Anti-inflammatory effects of flavonoids in Citrus jabara fruit peels

Seisho Azuma, Yoshinobu Murakami, Eiko Azuma, Kimiye Baba, Masahiko Taniguchi

Article ID: 844
Vol 4, Issue 1, 2020, Article identifier:5-14

VIEWS - 1274 (Abstract) 516 (PDF)


Currently, about half of people in Japan suffer from allergic diseases. Thus, Citrus jabara fruits have been paid attention as one of quite effective anti-allergic functional foods. C. jabara is an endemic species originally grown only in Kitayama village, Wakayama prefecture in Japan. Although genetic characterization and diversity of various Citrus fruits including C. jabara were researched, but there is room for the study on flavonoids characteristics in C. jabara fruit. For the alleviation of allergic symptom, anti-inflammatory effects are also important. In this study, characteristics of flavonoids in C. jabara fruit peels, and the anti-inflammatory effects of these purified flavonoids were investigated. Our results revealed that C. jabara is a unique Citrus that almost all of flavonoids in fruit peels was narirutin. There was no Citrus species with a flavanone glycosides content ratio like C. jabara. Although anti-inflammatory effects of narirutin was weak, but its aglycone naringenin exhibited following inhibitory effects: nitric oxide synthesis (IC50 = 105 μM), nitric oxide synthase induction, Interleukin-6 synthesis (IC50 = 65 μM), and inducible soluble epoxide hydrolase activity (IC50 = 267 μM). Since narirutin is deglycosylated to naringenin that is then absorbed by colonocytes, it is considered that narirutin exists like a prodrug and its aglycone naringenin works as an active form of anti-inflammatory effect in a living body at oral ingestion of C. jabara fruit peels.


Citrus jabara; anti-inflammatory effects; flavonoids; narirutin; naringenin

Full Text:



Kubo M, Yano M, Matsuda H. Pharmacological study on citrus fruits. I. Anti-allergic effect of fruit of Citrus unshiu Markovich (1). Yakugaku Zasshi 1989; 109(11): 835–842.

Matsuda H, Yano M, Kubo M, et al. Iinuma M, Oyama M, Mizuno M. Pharmacological study on citrus fruits. II. Anti-allergic effect of fruit of Citrus unshiu MARKOVICH (2). On flavonoid components. Yakugaku Zasshi 1991; 111(3): 193–198.

Nishiura H, Yasui T, Tanaka K. Cosmetic effect of Citrus jabara peel extract. Fragrance J 2007; 35: 86–88.

Minatoguchi K, Oono Y, Funaguchi N. Effect of “Jabara” juice on symptoms and QOL in patients with Japanese cedar pollinosis. Clin Immunol Allergol 2008–2009; 50: 360–364.

Iwashita J, Iguchi N, Takashima A, et al. Citrus jabara extracts suppress MUC5AC mucin production in human lung epithelial cells. Adv Biol Chem 2017; 7: 139–150. doi: 10.4236/abc.2017.73009.

Abkenar A, Isshiki S. Molecular characterization and genetic diversity among Japanese acid citrus (Citrus spp.) based on RAPD markers. J Hortic Sci Biotech 2003; 78: 108–112. doi: 10.1080/14620316.2003.11511574.

Penjor T, Yamamoto M, Uehara M, et al. Phylogenetic relationships of Citrus and its relatives based on matK gene sequences. PLoS One 2013; 8(4): e62574. doi: 10.1371/journal.pone.0062574.

Shimizu T, Kitajima A, Nonaka K, et al. Hybrid origins of citrus varieties inferred from DNA marker analysis of nuclear and organelle genomes. PLoS One 2016; 11(11): e0166969. doi: 10.1371/journal.pone.0166969.

Chen HJ, Chung CP, Chiang W. Anti-inflammatory effects and chemical study of a flavonoid-enriched fraction from adlay bran. Food Chem 2011; 126(4): 1741–1748. doi: 10.1016/j.foodchem.2010.12.074.

Sugiyama S, Umehara K, Kuroyanagi M, et al. Studies on the differentiation inducers of myeloid leukemic cells from Citrus species. Chem Pharm Bull (Tokyo) 1993; 41(4): 714–719. doi: 10.1248/cpb.41.714.

Lichius JJ, Thoison O, Montagnac A, et al. Antimitotic and cytotoxic flavonols from Zieridium pseudobtusifolium and Acronychia porter. J Nat Prod 1994; 57(7): 1012–1016. doi: 10.1021/np50109a024.

Akachi T, Shiina Y, Ohishi Y, et al. Hepatoprotective effects of flavonoids from Shekwasha (Citrus depressa) against D-galactosamine-induced liver injury in rats. J Nutr Sci Vitaminol (Tokyo) 2010; 56(1): 60–67. doi: 10.3177/jnsv.56.60.

Li S, Lo CY, Ho HT. Hydroxylated Poly­methoxyflavones and Methylated Flavonoids in Sweet Orange (Citrus sinensis) Peel. J Agric Food Chem 2006; 54(12): 4176–4185. doi: 10.1021/jf060234n.

Matsubara R, Yamada H, Ju-ichi M, et al. Polymethoxyflavonoids from the peel of Citrus jabara. Shoyakugaku Zasshi 2012; 66(1): 23–25.

Tosa S, Ishihara S, Toyota M, et al. Studies of flavonoid in Citrus. Analysis of flavanone glycosides in the peel of Citrus by high performance liquid chromatography. Shoyakugaku Zasshi 1988; 42(1): 41–47.

Bahl CD, Morisseau C, Bomberger JM, et al. Crystal structure of the cystic fibrosis transmembrane conductance regulator inhibitory factor Cif reveals novel active-site features of an epoxide hydrolase virulence factor. J Bacteriol 2010; 192: 1785–1795. doi: 10.1128/JB.01348-09.

Ratnasooriya WD, Abeysekera WPKM, Ratnasooriya CTD. In vitro anti-hyaluronidase activity of Sri Lankan low grown orthodox orange pekoe grade black tea (Camellia sinensis L.). Asian Pac J Trop Biomed 2014; 4(12): 959–963. doi: 10.12980/APJTB.4.2014APJTB-2014-0462.

Tani M, Gyobu Y, Sasaki T, et al. SF2809 compounds, novel chymase inhibitors from Dactylosporangium sp. 1. Taxonomy, fermentation, isolation and biological properties. J Antibiot (Tokyo) 2004; 57(2): 83–88. doi: 10.7164/antibiotics.57.83.

Kubo M, Fujita T, Nishimura Y, et al. Seasonal variation in anti-allergic activity of citrus fruits and flavanone glycoside content. Nat Med 2004; 58 (6): 284–294.

Kawaii S, Tomono Y, Katase E, et al. Quantitation of flavonoid constituents in citrus fruits. J Agric Food Chem 1999; 47(9): 3565–3571. doi: 10.1021/jf990153+.

Dou W, Zhang J, Sun A, et al. Protective effect of naringenin against experimental colitis via suppression of Toll-like receptor 4/NF-κB signalling. Br J Nutr 2013; 110(4): 599–608. doi: 10.1017/S0007114512005594.

Pinho-Ribeiro FA, Zarpelon AC, Mizokami SS, et al. The citrus flavonone naringenin reduces lipopolysaccharide-induced inflammatory pain and leukocyte recruitment by inhibiting NF-κB activation. J Nutr Biochem 2016; 33: 8–14. doi: 10.1016/j.jnutbio.2016.03.013.

Takano-Ishikawa Y, Goto M, Yamaki K. Structure-activity relations of inhibitory effects of various flavonoids on lipopolysaccharide-induced prosta­glandin E2 production in rat peritoneal macrophages: Comparison between subclasses of flavonoids. Phytomedicine 2006; 13(5): 310–317. doi: 10.1016/j.phymed.2005.01.016.

Walgren RA, Walle UK, Walle T. Transport of quercetin and its glucosides across human intestinal epithelial Caco-2 cells. Biochem Pharmacol 1998; 55(10): 1721–1727. doi: 10.1016/S0006-2952(98)00048-3.

Funaguchi N, Ohno Y, La BL, et al. Narirutin inhibits airway inflammation in an allergic mouse model. Clin Exp Pharmacol Physiol 2007; 34(8): 766–770. doi: 10.1111/j.1440-1681.2007.04636.x.

Murata K, Takano S, Masuda M, et al. Anti-degranulating activity in rat basophil leukemia RBL-2H3 cells of flavanone glycosides and their aglycones in citrus fruits. J Nat Med 2013; 67(3): 643–646. doi: 10.1007/s11418-012-0699-y.

Silveira JQ, Cesar TB, Manthey JA, et al. Pharma­cokinetics of flavanone glycosides after ingestion of single doses of fresh-squeezed orange juice versus commercially processed orange juice in healthy humans. J Agric Food Chem 2014; 62(52): 12576–12584. doi: 10.1021/jf5038163.

Aschoff JK, Riedl KM, Cooperstone JL et al. Urinary excretion of Citrus flavanones and their major catabolites after consumption of fresh oranges and pasteurized orange juice: A randomized cross-over study. Mol Nutr Food Res 2016; 60(12): 2602–2610. doi: 10.1002/mnfr.201600315.

Thomson SJ, Askari A, Bishop-Bailey D. Anti-inflammatory effects of epoxyeicosatrienoic acids. Int J Vasc Med 2012; 2012: 605101. doi: 10.1155/2012/605101.

Monzón ME1, Manzanares D, Schmid N, et al. Hyaluronidase expression and activity is regulated by pro-inflammatory cytokines in human airway epithelial cells. Am J Respir Cell Mol Biol 2008; 39(3): 289–295. doi: 10.1165/rcmb.2007-0361OC.

Lee JH, Kim GH. Evaluation of antioxidant and inhibitory activities for different subclasses flavonoids on enzymes for rheumatoid arthritis. J Food Sci. 2010; 75(7): H212–217. doi: 10.1111/j.1750-3841.2010.01755.x.

Day AJ, DuPont MS, Ridley S, et al. Deglycosylation of flavonoid and isoflavonoid glycosides by human small intestine and liver beta-glucosidase activity. FEBS Lett 1998; 436(1): 71–75. doi: 10.1016/S0014-5793(98)01101-6.

Bokkenheuser VD, Shackleton CH, Winter J. Hydrolysis of dietary flavonoid glycosides by strains of intestinal Bacteroides from humans. Biochem J 1987; 248(3): 953–956. doi: 10.1042/bj2480953.



  • There are currently no refbacks.

Copyright (c) 2020 Seisho Azuma, Yoshinobu Murakami, Eiko Azuma, Kimiye Baba, Masahiko Taniguchi

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Creative Commons License

This site is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.