Flavonoids and a Limonoid from the Fruits of Citrus unshiu and Their Biological Activity

Abstract

The fruits of Citrus unshiu are one of the most popular and most enjoyed fruits in Korea. As we continue to seek for bioactive metabolites from Korean natural resources, our study on the chemical constituents of the fruits of C. unshiu resulted in the isolation of a new flavonoid glycoside, limocitrunshin 1, along with seven other flavonoids 2-8 and a limonoid 9. All structures were identified by spectroscopic methods, namely 1D and 2D NMR, including HSQC, HMBC, and (1)H-(1)H COSY experiments, HRMS, and other chemical methods. Compounds 3, 5, and 9 are reported to be isolated from this fruit for the first time. The isolated compounds were applied to activity tests to verify their inhibitory effects on inflammation and nephrotoxicity. Compounds 6 and 9 showed the most potent inhibitory activity on renal cell damage and nitric oxide production, respectively. Thus, the fruits of C. unshiu could serve as a valuable natural source of bioactive components with health benefits for potential application in functional foods.

Chemical constituents from the fruits of Citrus unshiu and their inhibitory effects on acetylcholinesterase

“…In our previous study, we found that methyl nomilinate showed an anti-inflammatory effect by inhibiting NO production by LPS-activated RAW 264.7 macrophages and significantly abrogated cisplatin-induced nephrotoxicity in LLC-PK1 cells [7]. In addition, methyl nomilinate was reported to inhibit the proliferation of MCF-7 ER+ human breast cancer cells with an IC 50 of 0.01 μg/ml [30].…”

“…1). The compounds were identified as methyl nomilinate (1) [15], limocitrunshin (2) [7], nobiletin (3) [16], kaempferol 3-O-rutinoside (4) [17], limocitrin 3-glucoside (5) [18], kaempferol 3-(2 G -rhamnosylrutinoside) (6) [17], didymin (7) [19], (2S)-narirutin 4'-Oglucoside (8) [20] and naringenin 7-O-rutinoside (9) [21], respectively, based on comparison of their spectroscopic and physical data with those previously reported as well as by measurement of their specific rotations.…”

“…Citrus unshiu Markovich (Rutaceae), also known as the satsuma mandarin, is cultivated in countries in cool subtropical regions including Korea, and is consumed in a variety of forms such as fresh juice, citrus-based drinks, jam, salad dressing and tea [7,8]. Due to its sweet and fresh flavor, it is one of the most popular fruits in Korea.…”

“…In addition, for centuries it has been consumed not only as food but also as a medicine. The peel of C. unshiu, well-known as "Jin-pee", has been used for traditional herbal medicines against the common cold, exhaustion and cancer [7,9]. Previous studies have demonstrated that the peel has antitumor properties in a tumor-bearing murine model [9] as well as antioxidant activity [1012].…”

“…In our recent studies, we reported the isolation of a novel cyclic peptide, citrusin XI, and its anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells [13]. In addition, we discovered a new flavonoid glycoside, limocitrunshin, together with other flavonoids, and evaluated their inhibitory effects on renal cell damage and nitric oxide (NO) production [7]. NO is an important pro-inflammatory mediator that can accelerate the appearance of some neurodegenerative disorders such as AD [14].…”