Abstract
Pinocembrin is a natural flavanone found abundantly in diverse flora across various plant families and honey, globally. The purification and biosynthesis of both natural sources using different techniques yielded pinocembrin which demonstrated potent pharmacological properties in in vitro and in vivo models. Pinocembrin displayed significant protection and management of neurological disorders by the unveiling of its action mechanism. Accompanied beneficial effects include antioxidant, antiinflammatory, antibacterial, antimicrobial, antidiabetic, antifungal, antiviral, antifeedant, homeostasis regulation, immunomodulatory, hepatoprotection, antitumor, anticancer, antifibrotic, vasodilatory, vasorelaxant, vasoprotective, osteoprotective, and antiarrhythmic properties. The absorption, distribution, metabolism, and excretion pathways of pinocembrin are discussed, while toxicity evaluation revealed that pinocembrin is safe for consumption and administration without adverse effects or accumulation observed inside the body. Phase I human clinical trials disclosed that healthy female and male subjects tolerated pinocembrin injection well. There were no commercialized pinocembrin-related products, yet numerous patents documented advantageous inventions of pinocembrin in the food, pharmaceutical, medical, cosmetic, and production industries. Overall, this chapter provides a comprehensive insight into the bioactive dietary flavanone and suggests that pinocembrin is a promising phytochemical in functional food ingredient development and drug discovery in health care applications.
This is a preview of subscription content, log in via an institution to check access.
References
Adelmann J, Passos M, Breyer DH, dos Santos MHR, Lenz C, Leite NF, Lanças FM, Fontana JD (2007) Exotic flora dependence of an unusual Brazilian propolis: the pinocembrin biomarker by capillary techniques. J Pharm Biomed Anal 43(1):174–178. https://doi.org/10.1016/j.jpba.2006.07.014
Ahmed LA, Rizk SM, El Maraghy SA (2017) Pinocembrin ex vivo preconditioning improves the therapeutic efficacy of endothelial progenitor cells in monocrotaline-induced pulmonary hypertension in rats. Biochem Pharmacol 138:193–204. https://doi.org/10.1016/j.bcp.2017.04.024
Ajmala Shireen P, Muraleedharan K, Abdul Mujeeb VM (2017) Identification of flavanones from Boesenbergia rotunda as potential antioxidants and monoamine oxidase B inhibitors. Chem Pap 71(12):2473–2483. https://doi.org/10.1007/s11696-017-0241-5
Alcaráz LE, Blanco SE, Puig ON, Tomás F, Ferretti FH (2000) Antibacterial activity of flavonoids against methicillin-resistant Staphylococcus aureus strains. J Theor Biol 205(2):231–240. https://doi.org/10.1006/jtbi.2000.2062
Alzahrani AM, Rajendran P (2021) Pinocembrin attenuates benzo(a)pyrene-induced CYP1A1 expression through multiple pathways: an in vitro and in vivo study. J Biochem Mol Toxicol 35(4):1–13. https://doi.org/10.1002/jbt.22695
Antunes Viegas D, Palmeira-De-Oliveira A, Salgueiro L, Martinez-De-Oliveira J, Palmeira-De-Oliveira R (2014) Helichrysum italicum: From traditional use to scientific data. J Ethnopharmacol 151(1):54–65. https://doi.org/10.1016/j.jep.2013.11.005
Arias J, Martínez J, Stashenko E, del Valle JM, de la Fuente JC (2022) Supercritical CO2 extraction of pinocembrin from Lippia origanoides distillation residues. 1. Multicomponent solubility and equilibrium partition. J Supercrit Fluids 180:105426–105437. https://doi.org/10.1016/j.supflu.2021.105426
Bertelli D, Papotti G, Bortolotti L, Marcazzan GL, Plessi M (2012) 1H-NMR simultaneous identification of health-relevant compounds in propolis extracts. Phytochem Anal 23(3):260–266. https://doi.org/10.1002/pca.1352
Brasil FB, de Almeida FJS, Luckachaki MD, Dall’Oglio EL, de Oliveira MR (2021) Pinocembrin pretreatment counteracts the chlorpyrifos-induced HO-1 downregulation, mitochondrial dysfunction, and inflammation in the SH-SY5Y cells. Metab Brain Dis 36(8):2377–2391. https://doi.org/10.1007/s11011-021-00803-7
Cahyana Y, Adiyanti T (2021) Review: flavonoids as antidiabetic agents. Indones J Chem 21(2):512–526. https://doi.org/10.22146/ijc.58439
Cao G, Ying P, Yan B, Xue W, Li K, Shi A, Sun T, Yan J, Hu X (2015) Pharmacokinetics, safety, and tolerability of single and multiple-doses of pinocembrin injection administered intravenously in healthy subjects. J Ethnopharmacol 168:31–36. https://doi.org/10.1016/j.jep.2015.03.041
Cao P, Chen Q, Shi C, Pei M, Wang L, Gong Z (2022) Pinocembrin ameliorates acute liver failure via activating the Sirt1/PPARα pathway in vitro and in vivo. Eur J Pharmacol 915:174610–174623. https://doi.org/10.1016/j.ejphar.2021.174610
Celano R, Docimo T, Piccinelli AL, Rizzo S, Campone L, Di Sanzo R, Carabetta S, Rastrelli L, Russo M (2021) Specialized metabolite profiling of different Glycyrrhiza glabra organs by untargeted UHPLC-HRMS. Ind Crop Prod 170:113688–113699. https://doi.org/10.1016/j.indcrop.2021.113688
Chankhanittha T, Yenjai C, Nanan S (2022) Utilization of formononetin and pinocembrin from stem extract of Dalbergia parviflora as capping agents for preparation of ZnO photocatalysts for degradation of RR141 azo dye and ofloxacin antibiotic. Catal Today 384–386:279–293. https://doi.org/10.1016/j.cattod.2021.03.002
Charoensin S, Punvittayagul C, Pompimon W, Mevatee U, Wongpoomchai R (2010) Toxicological and clastogenic evaluation of pinocembrin and pinostrobin isolated from Boesenbergia pandurata in Wistar rats. Thai J Toxicol 25(1):29–40
Chen KS, Der Shi M, Chien CS, Shih YW (2014) Pinocembrin suppresses TGF-β1-induced epithelial-mesenchymal transition and metastasis of human Y-79 retinoblastoma cells through inactivating αvβ3 integrin/FAK/p38α signaling pathway. Cell Biosci 4(1):41–54. https://doi.org/10.1186/2045-3701-4-41
Chen X, Wan W, Guo Y, Ye T, Fo Y, Sun Y, Qu C, Yang B, Zhang C (2021) Pinocembrin ameliorates post-infarct heart failure through activation of Nrf2/HO-1 signaling pathway. Mol Med 27(1):100–112. https://doi.org/10.1186/s10020-021-00363-7
Chen X, Wan W, Ran Q, Ye T, Sun Y, Liu Z, Liu X, Shi S, Qu C, Zhang C, Yang B (2022) Pinocembrin mediates antiarrhythmic effects in rats with isoproterenol-induced cardiac remodeling. Eur J Pharmacol 920:174799–174812. https://doi.org/10.1016/j.ejphar.2022.174799
Cho H, Kim K, Kim N, Woo M, Kim HY (2020) Effect of propolis phenolic compounds on free fatty acid receptor 4 activation. Food Sci Biotechnol 29(4):579–584. https://doi.org/10.1007/s10068-019-00688-4
Danelutte AP, Lago JHG, Young MCM, Kato MJ (2003) Antifungal flavanones and prenylated hydroquinones from Piper crassinervium Kunth. Phytochemistry 64(2):555–559. https://doi.org/10.1016/S0031-9422(03)00299-1
Danert FC, Zampini C, Ordonẽz R, Maldonado L, Bedascarrasbure E, Isla MI (2014) Nutritional and functional properties of aqueous and hydroalcoholic extracts from argentinean propolis. Nat Prod Commun 9(2):167–170. https://doi.org/10.1177/1934578x1400900209
Celerino de Moraes Porto IC, Chaves Cardoso de Almeida D, Vasconcelos Calheiros de Oliveira Costa G, Sampaio Donato TS, Moreira Nunes L, Gomes do Nascimento T, dos Santos Oliveira JM, Batista da Silva C, Barbosa dos Santos N, de Alencar E Silva Leite ML, Diniz Basílio-Júnior I, Braga Dornelas C, Barnabé Escodro P, da Silva Fonseca EJ, Umeko Kamiya R (2018) Mechanical and aesthetics compatibility of Brazilian red propolis micellar nanocomposite as a cavity cleaning agent. BMC Complement Altern Med 18(1):1–17. https://doi.org/10.1186/s12906-018-2281-y
de Oliveira MR, Peres A, Ferreira GC (2017a) Pinocembrin attenuates mitochondrial dysfunction in human neuroblastoma SH-SY5Y cells exposed to methylglyoxal: Role for the Erk1/2–Nrf2 signaling pathway. Neurochem Res 42(4):1057–1072. https://doi.org/10.1007/s11064-016-2140-5
de Oliveira MR, Peres A, Gama CS, Bosco SMD (2017b) Pinocembrin provides mitochondrial protection by the activation of the Erk1/2-Nrf2 signaling pathway in SH-SY5Y neuroblastoma cells exposed to paraquat. Mol Neurobiol 54(8):6018–6031. https://doi.org/10.1007/s12035-016-0135-5
de Oliveira MR, da Costa FG, Brasil FB, Peres A (2018) Pinocembrin suppresses H2O2-induced mitochondrial dysfunction by a mechanism dependent on the Nrf2/HO-1 axis in SH-SY5Y cells. Mol Neurobiol 55(2):989–1003. https://doi.org/10.1007/s12035-016-0380-7
Déciga-Campos M, Mata R, Rivero-Cruz I (2017) Antinociceptive pharmacological profile of Dysphania graveolens in mouse. Biomed Pharmacother 89:933–938. https://doi.org/10.1016/j.biopha.2017.02.096
Derseh HB, Goodger JQD, Scheerlinck JPY, Samuel CS, Woodrow IE, Palombo EA, Cumming A, Snibson K (2021) The efficacy and safety of pinocembrin in a sheep model of bleomycin-induced pulmonary fibrosis. PLoS One 16(12):e0260719. https://doi.org/10.1371/journal.pone.0260719
Dezmirean DS, Mărghitaş LA, Chirilă F, Copaciu F, Simonca V, Bobiş O, Erler S (2017) Influence of geographic origin, plant source and polyphenolic substances on antimicrobial properties of propolis against human and honey bee pathogens. J Apic Res 56(5):588–597. https://doi.org/10.1080/00218839.2017.1356205
Diaz Napal GN, Palacios SM (2015) Bioinsecticidal effect of the flavonoids pinocembrin and quercetin against Spodoptera frugiperda. J Pest Sci 88(3):629–635. https://doi.org/10.1007/s10340-014-0641-z
Diaz Napal GN, Carpinella MC, Palacios SM (2009) Antifeedant activity of ethanolic extract from Flourensia oolepis and isolation of pinocembrin as its active principle compound. Bioresour Technol 100(14):3669–3673. https://doi.org/10.1016/j.biortech.2009.02.050
Egbuna C, Hassan S (2021) Dietary phytochemicals: A source of novel bioactive compounds for the treatment of obesity, cancer and diabetes. Springer Nature. https://doi.org/10.1007/978-3-030-72999-8
El-Demerdash AA, Menze ET, Esmat A, Tadros MG, Elsherbiny DA (2021) Protective and therapeutic effects of the flavonoid “pinocembrin” in indomethacin-induced acute gastric ulcer in rats: impact of anti-oxidant, anti-inflammatory, and anti-apoptotic mechanisms. Naunyn Schmiedeberg’s Arch Pharmacol 394(7):1411–1424. https://doi.org/10.1007/s00210-021-02067-5
Falcão SI, Vilas-Boas M, Estevinho LM, Barros C, Domingues MRM, Cardoso SM (2010) Phenolic characterization of Northeast Portuguese propolis: usual and unusual compounds. Anal Bioanal Chem 396(2):887–897. https://doi.org/10.1007/s00216-009-3232-8
Fu X, Belwal T, He Y, Xu Y, Li L, Luo Z (2022) UPLC-Triple-TOF/MS characterization of phenolic constituents and the influence of natural deep eutectic solvents on extraction of Carya cathayensis Sarg. peels: composition, extraction mechanism and in vitro biological activities. Food Chem 370:131042–131054. https://doi.org/10.1016/j.foodchem.2021.131042
Gan W, Li X, Cui Y, Xiao T, Liu R, Wang M, Wei Y, Cui M, Ren S, Helian K, Ning W, Zhou H, Yang C (2021) Pinocembrin relieves lipopolysaccharide and bleomycin induced lung inflammation via inhibiting TLR4-NF-κB-NLRP3 inflammasome signaling pathway. Int Immunopharmacol 90:107230–107243. https://doi.org/10.1016/j.intimp.2020.107230
Gao M, Zhang WC, Liu QS, Hu JJ, Liu GT, Du GH (2008) Pinocembrin prevents glutamate-induced apoptosis in SH-SY5Y neuronal cells via decrease of bax/bcl-2 ratio. Eur J Pharmacol 591(1–3):73–79. https://doi.org/10.1016/j.ejphar.2008.06.071
Gao J, Lin S, Gao Y, Zou X, Zhu J, Chen M, Wan H, Zhu H (2019) Pinocembrin inhibits the proliferation and migration and promotes the apoptosis of ovarian cancer cells through down-regulating the mRNA levels of N-cadherin and GABAB receptor. Biomed Pharmacother 120:109505–109512. https://doi.org/10.1016/j.biopha.2019.109505
Giri SS, Sen SS, Sukumaran V, Park SC (2016) Pinocembrin attenuates lipopolysaccharide-induced inflammatory responses in Labeo rohita macrophages via the suppression of the NF-κB signalling pathway. Fish Shellfish Immunol 56:459–466. https://doi.org/10.1016/j.fsi.2016.07.038
Gong LJ, Wang XY, Gu WY, Wu X (2020) Pinocembrin ameliorates intermittent hypoxia-induced neuroinflammation through BNIP3-dependent mitophagy in a murine model of sleep apnea. J Neuroinflammation 17(1):337–354. https://doi.org/10.1186/s12974-020-02014-w
Goodger JQD, Senaratne SL, van der Peet P, Browning R, Williams SJ, Nicolle D, Woodrow IE (2019) Eucalyptus subgenus Eucalyptus (Myrtaceae) trees are abundant sources of medicinal pinocembrin and related methylated flavanones. Ind Crop Prod 131:166–172. https://doi.org/10.1016/j.indcrop.2019.01.050
Gu X, Zhang Q, Du Q, Shen H, Zhu Z (2017) Pinocembrin attenuates allergic airway inflammation via inhibition of NF-κB pathway in mice. Int Immunopharmacol 53:90–95. https://doi.org/10.1016/j.intimp.2017.10.005
Gu J, Huang H, Liu C, Jiang B, Li M, Liu L, Zhang S (2021) Pinocembrin inhibited cardiomyocyte pyroptosis against doxorubicin-induced cardiac dysfunction via regulating Nrf2/Sirt3 signaling pathway. Int Immunopharmacol 95:107533–107540. https://doi.org/10.1016/j.intimp.2021.107533
Guang HM, Du GH (2006) Protections of pinocembrin on brain mitochondria contribute to cognitive improvement in chronic cerebral hypoperfused rats. Eur J Pharmacol 542(1–3):77–83. https://doi.org/10.1016/j.ejphar.2006.04.054
Guo L, Chen X, Li LN, Tang W, Pan YT, Kong JQ (2016) Transcriptome-enabled discovery and functional characterization of enzymes related to (2S)-pinocembrin biosynthesis from Ornithogalum caudatum and their application for metabolic engineering. Microb Cell Factories 15(1):1–19. https://doi.org/10.1186/s12934-016-0424-8
Hanieh H, Hairul Islam VI, Saravanan S, Chellappandian M, Ragul K, Durga A, Venugopal K, Senthilkumar V, Senthilkumar P, Thirugnanasambantham K (2017) Pinocembrin, a novel histidine decarboxylase inhibitor with anti-allergic potential in in vitro. Eur J Pharmacol 814:178–186. https://doi.org/10.1016/j.ejphar.2017.08.012
Jin X, Liu Q, Jia L, Li M, Wang X (2015) Pinocembrin attenuates 6-OHDA-induced neuronal cell death through Nrf2/ARE pathway in SH-SY5Y Cells. Cell Mol Neurobiol 35(3):323–333. https://doi.org/10.1007/s10571-014-0128-8
Kanchanapiboon J, Kongsa U, Pattamadilok D, Kamponchaidet S, Wachisunthon D, Poonsatha S, Tuntoaw S (2020) Boesenbergia rotunda extract inhibits Candida albicans biofilm formation by pinostrobin and pinocembrin. J Ethnopharmacol 261:113193–113202. https://doi.org/10.1016/j.jep.2020.113193
Kim BG, Lee H, Ahn JH (2014) Biosynthesis of pinocembrin from glucose using engineered Escherichia coli. J Microbiol Biotechnol 24(11):1536–1541. https://doi.org/10.4014/jmb.1406.06011
Kuhlmann T, Miron V, Cuo Q, Wegner C, Antel J, Brück W (2008) Differentiation block of oligodendroglial progenitor cells as a cause for remyelination failure in chronic multiple sclerosis. Brain 131(7):1749–1758. https://doi.org/10.1093/brain/awn096
Lago JHG, Ramos CS, Casanova DCC, Morandim ADA, Bergamo DCB, Cavalheiro AJ, Bolzani VDS, Furlan M, Guimarães EF, Young MCM, Kato MJ (2004) Benzoic acid derivatives from Piper species and their fungitoxic activity against Cladosporium cladosporioides and C. sphaerospermum. J Nat Prod 67(11):1783–1788. https://doi.org/10.1021/np030530j
Lan X, Wang W, Li Q, Wang J (2016) The natural flavonoid pinocembrin: Molecular targets and potential therapeutic applications. Mol Neurobiol 53(3):1794–1801. https://doi.org/10.1007/s12035-015-9125-2
Lan X, Han X, Li Q, Li Q, Gao Y, Cheng T, Wan J, Zhu W, Wang J (2017) Pinocembrin protects hemorrhagic brain primarily by inhibiting toll-like receptor 4 and reducing M1 phenotype microglia. Brain Behav Immun 61:326–339. https://doi.org/10.1016/j.bbi.2016.12.012
Lee JL, Loe MWC, Lee RCH, Chu JJH (2019) Antiviral activity of pinocembrin against Zika virus replication. Antivir Res 167(March):13–24. https://doi.org/10.1016/j.antiviral.2019.04.003
Li L, Pang XB, Chen BN, Gao L, Wang L, Wang SB, Wang SB, Liu DP, Du GH (2013) Pinocembrin inhibits angiotensin II-induced vasoconstriction via suppression of the increase of [Ca2+]i and ERK1/2 activation through blocking AT1R in the rat aorta. Biochem Biophys Res Commun 435(1):69–75. https://doi.org/10.1016/j.bbrc.2013.04.039
Li C, Wan W, Ye T, Sun Y, Chen X, Liu X, Shi S, Zhang Y, Qu C, Yang B, Zhang C (2021) Pinocembrin alleviates lipopolysaccharide-induced myocardial injury and cardiac dysfunction in rats by inhibiting p38/JNK MAPK pathway. Life Sci 277:119418–119427. https://doi.org/10.1016/j.lfs.2021.119418
Liu R, Gao M, Yang ZH, Du GH (2008) Pinocembrin protects rat brain against oxidation and apoptosis induced by ischemia-reperfusion both in vivo and in vitro. Brain Res 1216:104–115. https://doi.org/10.1016/j.brainres.2008.03.049
Liu R, Wu CX, Zhou D, Yang F, Tian S, Zhang L, Zhang TT, Du GH (2012) Pinocembrin protects against β-amyloid-induced toxicity in neurons through inhibiting receptor for advanced glycation end products (RAGE)-independent signaling pathways and regulating mitochondrion-mediated apoptosis. BMC Med 10:105–126. https://doi.org/10.1186/1741-7015-10-105
Liu R, Li JZ, Song JK, Zhou D, Huang C, Bai XY, Xie T, Zhang X, Li YJ, Wu CX, Zhang L, Li L, Zhang TT, Du GH (2014) Pinocembrin improves cognition and protects the neurovascular unit in Alzheimer related deficits. Neurobiol Aging 35(6):1275–1285. https://doi.org/10.1016/j.neurobiolaging.2013.12.031
López A, Dong SM, Towers GHN (2002) Antifungal activity of benzoic acid derivatives from Piper lanceaefolium. J Nat Prod 65(1):62–64. https://doi.org/10.1021/np010410g
Marghitas LA, Dezmirean DS, Pocol CB, Ilea M, Bobis O, Gergen I (2010) The development of a biochemical profile of acacia honey by identifying biochemical determinants of its quality. Not Bot Horti Agrobot Cluj-Napoca 38(2):84–90. https://doi.org/10.15835/nbha3824780
Massaro CF, Katouli M, Grkovic T, Vu H, Quinn RJ, Heard TA, Carvalho C, Manley-Harris M, Wallace HM, Brooks P (2014) Anti-staphylococcal activity of C-methyl flavanones from propolis of Australian stingless bees (Tetragonula carbonaria) and fruit resins of Corymbia torelliana (Myrtaceae). Fitoterapia 95:247–257. https://doi.org/10.1016/j.fitote.2014.03.024
Mazzotta S, Governa P, Borgonetti V, Marcolongo P, Nanni C, Gamberucci A, Manetti F, Pessina F, Carullo G, Brizzi A, Aiello F (2021) Pinocembrin and its linolenoyl ester derivative induce wound healing activity in HaCaT cell line potentially involving a GPR120/FFA4 mediated pathway. Bioorg Chem 108:104657–104666. https://doi.org/10.1016/j.bioorg.2021.104657
Meng F, Liu R, Gao M, Wang Y, Yu X, Xuan Z, Sun J, Yang F, Wu C, Du G (2011) Pinocembrin attenuates blood-brain barrier injury induced by global cerebral ischemia-reperfusion in rats. Brain Res 1391(2):93–101. https://doi.org/10.1016/j.brainres.2011.03.010
Metzner J, Bekemeier H, Schneidewind EM, Wenzel U (1979) Pharmacokinetic studies of the propolis constituent pinocembrin in the rat. Pharmazie 34(3):185–187
Mirza F, Canalis E (2015) Management of endocrine disease: secondary osteoporosis: pathophysiology and management. Eur J Endocrinol 173(3):R131–R151. https://doi.org/10.1530/eje-15-0118
Napal GND, Defagó MT, Valladares GR, Palacios SM (2010) Response of Epilachna paenulata to two flavonoids, Pinocembrin and quercetin, in a comparative study. J Chem Ecol 36(8):898–904. https://doi.org/10.1007/s10886-010-9823-1
Natsume N, Yonezawa T, Woo JT, Teruya T (2021) Effect of pinocembrin isolated from Alpinia zerumbet on osteoblast differentiation. Cytotechnology 73(3):307–317. https://doi.org/10.1007/s10616-020-00427-2
Nyokat N, Yen KH, Hamzah AS, Lim IF, Saaidin AS (2017) Isolation and synthesis of pinocembrin and pinostrobin from Artocarpus odoratissimus. Malaysian J Anal Sci 21(5):1156–1161. https://doi.org/10.17576/mjas-2017-2105-19
Oddo L, Bogdanov S (2004) Determination of honey botanical origin: problems and issues. Apidologie 35:S2–S3. https://doi.org/10.1051/apido
Okuno Y, Marumoto S, Miyazawa M (2017) Antimutagenic activity of flavonoids from Sozuku. Nat Prod Res 33(6):862–865. https://doi.org/10.1080/14786419.2017.1408104
Özkök A, Keskin M, Tanuğur Samancı AE, Yorulmaz Önder E, Takma Ç (2021) Determination of antioxidant activity and phenolic compounds for basic standardization of Turkish propolis. Appl Biol Chem 64(1):37–47. https://doi.org/10.1186/s13765-021-00608-3
Panche AN, Diwan AD, Chandra SR (2016) Flavonoids: an overview. J Nutr Sci 5(47):1–15. https://doi.org/10.1017/jns.2016.41
Pei B, Sun J (2018) Pinocembrin alleviates cognition deficits by inhibiting inflammation in diabetic mice. J Neuroimmunol 314:42–49. https://doi.org/10.1016/j.jneuroim.2017.11.006
Peng L, Yang S, Cheng YJ, Chen F, Pan S, Fan G (2012) Antifungal activity and action mode of pinocembrin from propolis against Penicillium italicum. Food Sci Biotechnol 21(6):1533–1539. https://doi.org/10.1007/s10068-012-0204-0
Pobłocka-Olech L, Inkielewicz-Stepniak I, Krauze-Baranowska M (2019) Anti-inflammatory and antioxidative effects of the buds from different species of Populus in human gingival fibroblast cells: role of bioflavanones. Phytomedicine 56:1–9. https://doi.org/10.1016/j.phymed.2018.08.015
Potipiranun T, Adisakwattana S, Worawalai W, Ramadhan R, Phuwapraisirisan P (2018) Identification of pinocembrin as an anti-glycation agent and α-glucosidase inhibitor from fingerroot (Boesenbergia rotunda): The tentative structure–activity relationship towards MG-trapping activity. Molecules 23(12):1–13. https://doi.org/10.3390/molecules23123365
Poulsen MW, Hedegaard RV, Andersen JM, de Courten B, Bügel S, Nielsen J, Skibsted LH, Dragsted LO (2013) Advanced glycation endproducts in food and their effects on health. Food Chem Toxicol 60:10–37. https://doi.org/10.1016/j.fct.2013.06.052
Punvittayagul C, Wongpoomchai R, Taya S, Pompimon W (2011) Effect of pinocembrin isolated from Boesenbergia pandurata on xenobiotic-metabolizing enzymes in rat liver. Drug Metab Lett 5(1):1–5. https://doi.org/10.2174/187231211794455226
Punvittayagul C, Pompimon Wilart W, Wanibuchi H, Fukushima S, Wongpoomchai R (2012) Effects of pinocembrin on the initiation and promotion stages of rat hepatocarcinogenesis. Asian Pacific J Cancer Prev 13(5):2257–2261. https://doi.org/10.7314/APJCP.2012.13.5.2257
Rameshkumar KB, Sheeja DBA, Nair MS, George V (2015) Curcuma ecalcarata – new natural source of pinocembrin and piperitenone. Nat Prod Res 29(13):1276–1279. https://doi.org/10.1080/14786419.2014.994210
Rasul A, Millimouno FM, Ali Eltayb W, Ali M, Li J, Li X (2013) Pinocembrin: a novel natural compound with versatile pharmacological and biological activities. Biomed Res Int 2013:1–9. https://doi.org/10.1155/2013/379850
Riccardi C, Levi-Schaffer F, Tiligada E (2018) Immunopharmacology and inflammation. Springer, Cham
Romero M, Freire J, Pastene E, García A, Aranda M, González C (2019) Propolis polyphenolic compounds affect the viability and structure of Helicobacter pylori in vitro. Rev Bras Farmacogn 29(3):325–332. https://doi.org/10.1016/j.bjp.2019.03.002
Rustamova SI, Tsiferova NA, Khamidova OJ, Kurbannazarova RS, Merzlyak PG, Khushbaktova ZA, Syrov VN, Botirov EK, Eshbakova KA, Sabirov RZ (2019) Effect of plant flavonoids on the volume regulation of rat thymocytes under hypoosmotic stress. Pharmacol Rep 71(6):1079–1087. https://doi.org/10.1016/j.pharep.2019.05.023
Saad MA, Abdel Salam RM, Kenawy SA, Attia AS (2015) Pinocembrin attenuates hippocampal inflammation, oxidative perturbations and apoptosis in a rat model of global cerebral ischemia reperfusion. Pharmacol Rep 67(1):115–122. https://doi.org/10.1016/j.pharep.2014.08.014
Said MM, Azab SS, Saeed NM, El-Demerdash E (2018) Antifibrotic mechanism of pinocembrin: Impact on oxidative stress, inflammation and TGF-B /Smad inhibition in rats. Ann Hepatol 17(2):307–317. https://doi.org/10.5604/01.3001.0010.8662
Sala A, Recio MC, Schinella GR, Máñez S, Giner RM, Cerdá-Nicolás M, Ríos JL (2003) Assessment of the anti-inflammatory activity and free radical scavenger activity of tiliroside. Eur J Pharmacol 461(1):53–61. https://doi.org/10.1016/S0014-2999(02)02953-9
Sampietro DA, Sampietro Vattuone MM, Vattuone MA (2016) Immunomodulatory activity of Apis mellifera propolis from the North of Argentina. LWT Food Sci Technol 70:9–15. https://doi.org/10.1016/j.lwt.2016.02.028
Sang H, Yuan N, Yao S, Li F, Wang J, Fang Y, Qin S (2012) Inhibitory effect of the combination therapy of simvastatin and pinocembrin on atherosclerosis in apoE-deficient mice. Lipids Health Dis 11(1):166–175. https://doi.org/10.1186/1476-511X-11-166
Santos LM, Fonseca MS, Sokolonski AR, Deegan KR, Araújo RPC, Umsza-Guez MA, Barbosa JDV, Portela RD, Machado BAS (2019) Propolis: types, composition, biological activities, and veterinary product patent prospecting. J Sci Food Agric 100(4):1369–1382. https://doi.org/10.1002/jsfa.10024
Sayre CL, Takemoto JK, Martinez SE, Davies NM (2013) Chiral analytical method development and application to pre-clinical pharmacokinetics of pinocembrin. Biomed Chromatogr 27(6):681–684. https://doi.org/10.1002/bmc.2853
Sayre CL, Alrushaid S, Martinez SE, Anderson HD, Davies NM (2015) Pre-clinical pharmacokinetic and pharmacodynamic characterization of selected chiral flavonoids: Pinocembrin and pinostrobin. J Pharm Pharm Sci 18(4):368–396. https://doi.org/10.18433/j3bk5t
Shao Q, Zhao M, Pei W, Pu Y, Liu M, Liu W, Yu Z, Chen K, Liu H, Deng B, Cao L (2021) Pinocembrin promotes OPC differentiation and remyelination via the mTOR signaling pathway. Neurosci Bull 37(9):1314–1324. https://doi.org/10.1007/s12264-021-00696-7
Shen X, Liu Y, Luo X, Yang Z (2019) Advances in biosynthesis, pharmacology, and pharmacokinetics of pinocembrin, a promising natural small-molecule drug. Molecules 24(12):2323–2337. https://doi.org/10.3390/molecules24122323
Soberón JR, Sgariglia MA, Carabajal Torrez JA, Aguilar FA, Pero EJI, Sampietro DA, Fernández de Luco J, Labadie GR (2020) Antifungal activity and toxicity studies of flavanones isolated from Tessaria dodoneifolia aerial parts. Heliyon 6(10):e05174–e05183. https://doi.org/10.1016/j.heliyon.2020.e05174
Soromou LW, Chu X, Jiang L, Wei M, Huo M, Chen N, Guan S, Yang X, Chen C, Feng H, Deng X (2012) In vitro and in vivo protection provided by pinocembrin against lipopolysaccharide-induced inflammatory responses. Int Immunopharmacol 14(1):66–74. https://doi.org/10.1016/j.intimp.2012.06.009
Sorucu A, Oruç HH (2019) Determination of biologically active phenolic compounds in propolis by LC–MS/MS according to seasons and altitudes. J Food Meas Charact 13(3):2461–2469. https://doi.org/10.1007/s11694-019-00166-9
Stashenko EE, Martínez JR, Ruíz CA, Arias G, Durán C, Salgar W, Cala M (2010) Lippia origanoides chemotype differentiation based on essential oil GC-MS and principal component analysis. J Sep Sci 33(1):93–103. https://doi.org/10.1002/jssc.200900452
Su Q, Sun Y, Ye Z, Yang H, Kong B, Li L (2018) Pinocembrin protects endothelial cells from oxidized LDL-induced injury. Cytokine 111(6):475–480. https://doi.org/10.1016/j.cyto.2018.05.033
Suárez GAP, Galindo NJP, Pardo Cuervo OH (2022) Obtaining Colombian propolis extracts using modern methods: a determination of its antioxidant capacity and the identification of its bioactive compounds. J Supercrit Fluids 182:105538–105548. https://doi.org/10.1016/j.supflu.2022.105538
Tanjung M, Tjahjandarie TS, Sentosa MH (2013) Antioxidant and cytotoxic agent from the rhizomes of Kaempferia pandurata. Asian Pacific J Trop Dis 3(5):401–404. https://doi.org/10.1016/S2222-1808(13)60091-2
Tanleque-Alberto F, Juan-Borrás M, Escriche I (2020) Antioxidant characteristics of honey from Mozambique based on specific flavonoids and phenolic acid compounds. J Food Compos Anal 86:103377. https://doi.org/10.1016/j.jfca.2019.103377
Tao J, Shen C, Sun Y, Chen W, Yan G (2018) Neuroprotective effects of pinocembrin on ischemia/reperfusion-induced brain injury by inhibiting autophagy. Biomed Pharmacother 106:1003–1010. https://doi.org/10.1016/j.biopha.2018.07.026
Tewtrakul S, Subhadhirasakul S, Puripattanavong J, Panphadung T (2003) HIV-1 protease inhibitory substances from the rhizomes of Boesenbergia pandurata Holtt. Songklanakarin J Sci Technol 25(4):503–508
Tuchinda P, Reutrakul V, Claeson P, Pongprayoon U, Sematong T, Santisuk T, Taylor WC (2002) Anti-inflammatory cyclohexenyl chalcone derivatives in Boesenbergia pandurata. Phytochemistry 59(2):169–173. https://doi.org/10.1016/S0031-9422(01)00451-4
Wang SB, Bin PX, Gao M, Fang LH, Du GH (2013) Pinocembrin protects rats against cerebral ischemic damage through soluble epoxide hydrolase and epoxyeicosatrienoic acids. Chin J Nat Med 11(3):207–213. https://doi.org/10.1016/S1875-5364(13)60018-7
Wang Y, Gao J, Miao Y, Cui Q, Zhao W, Zhang J, Wang H (2014) Pinocembrin protects SH-SY5Y cells against MPP+-induced neurotoxicity through the mitochondrial apoptotic pathway. J Mol Neurosci 53(4):537–545. https://doi.org/10.1007/s12031-013-0219-x
Wang A, Wang S, Jiang Y, Chen M, Wang Y, Lin L (2016a) Bio-assay guided identification of hepatoprotective polyphenols from: Penthorum chinense Pursh on t -BHP induced oxidative stress injured L02 cells. Food Funct 7(4):2074–2083. https://doi.org/10.1039/c6fo00110f
Wang H, Wang Y, Zhao L, Cui Q, Wang Y, Du G (2016b) Pinocembrin attenuates MPP+-induced neurotoxicity by the induction of heme oxygenase-1 through ERK1/2 pathway. Neurosci Lett 612:104–109. https://doi.org/10.1016/j.neulet.2015.11.048
Wang Y, Miao Y, Mir AZ, Cheng L, Wang L, Zhao L, Cui Q, Zhao W, Wang H (2016c) Inhibition of beta-amyloid-induced neurotoxicity by pinocembrin through Nrf2/HO-1 pathway in SH-SY5Y cells. J Neurol Sci 368:223–230. https://doi.org/10.1016/j.jns.2016.07.010
Wang W, Zhang H, Lee DH, Yu J, Cheng T, Hong M, Jiang S, Fan H, Huang X, Zhou J, Wang J (2017) Using functional and molecular MRI techniques to detect neuroinflammation and neuroprotection after traumatic brain injury. Brain Behav Immun 64:344–353. https://doi.org/10.1016/j.bbi.2017.04.019
Wang W, Zheng L, Xu L, Tu J, Gu X (2020a) Pinocembrin mitigates depressive-like behaviors induced by chronic unpredictable mild stress through ameliorating neuroinflammation and apoptosis. Mol Med 26(1):53–64. https://doi.org/10.1186/s10020-020-00179-x
Wang XY, Gong LJ, Huang JM, Jiang C, Yan ZQ (2020b) Pinocembrin alleviates glucocorticoid-induced apoptosis by activating autophagy via suppressing the PI3K/Akt/mTOR pathway in osteocytes. Eur J Pharmacol 880:173212–173221. https://doi.org/10.1016/j.ejphar.2020.173212
Xiao J, Capanoglu E, Jassbi AR, Miron A (2016) Advance on the Flavonoid C-glycosides and health benefits. Crit Rev Food Sci Nutr 56:S29–S45. https://doi.org/10.1080/10408398.2015.1067595
Xie Y, Yang W, Tang F, Chen X, Ren L (2015) Antibacterial activities of flavonoids: structure-activity relationship and mechanism. Curr Med Chem 22(1):132–149. https://doi.org/10.2174/0929867321666140916113443
Yan Y, Kohli A, Koffas MAG (2005) Biosynthesis of natural flavanones in Saccharomyces cerevisiae. Appl Environ Microbiol 71(9):5610–5613. https://doi.org/10.1128/AEM.71.9.5610-5613.2005
Yan B, Cao G, Sun T, Zhao X, Hu X, Yan J, Peng Y, Shi A, Li Y, Xue W, Li M, Li K, Liu Y (2014) Determination of pinocembrin in human plasma by solid-phase extraction and LC/MS/MS: application to pharmacokinetic studies. Biomed Chromatogr 28:1601–1606. https://doi.org/10.1002/bmc.3186
Yang N, Qin S, Wang M, Chen B, Yuan N, Fang Y, Yao S, Jiao P, Yu Y, Zhang Y, Wang J (2013) Pinocembrin, a major flavonoid in propolis, improves the biological functions of EPCs derived from rat bone marrow through the PI3K-eNOS-NO signaling pathway. Cytotechnology 65(4):541–551. https://doi.org/10.1007/s10616-012-9502-x
Yang S, Fan M, Li D, Zhou J, Fan G, Peng L, Zhang S (2020) Physiological and iTRAQ-based proteomic analyses reveal the mechanism of pinocembrin against Penicillium italicum through targeting mitochondria. Pestic Biochem Physiol 167:104534–104545. https://doi.org/10.1016/j.pestbp.2020.01.015
Ye T, Zhang C, Wu G, Wan W, Liang J, Liu X, Liu D, Yang B (2019) Pinocembrin attenuates autonomic dysfunction and atrial fibrillation susceptibility via inhibition of the NF-κB/TNF-α pathway in a rat model of myocardial infarction. Int Immunopharmacol 77:105926–105937. https://doi.org/10.1016/j.intimp.2019.105926
Ye M, Xu M, Fan S, Zhang M, Zhou B, Yang S, Wei W, Ji C, Ji J, Ji F (2020) Protective effects of three propolis-abundant flavonoids against ethanol-induced injuries in HepG2 cells involving the inhibition of ERK1/2-AHR-CYP1A1 signaling pathways. J Funct Foods 73:104166–104177. https://doi.org/10.1016/j.jff.2020.104166
Yuan Y, Yang QY, Tong YF, Chen F, Qi Y, Duan YB, Wu S (2008) Synthesis and enantiomeric resolution of (±)-pinocembrin. J Asian Nat Prod Res 10(10):999–1002. https://doi.org/10.1080/10286020802240418
Zheng Y, Wang K, Wu Y, Chen Y, Chen X, Hu CW, Hu F (2018) Pinocembrin induces ER stress mediated apoptosis and suppresses autophagy in melanoma cells. Cancer Lett 431(April):31–42. https://doi.org/10.1016/j.canlet.2018.05.026
Zhou LT, Wang KJ, Li L, Li H, Geng M (2015) Pinocembrin inhibits lipopolysaccharide-induced inflammatory mediators production in BV2 microglial cells through suppression of PI3K/Akt/NF-κB pathway. Eur J Pharmacol 761:211–216. https://doi.org/10.1016/j.ejphar.2015.06.003
Zhou F, Wang A, Li D, Wang Y, Lin L (2018) Pinocembrin from Penthorum chinense Pursh suppresses hepatic stellate cells activation through a unified SIRT3-TGF-β-Smad signaling pathway. Toxicol Appl Pharmacol 341:38–50. https://doi.org/10.1016/j.taap.2018.01.009
Zhu XM, Fang LH, Li YJ, Du GH (2007) Endothelium-dependent and -independent relaxation induced by pinocembrin in rat aortic rings. Vasc Pharmacol 46(3):160–165. https://doi.org/10.1016/j.vph.2006.09.003
Acknowledgment
The authors wish to thank Universiti Putra Malaysia for the grant (GP-IPS/2021/9699000) provided under Putra Graduates Initiative Grant Scheme. The first author delightedly acknowledges the support under Graduate Research Fellowship (GRF) scheme from Universiti Putra Malaysia.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2023 Springer Nature Switzerland AG
About this entry
Cite this entry
Wong, P.L., Ahmat, N., Abas, F. (2023). Pinocembrin: Insights into the Resources, Biosynthesis, Bioavailability, Safety, Biological Activities and Pharmacology. In: Xiao, J. (eds) Handbook of Dietary Flavonoids. Springer, Cham. https://doi.org/10.1007/978-3-030-94753-8_62-1
Download citation
DOI: https://doi.org/10.1007/978-3-030-94753-8_62-1
Received:
Accepted:
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-94753-8
Online ISBN: 978-3-030-94753-8
eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences