Anti-inflammatory effects of flavonoids in Citrus jabara fruit peels

Abstract

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.

The Inhibition Activity of Natural Methoxyflavonoid from Inula britannica on Soluble Epoxide Hydrolase and NO Production in RAW264.7 Cells

“…Methoxyl-flavone was found to have an IC 50 of ~15 µM [30]. On the other hand, flavonone had a very low activity with an IC 50 of ~250 µM [31]. Five flavonoids (eupatin, hispidulin, patuletin, nepetin, and isorhametin-3-O-glucoside) were isolated (1-5) and subsequently shown to be noncompetitive inhibitors of sEH, with k i values of 43.9, 19.8, 17.5, 63.5, and 68.7 µM, and IC 50 values against sEH of 42.6 ± 0.8, 22.2 ± 0.3, 12.1 ± 0.1, 40.9 ± 0.6, and 62.8 ± 1.8 µM, respectively.…”

The Effects of Jabara Juice on the Intestinal Permeation of Fexofenadine

“…Recently, jabara has become increasingly popular as a dietary supplement for relieving pollen allergy symptoms because it contains a high amount of narirutin, which is considered to reduce inflammation by decreasing interleukin-4 and immunoglobulin E (IgE) levels. [1][2][3] Fexofenadine, a histamine receptor antagonist, is widely used for the treatment of allergies. 4) Therefore, jabara and fexofenadine may be taken simultaneously by patients with allergies.…”

“…[19][20][21] Moreover, jabara peel contains various P-gp inhibitors, such as 3,3,′4′5,6,7,8-heptamethoxyflavone (HMF) and 3,3′4′6,7,8-hexamethoxyflavone (nobiletin; NBL). 2,[22][23][24] Therefore, jabara juice may affect the absorption of fexofenadine in different directions by inhibiting OATP1A2/2B1 and P-gp. However, the effects of jabara juice on the intestinal absorption of fexofenadine remain unclear.…”