Citrus species: Modern functional food and nutraceutical-based product ingredient

Main Article Content

Mariarosaria Leporini
Rosa Tundis
Vincenzo Sicari
Monica Rosa Loizzo

Keywords

bioactive compounds, by-products, citrus, health properties, juice, peels, pulp, seeds

Abstract

Citrus is the most cultivated fruit crop in the world and occupies a place of considerable importance in the country’s economy. Almost 33% of the citrus fruits are processed for juice production; however, a great amount of wastes, including peels, segment membranes, and seeds are also produced. Indeed, citrus fruits consist of 45% juice, 26% pulp, 27% peels, and 2% seeds. Pruning, a cultural practice involving the removal of tree branches and limbs, was applied to improve fruit’s quality. A large amount of leaves are produced through pruning. These agri-food matrices contain a wide range of bioactive phytochemicals compared to fruits. The present review covers the past 5 years of research carried out in chemistry, health properties, and applications in food and nutraceutical industries of all portions of citrus fruit and its major bioactive compounds. Additionally, patents are also included.

Abstract 2395 | PDF Downloads 1218 HTML Downloads 3242 XML Downloads 735

References

Abdallah E.M. 2020. Antibacterial potential of fresh fruit juices against multi-drug resistant pathogens. J Acute Dis. 9:83–88. 10.4103/2221-6189.281324

Aja P.M., Ekpono E.U., Awoke J.N., Famurewa A.C., Izekwe F.I., Okoro E.J., et al. 2020. Hesperidin ameliorates hepatic dysfunction and dyslipidemia in male Wistar rats exposed to cadmium chloride. Toxicol Rep. 7:1331–1338. 10.1016/j.toxrep.2020.09.014

Al-Aamri Maha S., Al-Abousi Nour M., Al-Jabri Sausan S., Alam T.K. and Shah A. 2018. Chemical composition and in-vitro antioxidant and antimicrobial activity of the essential oil of Citrus aurantifolia L. leaves grown in Eastern Oman. J Taibah Univ Med Sci. 13:108–112. 10.1016/j.jtumed.2017.12.002

Aladekoyi G., Omosulis V. and Orungbemi O. 2016. Evaluation of antimicrobial activity of oil extracted from three different citrus seeds (Citrus limon, Citrus aurantifolia and Citrus aurantium). Int. J. Sci. Res. Eng. Stud. 3:16–20.

Ali S. and Obaid Q. 2020. Lemon juice antioxidant activity against oxidative stress. Baghdad Sci J. 17:207. 10.21123/bsj.2020.17.1(Suppl.).0207

Ali M.Y., Zaib S., Rahman M.M., Jannat S., Iqbal J., Park S.K. and Chang M.S. 2019. Didymin, a dietary Citrus flavonoid exhibits anti-diabetic complications and promotes glucose uptake through the activation of PI3K/Akt signaling pathway in insulin-resistant HepG2 cells. Chemicobiol Interact. 305:180–194. 10.1016/j.cbi.2019.03.018

Alkhalidy H., Moore W., Wang A., Luo J., McMillan R.P., Wang Y., et al. 2018. Kaempferol ameliorates hyperglycemia through suppressing hepatic gluconeogenesis and enhancing hepatic insulin sensitivity in diet-induced obese mice. J. Nutr. Biochem. 58:90–101. 10.1016/j.jnutbio.2018.04.014

Allam Sabbah M., El-Bedawy T.M., Bakr M.H. and Mahmoud A.E.M. 2020. Effect of feeding dried orange pulp to lactating dairy cows on nutrients digestibility, blood constituents, plasma antioxidant biomarker, and pathogenic fecal bacteria. Pakistan J Zool. 52:79–86. 10.17582/journal.pjz/2020.52.1.79.86

Al-Numair K.S., Chandramohan G., Veeramani C. and Alsaif M.A. 2015. Ameliorative effect of kaempferol, a flavonoid, on oxidative stress in streptozotocin-induced diabetic rats. Redox Rep. 20:198–209. 10.1179/1351000214Y.0000000117

Ameh S.J. and Obodozie-Ofoegbu O. 2016. Essential oils as flavorings in carbonated cola and Citrus soft drinks. London: Academic Press.

Amorim J.L., Simas D.L.R., Pinheiro M.M.G., Moreno D.S.A., Alviano C.S., Da Silva A.J.R., et al. 2016. Anti-inflammatory properties and chemical characterization of the essential oils of four Citrus species. PLoS ONE. 11:1–18. 10.1371/journal.pone.0153643

Ani P.N. and Ochu K.E. 2020. Anti-diabetic, anti-hyperlipidemic and hepatoprotective potential of shaddock (Citrus maxima) peel extract. Acta Sci Polon Technol Aliment. 19:271–278. 10.17306/J.AFS.2020.0811

Arriagada F., Günther G., Nos J., Nonell S., Olea-Azar C. and Morales J. 2019. Antioxidant nanomaterial based on core shell silica nanospheres with surface-bound caffeic acid: a promising vehicle for oxidation-sensitive drugs. Nanomaterials (Basel). 9:214–230. 10.3390/nano9020214

Arumugam A., Nagarani G., Srinivasan G., Saipriya V. and Siddhuraju P. 2019. Antidiabetic and hypolipidemic activities of peel and pulp extract from underutilized fruits of Citrus hystrix and Citrus maxima in streptozotocin-induced diabetic rats. Indian J. Environ. Edu. In press.

Asemi Z., Alizadeh S.A., Ahmad K., Goli M. and Esmaillzadeh A. 2016. Effects of beta-carotene fortified synbiotic food on metabolic control of patients with type 2 diabetes mellitus: A double-blind randomized cross-over controlled clinical trial. Clin Nutr. 35:819–825. 10.1016/j.clnu.2015.07.009

Azadeh H., Zarshenas M.M., Jamshidzadeh A, Heidari R. and Pasdaran A. 2019. Citrus aurantium (bitter orange) seed oil: pharmacognostic, anti-inflammatory, and anti-nociceptive properties. Trends Pharm Sc. 5:153–164. 10.30476/TIPS.2019.82996.1020

Azhara S., Aryantib S. and Setiawanc B. 2020. Inhibition test of lemon juice (Citrus aurantifolia, Swingle) on the growth of Corynebacterium diphtheriae. J Xi’an Univ Arch Technol. 7:1359–1365.

Baldissera M.D., Souza C.F., Grando T.H., Doleski P.H., Boligon A.A., Stefani L.M. and Monteiro S.G. 2017. Hypolipidemic effect of β-caryophyllene to treat hyperlipidemic rats. Naunyn-Schmiedeberg Arch Pharmacol. 390:215–223. 10.1007/s00210-016-1326-3

Barberis A., Deiana M., Spissu Y., Azara E., Fadda A., Serra P., et al. 2020. Antioxidant, antimicrobial, and other biological properties of Pompia juice. Molecules. 25:3186. 10.3390/molecules25143186

Barreca D., Gattuso G., Bellocco E., Calderaro A., Trombetta D., Smeriglio A., et al. 2017. Flavanones: Citrus phytochemical with health-promoting properties. Biofactors. 43:495–506. 10.1002/biof.1363

Basha R.H. and Sankaranarayanan C. 2016. β-Caryophyllene, a natural sesquiterpene lactone attenuates hyperglycemia-mediated oxidative and inflammatory stress in experimental diabetic rats. Chemicobiol Interact. 245:50–58. 10.1016/j.cbi.2015.12.019

Ben Amara N., Tourniaire F., Maraninchi M., Attia N., Amiot-Carlin M.J., Raccah D., et al. 2015. Independent positive association of plasma β-carotene concentrations with adiponectin among non-diabetic obese subjects. Europ J Nutr. 54:447–454. 10.1007/s00394-014-0728-6

Bentahar A., Bouaziz A., Djidel S. and Khennouf S. 2020. Phenolic content and antioxidant activity of ethanolic extracts from Citrus sinensis L., and Citrus reticulata L. fruits. J. Drug Delivery Therap. 10:308–313. 10.22270/jddt.v10i5-s.4537

Bhuiyan F., Hasan M., Abdus M., Imran M., Sheikh R., Ahmed S., et al. 2019. Antimicrobial activity screening for three Citrus pulp extracts and phytochemical constituency profiling. J. Pharmacogn. Phytochem. 8:157–161. 10.5455/jabet.2021.d103

Bonesi M., Loizzo M.R., Leporini M., Tenuta M.C., Passalacqua N.G. and Tundis R. 2018. Comparative evaluation of petitgrain oils from six Citrus species alone and in combination as potential functional antiradicals and antioxidant agents. Plant Biosyst. 152:986–993. 10.1080/11263504.2017.1403396

Bora H., Kamle M., Mahato D.K., Tiwari P. and Kumar P. 2020. Citrus essential oils (CEOs) and their applications in food: an overview. Plants. 9:357. 10.3390/plants9030357

Braga P.R., Bonilla J., Moro de Sousa R.L., Micke M.A. and Sampaio B.P. 2020. Chemical composition and antibacterial activity of essential oils against pathogens often related to cattle endometritis. J Infect Develop Countries. 14:177–183. 10.3855/jidc.12076

Brasili E., Hassimotto N.M.A., Del Chierico F., Marini F., Quagliariello A., Sciubba F., et al. 2019. Daily consumption of orange juice from Citrus sinensis L. Osbeck cv. Cara Cara and cv. Bahia differently affects gut microbiota profiling as unveiled by an integrated meta-omics approach. J Agricul Food Chem. 67:1381–1391. 10.1021/acs.jafc.8b05408

Buket A., Zorba D., Nilüfer N. and Yılmaz E. 2018. Antimicrobial activity of cold pressed citrus seeds oils, some Citrus flavonoids and phenolic acids. Rivista Italiana Delle Sostanze Grasse. 95:119–131.

Burri B.J., La Frano M.R. and Zhu C. 2016. Absorption, metabolism, and functions of β-cryptoxanthin. Nutr Rev. 74:69–82. 10.1093/nutrit/nuv064

Caddeo C., Gabriele M., Fernàndez-Busquets X., Valenti D., Fadda A.M., Pucci L. and Manconi M. 2019. Antioxidant activity of quercetin in Eudragit-coated liposomes for intestinal delivery. Int J Pharm. 565:64–69. 10.1016/j.ijpharm.2019.05.007

Cardile V., Graziano A.C.E. and Venditti A. 2015. Clinical evaluation of Moro (Citrus sinensis (L.) Osbeck) orange juice supplementation for the weight management. Nat Prod Res. 29:2256–2260. 10.1080/14786419.2014.1000897

Cardoso L.A.C., Karp S.G., Vendruscolo F., Kanno K.Y.F., Zoz L.I.C. and Carvalho J.C. 2017. Chapter 8. Biotechnological production of carotenoids and their applications in food and pharmaceutical products. In: Dragan J. Cvetkovic and Goran S. Nikolic (Eds.), Carotenoids,. InTechOpen, London. 10.5772/67725

Casacchia T., Occhiuzzi M.A., Grande F., Rizzuti B., Granieri M.C., Rocca C., et al. 2019. Pilot study on the nutraceutical properties of the Citrus hybrid Tacle® as a dietary source of polyphenols for supplementation in metabolic disorders. J Funct Foods. 52:370–381. 10.1016/j.jff.2018.11.030

Caseiro M, Ascenso A., Costa A., Creagh-Flynn J., Johnson M. and Simões S. 2020. Lycopene in human health. LWT. 127:109323. 10.1016/j.lwt.2020.109323

Chen X.M., Tait A.R. and Kitts D.D. 2017. Flavonoid composition of orange peel and its association with antioxidant and anti-inflammatory activities. Food Chem. 218:15–21. 10.1016/j.foodchem.2016.09.016

Chen G. and Wang H. 2015. Application of nobiletin. Patent No. CN105030559A (China).

Chen Q., Wang D., Tan C., Hu Y., Sundararajan B. and Zhou Z. 2020. Profiling of flavonoid and antioxidant activity of fruit tissues from 27 Chinese local citrus cultivars. Plants (Basel, Switzerland). 9:196. 10.3390/plants9020196

Chi P.T.L., Van Hung P., Le Thanh H. and Phi N. 2020. Valorization of Citrus leaves: chemical composition, antioxidant and antibacterial activities of essential oils. Waste Biomass Valorization. 11:4849–4857. 10.1007/s12649-019-00815-6

Chilaka K.C., Ifediba E.C. and Ogamba J.O. 2015. Evaluation of the effects of Citrus sinensis seed oil on blood glucose, lipid profile and liver enzymes in rats injected with alloxan monohydrate. J Acute Dis. 4:129–134. 10.1016/S2221-6189(15)30022-6

Cho Y.G., Jung J.H., Kang J.H., Kwon J.S., Yu S.P. and Baik T.G. (2017). Effect of a herbal extract powder (YY-312) from Imperata cylindrica Beauvois, Citrus unshiu Markovich, and Evodia officinalis Dode on body fat mass in overweight adults: a 12-week, randomized, double-blind, placebo-controlled, parallel-group clinical trial. BMC Complement Altern Med, 17:375. 10.1186/s12906-017-1871-4

Cilla A., Rodrigo M.J., Zacarías L., De Ancos B., Sánchez-Moreno Citrus, Barberá R., et al. 2018. Protective effect of bioaccessible fractions of Citrus fruit pulps against H2O2-induced oxidative stress in Caco-2 cells. Food Res Int. 103:335–344. 10.1016/j.foodres.2017.10.066

Costanzo G., Iesce M.R., Naviglio D., Ciaravolo M., Vitale E. and Arena C. 2020. Comparative studies on different Citrus cultivars: a revaluation of waste mandarin components. Antioxidants. 9:51. 10.3390/antiox9060517

Cyndi B., Andriane Y. and Nur I.M. 2016. Pengaruh pemberian ekstrak etanol daun jeruk nipis (Citrus aurantifolia swingle) terhadap penurunan kadar kolesterol total darah pada mencit model hyperkolesterolemia. Prosiding Pendidikan Dokter. 2:911–918. 10.29313/kedokteran.v0i0.4414

Dai Y. and Li C. 2018. Luteolin compound preparation and application thereof in inhibiting gastric secretion. Patent No. CN108309971B (China).

Da Silva E.S., Oliveira B.G., Pereira A.C.H., Pimentel E.F., Pezzuto J.M., Lenz D., et al. 2018. Induction of NAD(P)H: quinone reductase 1 (QR1) and antioxidant activities in vitro of “Toranja Burarama” (Citrus maxima [Burm.]Merr.). Phytother Res. 32:2059–2068. 10.1002/ptr.6149

Değirmenci H. and Erkurt H. 2020. Relationship between volatile components, antimicrobial and antioxidant properties of the essential oil, hydrosol and extracts of Citrus aurantium L. flowers. J Infec Public Health. 13:58–67. 10.1016/j.jiph.2019.06.017

De Leo M., Piragine E., Pirone A., Braca A., Pistelli L., Calderone V., et al. 2020. Protective effects of bergamot (Citrus bergamia risso & poiteau) juice in rats fed with high-fat diet. Planta Med. 86:180–189. 10.1055/a-1070-9325

Demir A. and Celik I. 2019. Investigation of healing effects of lemon (Citrus limonum) seeds lyophilized extracts on experimental diabetic rats. Arch Physiol Biochem. 12:1–8. 10.1080/13813455.2019.1702061

De Oliveira Filho J.G., de Deus I.P.B., Valadares A.C.F., Fernandes C.C., Estevam E.B.B. and Egea M.B. 2020. Chitosan film with Citrus limonia essential oil: physical and morphological properties and antibacterial activity. Colloids Interfac. 4:18. 10.3390/colloids4020018

De Souza V.T., de Franco É.P., de Araújo M.E., Messias M.C., Priviero F.B., Frankland Sawaya A.C., et al. 2016. Characterization of the antioxidant activity of aglycone and glycosylated derivatives of hesperetin: an in vitro and in vivo study. J Mol Recog. 29:80–87. 10.1002/jmr.2509

De Souza M.C., Vieira A.J., Beserra F.P., Pellizzon C.H., Nóbrega R.H. and Rozza ALL 2019. Gastroprotective effect of limonene in rats: influence on oxidative stress, inflammation and gene expression. Phytomedicine. 53:37–42. 10.1016/j.phymed.2018.09.027

Denkova-Kostova R., Teneva D., Tomova T., Goranov B., Denkova Z., Shopska V., et al. 2020. Chemical composition, antioxidant and antimicrobial activity of essential oils from tangerine (Citrus reticulata L.), grapefruit (Citrus paradisi L.), lemon (Citrus lemon L.) and cinnamon (Cinnamomum zeylanicum Blume). Z Naturforsch C J. Biosci. 76:175–185. 10.1515/znc-2020-0126

Dhanya R. and Jayamurthy P. 2020. In vitro evaluation of antidiabetic potential of hesperidin and its aglycone hesperetin under oxidative stress in skeletal muscle cell line. Cell Biochem. Function. 38:419–427. 10.1002/cbf.3478

Dhuique-Mayer C., Gence L., Portet K., Tousch D. and Poucheret P. 2020. Preventive action of retinoids in metabolic syndrome/type 2 diabetic rats fed with citrus functional food enriched in β-cryptoxanthin. Food Funct. 11:9263–9271. 10.1039/d0fo02430a

Diab K.A., Shafik R.E. and Yasuda S. 2015. In vitro antioxidant and antiproliferative activities of novel orange peel extract and its fractions on leukemia HL-60 cells. Asian Pacific J Cancer Prevent. 16:7053–7060. 10.7314/APJCP.2015.16.16.7053

Di Folco U., Pollakova D., De Falco D., Nardone M.R., Tubili F. and Tubilia C. 2018. Effects of a nutraceutical multicompound including bergamot (Citrus Bergamia Risso) juice on metabolic syndrome: a pilot study. Mediterranean J Nutr Metabol. 11:119–126. 10.3233/MNM-17186

Dinesh S. and Hegde K. 2016. Antiobesity activity of ethanolic extract of Citrus maxima leaves on cafeteria diet induced and drug induced obese rats. Res J Pharm Technol. 9:907. 10.5958/0974-360X.2016.00173.6

Doustimotlagh A.H., Taheri S., Mansourian M. and Eftekharie M. 2020. Extraction and identification of two flavonoids in Phlomoides hyoscyamoides as endemic plant of Iran: the role of quercetin in the activation of the glutathione peroxidase, the improvement of the hydroxyproline and protein oxidation in bile duct-ligated rats. Curr Comp Aided Drug Design. 16:629–640. 10.2174/1573409915666190903163335

Eghtesadi S., Mohammadi M., Vafa M., Heidari I., Salehi M., Haghighian H.K., et al. 2016. Effects of hesperidin supplementation on glycemic control, lipid profile and inflammatory factors in patients with type 2 diabetes: a randomized, double-blind and placebo-controlled clinical trial. Endocr Abst. 43:OC16. 10.1530/endoabs.43.OC16

Eid H.M., Nachar A., Thong F., Sweeney G. and Haddad P.S. 2015. The molecular basis of the antidiabetic action of quercetin in cultured skeletal muscle cells and hepatocytes. Pharmacog Mag. 11:74–81. 10.4103/0973-1296.149708

Ernawita Z., Wahyuono R., Hesse-Macabata J., Hipler U.C., Elsner P. and Böhm V. 2016. Carotenoids of indigenous citrus species from Aceh and its in vitro antioxidant, antidiabetic and antibacterial activities. European Food Res Technol. 242:1869–1881. 10.1007/s00217-016-2686-0

Ernawita Z., Wahyuono R.A., Hesse J., Hipler U.C., Elsner P. and Böhm V. 2017. In vitro lipophilic antioxidant capacity, antidiabetic and antibacterial activity of citrus fruits extracts from Aceh, Indonesia. Antioxidants. 6:11–26. 10.3390/antiox6010011

Eryılmaz M., Cicek P.D., Akalın K. and Coskun M. 2018. Antimicrobial activity of grapefruit seed. Hacettepe Univ J Faculty Pharm. 38:1–3.

Fadillah Q., Chiuman L., Ginting C. and Girsang E. 2020. Effectiveness test of anti-bacterial lime juice (Citrus aurantifolia) on salmonella sp bacteria in salmon fish (Oncorhynchus nerka). BIOLINK (J Biol Lingkungan Industri Kesehatan). 7:81–89. 10.31289/biolink.v7i1.3322

Falcinelli B., Famiani F., Paoletti A., D’Egidio S., Stagnari F., Galieni A., et al. 2020. Phenolic compounds and antioxidant activity of sprouts from seeds of Citrus species. Agriculture. 10:33. 10.3390/agriculture10020033

Fancello F., Petretto G.L., Marceddu S., Venditti T., Pintore G., Zara G., et al. 2020. Antimicrobial activity of gaseous Citrus limon var pompia leaf essential oil against Listeria monocytogenes on ricotta salata cheese. Food Microbiol. 87:103386. 10.1016/j.fm.2019.103386

Farahmandfar R., Tirgarian B., Dehghan B. and Nemati A. 2020. Comparison of different drying methods on bitter orange (Citrus aurantium L.) peel waste: changes in physical (density and color) and essential oil (yield, composition, antioxidant and antibacterial) properties of powders. J Food Meas Characterization. 14:862–875. 10.1007/s11694-019-00334-x

Farooqi A.A., Wang Z., Hasnain S., Attar R., Aslam A., Mansoor Q., et al. 2015. Citrus fruits and their bioactive ingredients: leading four horsemen from front. Asian Pacific J Cancer Prevent. 16:2575–2580. 10.7314/apjcp.2015.16.6.2575

Favela-Hernández J.M.J., González-Santiago O., Ramírez-Cabrera M.A., Esquivel-Ferriño P.C., and del Rayo Camacho-Corona M. 2016. Chemistry and pharmacology of Citrus sinensis. Molecules. 21:247–271. 10.3390/molecules21020247

Fayek N.M., El-Shazly A.H., Abdel-Monem A.R., Mohamed M.Y., Abd-Elwahab S.M. and El-Tanbouly Nebal D. 2017. Comparative study of the hypocholesterolemic, antidiabetic effects of four agro-waste citrus peels cultivars and their HPLC standardization. Revista Brasileira de Farmacognosia. 27:488–494. 10.1016/j.bjp.2017.01.010

Ferreira P.S., Spolidorio L.C., Mantheyc J.A. and Cesar T.B. 2016. Citrus flavanones prevent systemic inflammation and ameliorate oxidative stress in C57BL/6J mice fed high-fat diet. Food Function. 7:2675–2681. 10.1039/C5FO01541c

Fidélix M., Milenkovic D., Sivieri K. and Cesar T. 2020. Microbiota modulation and effects on metabolic biomarkers by orange juice: a controlled clinical trial. Food & Funct. 11:1599–1610. 10.1039/c9fo02623a

Fratianni F., Cozzolino A., De Feo V., Coppola R., Ombra M.N. and Nazzaro F. 2019. Polyphenols, antioxidant, antibacterial, and biofilm inhibitory activities of peel and pulp of Citrus medica L., Citrus bergamia, and Citrus medica cv. Salò cultivated in southern Italy. Molecules. 24:4577. 10.3390/molecules24244577

Gao Y., Xu D., Ren D., Zeng K. and Wu X. 2020. Green synthesis of zinc oxide nanoparticles using Citrus sinensis peel extract and application to strawberry preservation: A comparison study. LWT Food Sci Technol. 126:109297. 10.1016/j.lwt.2020.109297

Gavarić N., Kovac J., Kretschmer N., Kladar, N., Smole M.S., Bucar, F., et al. 2015. Natural products as antibacterial agents—antibacterial potential and safety of post-distillation and waste material from Thymus vulgaris L., Lamiaceae. In: Concepts, compounds and the alternatives of antibacterials. InTech, London, pp. 123–151. 10.5772/60869

Ghorbani A. 2017. Mechanisms of antidiabetic effects of flavonoid rutin. Biomed Pharmacother. 96:305–312. 10.1016/j.biopha.2017.10.001

Gironés-Vilaplana A., Valentão P., Andrade P.B., Ferreres F., Moreno D.A. and García-Viguera C. 2015. Beverages of lemon juice and exotic noni and papaya with potential for anticholinergic effects. Food Chem. 170:16–21. 10.1016/j.foodchem.2014.08.021

Guo J., Gao Z., Xia J., Ritenour M., Li G. and Shan Y. 2018. Comparative analysis of chemical composition, antimicrobial and antioxidant activity of Citrus essential oils from the main cultivated varieties in China. LWT Food Sci Technol. 97:825–839. 10.1016/j.lwt.2018.07.060

Guo C., Shan Y., Yang Z., Zhang L., Ling W., Liang Y., Ouyang Z., Zhong B. and Zhang J. 2020. Chemical composition, antioxidant, antibacterial, and tyrosinase inhibition activity of extracts from Newhall navel orange (Citrus sinensis Osbeck cv. Newhall) peel. J Sci Food Agricul. 100:2664–2674. 10.1002/jsfa.10297

Guo J., Tao H., Cao Y., Ho C.T., Jin S. and Huang Q. 2016. Prevention of obesity and Type 2 diabetes with aged Citrus peels (chenpi) extract. J Agricul Food Chem. 64:2053–2061. 10.1021/acs.jafc.5b06157

Gupta S.K., Sharma H.P., Das U., Velpandian T. and Saklani R. 2019. Effect of rutin on retinal VEGF, TNF-α, aldose reductase, and total antioxidant capacity in diabetic rats: molecular mechanism and ocular pharmacokinetics. Int Ophthalmol. 40:159–168. 10.1007/s10792-019-01165-x

Haidari F., Heybar H., Jalali M.T., Ahmadi Engali K., Helli B. and Shirbeigiet E. 2015. Hesperidin supplementation modulates inflammatory responses following myocardial infarction. J Amer Coll Nutr. 34:205–211. 10.1080/07315724.2014.891269

Hamdan D., El-Shiekh R., El-Sayed M., Khalil H., Mousa M., Al-Gendy A. and El Sahzly A. 2020. Phytochemical characterization and anti-inflammatory potential of Egyptian Murcott Mandarin cultivar waste (stem, leaves and peel). Food Funct. 11:8214–8236. 10.1039/D0FO01796E

Han H., Cui W., Wang L., Xiong Y., Liu L., Sun X. and Hao L. 2015. Lutein prevents high fat diet-induced atherosclerosis in ApoE-deficient mice by inhibiting NADPH oxidase and increasing PPAR expression. Lipids. 50:261–273. 10.1007/s11745-015-3992-1

Haraoui N., Allem R., Mohammed Chaouche T. and Belouazni A. 2020. In vitro antioxidant and antimicrobial activities of some varieties Citrus grown in Algeria. Adv Trad Med. 20:23–34. 10.1007/s13596-019-00379-9

He B., Nohara K., Park N., Park Y.S., Guillory B., Zhao Z., et al. 2016. The small molecule nobiletin targets the molecular oscillator to enhance circadian rhythms and protect against metabolic syndrome. Cell Metabol. 23:610–621. 10.1016/j.cmet.2016.03.007

He X., Zheng S., Sheng Y., Miao T., Xu J., Xu W., et al. 2020. Chlorogenic acid ameliorates obesity by preventing energy balance shift in high-fat diet induced obese mice. J Sci Food Agricul. 19: 631–637. 10.1002/jsfa.10675

Homayouni F., Haidari F., Hedayati M., Zakerkish M. and Ahmadi K. 2017. Hesperidin supplementation alleviates oxidative DNA damage and lipid peroxidation in type 2 diabetes: a randomized double-blind placebo-controlled clinical trial. Phytother Res. 31:1539–1545. 10.1002/ptr.5881

Hsouna A., Gargouri M., Dhifi W., Ben S.R., Sayahi N., Mnif W. and Saibi W. 2018. Potential anti-inflammatory and antioxidant effects of Citrus aurantium essential oil against carbon tetrachloride-mediated hepatotoxicity: a biochemical, molecular and histopathological changes in adult rats. Environ Toxicol. 34:388–400. 10.1002/tox.22693

Hsu Y.L., Hsieh C.J., Tsai E.M., Hung JY., Chang W.A., Hou M.F., et al. 2016. Didymin reverses phthalate ester-associated breast cancer aggravation in the breast cancer tumor microenvironment. Oncol Lett. 11:1035–1042. 10.3892/ol.2015.4008

Hu Y., Zeng Z., Wang B. and Guo S. 2017. Trans-caryophyllene inhibits amyloid β (Aβ) oligomer-induced neuroinflammation in BV-2 microglial cells. Int Immunopharmacol 51:91–98. 10.1016/j.intimp.2017.07.009

Huang K., Liang X.C., Zhong Y.L., He W.Y. and Wang Z. 2015. 5-Caffeoylquinic acid decreases diet-induced obesity in rats by modulating PPARα and LXRα transcription. J Sci Food Agricul. 95:1903–1910. 10.1002/jsfa.6896

Huang R., Zhang Y., Shen S., Zhi Z., Cheng H., Chen S., et al. 2020. Antioxidant and pancreatic lipase inhibitory effects of flavonoids from different citrus peel extracts: an in vitro study. Food Chem. 326:126785. 10.1016/j.foodchem.2020.126785

Ibrahim F., Usman L., Akolade J., Idowu O., Abdulazeez A. and Amuzat A. 2019. Antidiabetic potentials of Citrus aurantifolia leaf essential oil. Drug Res. 69: 201–206. 10.1055/a-0662-5607

Ikoma Y., Matzsumoto H. and Kato M. 2016. Diversity in the carotenoid profiles and the expression of genes related to carotenoid accumulation among citrus genotypes. Breed Sci. 66:139–147. 10.1270/jsbbs.66.139

Impellizzeri D., Bruschetta G., di Paola R., Ahmad A., Campolo M., Cuzzocrea S., et al. 2015. The anti-inflammatory and antioxidant effects of bergamot juice extract (BJe) in an experimental model of inflammatory bowel disease. Clin Nutr. 34:1146–1154. 10.1016/j.clnu.2014.11.012

İnan Ö., Özcan M.M. and Aljuhaimi F. 2018. Effect of location and Citrus species on total phenolic, antioxidant, and radical scavenging activities of some Citrus seed and oils. J Food Proc Pres 42:e13555. 10.1111/jfpp.13555

Itoh K., Matsukawa T., Murata K., Nishitani R., Yamagami M., Tomohiro N., et al. 2019. Pancreatic lipase inhibitory activity of Citrus unshiu leaf extract. Nat Prod Comm. 14:Art. No. 1934578X1987343. 10.1177/1934578X19873439

Jayaraman R., Subramani S., Sheik Abdullah S.H. and Udaiyar M. 2018. Antihyperglycemic effect of hesperetin, a Citrus flavonoid, extenuates hyperglycemia and exploring the potential role in antioxidant and antihyperlipidemic in streptozotocin-induced diabetic rats. Biomed Pharmacother. 97:98–106. 10.1016/j.biopha.2017.10.102

Jia S., Hu Y., Zhang W., Zhao X., Chen Y., Sun C., et al. 2015. Hypoglycemic and hypolipidemic effects of neohesperidin derived from Citrus aurantium L. in diabetic KK-A(y) mice. Food Funct. 6:878–86. 10.1039/c4fo00993b

Jin S., Chang C., Zhang L., Liu Y., Huang X. and Chen Z. 2015. Chlorogenic acid improves late diabetes through adiponectin receptor signaling pathways in db/db mice. PLoS One. 10:e0120842. 10.1371/journal.pone.0120842.

Kahkeshani N., Farzaei F., Fotouhi M., Alavi S.S., Bahramsoltani R., Naseri R., et al. (2019). Pharmacological effects of gallic acid in health and diseases: A mechanistic review. Iran J Basic Med Sci. 22:225–237. 10.22038/ijbms.2019.32806.7897

Kamel I.H., Salib J.Y., El-Toumy S.A., Awad A.H. and Elmenabbawy M.K. 2019. Citrus reticulata peel extract: an anti-obesity therapy for adolescents. Middle East J Appl Sci Technol. 9:117–124

Kang S.I., Shin H.S. and Kim S.J. 2015. Sinensetin enhances adipogenesis and lipolysis by increasing cyclic adenosine monophosphate levels in 3T3-L1 adipocytes. Bio Pharmaceut Bull. 38:552–558. 10.1248/bpb.b14-00700

Kasim V.N., Hatta M., Natzir R., Hadju V., Hala Y., Budu B., et al. 2020. Antibacterial and anti-inflammatory effects of lime (Citrus aurantifolia) peel extract in mice balb/c induced salmonella typhi. J Bio Res93:2. 10.4081/jbr.0.8951

Kaur J. 2014. A comprehensive review on metabolic syndrome. Cardiol Res Pract. 2014:943162. 10.1155/2014/943162

Kaurinovic B. and Vastag D. 2019. Chapter 5. Flavonoids and phenolic acids as potential natural antioxidants. In: Shalaby, E. (ed.) Antioxidants. IntechOpen, London, pp. 1–20. 10.5772/intechopen.83731

Kegele C.S., Oliviera J., Magrani T., Ferreira A., de Souza R., Sabbaghi A., et al. 2019. A randomized trial on the effects of CitrusiM® (Citrus sinensis (L.) Osbeck dried extract) on body composition. Clin Nutr Exp. 27:29–36. 10.1016/j.yclnex.2019.08.002

Khan A., Ikram M., Hahm J.R. and Kim M.O. 2020. Antioxidant and anti-inflammatory effects of Citrus flavonoid hesperetin: special focus on neurological disorders. Antioxidants. 9:609. 10.3390/antiox9070609

Khan A., Siddiqui H., Mahmood T. and Ahsan F. 2019. A comparative evaluation study of Citrus limetta and metformin against hyperlipidemia in diabetic and non-diabetic rats. Res J Pharm Technol. 12:1244–1250. 10.5958/0974-360X.2019.00207.5

Khettal B., Kadri N., Tighilet K., Adjebli A., Dahmoune F. and Maiza-Benabdeslam F. 2017. Phenolic compounds from Citrus leaves: antioxidant activity and enzymatic browning inhibition. J Complement Integ Med. 14:1–6. 10.1515/jcim-2016-0030

Khidr A., Elshazly S., Elfayoumy H. and El-Maraghy N.N. 2020. Protective effect of hesperidin modulates inflammatory response, oxidative stress status and blood pressure following renal artery stenosis in rats. Zagazig Univ Med J. In press. 10.21608/ZUMJ.2020.27909.1813

Kim G.N., Shin M.R., Shin S.H., Lee A.R., Lee J.Y., Seo B.I., et al. (2016). Study of Antiobesity Effect through Inhibition of Pancreatic Lipase Activity of Diospyros kaki Fruit and Citrus unshiu Peel. Biomed Res Int. 2016:1723042. 10.1155/2016/1723042

Kim G. and Lee S. 2018. Composition for prevention, improvement or treatment of liver cancer or stomach cancer comprising sinensetin as active ingredient., Patent No. KR20190050535A (Korea).

Kim J.A., Ha S.E., Kim S.M., Vetrivel P., Kim G.S. and Kim E.H. 2019a. Anti-inflammatory activities of sinensetin on LPS-stimulated L6 skeletal muscle cells. J Biomed Translat Res. 20:1–7. 10.12729/jbtr.2019.20.1.001

Kim C., Ji J., Baek S.H., Lee J.H., Ha I.J., Lim S.S., et al. 2019b. Fermented dried Citrus unshiu peels extracts exert anti-inflammatory activities in LPS-induced RAW264.7 macrophages and improve skin moisturizing efficacy in immortalized human HaCaT keratinocytes. Pharmaceut Bio. 57:392–402. 10.1080/13880209.2019.1621353

Kim D.S. and Lim S.B. 2020. Semi-continuous subcritical water extraction of flavonoids from citrus unshiu peel: their antioxidant and enzyme inhibitory activities. Antioxidants. 9:360–376. 10.3390/antiox9050360

Kirtikar S., Himangshu S., Ashish S. and Kota V.R. 2018. Didymin prevents hyperglycemia-induced human umbilical endothelial cells dysfunction and death. Biochem Pharmacol. 152:1–10. 10.1016/j.bcp.2018.03.012

Ko E.A., Seung-Hee N., Hana J., Bo Y.K., Sang H.K., Sunyoung K., et al. 2020. Antioxidant, anti-inflammatory and anti-allergenic effects of Citrus junos seed oil and its human skin protection. J Soc Cosm Scientists Korea. 46:283–294. 10.15230/SCSK.2020.46.3.283

Kobayashi H., Mitani M., Minatogawa Y., Hayashi S., Nakamoto M., Shuto E., et al. 2017. Extracts of Citrus Sudachi peels attenuate body weight gain in C57BL/6 mice fed a high-fat diet. J Med Invest. 64:20–23. 10.2152/jmi.64.20

Kobori M., Takahashi Y., Sakurai M., Akimoto Y., Tsushida T., Oike H., et al. 2016. Quercetin suppresses immune cell accumulation and improves mitochondrial gene expression in adipose tissue of diet-induced obese mice. Mol Nutr and Food Res. 60:300–312. 10.1002/mnfr.201500595

Kodimule S.P. 2018. Chlorogenic acid composition for the treatment of metabolic disorders. Patent No. US20190111015A1 (United States).

Kometsi L., Govender K., Mato-Mofo E., Hurchund R. and Owira P. 2020. By reducing oxidative stress, naringenin mitigates hyperglycaemia-induced upregulation of hepatic nuclear factor erythroid 2-related factor 2 protein: naringenin and hepatic Nrf2 protein expression. J Pharm Pharmacol. 72:1394–1404. 10.1111/jphp.13319

Konglong F., Zhu X., Liu G., Kan Q., Chen T., Chen Y., et al. 2020. Dietary Citrus peel essential oil ameliorates hypercholesterolemia and hepatic steatosis by modulating lipid and cholesterol homeostasis. Food Funct. 11:7217–7230. 10.1039/D0FO00810A

Kumar P., Sharma H., Dev K., Rana A.C. and Kumar S. 2019. Preclinical studies of the lemon hill as a multiapproach antioxidant and antidiabetic plant: Citrus pseudolimon tanaka. J Herbs Spices Med Plants. 25:69–87. 10.1080/10496475.2019.1570994

Kumar K., Yadav A.N., Kumar V., Vyas P. and Dhaliwal H.S. 2017. Food waste: a potential bioresource for extraction of nutraceuticals and bioactive compounds. Bioresour Bioproc. 4:1–14. 10.1186/s40643-017-0148-6

Kusumawardhani N., Thuraidah A. and Nurlailah N. 2020. Citrus hystrix D.C juice inhibits the growth of Staphylococcus aureus. Tropical Health Med Res. 2:34–38. 10.35916/thmr.v0i0.17.

Kwon E.Y. and Choi M.S. 2020. Eriocitrin improves adiposity and related metabolic disorders in high-fat diet-induced obese mice. J Med Food. 23:233–241. 10.1089/jmf.2019.4638

Lala M., Modak D., Paul S., Sarkar I., Dutta A., Bhattacharjee S., et al. 2020. Potent bioactive methanolic extract of wild orange (Citrus macroptera Mont.) shows antioxidative, anti-inflammatory, and antimicrobial properties in in vitro, in vivo, and in silico studies. Bull National Res Centre. 44:81. 10.1186/s42269-020-00329-5

Lee J.S. Cha Y.J. Lee K.H., and Yim J.E. 2016. Onion peels extract reduces the percentage of body fat in overweight and obese subjects: a 12-week, randomized, double-blind, placebo-controlled study. Nutrit Res Prac. 10:175–181. 10.4162/nrp.2016.10.2.175

Lee B., Fleet D. and Lee H. 2018. Compositions comprising tangeretin for preventing or treating post traumatic stress disorder. Patent No. KR102015221B1 (Korea).

Leoncini E., Edefonti V., Hashibe M., Parpinel M., Cadoni G., Ferraroni M., et al. 2016. Carotenoid intake and head and neck cancer: a pooled analysis in the international head and neck cancer epidemiology consortium. Eur J Epidemiol. 31:369–383. 10.1007/s10654-015-0036-3

Leporini M., Loizzo M.R., Sicari V., Pellicanò T.M., Reitano A., Dugay A., et al. 2020a. Citrus × clementina Hort. juice enriched with its by-products (peels and leaves): chemical composition, in vitro bioactivity, and impact of processing. Antioxidants. 9:298. 10.3390/antiox9040298

Leporini M., Tundis R., Sicari V., Pellicanò T.M., Dugay A., Deguin B., et al. 2020b. Impact of extraction processes on phytochemicals content and biological activity of Citrus × clementina Hort. Ex Tan. leaves: New opportunity for under-utilized food by-products. Food Res Int. 127:108742. 10.1016/j.foodres.2019.108742

Li Q. 2019. Application of the Nobiletin in preparation treatment gastric accommodation disorder remedies. Patent No. CN108619130B (China).

Li K., Cai X., Ye J. and Huang Y. 2018. Hesperetin, hesperetin and enoxolone are inhibiting the application in chloride channel. Patent No. CN108815154A (China).

Li C. and Schluesener H. 2017. Health-promoting effects of the citrus flavanone hesperidin. Crit Rev Food Sci Nutrit. 57:613–631. 10.1080/10408398.2014.906382

Liang W., Zhang C., Zeng W., Zhang C. and Wang L. 2015. Application of naringenin and naringin in tumor radiotherapy. Patent No. CN104940932A (China).

Liao Y. 2018. The application of naringenin and its derivative in preventing Alzheimer disease. Patent No. CN108785301A (China).

Lim Y.J., Kim J.H., Pan J.H., Kim J.K., Park T.S., Kim Y.J., et al. 2018. Naringin protects pancreatic β-Cells against oxidative stress-induced apoptosis by inhibiting both intrinsic and extrinsic pathways in insulin-deficient diabetic mice. Mol Nutrit Food Res. 62:1700810–1700820. 10.1002/mnfr.201700810

Lima A.C.D., Cecatti C., Fidélix M.P., Adorno M.A.T., Sakamoto I.K., Cesar T.B., et al. 2019. Effect of daily consumption of orange juice on the levels of blood glucose, lipids, and gut microbiota metabolites: controlled clinical trials. J Med Food. 22:1–9. 10.1089/jmf.2018.0080

Lin X., Bai F., Nie J., Lu S., Lu C., Zhu X., et al. 2016. Didymin alleviates hepatic fibrosis through inhibiting ERK and PI3K/Akt pathways via regulation of RAF kinase inhibitor protein. Cell Physiol Biochem. 40:1422–1432. 10.1159/000453194

Lin L.Y., Chuang C.H., Chen H.C. and Yang K.M. 2019. Lime (Citrus aurantifolia (Christm.) Swingle) essential oils: volatile compounds, antioxidant capacity, and hypolipidemic effect. Foods. 8:398. 10.3390/foods8090398

Liu J., Bi R., Geng G., Cao X., He Y., Cai T., et al. 2019a. Flavonoid micromolecule compound inhibits the application in alpha-glucosidase activity drug in preparation. Patent No. CN109806272A (China).

Liu D., Cao X., Kong Y., Mu T. and Liu J. 2020. Inhibitory mechanism of sinensetin on α-glucosidase and non-enzymatic glycation: Insights from spectroscopy and molecular docking analyses. Int J Biol Macromol. 8130:34826–34831. 10.1016/j.ijbiomac.2020.10.174

Liu Y., Han J., Zhou Z. and Li D. 2019b. Tangeretin inhibits streptozotocin-induced cell apoptosis via regulating NF-κB pathway in INS-1 cells. J Cell Biochem. 120:3286–3293. 10.1002/jcb.27596

Loizzo M.R., Leporini M., Sicari V., Falco T., Pellicanò T.M. and Tundis R. 2018. Investigating the in vitro hypoglycaemic and antioxidant properties of Citrus × clementina hort. juice. Eur Food Res Technol. 244:523–534. 10.1007/s00217-017-2978-z

Loizzo M.R., Sicari V., Tundis R., Leporini M., Falco T. and Calabrò V. 2019. The influence of ultrafiltration of Citrus limon L. Burm. cv. Femminello comune juice on its chemical composition and antioxidant and hypoglycemic properties. Antioxidants. 8:23–43. 10.3390/antiox8010023

Lombardo G.E., Cirmi S., Musumeci L., Pergolizzi S., Maugeri A., Russo C., et al. 2020. Mechanisms underlying the anti-inflammatory activity of bergamot essential oil and its antinociceptive effects. Plants. 9:704. 10.3390/plants9060704

Lone J., Parray H.A. and Yun J.W. 2018. Nobiletin induces brown adipocyte-like phenotype and ameliorates stress in 3T3-L1 adipocytes. Biochimie. 146:197–104. 10.1016/j.biochi.2017.11.021

Long X., Zeng X., Yan H., Xu M., Zeng Q., Xu Citrus, et al. 2021. Flavonoids composition and antioxidant potential assessment of extracts from Gannanzao Navel Orange (Citrus sinensis Osbeck cv. Gannanzao) peel. Nat Prod Res. 35:702–706. 10.1080/14786419.2019.1593162

López Muñozmaría F., González Trujano E. and Carballo Villalobos A. 2015. Pharmaceutical composition combining diosmin and hesperidin and its use in neuropathic pain. Patent No. WO2015019334A1 (Worldwide).

Lu J.F., Zhu M.Q., Zhang H., Liu H., Xia B., Wang Y.L., et al. 2020. Neohesperidin attenuates obesity by altering the composition of the gut microbiota in high-fat diet-fed mice. FASEB J. 34:12053–12071. 10.1096/fj.201903102RR

Lv X., Zhao S., Ning Z., Zeng H., Shu Y., Tao O., et al. 2015. Citrus fruits as a treasure trove of active natural metabolites that potentially provide benefits for human health. Chem. Central J. 9:68–82. 10.1186/s13065-015-0145-9

Magalhães M., Ionta M., Ferreira G., Campidelli M., Nelson D., Ferreira V., et al. 2019. Biological activities of the essential oil from the Moro orange peel (Citrus sinensis (L.) Osbeck). Flavour Frag J. 35:294–301. 10.1002/ffj.3561

Mahato N., Sharma K., Sinha M. and Choa M.H. 2018. Citrus waste derived nutra-pharmaceuticals for health benefits: current trends and future perspectives. J Funct Foods. 40:307–316. 10.1016/j.jff.2017.11.015

Mahato N., Sinha M., Sharma K., Koteswararao R. and Cho M.H. 2019. Modern extraction and purification techniques for obtaining high purity food-grade bioactive compounds and value-added co-products from Citrus wastes. Foods. 8:523–604. 10.3390/foods8110523

Mahmoud A.M., Ahmed O.M., Ashour M.B. and Abdel-Moneim A. 2015. In vivo and in vitro antidiabetic effects of Citrus flavonoids; a study on the mechanism of action. Int J Diabetes Developing Countries. 35:250–263. 10.1007/s13410-014-0268-x

Mandal S.M., Chakraborty D. and Dey S. 2010. Phenolic acids act as signaling molecules in plant-microbe symbioses. Plant Signal Behav. 5:359–368. 10.4161/psb.5.4.10871

Mathesius U. 2018. Flavonoid functions in plants and their interactions with other organisms. Plants. 7:30. 10.3390/plants7020030

Matias E.E.F., Alves E.F., Silva M.K.N., Carvalho V.R.A., Figueredo F.G., Ferreira J.V.A., et al. 2016. Seasonal variation, chemical composition and biological activity of the essential oil of Cordia verbenacea DC (Boraginaceae) and the sabinene. Ind Crops Prods. 87:45–53. 10.1016/j.indcrop.2016.04.028

Menichini F., Tundis R., Loizzo M.R., Bonesi M., D’Angelo D., Lombardi P. et al. 2016. Citrus medica L. cv. Diamante (Rutaceae) peels extract improves glycaemic status of Zucker diabetic fatty (ZDF) rats and protects against oxidative stress. J Enzy Inhib Med Chem. 31:1270–1276. 10.3109/14756366.2015.1115400

Milanezi F.G., Meireles L.M., De Christo Scherer M.M., Oliveira J., Da Silva A.R., De Araujo M.L., et al. 2019. Antioxidant, antimicrobial and cytotoxic activities of gold nanoparticles capped with quercetin. Saudi Pharm J. 27:968–974. 10.1016/j.jsps.2019.07.005

Milne G.W.A. 2005. “Gardner’s Commercially Important Chemicals: Synonyms, Trade Names, and Properties,” 1st ed. Wiley-Interscience, New York, NY, USA.

Mitrea D.R., Malkey R., Florian T.L., Filip A., Clichici S., Bidian C., et al. 2020. Daily oral administration of chlorogenic acid prevents the experimental carrageenan-induced oxidative stress. J Physiol Pharmacol. 71:55–65. 10.26402/jpp.2020.1.04

Mitropoulou G., Nikolaou A., Santarmaki V., Sgouros G. and Kourkoutas Y. 2020. Citrus medica and Cinnamomum zeylanicum essential oils as potential biopreservatives against spoilage in low alcohol wine products. Foods. 9:577. 10.3390/foods9050577

Mohammadi M., Eghtesadi S., Vafa M., Heidari I., Salehi M., Shirbeigi M., et al. 2016. The effect of hesperidin supplementation on indices of glucose and lipid, insulin levels and insulin resistance in patients with type 2 diabetes: a randomized double-blind clinical trial. Razi J Med Sci. 23:71–80.

Nair S.A., Sr R.K., Nair A.S. and Baby S. 2018. Citrus peels prevent cancer. Phytomedicine. 50:231–237. 10.1016/j.phymed.2017.08.011

Nakajima A., Aoyama Y., Shin E.J., Nam Y., Kim H.C., Nagai T., et al. 2015. 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 289:69–77. 10.1016/j.bbr.2015.04.028

Nakajima A. and Ohizumi Y. 2019. Potential benefits of nobiletin, a Citrus flavonoid, against Alzheimer’s disease and Parkinson’s disease. Int J Mol Sci. 20:3380. 10.3390/ijms20143380

Nataraj J., Manivasagam T., Thenmozhi A.J. and Essa M.M. 2016. Lutein protects dopaminergic neurons against MPTP-induced apoptotic death and motor dysfunction by ameliorating mitochondrial disruption and oxidative stress. Nutr. Neurosci. 19:237–246. 10.1179/1476830515Y.0000000010

Nidhi P., Rolta R., Kumar V., Dev K. and Sourirajan A. 2020. Synergistic potential of Citrus aurantium L. essential oil with antibiotics against Candida albicans. J Ethnopharmacol. 262:113–135. 10.1016/j.jep.2020.113135

Nyane N.A., Tlaila T.B., Malefane T.G., Ndwandwe D.E. and Owira P.M.O. 2017. Metformin-like antidiabetic, cardio-protective and non-glycemic effects of naringenin: Molecular and pharmacological insights. Eur J Pharmacol. 803:103–111. 10.1016/j.ejphar.2017.03.042

Oboh G., Agunloye O.M., Adefegha S.A., Akinyemi A.J. and Ademiluyi A.O. 2015a. Caffeic and chlorogenic acids inhibit key enzymes linked to type 2 diabetes (in vitro): a comparative study. J Basic Clin Physiol Pharmacol. 26:165–170. 10.1515/jbcpp-2013-0141

Oboh G., Bello F., Ademosun A., Akinyemi A. and Adewuni T. 2015b. Antioxidant, hypolipidemic, and anti-angiotensin-1-converting enzyme properties of lemon (Citrus limon) and lime (Citrus aurantifolia) juices. Comp Clin Pathol. 24:1395–1406. 10.1007/s00580-015-2088-x

Oboh G., Olasehinde T.A. and Ademosun A.O. 2017. Inhibition of enzymes linked to type-2 diabetes and hypertension by essential oils from peels of orange and lemon. Int J Food Prop. 20:586–594. 10.1080/10942912.2017.1303709

Oikeh E., Oviasogie F. and Omoregie E. 2020. Evaluation of antimicrobial efficacy of ethanol extracts of fresh Citrus sinensis (sweet orange) seeds against selected bacterial strains. J Appl Sci Environ Manag. 24.249–252. 10.4314/jasem.v24i2.9

Olabanji O., Olukayode A., Ezekiel A., Olugbenga K.O. and Adefemi G. 2016. Physicochemical and in vitro antimicrobial activity of the oils and soap of the seed and peel of Citrus sinensis. African J Microbiol Res. 10:245–253. 10.5897/AJMR2015.7797

Ordóñez-Díaz J.L., Hervalejo A., Pereira-Caro G., Muñoz-Redondo J.M., Romero-Rodríguez E., Arenas-Arenas F.J., et al. 2020. Effect of rootstock and harvesting period on the bioactive compounds and antioxidant activity of two orange cultivars (“Salustiana” and “‘Sanguinelli”) widely used in juice industry. Processes, 8:1212. 10.3390/pr8101212

Osarumwense O. 2017. Anti-inflammatory activity of methanoilc and ethanolic extracts of Citrus sinensis peel (L) Osbeck on carrageenan-induced paw oedema in wistar rats. J Appl Sci Environ Manag. 21:1223–1242. 10.4314/jasem.v21i6.37

Oyedemi S., Nwaogu G., Chukwuma C., Adeyemi O., Matsabisa M., Swain S., et al. 2019. Quercetin modulates hyperglycemia by improving the pancreatic antioxidant status and enzymes activities linked with glucose metabolism in type 2 diabetes model of rats: in silico studies of molecular interaction of quercetin with hexokinase and catalase. J Food Biochem. 44:e13127. 10.1111/jfbc.13127

Pallavi M., Ramesh C.K., Krishna V. and Sameera P. 2018. Peels of Citrus fruits: a potential source of anti-inflammatory and antinociceptive agents. Pharmacog J. 10:172–178. 10.5530/pj.2018.6s.30

Park J., Kim H.L., Jung Y., Ahn K.S., Kwak H.J. and Um J.Y. 2019. Bitter orange (Citrus aurantium Linné) improves obesity by regulating adipogenesis and thermogenesis through AMPK activation. Nutrients. 11:1988–2004. 10.3390/nu11091988

Paul S., Das S., Tanvir E.M., Hossen M.S., Saha M., Afroz R., et al. 2017. Protective effects of ethanolic peel and pulp extracts of Citrus macroptera fruit against isoproterenol-induced myocardial infarction in rats. Biomed Pharmacother. 94:256–264. 10.1016/j.biopha.2017.07.080

Paul S., Hossen Md. S., Tanvir E.M., Islam A., Afroz R., Ahmmed I., et al. 2015. Antioxidant properties of Citrus macroptera fruit and tts in vivo effects on the liver, kidney and pancreas in wistar rats. Int J Pharmacol. 11:899–909. 10.3923/ijp.2015.899.909

Perdones A., Escriche I., Chiralt A. and Vargas M. 2015. Effect of chitosan-lemon essential oil coatings on volatile profile of strawberries during storage. Food Chem. 197:979–986. 10.1016/j.foodchem.2015.11.054

Pereira I.M.C., Matos Neto J.D., Figueiredo R.W, Carvalho J.D.G., Figueiredo E.A.T., de Menezes N.V.S., et al. 2020. Physicochemical characterization, antioxidant activity, and sensory analysis of beers brewed with cashew peduncle (Anacardium occidentale) and orange peel (Citrus sinensis). Food Sci Technol. 40:749–755. 10.1590/fst.17319

Pisoschi A.M. and Pop A. 2015. The role of antioxidants in the chemistry of oxidative stress: A review. Eur J Med Chem. 97:55–74. 10.1016/j.ejmech.2015.04.040

Prakash S., Nagaraj E., Subashini K., Kanaga S., Dhandapani R., Magudeeswaran S., et al. 2020. Isolation of hesperetin–a flavonoid from Cordia sebestena flower extract through antioxidant assay guided method and its antibacterial, anticancer effect on cervical cancer via in vitro and in silico molecular docking studies. J Mol Struc. 1207:127751. 10.1016/j.molstruc.2020.127751

Prasatthong P., Meephat S., Rattanakanokchai S., Bunbupha S., Prachaney P., Maneesai P., et al. 2021. Hesperidin ameliorates signs of the metabolic syndrome and cardiac dysfunction via IRS/Akt/GLUT4 signaling pathway in a rat model of diet-induced metabolic syndrome. Eur J Nutrit. 60: 833–848. 10.1007/s00394-020-02291-4

Prudêncio E.R-. Cardoso C.M., Castro R.N. and Riger C.J. 2019. Antioxidant effect of caffeic acid derivatives on SOD and glutathione defective yeasts. Appl Biochem Microbiol. 55:264–269 10.1134/S0003683819030116

Qi G., Mi Y., Fan R., Li R., Liu Z. and Liu X. 2019. Nobiletin protects against systemic inflammation-stimulated memory impairment via MAPK and NF-κB signaling pathways. J Agri Food Chem. 67:5122–5134. 10.1021/acs.jafc.9b00133

Qori F., Chiuman L., Ginting C.N. and Girsang E. 2020. Effectiveness test of anti-bacterial lime juice (Citrus aurantifolia) on salmonella sp bacteria in salmon fish (Oncorhynchus nerka). J Biol Lingkungan Industri Kesehatan. 7:81–89. 10.31289/biolink.v7i1.3322

Rafiq S., Kaul S., Sofi S.A., Bashir N., Nazir F. and NayiK G.A. 2018. Citrus peel as a source of functional ingredient: a review. Saudi J Biol Sci 17:351–358. 10.1016/j.jssas.2016.07.006

Ramli R., Ahmad Zaghlul N.S. and Ahmad Nasir N.A.H. (2020) The Potential of Antioxidants and Phytochemicals Components in Fruit Waste (Peel) of Citrus hystrix and Ananas comosus. P. 123–135. In: Alias N. and Yusof R. (eds) Charting the Sustainable Future of ASEAN in Science and Technology. Springer, Singapore. 10.1007/978-981-15-3434-8_11

Raspo M., Vignola M., Andreatta A. and Juliani H. 2020. Antioxidant and antimicrobial activity of Citrus essential oils from Argentina and the United States. Food Biosci 36:100651. 10.1016/j.fbio.2020.100651

Rehab M.A.E., Areej S.B.S. and Heelah F.A. 2018. The phytochemical and antimicrobial effect of Citrus sinensis (orange) peel powder extracts on some animal pathogens as eco-friendly. EC Microbiol. 14:312–318.

Rehman S.U., Abbasi K.S., Ul Haq N., Ahmad Q., Taran N.U., Ullah S., et al. 2020a. Comparative nutraceutical properties of seeds of eight Citrus varieties grown in Rawalpindi region. Pure Appl Biol. 9:1–9. 10.1590/fst.07519

Rehman K., Khan I.J., Akash M.S.H., Jabeen K., Haider K. and Tariq M. 2020b. Naringenin downregulates inflammation-mediated nitric oxide overproduction and potentiates endogenous antioxidant status during hyperglycemia. J Food Biochem. 44:e13422. 10.1111/jfbc.13422

Rehman K., Munawar S.M., Akash M.S.H., Buabeid M.A., Chohan T.A., Tariq M., et al. 2020c. Hesperidin improves insulin resistance via downregulation of inflammatory responses: biochemical analysis and in silico validation. PLoS ONE 15:e0227637. 10.1371/journal.pone.0229348

Roberto D., Micucci P., Sebastian T., Graciela F. and Anesini C. 2010. Antioxidant activity of limonene on normal murine lymphocytes: relation to H2O2 modulation and cell proliferation. Basic Clin Pharmacol Toxicol. 106:38–44. 10.1111/j.1742-7843.2009.00467.x

Rombaut N., Tixier S., Bily A. and Chemat F. 2014. Green extraction processes of natural products as tools for biorefinery. Biofuels Bioprod Bioref. 8:530–544. 10.1002/bbb.1486

Saeb S., Mansour A., Gooybari R. and Aghel N. 2016. Evaluation of antibacterial activities of Citrus limon, Citrus reticulata, and Citrus grandis against pathogenic bacteria. Int J Enteric Pathog. 4:11–15. 10.15171/ijep.2016.13

Sahlan M., Damayanti V., Tristantini D., Hermansyah H., Wijanarko A. and Olivia Y. 2018. Antimicrobial activities of pummelo (Citrus maxima) seed and pulp ethanolic extract. AIP Conf Proc. 1993:30002. 10.1063/1.5023949

Sahnoun M., Trabelsi S. and Bejar S. 2017. Citrus flavonoids collectively dominate the α-amylase and α-glucosidase inhibitions. Biologia. 72:764–773. 10.1515/biolog-2017-0091

Saleem M. and Saeed M.T. 2020. Potential application of waste fruit peels (orange, yellow lemon and banana) as wide range natural antimicrobial agent. J King Saud Univ Sci. 32:805–810. 10.1016/j.jksus.2019.02.013

Samie A., Sedaghat R., Baluchnejadmojarad T. and Roghani M. 2018. Hesperetin, a citrus flavonoid, attenuates testicular damage in diabetic rats via inhibition of oxidative stress, inflammation, and apoptosis. Life Sci 210:132–139. 10.1016/j.lfs.2018.08.074

Sangeetha R. 2019. Luteolin in the management of type 2 diabetes mellitus. Curr Res Nutrit Food Sci J. 7:393–398. 10.12944/CRNFSJ.7.2.09

Sathiyabama R.G., Rajiv Gandhi G., Denadai M., Sridharan G., Jothi G., Sasikumar P., et al. 2018. Evidence of insulin-dependent signalling mechanisms produced by Citrus sinensis (L.) Osbeck fruit peels in an insulin resistant diabetic animal model. Food Chem Toxicol. 116:86–99. 10.1016/j.fct.2018.03.050

Sato M., Goto T., Inoue E., Miyaguchi Y.T. and Oyoda A. 2019. Dietary intake of immature citrus tumida Hort. ex Tanaka peels suppressed body weight gain and fat accumulation in a mouse model of acute obesity. J Nutr. Sci Vitaminol. 65:19–23. 10.3177/jnsv.65.19

Selim Y.A., Mohamed H. and Hussien S.Y. 2019. Efficacious anti-cancer property of liver from peels extract of egyptian Citrus reticulata. Austin J Nutrit Food Sci. 7:1118–1124

Shagirtha K., Bashir N. and Milton Prabu S. 2017. Neuroprotective efficacy of hesperetin against cadmium induced oxidative stress in the brain of rats. Toxicol Ind Health. 33:454–468. 10.1177/0748233716665301

Sharma A. and Tyagi S. 2019. Antimicrobial screening and phytochemical analysis of Citrus cultivars growing in vivo & in vitro. J Phytologic Res. 32:35–42.

Shehata, S.A., Abdeldaym E.A., Ali, M.R., Mohamed R.M., Bob R.I. and Abdelgawad K.F. 2020. Effect of some Citrus essential oils on post-harvest shelf life and physicochemical quality of strawberries during cold storage. Agronomy. 10:1466. 10.3390/agronomy10101466

Shi G.J., Li Y., Cao Q.H., Wu H.X., Tang X.Y., Gao X.H., et al. 2019. In vitro and in vivo evidence that quercetin protects against diabetes and its complications: a systematic review of the literature. Biomed Pharmacother. 109:1085–1099. 10.1016/j.biopha.2018.10.130

Shi X. and Yang Y. 2018.The pharmaceutic usage of neohesperidin. Patent No. CN108478586 (China).

Shin H.S., Kang S.I., Ko H.C., Park D.B. and Kim S.J. 2017. Tangeretin improves glucose uptake in a coculture of hypertrophic adipocytes and macrophages by attenuating inflammatory changes. Develop Reprod 21:93–100. 10.12717/DR.2017.21.1.093

Shojaemehr M., Alamholo M. and Soltani J. 2020. Investigation of antibacterial and antioxidant activity of Citrus medica extract on human pathogenic bacteria. Avicenna J Clin Microbiol Infect. 8:14. 10.34172/ajcmi.2020.02

Sicari V., Pellicanò T., Giuffrè A., Zappia C., Capocasale M. and Poiana M. 2018. Physical chemical properties and antioxidant capacities of grapefruit juice (Citrus paradisi) extracted from two different varieties. Int Food Res J. 25:1978–1984.

Singh B. and Sharma R.A. 2015. Plant terpenes: defense responses, phylogenetic analysis, regulation and clinical applications. Biotechnol Acad Sci. 5:129–151. 10.1007/s13205-014-0220-2

Singh B., Singh J.P., Kaur A. and Singh N. 2020. Phenolic composition, antioxidant potential and health benefits of Citrus peel. Food Res Int. 132:109114. 10.1016/j.foodres.2020.109114

Smeriglio A., Alloisio S., Raimondo F.M., Denaro M., Xiao J., Cornara L., et al. 2018. Essential oil of Citrus lumia Risso: Phytochemical profile, antioxidant properties and activity on the central nervous system. Food Chem Toxicol. 119:407–416. 10.1016/j.fct.2017.12.053

Smeriglio A., Cornara L., Denaro M., Barreca D., Burlando B., Xiao J., et al. 2019. Antioxidant and cytoprotective activities of an ancient Mediterranean Citrus (Citrus lumia Risso) albedo extract: microscopic observations and polyphenol characterization. Food Chem. 279:347–355. 10.1016/j.foodchem.2018.11.138

Su S., Li X., Li S., Ming P., Huang Y., Dong Y., et al. 2019. Rutin protects against lipopolysaccharide-induced mastitis by inhibiting the activation of the NF-κB signaling pathway and attenuating endoplasmic reticulum stress. Inflammopharmacology. 27:77–88. 10.1007/s10787-018-0521-x

Sun T., Yuan H., Cao H., Yazdani M., Tadmor Y. and Li L. 2018. Carotenoid metabolism in plants: the role of plastids. Mol Plant. 11:58–74. 10.1016/j.molp.2017.09.010

Supatra S. 2019. The chemistry and biology of lycopene: antioxidant for human health. Int J Adv Life Sci Res. 2:8–14. 10.31632/ijalsr.2019v02i04.002

Tang X.P., Guo X.H., Geng D. and Weng L.J. 2019. D-Limonene protects PC12 cells against corticosterone-induced neurotoxicity by activating the AMPK pathway. Environ Toxicol Pharmacol. 70:1–6. 10.1016/j.etap.2019.05.001

Teneva D., Denkova-Kostova R., Goranov B., Hristova-Ivanova Y., Slavchev A., Denkova Z., et al. 2019. Chemical composition, antioxidant activity and antimicrobial activity of essential oil from Citrus aurantium L zest against some pathogenic microorganisms. Zeitschrift für Naturforschung C. 74:105–111. 10.1515/znc-2018-0062

Terao J. 2009. Dietary flavonoids as antioxidants. Forum Nutr Home. 61:87–94. 10.1159/000212741

Thandiswa M., Opeoluwa O., Mavuto G. and Adebola O. 2020. Chemical composition and in vivo anti-inflammatory activity of essential oils from C itrus sinensis (l.) osbeck growing in South Africa. J Essential Oil Bear Plants. 23:638–647. 10.1080/0972060X.2020.1819885

Thenmozhi J.A., Raja T.R., Janakiraman U. and Manivasagam T. 2015. Neuroprotective effect of hesperidin on aluminium chloride induced Alzheimer’s disease in Wistar rats. Neurochemi Res. 40:767–776. 10.1007/s11064-015-1525-1

Thomas L. and Kamath J.V. 2017. Anti-hyperglycemic activity of Citrus limon leaves in streptozotocin induced diabetic rats. Indian Drugs. 54:74–80.

Torregrosa-Crespo J., Montero Z., Fuentes J.L., García-Galbis M.R., Garbayo I., Vílchez C., et al. 2018. Exploring the valuable carotenoids for the large-scale production by marine microorganisms. Marine Drugs.16:203–228. 10.3390/md16060203

Torres-Villarreal D., Camacho A., Castro H., Ortiz-Lopez R. and De la Garza A.L. 2019. Anti-obesity effects of kaempferol by inhibiting adipogenesis and increasing lipolysis in 3T3-L1 cells. J Physiol Biochem. 75:83–88. 10.1007/s13105-018-0659-4

Toth P.P., Patti A.M., Nikolic D., Giglio R.V., Castellino G., Biancucci T., et al. 2016. Bergamot reduces plasma lipids, atherogenic small dense LDL, and subclinical atherosclerosis in subjects with moderate hypercholesterolemia: a 6 months prospective study. Front Pharmacol. 6:299–308. 10.3389/fphar.2015.00299

Tundis R., Bonesi M., Sicari V., Pellicanò T.M., Tenuta M.C., Leporini M., et al. 2016. Poncirus trifoliata (L.) Raf.: chemical composition, antioxidant properties and hypoglycaemic activity via the inhibition of α-amylase and α-glucosidase enzymes. J Funct Foods. 25:477–485. 10.1016/j.jff.2016.06.034

Tundis R., Loizzo M.R. and Menichini F. 2010. Natural products as alpha-amylase and alpha-glucosidase inhibitors and their hypoglycaemic potential in the treatment of diabetes: an update. Mini Rev Med Chem. 10:315–331. 10.2174/138955710791331007

Valls R., Pedret A., Calderón-Pérez L., Llauradó E., Pla Pagà L., Companys J., et al. 2021. Effects of hesperidin in orange juice on blood and pulse pressures in mildly hypertensive individuals: a randomized controlled trial (Citrus study). Eur J Nutr. 60:1277–1288. 10.1007/s00394-020-02279-0

Varga Z.V., Matyas C. Erdelyi K., Cinar R., Nieri D., Chicca A., et al. 2018. β-Caryophyllene protects against alcoholic steatohepatitis by attenuating inflammation and metabolic dysregulation in mice. Br J Pharmacol. 175:320–334. 10.1111/bph.13722

Verma N., Yadav A., Bal S., Gupta R. and Aggarwal N. 2019. In vitro studies on ameliorative effects of limonene on cadmium-induced genotoxicity in cultured human peripheral blood lymphocytes. Biotechnol Appl Biochem. 187:1384–1397. 10.1007/s12010-018-2881-5

Wang Y.B., Ge Z.M., Kang W.Q., Lian Z.X., Yao J. and Zhou C.Y. 2015. Rutin alleviates diabetic cardiomyopathy in a rat model of type 2 diabetes. Exp Therap Med. 9:451–455. 10.3892/etm.2014.2090

Wang M., Meng D., Zhang P., Wang X., Du G., Brennan C., et al. 2018. Antioxidant protection of nobiletin, 5-demethylnobiletin, tangeretin, and 5-demethyltangeretin from Citrus peels in Saccharomyces cerevisiae. J Agri Food Chem. 66:3155–3160. 10.1021/acs.jafc.8b00509

Wang D., Tian L., Lv H., Pang Z., Li D., Yao Z., Wang S. 2020. Chlorogenic acid prevents acute myocardial infarction in rats by reducing inflammatory damage and oxidative stress. Biomed Pharmacother. 132:110773. 10.1016/j.biopha.2020.110773

Wen-Zhe M., Sen-ling F., Xiao-Jun Y., Zhong-wen Y., Liang L. and Ying X. 2015. Use of nobiletin in cancer treatment. US Patent No. US9808477B2.

Wu L.H., Lin C., Lin H.Y., Liu Y.S., Wu C.Y., Tsai C.F., et al. (2016). Naringenin Suppresses Neuroinflammatory Responses Through Inducing Suppressor of Cytokine Signaling 3 Expression. Mol Neurobiol. 53:1080–1091. 10.1007/s12035-014-9042-9

Xu H., Linn B.S., Zhang Y. and Ren J. 2019. A review on the antioxidative and prooxidative properties of luteolin. React Oxygen Species. 7:136–147. 10.20455/ros.2019.833

Yang H. 2018. A kind of anti-oxidant lightening compositions and its application. Patent No. CN108464949A (China).

Yang T., Feng C., Wang D., Qu Y., Yang Y., Wang Y. and Sun Z. 2020. Neuroprotective and anti-inflammatory effect of tangeretin against cerebral ischemia-reperfusion injury in rats. Inflammation. 43:2332–2343. 10.1007/s10753-020-01303-z

Yang D.K. and Kang H.S. 2018. Anti-diabetic effect of cotreatment with quercetin and resveratrol in streptozotocin-induced diabetic rats. Biomol Therap. 26:130–138. 10.4062/biomolther.2017.254

Young-hee K. and Min-kyung KD. 2018. Composition of improvement, prevention and treatment in renal fibrosis or cirrhosis of the kidney glomerulus or albuminuria. Patent No. KR101949471B1 (Korea).

Yu L., Yan J. and Sun Z. 2017. D-limonene exhibits anti-inflammatory and antioxidant properties in an ulcerative colitis rat model via regulation of iNOS, COX-2, PGE2 and ERK signaling pathways. Mol Medicine Rep. 15:2339–2346. 10.3892/mmr.2017.6241

Yuan X., Wei G., You Y., Huang Y., Lee H.J., Dong M., et al. 2017. Rutin ameliorates obesity through brown fat activation. FASEB J. 31:333–345. 10.1096/fj.201600459RR

Zareei S., Boojar M.M.A. and Amanlou M. 2017. Inhibition of liver alanine aminotransferase and aspartate aminotransferase by hesperidin and its aglycone hesperetin: An in vitro and in silico study. Life Sci. 178:49–55. 10.1016/j.lfs.2017.04.001

Zeng, Z., He, W., Jia, Z. and Hao, S. 2017. Lycopene improves insulin sensitivity through inhibition of STAT3/Srebp-1c-mediated lipid accumulation and inflammation in mice fed a high-fat diet. Exp Clin Endocrinol Diabetes. 125:610–617. 10.1055/s-0043-101919

Zeng S.L., Li S.Z., Lai C., Wei M.Y., Chen B.Z., Li P., et al. 2018. Evaluation of anti-lipase activity and bioactive flavonoids in the Citri Reticulatae pericarpium from different harvest time. Phytomedicine. 43:103–109. 10.1016/j.phymed.2018.04.008

Zhang J., Fu X., Yang L., Wen H., Zhang L., Liu F., et al. 2020. Neohesperidin inhibits cardiac remodeling induced by Ang II in vivo and in vitro. Biomed Pharmacother. 129:110364. 10.1016/j.biopha.2020.110364

Zhang L., Zhang X., Zhang C., Bai X., Zhang J., Zhao X., et al. 2016. Nobiletin promotes antioxidant and anti-inflammatory responses and elicits protection against ischemic stroke in vivo. Brain Res. 1636:130–141. 10.1016/j.brainres.2016.02.013

Zhang Z., Yang Citrus, Dai X., Ao Y. and Li Y. 2017. Inhibitory effect of trans-caryophyllene (TC) on leukocyte-endothelial attachment. Toxicol Appl Pharmacol. 329:326–333. 10.1016/j.taap.2017.06.016

Zulvikar S.U., Tenta H.H., Faizanah H. and Dewi S. 2020. Antibacterial activity of Citrus hystrix toward Salmonella spp. infection. Enfermedades Infecciosas y Microbiología Clínica. In Press. 10.1016/j.eimc.2020.05.016