. S.; Selvaraj, M.; Teh, L. K.; Salleh, M. Z. Discovery of Polymethoxyflavones as Potential Cyclooxygenase-2 (COX-2), 5-Lipoxygenase (5-LOX) and Phosphodiesterase 4B (PDE4B) Inhibitors. J. Recept. Signal Transduction. 2022, 42(4), 325–337. DOI: 10.1080/10799893.2021.1951756.
  • Gao, Z.; Wang, Z. Y.; Guo, Y.; Chu, C.; Zheng, G. D.; Liu, E. H.; Li, F. Enrichment of Polymethoxyflavones from Citrus Reticulata ‘Chachi’peels and Their Hypolipidemic Effect. J. Chromatogr. B. 2019, 1124, 226–232. DOI: 10.1016/j.jchromb.2019.06.010.
  • Wang, R. L.; Li, S.; Ho, C. T. Absorption of Polymethoxyflavones and Their Derivatives. J. Food Bioactives. 2018, 2, 82–90. DOI: 10.31665/JFB.2018.2142.
  • Shajib, M. S.; Rashid, R. B.; Ming, L. C.; Islam, S.; Sarker, M. M. R.; Nahar, L.; Rashid, M. A.; Datta, B. K.; Rashid, M. A. Polymethoxyflavones from Nicotiana Plumbaginifolia (Solanaceae) Exert Antinociceptive and Neuropharmacological Effects in Mice. Front. Pharmacol. 2018, 9, 85. DOI: 10.3389/fphar.2018.00085.
  • Faqueti, L. G.; Brieudes, V.; Halabalaki, M.; Skaltsounis, A. L.; Nascimento, L. F.; Barros, W. M.; Santos, A. R. S.; Biavatti, M. W. Antinociceptive and Anti-Inflammatory Activities of Standardized Extract of Polymethoxyflavones from Ageratum Conyzoides. J. Ethnopharmacol. 2016, 194, 369–377. DOI: 10.1016/j.jep.2016.09.025.
  • Dong, Y.; Cao, A.; Shi, J.; Yin, P.; Wang, L.; Ji, G.; Xie, J.; Wu, D. Tangeretin, a Citrus Polymethoxyflavonoid, Induces Apoptosis of Human Gastric Cancer AGS Cells Through Extrinsic and Intrinsic Signaling Pathways. Oncol. Rep. 2014, 31(4), 1788–1794. DOI: 10.3892/or.2014.3034.
  • Ting, Y.; Jiang, Y.; Ho, C. T.; Huang, Q. Common Delivery Systems for Enhancing in vivo Bioavailability and Biological Efficacy of Nutraceuticals. J. Funct. Foods. 2014, 7, 112–128. DOI: 10.1016/j.jff.2013.12.010.
  • Rein, M. J.; Renouf, M.; Cruz‐hernandez, C.; Actis‐goretta, L.; Thakkar, S. K.; da Silva Pinto, M. Bioavailability of Bioactive Food Compounds: A Challenging Journey to Bioefficacy. Br. J. Clin. Pharmacol. 2013, 75(3), 588–602. DOI: 10.1111/j.1365-2125.2012.04425.x.
  • Zhang, M.; Zhu, S.; Yang, W.; Huang, Q.; Ho, C. T. The Biological Fate and Bioefficacy of Citrus Flavonoids: Bioavailability, Biotransformation, and Delivery Systems. Food & Function. 2021, 12(8), 3307–3323. DOI: 10.1039/D0FO03403G.
  • Alfei, S.; Schito, A. M.; Zuccari, G. Nanotechnological Manipulation of Nutraceuticals and Phytochemicals for Healthy Purposes: Established Advantages Vs. Still Undefined Risks. Poly. 2021, 13(14), 2262. DOI: 10.3390/polym13142262.
  • Xu, Y.; Li, Y.; Xie, J.; Xie, L.; Mo, J.; Chen, W. Bioavailability, Absorption, and Metabolism of Pelargonidin-Based Anthocyanins Using Sprague–Dawley Rats and Caco-2 Cell Monolayers. J. Agric. Food Chem. 2021, 69(28), 7841–7850. DOI: 10.1021/acs.jafc.1c00257.
  • Zhang, M.; Pan, Y.; Dong, Q.; Tang, X.; Xin, Y.; Yin, B.; Zhu, J.; Kou, X.; Ho, C. T.; Huang, Q. Development of Organogel-Based Emulsions to Enhance the Loading and Bioaccessibility of 5-Demethylnobiletin. Food Res. Int. 2021, 148, 110592. DOI: 10.1016/j.foodres.2021.110592.
  • Singh, A. P.; Kandpal, J. B.; Sharma, R. K.; Chitme, H. Nobiletin a Biologically Active Phytoconstituent: Systematic Review. J. Biol. Act. Prod. Nat. 2021, 11(3), 204–211. DOI: 10.1080/22311866.2021.1920461.
  • Wijaya, W.; Zheng, H.; Zheng, T.; Su, S.; Patel, A. R.; Van der Meeren, P.; Huang, Q. Improved Bioaccessibility of Polymethoxyflavones Loaded into High Internal Phase Emulsions Stabilized by Biopolymeric Complexes: A Dynamic Digestion Study via Tno’s Gastrointestinal Model. Curr. Res. Food Sci. 2020, 2, 11–19. DOI: 10.1016/j.crfs.2019.11.007.
  • Ting, Y.; Jiang, Y.; Lan, Y.; Xia, C.; Lin, Z.; Rogers, M. A.; Huang, Q. Viscoelastic Emulsion Improved the Bioaccessibility and Oral Bioavailability of Crystalline Compound: A Mechanistic Study Using in vitro and in vivo Models. Mol. Pharmaceutics. 2015, 12(7), 2229–2236. DOI: 10.1021/mp5007322.
  • Ting, Y.; Xia, Q.; Li, S.; Ho, C. T.; Huang, Q. Design of High-Loading and High-Stability Viscoelastic Emulsions for Polymethoxyflavones. Food Res. Int. 2013, 54(1), 633–640. DOI: 10.1016/j.foodres.2013.07.047.
  • Bajraktari-Sylejmani, G.; Weiss, J. Potential Risk of Food-Drug Interactions: Citrus Polymethoxyflavones and Flavanones as Inhibitors of the Organic Anion Transporting Polypeptides (OATP) 1B1, 1B3, and 2B1. Eur. J. Drug Metab. Pharmacokinet. 2020, 45(6), 809–815. DOI: 10.1007/s13318-020-00634-4.
  • Guo, J.; Tao, H.; Cao, Y.; Ho, C. T.; Jin, S.; Huang, Q. Prevention of Obesity and Type 2 Diabetes with Aged Citrus Peel (Chenpi) Extract. J. Agric. Food Chem. 2016, 64(10), 2053–2061. DOI: 10.1021/acs.jafc.5b06157.
  • Cao, X.; Ma, C.; Gao, Z.; Zheng, J.; He, L.; McClements, D. J.; Xiao, H. Characterization of the Interactions Between Titanium Dioxide Nanoparticles and Polymethoxyflavones Using Surface-Enhanced Raman Spectroscopy. J. Agric. Food Chem. 2016, 64(49), 9436–9441. DOI: 10.1021/acs.jafc.6b03906.
  • Faqueti, L. G.; Sandjo, L. P.; Biavatti, M. W. Simultaneous Identification and Quantification of Polymethoxyflavones, Coumarin and Phenolic Acids in Ageratum Conyzoides by UPLC-ESI-QToF-MS and UPLC-PDA. J. Pharm. Biomed. Anal. 2017, 145, 621–628. DOI: 10.1016/j.jpba.2017.07.034.
  • Ververidis, F.; Trantas, E.; Douglas, C.; Vollmer, G.; Kretzschmar, G.; Panopoulos, N. Biotechnology of Flavonoids and Other Phenylpropanoid-Derived Natural Products. Part I: Chemical Diversity, Impacts on Plant Biology and Human Health. Biotechnol. J. 2007, 2(10), 1214–1234. DOI: 10.1002/biot.200700084.
  • Xing, T. T.; Zhao, X. J.; Zhang, Y. D.; Li, Y. F. Fast Separation and Sensitive Quantitation of Polymethoxylated Flavonoids in the Peels of Citrus Using UPLC-Q-TOF-MS. J. Agric. Food Chem. 2017, 65(12), 2615–2627. DOI: 10.1021/acs.jafc.6b05821.
  • Xu, J. J.; Wu, X.; Li, M. M.; Li, G. Q.; Yang, Y. T.; Luo, H. J.; Huang, W. H.; Chung, H. Y.; Ye, W. C.; Wang, G. C. L., et al. Antiviral Activity of Polymethoxylated Flavones from “Guangchenpi”, the Edible and Medicinal Pericarps of Citrus Reticulata ‘Chachi’. J. Agric. Food Chem. 2014, 62(10), 2182–2189. DOI: 10.1021/jf404310y.
  • Salehi, B.; Jornet, P. L.; López, E. P. F.; Calina, D.; Sharifi-Rad, M.; Ramírez-Alarcón, K.; Forman, K.; Fernández, M.; Martorell, M.; Setzer, W. N., et al. Plant-Derived Bioactives in Oral Mucosal Lesions: A Key Emphasis to Curcumin, Lycopene, Chamomile, Aloe Vera, Green Tea and Coffee Properties. Biomol. 2019, 9(3), 106. DOI: 10.3390/biom9030106.
  • Docea, A. O.; Mitrut, P.; Grigore, D.; Pirici, D.; Calina, D. C.; Gofita, E. Immunohistochemical Expression of TGF Beta (TGF-Beta), TGF Beta Receptor 1 (TGFBR1), and Ki67 in Intestinal Variant of Gastric Adenocarcinomas. Rom. J. Morphol. Embryol. 2012, 53(3), 683–692.
  • Tung, Y. C.; Chou, Y. C.; Hung, W. L.; Cheng, A. C.; Yu, R. C.; Ho, C. T.; Pan, M. H. Polymethoxyflavones: Chemistry and Molecular Mechanisms for Cancer Prevention and Treatment. Curr. Pharmacol. Rep. 2019, 5(2), 98–113. DOI: 10.1007/s40495-019-00170-z.
  • Surichan, S.; Arroo, R. R.; Ruparelia, K.; Tsatsakis, A. M.; Androutsopoulos, V. P. Nobiletin Bioactivation in MDA-MB-468 Breast Cancer Cells by Cytochrome P450 CYP1 Enzymes. Food Chem. Toxicol. 2018, 113, 228–235. DOI: 10.1016/j.fct.2018.01.047.
  • Zhu, W. B.; Xiao, N.; Liu, X. J. Dietary Flavonoid Tangeretin Induces Reprogramming of Epithelial to Mesenchymal Transition in Prostate Cancer Cells by Targeting the PI3K/Akt/mTor Signaling Pathway. Oncol. Letters. 2018, 15(1), 433–440. DOI: 10.3892/ol.2017.7307.
  • Li, J.; Li, Z.; Zheng, F. Nobiletin Inhibits Proliferation, Invasion, Migration and Angiogenesis in Colorectal Cancer Cells. J. Biomater. Tissue Eng. 2019, 9(5), 662–667. DOI: 10.1166/jbt.2019.2022.
  • Goh, J. X. H.; Tan, L. T. H.; Goh, J. K.; Chan, K. G.; Pusparajah, P.; Lee, L. H.; Goh, B. H. Nobiletin and Derivatives: Functional Compounds from Citrus Fruit Peel for Colon Cancer Chemoprevention. Cancers. 2019, 11(6), 867. DOI: 10.3390/cancers11060867.
  • Li, G. J.; Wang, J.; Cheng, Y. J.; Tan, X.; Zhai, Y. L.; Wang, Q.; Gao, F. J.; Liu, G. L.; Zhao, X.; Wang, H. Prophylactic Effects of Polymethoxyflavone-Rich Orange Peel Oil on Nω-Nitro-L-Arginine-Induced Hypertensive Rats. Appl. Sci. 2018, 8(5), 752. DOI: 10.3390/app8050752.
  • Wu, J. C.; Tsai, M. L.; Lai, C. S.; Lo, C. Y.; Ho, C. T.; Wang, Y. J.; Pan, M. H. Polymethoxyflavones Prevent Benzo [A] Pyrene/Dextran Sodium Sulfate‐induced Colorectal Carcinogenesis Through Modulating Xenobiotic Metabolism and Ameliorate Autophagic Defect in ICR Mice. Int. J. Cancer. 2018, 142(8), 1689–1701. DOI: 10.1002/ijc.31190.
  • Pereira, C. V.; Duarte, M.; Silva, P.; Bento da Silva, A.; Duarte, C. M.; Cifuentes, A.; García-Cañas, V.; Bronze, M. R.; Albuquerque, C.; Serra, A. T. Polymethoxylated Flavones Target Cancer Stemness and Improve the Antiproliferative Effect of 5-Fluorouracil in a 3D Cell Model of Colorectal Cancer. Nutrients. 2019, 11(2), 326. DOI: 10.3390/nu11020326.
  • Li, Y. R.; Li, S.; Ho, C. T.; Chang, Y. H.; Tan, K. T.; Chung, T. W.; Wang, B. Y.; Chen, Y. K.; Lin, C. C. Tangeretin Derivative, 5-Acetyloxy-6, 7, 8, 4′-Tetramethoxyflavone Induces G2/M Arrest, Apoptosis and Autophagy in Human Non-Small Cell Lung Cancer Cells in vitro and in vivo. Cancer. Biol & Therapy. 2016, 17(1), 48–64. DOI: 10.1080/15384047.2015.1108491.
  • Zhang, H.; Tian, G.; Zhao, C.; Han, Y.; DiMarco-Crook, C.; Lu, C.; Bao, Y.; Li, C.; Xiao, H.; Zheng, J. Characterization of Polymethoxyflavone Demethylation During Drying Processes of Citrus Peels. Food & Function. 2019, 10(9), 5707–5717. DOI: 10.1039/C9FO01053J.
  • Tan, K. T.; Li, S.; Li, Y. R.; Cheng, S. L.; Lin, S. H.; Tung, Y. T. Synergistic Anticancer Effect of a Combination of Paclitaxel and 5-Demethylnobiletin Against Lung Cancer Cell Line in vitro and in vivo. Appl. Biochem. Biotechnol. 2019, 187, 1328–1343. DOI: 10.1007/s12010-018-2869-1.
  • Abe, S.; Hirose, S.; Nishitani, M.; Yoshida, I.; Tsukayama, M.; Tsuji, A.; Yuasa, K. Citrus Peel Polymethoxyflavones, Sudachitin and Nobiletin, Induce Distinct Cellular Responses in Human Keratinocyte HaCat Cells. Biosci. Biotechnol. Biochem. 2018, 82(12), 2064–2071. DOI: 10.1080/09168451.2018.1514246.
  • Yoshizaki, N.; Hashizume, R.; Masaki, H. A Polymethoxyflavone Mixture Extracted from Orange Peels, Mainly Containing Nobiletin3, 3’, 4’, 5, 6, 7, 8-Heptamethoxyflavone and Tangeretin, Suppresses Melanogenesis Through the Acidification of Cell Organelles, Including Melanosomes. J. Dermatol. Sci. 2017, 88(1), 78–84. DOI: 10.1016/j.jdermsci.2017.06.008.
  • Sousa, D. P.; Pojo, M.; Pinto, A. T.; Leite, V.; Serra, A. T.; Cavaco, B. M. Nobiletin Alone or in Combination with Cisplatin Decreases the Viability of Anaplastic Thyroid Cancer Cell Lines. Nutr. Cancer. 2020, 72(2), 352–363. DOI: 10.1080/01635581.2019.1634745.
  • Wei, G. J.; Chao, Y. H.; Tung, Y. C.; Wu, T. Y.; Su, Z. Y. A Tangeretin Derivative Inhibits the Growth of Human Prostate Cancer LNCaP Cells by Epigenetically Restoring P21 Gene Expression and Inhibiting Cancer Stem-Like Cell Proliferation. Aaps. J. 2019, 21(5), 1–12. DOI: 10.1208/s12248-019-0345-7.
  • Lin, C. C.; Chen, K. B.; Tsai, C. H.; Tsai, F. J.; Huang, C. Y.; Tang, C. H.; Yang, J. S.; Hsu, Y. M.; Peng, S. F.; Chung, J. G. Casticin Inhibits Human Prostate Cancer DU 145 Cell Migration and Invasion via Ras/Akt/Nf‐κb Signaling Pathways. J. Food Biochem. 2019, 43(7), e12902. DOI: 10.1111/jfbc.12902.
  • Docea, A. O.; Calina, D.; Buga, A. M.; Zlatian, O.; Paoliello, M. M. B.; Mogosanu, G. D.; Streba, C. T.; Popescu, E. L.; Stoica, A. E.; Bîrcă, A. C., et al. The Effect of Silver Nanoparticles on Antioxidant/pro-Oxidant Balance in a Murine Model. Int. J. Mol. Sci. 2020, 21(4), 1233. DOI: 10.3390/ijms21041233.
  • Padureanu, R.; Albu, C. V.; Mititelu, R. R.; Bacanoiu, M. V.; Docea, A. O.; Calina, D.; Padureanu, V.; Olaru, G.; Sandu, R. E.; Malin, R. D., et al. Oxidative Stress and Inflammation Interdependence in Multiple Sclerosis. J. Clin. Med. 2019, 8(11), 1815. DOI: 10.3390/jcm8111815.
  • Mititelu, R. R.; Pădureanu, R.; Băcănoiu, M.; Pădureanu, V.; Docea, A. O.; Calina, D.; Barbulescu, A. L.; Buga, A. M. Inflammatory and Oxidative Stress Markers—mirror Tools in Rheumatoid Arthritis. Biomed. 2020, 8(5), 125. DOI: 10.3390/biomedicines8050125.
  • Salehi, B.; Sestito, S.; Rapposelli, S.; Peron, G.; Calina, D.; Sharifi-Rad, M.; Sharopov, F.; Martins, N.; Sharifi-Rad, J. Epibatidine: A Promising Natural Alkaloid in Health. Biomol. 2018, 9(1), 6. DOI: 10.3390/biom9010006.
  • Lakshmi, A.; Subramanian, S. P. Tangeretin Ameliorates Oxidative Stress in the Renal Tissues of Rats with Experimental Breast Cancer Induced by 7, 12-Dimethylbenz [A] Anthracene. Toxicol. Lett. 2014, 229(2), 333–348. DOI: 10.1016/j.toxlet.2014.06.845.
  • Daniyal, A.; Sue, E. S.; Ashok Kumar, G. How Effective are Antioxidant Supplements in Obesity and Diabetes? Med. Prin and Practice. 2015, 24(3), 201–215. DOI: 10.1159/000375305.
  • Chen, X. Y.; Zhang, J.; Zhu, J. S.; Chen, X.; Han, X.; Yu, J.; Wang, W.; Liang, L.; Liu, Z.; Zheng, Y., et al. Epigenetically Upregulated Oncoprotein PLCE1 Drives Esophageal Carcinoma Angiogenesis and Proliferation via Activating the PI-PLCε-NF-Κb Signaling Pathway and VEGF-C/ Bcl-2 Expression. Mol. Cancer. 2019, 18(1), 1–9. DOI: 10.1186/s12943-018-0930-x.
  • Wang, Y.; Chen, Y.; Zhang, H.; Chen, J.; Cao, J.; Chen, Q.; Li, X.; Sun, C. Polymethoxyflavones from Citrus Inhibited Gastric Cancer Cell Proliferation Through Inducing Apoptosis by Upregulating RARβ, Both in vitro and in vivo. Food Chem. Toxicol. 2020, 146, 111811. DOI: 10.1016/j.fct.2020.111811.
  • Liang, F.; Fang, Y.; Cao, W.; Zhang, Z.; Pan, S.; Xu, X. Attenuation of Tert-Butyl Hydroperoxide (T-BHP)-Induced Oxidative Damage in HepG2 Cells by Tangeretin: Relevance of the Nrf2–ARE and MAPK Signaling Pathways. J. Agric. Food Chem. 2018, 66(25), 6317–6325. DOI: 10.1021/acs.jafc.8b01875.
  • Hagenlocher, Y.; Feilhauer, K.; Schäffer, M.; Bischoff, S. C.; Lorentz, A. Citrus Peel Polymethoxyflavones Nobiletin and Tangeretin Suppress LPS-And IgE-Mediated Activation of Human Intestinal Mast Cells. Eur. J. Nutr. 2017, 56(4), 1609–1620. DOI: 10.1007/s00394-016-1207-z.
  • Lai, C. S.; Tsai, M. L.; Cheng, A. C.; Li, S.; Lo, C. Y.; Wang, Y.; Xiao, H.; Ho, C. T.; Wang, Y. J.; Pan, M. H. Chemoprevention of Colonic Tumorigenesis by Dietary Hydroxylated Polymethoxyflavones in Azoxymethane‐treated Mice. Mole. Nutri & Food Res. 2011, 55(2), 278–290. DOI: 10.1002/mnfr.201000224.
  • Wu, X.; Song, M.; Rakariyatham, K.; Zheng, J.; Guo, S.; Tang, Z.; Zhou, S.; Xiao, H. Anti-Inflammatory Effects of 4′-Demethylnobiletin, a Major Metabolite of Nobiletin. J. Funct. Foods. 2015, 19, 278–287. DOI: 10.1016/j.jff.2015.09.035.
  • Kim, T. W.; Lee, D. R.; Choi, B. K.; Kang, H. K.; Jung, J. Y.; Lim, S. W.; Yang, S. H.; Suh, J. W. Hepatoprotective Effects of Polymethoxyflavones Against Acute and Chronic Carbon Tetrachloride Intoxication. Food Chem. Toxicol. 2016, 91, 91–99. DOI: 10.1016/j.fct.2016.03.004.
  • Devi, A. D.; Devi, O. I.; Singh, T. C.; Singh, E. J. A Study of Aromatic Plant Species Especially in Thoubal District, Manipur, North East India. Int. J. Sci. Res. Publ. 2014, 4, 2250–3153.
  • Lee, Y. Y.; Lee, E. J.; Park, J. S.; Jang, S. E.; Kim, D. H.; Kim, H. S. Anti-Inflammatory and Antioxidant Mechanism of Tangeretin in Activated Microglia. J. Neuroimmune Pharmacol. 2016, 11(2), 294–305. DOI: 10.1007/s11481-016-9657-x.
  • Shu, Z.; Yang, B.; Zhao, H.; Xu, B.; Jiao, W.; Wang, Q.; Wang, Z.; Kuang, H. Tangeretin Exerts Anti-Neuroinflammatory Effects via NF-Κb Modulation in Lipopolysaccharide-Stimulated Microglial Cells. Int. Immunopharmacol. 2014, 19(2), 275–282. DOI: 10.1016/j.intimp.2014.01.011.
  • Gosslau, A.; Chen, K. Y.; Ho, C. T.; Li, S. Anti-Inflammatory Effects of Characterized Orange Peel Extracts Enriched with Bioactive Polymethoxyflavones. Food Sci. Hum. Wellness. 2014, 3(1), 26–35. DOI: 10.1016/j.fshw.2014.02.002.
  • Zhang, D.; Hou, L.; Peng, W. Tangeritin Attenuates Oxidative Stress, Apoptosis and Inflammation in Cadmium-Induced Cardiotoxicity in Rats by Activating Nrf2 Signaling Pathway. Trop. J. Pharm. Res. 2018, 17(12), 2421–2426. DOI: 10.4314/tjpr.v17i12.16.
  • Sharifi-Rad, J.; Rodrigues, C. F.; Sharopov, F.; Docea, A. O.; Can Karaca, A.; Sharifi-Rad, M.; Kahveci Karıncaoglu, D.; Gülseren, G.; Şenol, E.; Demircan, E., et al. Diet, Lifestyle and Cardiovascular Diseases: Linking Pathophysiology to Cardioprotective Effects of Natural Bioactive Compounds. Int. J. Environ. Res. Public Health. 2020, 17(7), 2326. DOI: 10.3390/ijerph17072326.
  • Sharifi-Rad, M.; Anil Kumar, N. V.; Zucca, P.; Varoni, E. M.; Dini, L.; Panzarini, E.; Rajkovic, J.; Tsouh Fokou, P. V.; Azzini, E.; Peluso, I., et al. Lifestyle, Oxidative Stress, and Antioxidants: Back and Forth in the Pathophysiology of Chronic Diseases. Front. Physiol. 2020, 11, 694. DOI: 10.3389/fphys.2020.00694.
  • Shammugasamy, B.; Valtchev, P.; Dong, Q.; Dehghani, F. Effect of Citrus Peel Extracts on the Cellular Quiescence of Prostate Cancer Cells. Food & Function. 2019, 10(6), 3727–3737. DOI: 10.1039/C9FO00455F.
  • Zhou, M. X.; Li, G. H.; Wu, X. Y.; Sun, L.; Li, Y. R.; Yang, W. J.; Ren, D. M.; Wang, X. N.; Xiang, L.; Lou, H. X., et al. (2S)-5,6,7,3′,4′-Pentamethoxyflavanone, a Citrus Polymethoxyflavone Ameliorates Arsenic- and Cigarette Smoke Extract-Induced Cytotoxicity via Activating Nrf2-Mediated Defense System. J. Funct. Foods. 2019, 54(54), 337–347. DOI: 10.1016/j.jff.2019.01.019.
  • Lakshmi, A.; Subramanian, S. Chemotherapeutic Effect of Tangeretin, a Polymethoxylated Flavone Studied in 7, 12-Dimethylbenz (A) Anthracene Induced Mammary Carcinoma in Experimental Rats. Biochimie. 2014, 99, 96–109. DOI: 10.1016/j.biochi.2013.11.017.
  • Salehi, B.; Prakash Mishra, A.; Nigam, M.; Karazhan, N.; Shukla, I.; Kiełtyka‐dadasiewicz, A.; Sawicka, B.; Głowacka, A.; Abu‐darwish, M. S.; Hussein Tarawneh, A., et al. Ficus Plants: State of the Art from a Phytochemical, Pharmacological, and Toxicological Perspective. Phytotherapy. Res. 2021, 35(3), 1187–1217. DOI: 10.1002/ptr.6884.
  • Ochiai, M.; Takeuchi, T.; Nozaki, T.; Ishihara, K. O.; Matsuo, T. Kaempferia Parviflora Ethanol Extract, a Peroxisome Proliferator‐activated Receptor γ Ligand‐binding Agonist, Improves Glucose Tolerance and Suppresses Fat Accumulation in Diabetic NSY Mice. J. Food Sci. 2019, 84(2), 339–348. DOI: 10.1111/1750-3841.14437.
  • Wang, L.; Wang, J.; Fang, L.; Zheng, Z.; Zhi, D.; Wang, S.; Li, S.; Ho, C. T.; Zhao, H. Anticancer Activities of Citrus Peel Polymethoxyflavones Related to Angiogenesis and Others. Biomed Res. Int. 2014, 2014, 1–10. DOI: 10.1155/2014/453972.
  • Guo, J. Application of 5-oh polymethoxyflavones and safe mitochondrial uncouplers in preventing and treating type 2 diabetes and fatty liver diseases. (Doctoral dissertation, Rutgers University-School of Graduate Studies). 2019.
  • Fayek, N. M.; El-Shazly, A. H.; Abdel-Monem, A. R.; Moussa, M. Y.; Abd-Elwahab, S. M.; El-Tanbouly, N. D. Comparative Study of the Hypocholesterolemic, Antidiabetic Effects of Four Agro-Waste Citrus Peels Cultivars and Their HPLC Standardization. Rev. Bras. Farmacogn. 2017, 27(4), 488–494. DOI: 10.1016/j.bjp.2017.01.010.
  • Keshtkar, S.; Kaviani, M.; Jabbarpour, Z.; Geramizadeh, B.; Motevaseli, E.; Nikeghbalian, S.; Shamsaeefar, A.; Motazedian, N.; Al-Abdullah, I. H.; Ghahremani, M. H., et al. Protective Effect of Nobiletin on Isolated Human Islets Survival and Function Against Hypoxia and Oxidative Stress-Induced Apoptosis. Sci. Rep. 2019, 9(1), 1–13. DOI: 10.1038/s41598-019-48262-6.
  • Yuk, T.; Kim, Y.; Yang, J.; Sung, J.; Jeong, H. S.; Lee, J. Nobiletin Inhibits Hepatic Lipogenesis via Activation of AMP-Activated Protein Kinase. Evid. Based Complement. Altern. Med. 2018, 2018, 1–8. DOI: 10.1155/2018/7420265.
  • Feng, K.; Zhu, X.; Chen, T.; Peng, B.; Lu, M.; Zheng, H.; Huang, Q.; Ho, C. T.; Chen, Y.; Cao, Y. Prevention of Obesity and Hyperlipidemia by Heptamethoxyflavone in High-Fat Diet-Induced Rats. J. Agric. Food Chem. 2019, 67(9), 2476–2489. DOI: 10.1021/acs.jafc.8b05632.
  • Pan, M. H.; Yang, G.; Li, S.; Li, M. Y.; Tsai, M. L.; Wu, J. C.; Badmaev, V.; Ho, C. T.; Lai, C. S. Combination of Citrus Polymethoxyflavones, Green Tea Polyphenols, and Lychee Extracts Suppresses Obesity and Hepatic Steatosis in High‐fat Diet Induced Obese Mice. Mole.Nutri & Food Res. 2017, 61(11), 1601104. DOI: 10.1002/mnfr.201601104.
  • Guo, J.; Cao, Y.; Ho, C. T.; Jin, S.; Huang, Q. Aged Citrus Peel (Chenpi) Extract Reduces Lipogenesis in Differentiating 3T3-L1 Adipocytes. J. Funct. Foods. 2017, 34, 297–303. DOI: 10.1016/j.jff.2017.04.042.
  • Yun, Y. R.; Lee, J. E. Alliin, Capsaicin, and Gingerol Attenuate Endoplasmic Reticulum Stress-Induced Hepatic Steatosis in HepG2 Cells and C57BL/6N Mice. J. Funct. Foods. 2022, 95, 105186. DOI: 10.1016/j.jff.2022.105186.
  • Tung, Y. C.; Li, S.; Huang, Q.; Hung, W. L.; Ho, C. T.; Wei, G. J.; Pan, M. H. 5-Demethylnobiletin and 5-Acetoxy-6, 7, 8, 3′, 4′-Pentamethoxyflavone Suppress Lipid Accumulation by Activating the LKB1-AMPK Pathway in 3T3-L1 Preadipocytes and High Fat Diet-Fed C57BL/6 Mice. J. Agric. Food Chem. 2016, 64(16), 3196–3205. DOI: 10.1021/acs.jafc.6b00706.
  • Tsatsakis, A.; Docea, A. O.; Calina, D.; Tsarouhas, K.; Zamfira, L. M.; Mitrut, R.; Sharifi-Rad, J.; Kovatsi, L.; Siokas, V.; Dardiotis, E., et al. A Mechanistic and Pathophysiological Approach for Stroke Associated with Drugs of Abuse. J. Clin. Med. 2019, 8(9), 1295. DOI: 10.3390/jcm8091295.
  • Salehi, B.; Sharifi-Rad, J.; Cappellini, F.; Reiner, Ž.; Zorzan, D.; Imran, M.; Sener, B.; Kilic, M.; El-Shazly, M.; Fahmy, N. M., et al. The Therapeutic Potential of Anthocyanins: Current Approaches Based on Their Molecular Mechanism of Action. Front. Pharmacol. 2020, 11, 1300. DOI: 10.3389/fphar.2020.01300.
  • Kang, S. I.; Shin, H. S.; Kim, S. J. Sinensetin Enhances Adipogenesis and Lipolysis by Increasing Cyclic Adenosine Monophosphate Levels in 3T3-L1 Adipocytes. Biol. Pharm. Bull. 2015, 38(4), 552–558. DOI: 10.1248/bpb.b14-00700.
  • Adebiyi, A. O.; Adebiyi, O. O.; Owira, P. M. Naringin Mitigates Cardiac Hypertrophy by Reducing Oxidative Stress and Inactivating C-Jun Nuclear Kinase-1 Protein in Type I Diabetes. J. Cardiovasc. Pharmacol. 2016, 67(2), 136–144. DOI: 10.1097/FJC.0000000000000325.
  • Jenie, R. I.; Setiawan, I. M.; Jenie, I. M.; Muflikhasari, H. A. Cytoprotective Effect of Tangeretin in Hydrogen Peroxyde-Induced oxidative Stress on Human Umbilical Vein Endothelial Cells (HUVECs). J. Ilm. Farm. 2015, 11(1), 16–19. DOI: 10.20885/jif.vol11.iss1.art3.
  • Kim, J. J.; Kim, K.; Jung, Y. R.; Bian, Y.; Ngo, T.; Bae, O. N.; Lim, K. M.; Chung, J. H. Co-Existence of Hypertensive and Anti-Hypertensive Constituents, Synephrine, and Nobiletin in Citrus Unshiu Peel. Molecules. 2019, 24(7), 1197. DOI: 10.3390/molecules24071197.
  • Cummings, J. L.; Tong, G.; Ballard, C. Treatment Combinations for Alzheimer’s Disease: Current and Future Pharmacotherapy Options. J. Alzheimer’s dis. 2019, 67(3), 779–794. DOI: 10.3233/JAD-180766.
  • Calina, D.; Buga, A. M.; Mitroi, M.; Buha, A.; Caruntu, C.; Scheau, C.; Bouyahya, A.; El Omari, N.; El Menyiy, N.; Docea, A. O. The Treatment of Cognitive, Behavioural and Motor Impairments from Brain Injury and Neurodegenerative Diseases Through Cannabinoid System Modulation—evidence from in vivo Studies. J. Clin. Med. 2020, 9(8), 2395. DOI: 10.3390/jcm9082395.
  • Youn, K.; Yu, Y.; Lee, J.; Jeong, W. S.; Ho, C. T.; Jun, M. Polymethoxyflavones: Novel β-Secretase (BACE1) Inhibitors from Citrus Peels. Nutrients. 2017, 9(9), 973. DOI: 10.3390/nu9090973.
  • Nakajima, A.; Aoyama, Y.; Shin, E. J.; Nam, Y.; Kim, H. C.; Nagai, T.; Yokosuka, A.; Mimaki, Y.; Yokoi, T.; Ohizumi, Y., et al. Nobiletin, a Citrus Flavonoid, Improves Cognitive Impairment and Reduces Soluble Aβ Levels in a Triple Transgenic Mouse Model of Alzheimer’s Disease (3xtg-AD). Behav. Brain Res. 2015, 289, 69–77. DOI: 10.1016/j.bbr.2015.04.028.
  • Youn, K.; Lee, S.; Jun, M. Discovery of Nobiletin from Citrus Peel as a Potent Inhibitor of β-Amyloid Peptide Toxicity. Nutrients. 2019, 11(11), 2648. DOI: 10.3390/nu11112648.
  • Kawahata, I.; Yoshida, M.; Sun, W.; Nakajima, A.; Lai, Y.; Osaka, N.; Matsuzaki, K.; Yokosuka, A.; Mimaki, Y.; Naganuma, A., et al. Potent Activity of Nobiletin-Rich Citrus Reticulata Peel Extract to Facilitate cAmp/PKA/ERK/CREB Signaling Associated with Learning and Memory in Cultured Hippocampal Neurons: Identification of the Substances Responsible for the Pharmacological Action. J. Neural Trans. 2013, 120(10), 1397–1409. DOI: 10.1007/s00702-013-1025-x.
  • Nakajima, A.; Ohizumi, Y. Potential Benefits of Nobiletin, a Citrus Flavonoid, Against Alzheimer’s Disease and Parkinson’s Disease. Int. J. Mol. Sci. 2019, 20(14), 3380. DOI: 10.3390/ijms20143380.
  • Cioboată, R.; Găman, A.; Traşcă, D.; Ungureanu, A.; Docea, A. O.; Tomescu, P.; Gherghina, F.; Arsene, A. L.; Badiu, C.; Tsatsakis, A. M., et al. Pharmacological Management of Non-Alcoholic Fatty Liver Disease: Atorvastatin versus Pentoxifylline. Exp. Ther. Med. 2017, 13(5), 2375–2381. DOI: 10.3892/etm.2017.4256.
  • Han, H. Y.; Lee, S. K.; Choi, B. K.; Lee, D. R.; Lee, H. J.; Kim, T. W. Preventive Effect of Citrus Aurantium Peel Extract on High-Fat Diet-Induced Non-Alcoholic Fatty Liver in Mice. Biol. Pharm. Bull. 2019, 42(2), 255–260. DOI: 10.1248/bpb.b18-00702.
  • Yen, J. H.; Weng, C. Y.; Li, S.; Lo, Y. H.; Pan, M. H.; Fu, S. H.; Ho, C. T.; Wu, M. J. Citrus Flavonoid 5‐demethylnobiletin Suppresses Scavenger Receptor Expression in THP‐1 Cells and Alters Lipid Homeostasis in HepG2 Liver Cells. Mole. Nutri & Food Res. 2011, 55(5), 733–748. DOI: 10.1002/mnfr.201000226.
  • Cushnie, T. T.; Hamilton, V. E.; Lamb, A. J. Assessment of the Antibacterial Activity of Selected Flavonoids and Consideration of Discrepancies Between Previous Reports. Microbiol. Res. 2003, 158(4), 281–289. DOI: 10.1078/0944-5013-00206.
  • Cushnie, T. T.; Lamb, A. J. Antimicrobial Activity of Flavonoids. Int. J. Antimicrob. Agents. 2005, 26(5), 343–356. DOI: 10.1016/j.ijantimicag.2005.09.002.
  • Alvarez, M. A.; Debattista, N. B.; Pappano, N. B. Antimicrobial Activity and Synergism of Some Substituted Flavonoids. Folia. microbiologica. 2008, 53(1), 23. DOI: 10.1007/s12223-008-0003-4.
  • Basile, A.; Giordano, S.; López-Sáez, J. A.; Cobianchi, R. C. Antibacterial Activity of Pure Flavonoids Isolated from Mosses. Phytochemistry. 1999, 52(8), 1479–1482. DOI: 10.1016/S0031-9422(99)00286-1.
  • Basile, A.; Sorbo, S.; Lopez-Saez, J. A.; Cobianchi, R. C. Effects of Seven Pure Flavonoids from Mosses on Germination and Growth of Tortula Muralis Hedw.(bryophyta) and Raphanus Sativus L.(magnoliophyta). Phytochemistry. 2003, 62(7), 1145–1151. DOI: 10.1016/S0031-9422(02)00659-3.
  • Mori, A.; Nishino, C.; Enoki, N.; Tawata, S. Antibacterial Activity and Mode of Action of Plant Flavonoids Against Proteus Vulgaris and Staphylococcus Aureus. Phytochemistry. 1987, 26(8), 2231–2234. DOI: 10.1016/S0031-9422(00)84689-0.
  • Cushnie, T. T.; Lamb, A. J. Detection of Galangin-Induced Cytoplasmic Membrane Damage in Staphylococcus Aureus by Measuring Potassium Loss. J. Ethnopharmacol. 2005, 101(1–3), 243–248. DOI: 10.1016/j.jep.2005.04.014.
  • Butler, E. E.; Hine, R. B. Use of Novobiocin for Isolation of Fungi from Soil. Soil. Sci. 1958, 85(5), 250–254. DOI: 10.1097/00010694-195805000-00003.
  • Tanaka, H.; Sato, M.; Fujiwara, S.; Hirata, M.; Etoh, H.; Takeuchi, H. Antibacterial Activity of Isoflavonoids Isolated from Erythrina Variegata Against Methicillin‐resistant Staphylococcus Aureus. Lett Appl. Microbiol. 2002, 35(6), 494–498. DOI: 10.1046/j.1472-765X.2002.01222.x.
  • Chew, Y. L.; Ling Chan, E. W.; Tan, P. L.; Lim, Y. Y.; Stanslas, J.; Goh, J. K. Assessment of Phytochemical Content, Polyphenolic Composition, Antioxidant and Antibacterial Activities of Leguminosae Medicinal Plants in Peninsular Malaysia. BMC Complementary Altern. Med. 2011, 11(1), 1–10. DOI: 10.1186/1472-6882-11-12.
  • Tsuchiya, H.; Sato, M.; Miyazaki, T.; Fujiwara, S.; Tanigaki, S.; Ohyama, M.; Tanaka, T.; Iinuma, M. Comparative Study on the Antibacterial Activity of Phytochemical Flavanones Against Methicillin-Resistant Staphylococcus Aureus. J. Ethnopharmacol. 1996, 50(1), 27–34. DOI: 10.1016/0378-8741(96)85514-0.
  • García-Mediavilla, V.; Crespo, I.; Collado, P. S.; Esteller, A.; Sánchez-Campos, S.; Tuñón, M. J.; González-Gallego, J. The Anti-Inflammatory Flavones Quercetin and Kaempferol Cause Inhibition of Inducible Nitric Oxide Synthase, Cyclooxygenase-2 and Reactive C-Protein, and Down-Regulation of the Nuclear Factor kappaB Pathway in Chang Liver Cells. Eur. J. Pharmacol. 2007, 557(2–3), 221–229. DOI: 10.1016/j.ejphar.2006.11.014.
  • Gado, D. A.; Abdalla, M. A.; Ahmed, A. S.; Madikizela, B.; Nkadimeng, S. M.; Ehlers, M. M.; McGaw, L. J. In vitro Antibacterial Activity of Loxostylis Alata Extracts and Isolated Compounds Against Salmonella Species. BMC Comple. Med and Therap. 2021, 21(1), 1–16. DOI: 10.1186/s12906-021-03292-4.
  • Li, S.; Lo, C. Y.; Ho, C. T. Hydroxylated Polymethoxyflavones and Methylated Flavonoids in Sweet Orange (Citrus Sinensis) Peel. J. Agric. Food Chem. 2006, 54(12), 4176–4185. DOI: 10.1021/jf060234n.
  • Manvar, D.; Mishra, M.; Kumar, S.; Pandey, V. N. Identification and Evaluation of Anti Hepatitis C Virus Phytochemicals from Eclipta Alba. J. Ethnopharmacol. 2012, 144(3), 545–554. DOI: 10.1016/j.jep.2012.09.036.
  • Farkas, O.; Palócz, O.; Pászti-Gere, E.; Gálfi, P. Polymethoxyflavone Apigenin-Trimethylether Suppresses LPS-Induced Inflammatory Response in Nontransformed Porcine Intestinal Cell Line IPEC-J2. Oxid. Med. Cell. Longev. 2015, 2015, 1–10. DOI: 10.1155/2015/673847.
  • Bachmetov, L.; Gal‐tanamy, M.; Shapira, A.; Vorobeychik, M.; Giterman‐galam, T.; Sathiyamoorthy, P.; Golan‐goldhirsh, A.; Benhar, I.; Tur‐kaspa, R.; Zemel, R. Suppression of Hepatitis C Virus by the Flavonoid Quercetin is Mediated by Inhibition of NS3 Protease Activity. J. Viral. Hepatitis. 2012, 19(2), e81–88. DOI: 10.1111/j.1365-2893.2011.01507.x.
  • Huang, H. C.; Tao, M. H.; Hung, T. M.; Chen, J. C.; Lin, Z. J.; Huang, C. (−)-Epigallocatechin-3-Gallate Inhibits Entry of Hepatitis B Virus into Hepatocytes. Antiviral. Res. 2014, 111, 100–111. DOI: 10.1016/j.antiviral.2014.09.009.
  • Zhang, Y.; Wang, R.; Wu, J.; Shen, Q. Characterization and Evaluation of Self-Microemulsifying Sustained-Release Pellet Formulation of Puerarin for Oral Delivery. Int. J. Pharmaceutics. 2012, 427(2), 337–344. DOI: 10.1016/j.ijpharm.2012.02.013.
  • Le Lee, J.; Loe, M. W. C.; Lee, R. C. H.; Chu, J. J. H. Antiviral Activity of Pinocembrin Against Zika Virus Replication. Antiviral. Res. 2019, 167, 13–24. DOI: 10.1016/j.antiviral.2019.04.003.
  • Ghildiyal, R.; Prakash, V.; Chaudhary, V. K.; Gupta, V.; Gabrani, R. Phytochemicals as Antiviral Agents: Recent Updates. Plant-Derived Bioactives: Production, Properties and Therapeutic Applications; Springer: Singapore, 2020, 279–295. ISBN: 978-981-15-1761 DOI: 10.1007/978-981-15-1761-7_12.
  • Fahmy, N. M.; Al‐sayed, E.; Moghannem, S.; Azam, F.; El‐shazly, M.; Singab, A. N. Breaking Down the Barriers to a Natural Antiviral Agent: Antiviral Activity and Molecular Docking of Erythrina Speciosa Extract, Fractions, and the Major Compound. Chem. Biodivers. 2020, 17(2), e1900511. DOI: 10.1002/cbdv.201900511.
  • Moghaddam, E.; Teoh, B. T.; Sam, S. S.; Lani, R.; Hassandarvish, P.; Chik, Z.; Yueh, A.; Abubakar, S.; Zandi, K. Baicalin, a Metabolite of Baicalein with Antiviral Activity Against Dengue Virus. Sci. Rep. 2014, 4(1), 1–8. DOI: 10.1038/srep05452.
  • Li, S.; Hattori, T.; Kodama, E. N. Epigallocatechin Gallate Inhibits the HIV Reverse Transcription Step. Antivir. Chem. Chemother. 2011, 21(6), 239–243. DOI: 10.3851/IMP1774.
  • Ahmed-Belkacem, A.; Guichou, J. F.; Brillet, R.; Ahnou, N.; Hernandez, E.; Pallier, C.; Pawlotsky, J. M. Inhibition of RNA Binding to Hepatitis C Virus RNA-Dependent RNA Polymerase: A New Mechanism for Antiviral Intervention. Nucleic Acids. Res. 2014, 42(14), 9399–9409. DOI: 10.1093/nar/gku632.
  • Zetterberg, C.; Öfverholm, T. Carpal Tunnel Syndrome and Other Wrist/Hand Symptoms and Signs in Male and Female Car Assembly Workers. Int. J. Ind. Ergon. 1999, 23(3), 193–204. DOI: 10.1016/S0169-8141(97)00054-1.
  • Yasuda, H.; Shima, N.; Nakagawa, N.; Yamaguchi, K.; Kinosaki, M.; Mochizuki, S. I.; Tomoyasu, A.; Yano, K.; Goto, M.; Murakami, A., et al. Osteoclast Differentiation Factor is a Ligand for Osteoprotegerin/osteoclastogenesis-Inhibitory Factor and is Identical to TRANCE/RANKL. Proce. National Acade. Sci, 1998, 95(7), 3597–3602.
  • Tanabe, N.; Maeno, M.; Suzuki, N.; Fujisaki, K.; Tanaka, H.; Ogiso, B.; Ito, K. IL-1α Stimulates the Formation of Osteoclast-Like Cells by Increasing M-CSF and PGE2 Production and Decreasing OPG Production by Osteoblasts. Life. Sci. 2005, 77(6), 615–626. DOI: 10.1016/j.lfs.2004.10.079.
  • Suda, K.; Udagawa, N.; Sato, N.; Takami, M.; Itoh, K.; Woo, J. T.; Takahashi, N.; Nagai, K. Suppression of Osteoprotegerin Expression by Prostaglandin E2 is Crucially Involved in Lipopolysaccharide-Induced Osteoclast Formation. J. Immunol. 2004, 172(4), 2504–2510. DOI: 10.4049/jimmunol.172.4.2504.
  • Hirata, M.; Kobayashi, M.; Takita, M.; Matsumoto, C.; Miyaura, C.; Inada, M. Hyaluronan Inhibits Bone Resorption by Suppressing Prostaglandin E Synthesis in Osteoblasts Treated with Interleukin-1. Biochem. Biophys. Res. Commun. 2009, 381(2), 139–143. DOI: 10.1016/j.bbrc.2009.01.146.
  • Juluri, R.; Prashanth, E.; Gopalakrishnan, D.; Kathariya, R.; Devanoorkar, A.; Viswanathan, V.; Romanos, G. E. Association of Postmenopausal Osteoporosis and Periodontal Disease: A Double-Blind Case-Control Study. J. Int. Oral. Health. 2015, 7(9), 119.
  • Miyaura, C.; Kusano, K.; Masuzawa, T.; Chaki, O.; Onoe, Y.; Aoyagi, M.; Sasaki, T.; Tamura, T.; Koishihara, Y.; Ohsugi, Y., et al. Endogenous Bone‐resorbing Factors in Estrogen Deficiency: Cooperative Effects of IL‐1 and IL‐6. J. Bone Miner. Res. 1995, 10(9), 1365–1373. DOI: 10.1002/jbmr.5650100914.
  • Lai, C. S.; Li, S.; Chai, C. Y.; Lo, C. Y.; Dushenkov, S.; Ho, C. T.; Pan, M. H.; Wang, Y. J. Anti-Inflammatory and Antitumor Promotional Effects of a Novel Urinary Metabolite, 3′, 4′-Didemethylnobiletin, Derived from Nobiletin. Carcinogenesis. 2008, 29(12), 2415–2424. DOI: 10.1093/carcin/bgn222.
  • Matsumoto, C.; Inoue, H.; Tominari, T.; Watanabe, K.; Hirata, M.; Miyaura, C.; Inada, M. Heptamethoxyflavone, a Citrus Flavonoid, Suppresses Inflammatory Osteoclastogenesis and Alveolar Bone Resorption. Biosci. Biotechnol. Biochem. 2015, 79(1), 155–158. DOI: 10.1080/09168451.2014.952616.
  • Tominari, T.; Hirata, M.; Matsumoto, C.; Inada, M.; Miyaura, C. Polymethoxy Flavonoids, Nobiletin and Tangeretin, Prevent Lipopolysaccharide-Induced Inflammatory Bone Loss in an Experimental Model for Periodontitis. J. Pharmacol. Sci. 2012, 119(4), 390–394. DOI: 10.1254/jphs.11188SC.
  • Yoshizaki, N.; Fujii, T.; Hashizume, R.; Masaki, H. A Polymethoxyflavone Mixture, Extracted from Orange Peels, Suppresses the UVB‐induced Expression of MMP‐1. Experi. dermatol. 2016, 25, 52–56. DOI: 10.1111/exd.13087.
  • Murakami, A.; Song, M.; Katsumata, S. I.; Uehara, M.; Suzuki, K.; Ohigashi, H. Citrus Nobiletin Suppresses Bone Loss in Ovariectomized ddY Mice and Collagen-Induced Arthritis in DBA/1J Mice: Possible Involvement of Receptor Activator of NF-kappaB Ligand (RANKL)-Induced Osteoclastogenesis Regulation. Bio. Factors. 2007, 30(3), 179–192. DOI: 10.1002/biof.5520300305.
  • Padalhin, A. R. Brief Retrospect on the Use of Photobiomodulation (PBM) Therapy for Augmented Bone Regeneration (ABR). Med. Las; Engine, Basic Res, and Clin. Appl. 2021, 10(1), 15–21. DOI: 10.25289/ML.2021.10.1.15.
  • Kawaii, S.; Ikuina, T.; Hikima, T.; Tokiwano, T.; Yoshizawa, Y. Relationship Between Structure and Antiproliferative Activity of Polymethoxyflavones Towards HL60 Cells. Anticancer. Res. 2012, 32(12), 5239–5244.
  • Ianoşi, S.; Ianoşi, G.; Neagoe, D.; Ionescu, O.; Zlatian, O.; Docea, A. O.; Badiu, C.; Sifaki, M.; Tsoukalas, D.; Tsatsakis, A. M., et al. Age-Dependent Endocrine Disorders Involved in the Pathogenesis of Refractory Acne in Women. Mol. Med. Rep. 2016, 14(6), 5501–5506. DOI: 10.3892/mmr.2016.5924.
  • Phung, H. M.; Lee, S.; Hong, S.; Lee, S.; Jung, K.; Kang, K. S. Protective Effect of Polymethoxyflavones Isolated from Kaempferia Parviflora Against TNF-α-Induced Human Dermal Fibroblast Damage. Antioxidants. 2021, 10(10), 1609. DOI: 10.3390/antiox10101609.
  • Vogiatzoglou, A.; Mulligan, A. A.; Lentjes, M. A.; Luben, R. N.; Spencer, J. P.; Schroeter, H.; Khaw, K. T.; Kuhnle, G. G.; Wang, D. Flavonoid Intake in European Adults (18 to 64 Years). PLoS One. 2015, 10(5), e0128132. DOI: 10.1371/journal.pone.0128132.
  • Shitara, Y.; Maeda, K.; Ikejiri, K.; Yoshida, K.; Horie, T.; Sugiyama, Y. Clinical Significance of Organic Anion Transporting Polypeptides (OATPs) in Drug Disposition: Their Roles in Hepatic Clearance and Intestinal Absorption. Biopharm. Drug Dispos. 2013, 34(1), 45–78. DOI: 10.1002/bdd.1823.
  • Tamai, I.; Nakanishi, T. OATP Transporter-Mediated Drug Absorption and Interaction. Curr. Opin. Pharmacol. 2013, 13(6), 859–863. DOI: 10.1016/j.coph.2013.09.001.
  • Hung, W. L.; Chang, W. S.; Lu, W. C.; Wei, G. J.; Wang, Y.; Ho, C. T.; Hwang, L. S. Pharmacokinetics, Bioavailability, Tissue Distribution and Excretion of Tangeretin in Rat. J. Food Drug Anal. 2018, 26(2), 849–857. DOI: 10.1016/j.jfda.2017.08.003.
  • Kumar, A.; Devaraj, V. C.; Giri, K. C.; Giri, S.; Rajagopal, S.; Mullangi, R. Development and Validation of a Highly Sensitive Lc‐ms/Ms‐esi Method for the Determination of Nobiletin in Rat Plasma: Application to a Pharmacokinetic Study. Biomed. Chromatogr. 2012, 26(12), 1464–1471. DOI: 10.1002/bmc.2717.
  • Bailey, D. G. Fruit Juice Inhibition of Uptake Transport: A New Type of Food–Drug Interaction. Br. J. Clin. Pharmacol. 2010, 70(5), 645–655. DOI: 10.1111/j.1365-2125.2010.03722.x.
  • Tapaninen, T.; Neuvonen, P. J.; Niemi, M. Orange and Apple Juice Greatly Reduce the Plasma Concentrations of the OATP2B1 Substrate Aliskiren. Br. J. Clin. Pharmacol. 2011, 71(5), 718–726. DOI: 10.1111/j.1365-2125.2010.03898.x.
  • Lilja, J. J.; Juntti‐patinen, L.; Neuvonen, P. J. Orange Juice Substantially Reduces the Bioavailability of the Β‐adrenergic–Blocking Agent Celiprolol. Clin. Pharmacol & Therapeutics. 2004, 75(3), 184–190. DOI: 10.1016/j.clpt.2003.11.002.

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