Role of Natural Flavonoid Products in Managing Osteoarthritis

Revista Brasileira de Farmacognosia - Tập 33 Số 4 - Trang 663-675
Roopal Pal1, Lakhan Kumar1, Shaubhik Anand1, Navneeta Bharadvaja1
1Plant Biotechnology Laboratory, Department of Biotechnology, Delhi Technological University, Shahbad Daulatpur, Main Bawana Road, Delhi, 110042, India

Tóm tắt

Từ khóa


Tài liệu tham khảo

Ahmad N, Ansari MY, Haqqi TM (2020) Role of iNOS in osteoarthritis: pathological and therapeutic aspects. J Cell Physiol 235:6366–6376. https://doi.org/10.1002/jcp.29607

Ahmed S, Anuntiyo J, Malemud CJ, Haqqi TM (2005) Biological basis for the use of botanicals in osteoarthritis and rheumatoid arthritis: a review. Evid Based Complement Alt Med 2:301–308. https://doi.org/10.1093/ecam/neh117

Ahmed YM, Messiha BAS, Abo-Saif AA (2015) Protective effects of s imvastatin and hesperidin against complete Freund’s adjuvant-induced rheumatoid arthritis in rats. Pharmacology 96:217–225. https://doi.org/10.1159/000439538

Ameye LG, Chee WSS (2006) Osteoarthritis and nutrition. From nutraceuticals to functional foods: a systematic review of the scientific evidence. Arthritis Res Ther 8:R127. https://doi.org/10.1186/ar2016

Andriacchi TP, Mündermann A, Smith RL, Alexander E, Dyrby C, Koo S (2004) A framework for the in vivo pathomechanics of osteoarthritis at the knee. Ann Biomed Eng 32:447–457. https://doi.org/10.1023/B:ABME.0000017541.82498.37

Babaskina LI, Litvinova TM, Babaskin DV, Krylova OV (2019) Control of the transdermal delivery process of active substances of the phytocomplex during phonophoresis in model experiments. Open Access Maced J Med Sci 7:2079–2083. https://doi.org/10.3889/oamjms.2019.607

Bae J, Kim N, Shin Y, Kim Y, Kim S (2020) Activity of catechins and their applications. BMC Dermatol 4:8. https://doi.org/10.1186/s41702-020-0057-8

Biswas SK (2016) Does the interdependence between oxidative stress and inflammation explain the antioxidant paradox? Oxid Med Cell Longev 2016:17–19. https://doi.org/10.1155/2016/5698931

Bonaterra GA, Schwarzbach H, Kelber O, Weiser D, Kinscherf R (2019) Anti-inflammatory effects of Phytodolor® (STW 1) and components (poplar, ash and goldenrod) on human monocytes/macrophages. Phytomedicine 58:152868. https://doi.org/10.1016/j.phymed.2019.152868

Burnett BP, Levy RM (2012) Flavocoxid (Limbrel®) manages osteoarthritis through modification of multiple inflammatory pathways: a review. Funct Food Health Dis. 2:379–413. https://doi.org/10.31989/ffhd.v2i11.74

Cencic A, Chingwaru W (2010) The role of functional foods, nutraceuticals, and food supplements in intestinal health. Nutrients 2:611–625. https://doi.org/10.3390/nu2060611

Chu C, Deng J, Man Y, Qu Y (2017) Green tea extracts epigallocatechin-3-gallate for different treatments. Biomed Res Int 2017:5615647. https://doi.org/10.1155/2017/5615647

Curtis JR, Owensby JK, Xie F (2020) Comparative safety of flavocoxid vs prescription NSAIDs among osteoarthritis patients. Osteoarthr Cartil 28:917–923. https://doi.org/10.1016/j.joca.2020.03.017

D’Adamo S, Cetrullo S, Panichi V, Mariani E, Flamigini F, Borzi RM (2020) Nutraceutical activity in osteoarthritis biology: A focus on the nutrigenomic role. Cells 9:1232. https://doi.org/10.3390/cells9051232

D’Amelia V, Aversano R, Chiaiese P, Carputo D (2018) The antioxidant properties of plant flavonoids: their exploitation by molecular plant breeding. Phytochem Rev 17:611–625. https://doi.org/10.1007/s11101-018-9568-y

Das B, Samanta S (2015) Chalcone as potent molecule: Anti-inflammatory, antiarthritic, antioxidant and antiulcer: a review. Int J Pharma Res 7:1–8

Devi A, Dwibedi V, Khan ZA (2021) Natural antioxidants in new age-related diseases. Rev Bras Farmacogn 31:387–407. https://doi.org/10.1007/s43450-021-00175-0

Dias MC, Pinto DCGA, Silva AMS (2021) Plant flavonoids: chemical characteristics and biological activity. Molecules 26:5377. https://doi.org/10.3390/molecules26175377

Elakkiya V, Krishnan K, Bhattacharyya A, Selvakumar R (2020) Advances in Ayurvedic medicinal plants and nanocarriers for arthritis treatment and management: a review. J Herb Med 24:100412. https://doi.org/10.1016/j.hermed.2020.100412

Engwa GA (2018) Free radicals and the role of plant phytochemicals as antioxidants against oxidative stress-related diseases. In: Asao T, Asaduzzaman M (ed) Phytochemicals – Source of antioxidants and role in disease prevention. InTech. https://doi.org/10.5772/intechopen.76719

Ernst E, Chrubaslk S (2000) A systematic review of randomized, placebo-controlled, double-blindtrials. Rheum Dis Clin 26:13–27. https://doi.org/10.1016/S0889-857X(05)70117-4

Ferraz CR, Carvalho TT, Manchope MF, Rasquel-Oliveira FS, Fattori V, Casagrande R, Verri WA (2020) Therapeutic potential of flavonoids in pain and inflammation: mechanisms of action, pre-clinical and clinical data, and pharmaceutical development. Molecules 25:762. https://doi.org/10.3390/molecules25030762

Fu Z, Chen Z, Xie Q, Lei H, Xiang S (2018) Hesperidin protects against IL-1β-induced inflammation in human osteoarthritis chondrocytes. Exp Ther Med 16:3721–3727. https://doi.org/10.3892/etm.2018.6616

Ginwala R, Bhavsar R, Chigbu DGI, Jain P (2019) Potential role of flavonoids in treating chronic inflammatory diseases with a special focus on the anti-inflammatory activity of apigenin. Molecules 8:35. https://doi.org/10.3390/antiox8020035

Goh YX, Jalil J, Lam KW, Husain K, Premakumar CM (2022) Genistein: a review on its anti-inflammatory properties. Front Pharmacol 13:820969. https://doi.org/10.3389/fphar.2022.820969

Goldring MB (2000) Osteoarthritis and cartilage: the role of cytokines. Curr Rheumatol Rep 2:459–465. https://doi.org/10.1007/s11926-000-0021-y

Green JA, Hirst-Jones KL, Davidson RK, Jupp O, Bao Y, MacGregor A, Donell S, Cassidy K, Clark I (2014) The potential for dietary factors to prevent or treat osteoarthritis. In: Proceedings of the Nutrition Society. Cambridge University Press, 73:278–288. https://doi.org/10.1017/S0029665113003935

Gundermann KJ, Müller J (2007) Phytodolor® - Effects and efficacy of a Herbal Medicine. Wien Med Wochenschr 157:343–347. https://doi.org/10.1007/s10354-007-0436-4

Hajialyani M, Hosein Farzaei M, Echeverría J, Nabavi S, Uriate E, Sobarzo-Sánchez E (2019) Hesperidin as a neuroprotective agent: a review of animal and clinical evidence. Molecules 24:648. https://doi.org/10.3390/molecules24030648

Hassimotto NMA, Moreira V, Nascimento NG, Souto P, Teixeira C, Lajolo F (2013) Inhibition of carrageenan-induced acute inflammation in mice by oral administration of anthocyanin mixture from wild mulberry and cyanidin-3-glucoside. Biomed Res Int 2013:146716. https://doi.org/10.1155/2013/146716

Hooshmand S, Soung DY, Lucas EA, Madihally S, Levenson C, Arjmandi B (2007) Genistein reduces the production of proinflammatory molecules in human chondrocytes. J Nutr Biochem 18:609–614. https://doi.org/10.1016/j.jnutbio.2006.11.006

Hu Q, Ecker M (2021) Overview of MMP-13 as a promising target for the treatment of osteoarthritis. Int J Mol Sci 22:1472. https://doi.org/10.3390/ijms22041742

Huang H, Liu Q, Liu L, Wu L, Zheng L (2015) Effect of epigallocatechin-3-gallate on proliferation and phenotype maintenance in rabbit articular chondrocytes in vitro. Exp Ther Med 9:213–218. https://doi.org/10.3892/etm.2014.2057

Hughes SD, Ketheesan N, Haleagrahara N (2017) The therapeutic potential of plant flavonoids on rheumatoid arthritis. Crit Rev Food Sci Nutr 57:3601–3613. https://doi.org/10.1080/10408398.2016.1246413

Hwang TL, Leu YL, Kao SH, Tang M, Chang H (2006) Viscolin, a new chalcone from Viscum coloratum, inhibits human neutrophil superoxide anion and elastase release via a cAMP-dependent pathway. Free Radic Biol Med 41:1433–1441. https://doi.org/10.1016/j.freeradbiomed.2006.08.001

Jahromy M, Kermani (2008) Chondroprotective effects of pomegranate juice on monoiodoacetate-induced osteoarthritis of the knee joint of mice. Phytother Res 22:544–549. https://doi.org/10.1002/ptr

Jantan I, Bukhari SNA, Adekoya OA, Sylte I (2014) Studies of synthetic chalcone derivatives as potential inhibitors of secretory phospholipase A2, cyclooxygenases, lipoxygenase and pro-inflammatory cytokines. Drug Des Devel Ther 8:1405–1418. https://doi.org/10.2147/DDDT.S67370

Karliana D, Anwar E, Bahtiar A (2019) Formulation and evaluation of quercetin nanoparticle gel for osteoarthritis. Int J Appl Pharm 11:54–59. https://doi.org/10.22159/ijap.2019v11i5.33191

Katarzyna MB (2017) Natural flavonoids: classification, potential role, and application of flavonoid analogues. Eur J Biol Res 7:108–123. https://doi.org/10.5281/zenodo.545778

Khoo HE, Azlan A, Tang ST, Lim SM (2017) Anthocyanidins and anthocyanins: colored pigments as food, pharmaceutical ingredients, and the potential health benefits. Food Nutr Res 61:1361779. https://doi.org/10.1080/16546628.2017.1361779

Kontogiorgis C, Mantzanidou M, Hadjipavlou-Litina D (2008) Chalcones and their potential role in inflammation. Mini Rev Med Chem 8:1224–1242. https://doi.org/10.2174/138955708786141034

Kulkarni RR, Patki PS, Jog VP, Gandage SG, Patwardhan B (1991) Treatment of osteoarthritis with a herbomineral formulation: a double-blind, placebo-controlled, cross-over study. J Ethnopharmacol 33:91–95. https://doi.org/10.1016/0378-8741(91)90167-C

Lee JH, Zhou HY, Cho SY, Kim Y, Lee Y, Jeong C (2007) Anti-inflammatory mechanisms of apigenin: inhibition of cyclooxygenase-2 expression, adhesión of monocytes to human umbilical vein endothelial cells, and expression of cellular adhesion molecules. Arch Pharm Res 30:1318–1327. https://doi.org/10.1007/bf02980273

Li XZ, Zhang SN (2020) Recent advance in treatment of osteoarthritis by bioactive components from herbal medicine. Chin Med 15:80. https://doi.org/10.1186/s13020-020-00363-5

Li J, Li J, Yue Y, Zhang P, Li J, Hu Y, Cheng W, Pan X (2014) Genistein suppresses tumor necrosis factor α-induced inflammation via modulating reactive oxygen species/Akt/nuclear factor κB and adenosine monophosphate-activated protein kinase signal pathways in human synoviocyte MH7A cells. Drug Des Devel Ther 8:315–323. https://doi.org/10.2147/DDDT.S52354

Li D, Wang P, Luo Y, Zhao M, Chen F (2017) Health benefits of anthocyanins and molecular mechanisms: update from recent decade. Crit Rev Food Sci Nutr 57:1729–1741. https://doi.org/10.1080/10408398.2015.1030064

Lim R, Barker G, Wall CA, Lappas M (2013) Dietary phytophenols curcumin, naringenin and apigenin reduce infection-induced inflammatory and contractile pathways in human placenta, foetal membranes and myometrium. Mol Hum Repod 19:451–462. https://doi.org/10.1093/molehr/gat015

Lim H, Heo MY, Kim HP (2019) Flavonoids: broad spectrum agents on chronic inflammation. Biomol Ther 27:241–253. https://doi.org/10.4062/biomolther.2019.034

Lin YL, Lin JK (1997) (-)-Epigallocatechin-3-gallate blocks the induction of nitric oxide synthase by down-regulating lipopolysaccharide-induced activity of transcription factor nuclear factor-κB. Mol Pharmacol 52:465–472. https://doi.org/10.1124/mol.52.3.465

Lindler BN, Long KE, Taylor NA, Lei W (2020) Use of herbal medications for treatment of osteoarthritis and rheumatoid arthritis. Medicines 7:67. https://doi.org/10.3390/medicines7110067

Liu FC, Wang CC, Lu JW, Lee C, Chen S, Ho Y, Peng Y (2019) Chondroprotective effects of genistein against osteoarthritis induced joint inflammation. Nutrients 11:1180. https://doi.org/10.3390/nu11051180

Loeser RF (2011) Aging and osteoarthritis. Curr Opin Rheumatol 23:492–496. https://doi.org/10.1097/BOR.0b013e3283494005

Loeser RF, Goldring SR, Scanzello CR, Goldring MB (2012) Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum 64:1697–1707. https://doi.org/10.1002/art.34453

Long L, Soeken K, Ernst E (2001) Herbal medicines for the treatment of osteoarthritis: A systematic review. Rheumatology 40(7):779–793. https://doi.org/10.1093/rheumatology/40.7.779

Luk HY, Appell C, Chyu MC, Chen C, Wang C, Yang R, Shen C (2020) Impacts of green tea on joint and skeletal muscle health: prospects of translational nutrition. Antioxidants 9:1050. https://doi.org/10.3390/antiox9111050

Mah SH (2020) Chalcones in diets. In: Xiao J, Sarkar SD, Asakawa Y (eds) Handbook of Dietary Phytochemicals, 1st edn. Springer, Singapore, pp 1–52

Maiti K, Mukherjee K, Gantait A, Ahamad HN, Saha BP, Mukherjee PK (2005) Enhanced therapeutic benefit of quercetin-phospholipid complex in carbontetrachloride-induced acute liver injury in rats: a comparative study. Iran J PharmacolTher 4:84–90

Martinez RM, Pinho-Ribeiro FA, Steffen VS, Caviglione CV, Vignoli JA, Baracat MM, Georgetti SR, Verri WA, Casagrande R (2015) Hesperidin methyl chalcone inhibits oxidative stress and inflammation in a mouse model of ultraviolet B irradiation-induced skin damage. J Photochem Photobiol B 148:145–153. https://doi.org/10.1016/j.jphotobiol.2015.03.030

Mathur M (2013) Phyto-complex and their role in enhancing efficacy of herbal drugs. Med Plants - Int J Phytomed Relat Ind 5:118. https://doi.org/10.5958/j.0975-6892.5.3.018

Mattioli R, Francioso A, Mosca L, Silva P (2020) Anthocyanins: a comprehensive review of their chemical properties and health effects on cardiovascular and neurodegenerative diseases. Molecules 25:3809. https://doi.org/10.3390/molecules25173809

Mieszczak CI, Kharazmi A, Rein J, Winther AK (1998) Gitadyl versus ibuprofen in patients with osteoarthritis: a double-blind, randomized, cross-over study of clinical efficacy and effects on platelets and pmns. Inflammopharmacology 6:67–73. https://doi.org/10.1007/s10787-998-0007-3

Nagai K, Jiang MH, Hada J, Nagata T, Yajima Y, Yamamoto S, Nishizaki T (2002) (−)-Epigallocatechin gallate protects against NO stress-induced neuronal damage after ischemia by acting as an anti-oxidant. Brain Res 956:319–322. https://doi.org/10.1016/S0006-8993(02)03564-3

Nunes CR, Arantes MB, de Faria Pereira SM, Leandro da Cruz L, de Souza Passos M, Pereira de Moraes L, Vieira IJC, Barros de Oliveira D (2020) Plants as sources of anti-inflammatory agents. Molecules 25:3726. https://doi.org/10.3390/molecules25163726

Olajide OA, Sarker SD (2020) Anti-inflammatory natural products. In: Sarkar SD, Nahar L (ed) Annual Reports in Medicinal Chemistry. Academic Press Inc. 55:153–177. https://doi.org/10.1016/bs.armc.2020.02.002

Panda VS, Naik SR (2008) Cardioprotective activity of Ginkgo biloba phytosomes in isoproterenol-induced myocardial necrosis in rats: a biochemical and histoarchitectural evaluation. Exp Toxicol Pathol 60:397–404. https://doi.org/10.1016/j.etp.2008.03.010

Parhiz H, Roohbakhsh A, Soltani F, Rezaee R, Iranshahi (2015) Antioxidant and anti-inflammatory properties of the citrus flavonoids hesperidin and hesperetin: an updated review of their molecular mechanisms and experimental models. Phytother Res 29:323–331. https://doi.org/10.1002/ptr.5256

Pierro FA, Menghi B, Barreca A, Lucarelli M, Calanderlli A (2009) GreenSelect® phytosome as an adjunctto a low-calorie diet for treatment of obesity: a clinical trial. Altern Med Rev 14:154–160

Primorac D, Molnar V, Rod E, Jeleč Ž, Čukelj F, Matišić V, Vrdoljak T, Hudetz D, Hajsok H, Borić I (2020) Knee osteoarthritis: a review of pathogenesis and state-of-the-art non-operative therapeutic considerations. Genes 11:854. https://doi.org/10.3390/genes11080854

Rasheed Z, Rasheed N, Al-Shobaili HA (2016) Epigallocatechin-3-O-gallate up-regulates microRNA-199a-3p expression by down-regulating the expression of cyclooxygenase-2 in stimulated human osteoarthritis chondrocytes. J Cell Mol Med 20:2241–2248. https://doi.org/10.1111/jcmm.12897

Rasquel-Oliveira FS, Manchope MF, Staurengo-Ferrari L, Ferraz CR, Saraiva-Santos T, Zaninelli TH, Fattori V, Artero NA, Badaro-Garcia S, de Freitas A, Casagrande R, Verri WA Jr (2020) Hesperidin methyl chalcone interacts with NFκB Ser276 and inhibits zymosan-induced joint pain and inflammation, and RAW 264.7 macrophage activation. Inflammopharmacology 28:979–992. https://doi.org/10.1007/s10787-020-00686-7

Rehman S, Nabi B, Baboota S, Ali J (2019) Natural anti-inflammatory agents for the management of osteoarthritis. In: Brahmachari G (ed) Discovery and development of anti-inflammatory agents from natural products. Elsevier Inc., pp 101–140. https://doi.org/10.1016/B978-0-12-816992-6.00004-8

Robert Levy R, Pillai L, Burnett BP (2010) Nutritional benefits of flavocoxid in patients with osteoarthritis: efficacy and safety. Nutr Diet Suppl 12:27–38. https://doi.org/10.2147/nds.s6410

Salehi B, Venditti A, Sharifi-Rad M, Kręgiel D, Sharifi-Rad J, Durazzo A, Lucarini M, Santini A, Souto EB, Novellino E, Antolak H, Azzini E, Setzer WN, Martins N (2019) The therapeutic potential of apigenin. Int J Mol Sci 20:1305. https://doi.org/10.3390/ijms20061305

Salehi B, Machin L, Monzote L, Sharifi-Rad J, Ezzat SM, Salem MA, Merghany RM, El Mahdy NM, Kılıç CS, Sytar O, Sharifi-Rad M, Sharopov F, Martins N, Martorell M, Cho WC (2020) Therapeutic potential of quercetin: new insights and perspectives for human health. ACS Omega 5:11849–11872. https://doi.org/10.1021/acsomega.0c01818

Scher JU, Pillinger MH, Abramson SB (2007) Nitric oxide synthases and osteoarthritis. Curr Rheumatol Rep 9:9–15. https://doi.org/10.1007/s11926-007-0016-z

Sellami M, Ghariani B, Louati H, Miled N, Gargouri Y (2019) Biological activities of extracts of different spices and plants. Int J Eng Technol 3:1051–1060

Sethi V, Garg M, Herve M, Mobasheri A (2022) Potential complementary and/or synergistic effects of curcumin and boswellic acids for management of osteoarthritis. Ther Adv Musculoskelet Dis 14:1759720X2211245. https://doi.org/10.1177/1759720X221124545

Singh A, Kumar S, Bajpai V, Reddy T, Rameshkumar K, Kumar B (2015) Structural characterization of flavonoid C- and O-glycosides in an extract of Adhatoda vasica leaves by liquid chromatography with quadrupole time-of-flight mass spectrometry. Rapid Commun Mass Spectrom 29:1095–1106. https://doi.org/10.1002/rcm.7202

Srinivasan S, Vinothkumar V, Murali R (2019) Antidiabetic efficacy of citrus fruits with special allusion to flavone glycosides. In: Watson RR, Preedy VR (ed) Bioactive food as dietary interventions for diabetes (2nd edn), Academic Press, pp 335–346. https://doi.org/10.1016/B978-0-12-813822-9.00022-9

Stojanov S, Kreft S (2020) Gut microbiota and the metabolism of phytoestrogens. Rev Bras Farmacogn 30:145–154. https://doi.org/10.1007/s43450-020-00049-x

Tang Y, Matsuoka I, Ono T, Inoue K, Kimura J (2008) Selective up-regulation of p2x4-receptor gene expresión by interferon-γ in vascular endotelial cells. J Pharmacol Sci 107:419–427. https://doi.org/10.1254/jphs.08073FP

Tedeschi E, Menegazzi M, Yao Y, Suzuki H, Förstermann U, Kleinert H (2004) Green tea inhibits human inducible nitric-oxide synthase expresión by down-regulating signal transducer and activatorof transcription-1 activation. Mol Pharmacol 65:111–120. https://doi.org/10.1124/mol.65.1.111

Thomas S, Browne H, Mobasheri A, Rayman MP (2018) What is the evidence for a role for diet and nutrition in osteoarthritis? Rheumatology 57:61–74. https://doi.org/10.1093/rheumatology/key011

Tsai YF, Chen YR, Chen JP, Tang Y, Yang KC (2019) Effect of hesperidin on anti-inflammation and celular antioxidant capacity in hydrogen peroxide-stimulated human articular chondrocytes. Process Biochem 85:175–184. https://doi.org/10.1016/j.procbio.2019.07.014

Tu M, Yang M, Yu N, Zhen G, Wan M, Liu W, Ji B, Ma H, Guo Q, Tong P, Cao L, Luo X, Cao X (2019) Inhibition of cyclooxygenase-2 activity in subcondral bone modifies a subtype of osteoarthritis. Bone Res 7:29. https://doi.org/10.1038/s41413-019-0071-x

ur Rashid H, Xu Y, Ahmad N, Muhammad Y, Wang L (2019) Promising anti-inflammatory effects of chalcones via inhibition of cyclooxygenase, prostaglandin E2, inducible NO synthase and nuclear factor κbactivities. Bioorg Chem 87:335–365. https://doi.org/10.1016/j.bioorg.2019.03.033

van der Kraan PM, Blaney Davidson EN, van den Berg WB (2010) A role forage-related changes in TGFβ signaling in aberrant chondrocyte differentiation and osteoarthritis. Arthritis Res Ther 12:201. https://doi.org/10.1186/ar2896

Villa-Rodriguez JA, Kerimi A, Abranko L, Tumova S, Ford L, Blackburn RS, Rayner C, Williamson G (2018) Acute metabolic actions of the major polyphenols in chamomile: an in vitro mechanistic study on their potential to attenuate postprandial hyperglycaemia. Sci Rep 8:5471. https://doi.org/10.1038/s41598-018-23736-1

Wei B, Zhang Y, Tang L, Ji Y, Yan C, Zhang X (2019) Protective effects of quercetin against inflammation and oxidative stress in a rabbit model of knee osteoarthritis. Drug Dev Res 80:360–367. https://doi.org/10.1002/ddr.21510

Yuan J, Ding W, Wu N, Jiang S, Li W (2019) Protective effect of genistein on condylar cartilage through downregulating NF- B expression in experimentally created osteoarthritis rats. Biomed Res Int 2019:2629791. https://doi.org/10.1155/2019/2629791

Zhang YJ, Gan RY, Li S, Zhou Y, Li AN, Xu DP, Li HB (2015) Antioxidant phytochemicals for the prevention and treatment of chronic diseases. Molecules 20:21138–21156. https://doi.org/10.3390/molecules201219753

Zhao G, Han X, Cheng W, Ni J, Zhang Y, Lin J, Song Z (2017) Apigen ininhibits proliferation and invasion, and induces apoptosis and cell cycle arrestin human melanoma cells. Oncol Rep 34:2277–2285. https://doi.org/10.3892/or.2017.5450

Zhou Z, Zhang Y, Lin L, Zhou J (2018) Apigenin suppresses the apoptosis of H9C2 ratcardiomyocytessubjectedtomyocardialischemia-reperfusioninjuryviaupregulationofthe PI3K/Akt pathway. Mol Med Rep 18:1560–1570. https://doi.org/10.3892/mmr.2018.9115

Zhuang C, Zhang W, Sheng C, Zhang W, Xing C, Miao Z (2017) Chalcone: a privileged structure in medicinal chemistry. Chem Rev 117:7762–7810. https://doi.org/10.1021/acs.chemrev.7b00020

Zou Y, Liu Q, Guo P, Huang Y, Ye Z, Hu J (2020) Anti-chondrocyte apoptosis effect of genistein in treating inflammation-induced osteoarthritis. Mol Med Rep 22:2032–2042. https://doi.org/10.3892/mmr.2020.11254