• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.3
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• pp.331-337
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• 2015

Citrus and its peels, which are by-products from juice and/or jam processing, have long been used in Asian folk medicine. Citrus peels show an abundant variety of flavanones, and these flavanones have glycone and aglycone forms. Aglycones are more potent than glycones with a variety of physiological functions since aglycone absorption is more efficient than glycones. Bioconversion with cytolase converted narirutin and naringin into naringenin and hesperidin into hesperetin. Therefore, this study aimed to investigate the anti-oxidant and anti-inflammatory effects of bioconversion of Citrus unshiu (CU) peel extracts with cytolase (CU-C) in RAW264.7 cells. HPLC chromatograms showed that CU and CU-C had 23.42% and 29.39% total flavonoids, respectively. There was substantial bioconversion of narirutin to naringenin and of hesperidin to hesperetin. All citrus peel extracts showed DPPH scavenging activities in a dose-dependent manner, and CU-C was more potent than intact CU. RAW264.7 cells were pre-treated with $0{\sim}500{\mu}g/mL$ of citrus peel extracts for 4 h and then stimulated by $1{\mu}g/mL$ of lipopolysaccharide (LPS) for 8 h. All citrus peel extracts showed decreased mRNA levels and protein expression of LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in a dose-dependent manner. Especially, CU-C markedly inhibited mRNA and protein expression of iNOS and COX-2 compared to intact citrus peel extracts. All citrus peel extracts showed decreased NO production by iNOS activity. This result suggests that bioconversion of citrus peel extracts with cytolase may provide potent functional food materials for prevention of chronic diseases attributable to oxidation and inflammation by boosting the anti-inflammatory effects of citrus peels.

• Nutrition Research and Practice
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• v.12 no.2
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• pp.129-134
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• 2018

BACKGROUND/OBJECTIVES: Although several recent studies have reported the anti-cancer effects of extracts or components of Citrus unshiu peel, which has been used for various purposes in traditional medicine, the molecular mechanisms for their effects remain unclear. In the present study, the anti-cancer activity of a water-soluble extract of C. unshiu peel (WECU) in MDA-MB-231 human breast carcinoma cells at the level of apoptosis induction was investigated. MATERIALS/METHODS: Cytotoxicity was evaluated using the MTT assay. Apoptosis was detected using DAPI staining and flow cytometry analyses. Mitochondrial membrane potential, reactive oxygen species (ROS) assay, caspase activity and Western blotting were used to confirm the basis of apoptosis. RESULTS: The results indicated that WECU-induced apoptosis was related to the activation of caspase-8, and -9, representative initiator caspases of extrinsic and intrinsic apoptosis pathways, respectively, and caspase-3 accompanied by proteolytic degradation of poly(ADP-ribose) polymerase and down-regulation of the inhibitors of apoptosis protein family members. WECU also increased the pro-apoptotic BAX to anti-apoptotic BCL-2 ratio, loss of mitochondrial membrane potential and cytochrome c release from mitochondria to cytoplasm. Furthermore, WECU provoked the generation of ROS, but the reduction of cell viability and induction of apoptosis by WECU were prevented when ROS production was blocked by antioxidant N-acetyl cysteine. CONCLUSIONS: These results suggest that WECU suppressed proliferation of MDA-MB-231 cells by activating extrinsic and intrinsic apoptosis pathways in a ROS-dependent manner.

• Korean Journal of Food Science and Technology
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• v.54 no.1
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• pp.28-34
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• 2022

Glioblastoma is the most common primary malignant brain tumor and has an extremely poor prognosis. Glioblastoma stem cells (GSCs) contribute to tumor initiation, recurrence, and resistance to therapy, and are thus a key therapeutic target. The peel of Citrus unshiu Markovich has been used in traditional medicine in East Asia to treat various diseases. In this study, we investigated the anticancer activity and molecular mechanism of the chloroform extract of this natural product (CECU) in U87MG GSCs. The results show that CECU inhibited the proliferation, tumorsphere formation, and migration of U87MG GSCs by causing cell cycle arrest at the G0/G1 phase and apoptosis. In addition, CECU downregulated key cancer stemness regulators, including CD133, Oct4, Nanog, integrin α6, ALDH1A1, and STAT3 signaling in U87MG GSCs. Furthermore, CECU significantly suppressed in vivo tumor growth of U87MG GSCs in a chorioallantoic membrane model. Therefore, CECU can be utilized as a natural medicine for the prevention and treatment of glioblastoma.

• Korean Journal of Food Science and Technology
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• v.54 no.3
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• pp.288-296
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• 2022

This study aimed to verify the effect of Citrus unshiu peel water extract (CUP) on a mouse model of acute gastritis (AG) induced by HCl/ethanol. Several studies have found that CUP has anti-inflammatory effects. The AG model was induced by oral administration of 150 mM HCl/60% ethanol (550 µL) to all groups except the control group. Also, for drug treatment, sucralfate (10 mg/kg) and CUP (100 or 200 mg/kg) were orally administered for 90 minutes before induction. The effect of CUP treatment was confirmed by gross gastric mucosal damage measurement, and the levels of Glutamic Oxaloacetic Transaminase (GOT), Glutamic Pyruvic Transaminase (GPT), and myeloperoxidase were reduced as well as the levels of oxidative stress biomarkers and their related proteins. In addition, the levels of inflammatory proteins, mediators, and cytokines were significantly downregulated byPI3K/Akt signaling. Taken together, these results show that CUP treatment alleviates AG by regulating PI3K/Akt signaling.

• Food Science and Preservation
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• v.30 no.2
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• pp.235-246
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• 2023

Yellowball (Citrus hybrid cv. Yellowball ) is a new citrus hybrid between Haruka (C. tamurana × natsudaidai ) and Kiyomi (C. unshiu × sinensis) and is known to possess strong antioxidant activity. However, detailed information on the antioxidant components of its peel has not yet been reported. This study evaluated the antioxidant activity of the peel and identified the antioxidant components by fractionating a methanolic extract of Yellowball peels using liquid-liquid extraction with n-hexane, ethyl ether (ether), ethyl acetate (EA), butanol, and water. The phenolic contents and antioxidant activities of the n-hexane, ether, and EA fractions were higher than those of the other fractions, and these fractions were further separated by semi-preparative high-performance liquid chromatography (HPLC). Four antioxidant peaks, EA1, EA2, EA3, and He1, were isolated and analyzed using ultra-performance liquid chromatography-quadrupole-time- of-flight mass spectrometry (UPLC-Q-TOF MS). Sinapoyl glucoside and hesperidin were identified in EA2 and EA3, respectively, and a polymethoxylated flavone (PMF) complex (5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone, natsudaidain, tetrameth- oxyflavone, and tangeretin) was identified in He1. A compound in EA1 with m/z 223.0246 [M-H] could not be identified and was named unknown2. The antioxidant activity of unknown2 (IC₅₀=69.17 ㎍/mL) was similar to that of Trolox, which was noted as a major antioxidant in Yellowball peel. Further studies on the antioxidant capacity of Yellowball peel are required; however, these results provide a foundation for using Yellowball peel as an antioxidant.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.2
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• pp.187-193
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• 2014

This study investigated whether or not Citrus unshiu peel extract (CPE) affects fat accumulation in livers of rats fed an ethanol-containing liquid diet. Initially, male Sprague-Dawley rats were housed individually in stainless steel, wire-bottomed cages with free access to a Lieber-Decarli control liquid diet. Rats were divided by body weight into three groups of eight each: one group of rats was fed the Lieber-Decarli control liquid diet devoid of ethanol (control), another was fed the Lieber-Decarli ethanol diet (ethanol), and third was fed the same ethanol diet except containing CPE. All three groups were fed their respective diets for 6 weeks. Serum and liver lipids were analyzed and liver histology performed. Body weight did not differ among the groups over the 6-wk duration. Histology images showed that CPE administration significantly improved fat accumulation in livers, which was induced by ethanol diet. Serum levels of transaminases and lipids also were reduced by CPE consumption. Taken together, the results indicate that CPE may protect ethanol-induced fatty liver by lowering fat accumulation in both the liver and blood. The protective effects of CPE appear to be due to its phenolic contents.

• The Journal of Korean Medicine
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• v.26 no.2 s.62
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• pp.195-200
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• 2005

Objecitves: Peel of Citrus unshiu (Rutaceae) has been used in traditional herbal prescriptions. Hesperidin and naringin contents of Citri Unshii Pericarpium were determined and compared to herbal prescriptions. Then, the different extractions from prescriptions are explained with traditional herbal theories. Methods: The herb and herbal prescriptions were extracted in boiled water. A quantitative analysis was made of hesperidin and naringin using HPLC with-reversed-phase CIS column and a UV detector at 204nm. Elution was carried out at 1.0ml/min with $38\%$ methanol. Results and Conclusions: The extract of Citri Unshii Pericarpium for 180 min was the better method for extracting naringin and hesperidin. The flavonoid contents in remedies are different among several traditional herbal prescriptions. The reason for the difference can be explained with traditional drug interaction theories.

• The Korea Journal of Herbology
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• v.36 no.1
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• pp.1-8
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• 2021

Objective : Citri Unshius Pericarpium (Citrus unshiu peel) has been used in Korean medicine to treat indigestion, vomiting, coughing and phlegm. This study investigated the hepatoprotective effect of ethanol extract of Citrus unshiu peel (CEE) in cadmium (CdCl2)-treated mouse model. Methods : CEE was dissolved in water and administered orally to mice once a day for 7 consecutive days. The mice were then exposed to a single intraperitoneal (i.p.) injection of cadmium (4 mg/kg body weight) to induce acute hepatotoxicity. At the end of the experiment, blood and liver tissue samples were collected, analyzed for alanine aminotransferase (ALT), aspartate aminotransferase (AST), and histopathological evaluation. Liver damage was assessed as the percentage of degenerative areas of the hepatic parenchyma, the number of degenerative hepatocytes, and the number of infiltrated inflammatory cells. Results : In cadmium-treated rats, pretreatment with CEE significantly reduced the serum ALT and AST levels associated with liver damage. Histopathologically, CEE prevented degenerative changes on the hepatic tissues including confluent necrosis, congestions and infiltration of inflammatory cells. CEE also reduced the elevation of oxidative stress markers (nitrotyrosine and 4-hydroxynonenal) and apoptosis markers (cleaved caspase-3 and cleaved PARP) positive cells. PARP protein expression in liver tissue was also restored by CEE. Conclusion : This study showed that CEE exerted antioxidant and anti-apoptotic effects against cadmium-induced liver injury. Thus, it can be concluded that CEE can be used to prevent liver damage caused by cadmium.

• Korean Journal of Food Science and Technology
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• v.53 no.2
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• pp.149-153
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• 2021

Mandarin peel (MP) is a by-product of the processing of citrus juice or other products. This study aimed to investigate the potential anti-obesity effect of an enzymatic extract of MP on the inhibition of adipogenesis in 3T3-L1 adipocytes. The enzymatic extract (MPCE) was prepared using the commercial food-grade carbohydrase Celluclast. Lipid accumulation and triglyceride levels were significantly lower in MPCE-treated cells than in untreated cells. In addition, MPCE treatment reduced the protein expression levels of peroxisome proliferator-activated receptor-γ, CCAAT/enhancer-binding protein α, sterol regulatory element-binding protein 1, and fatty acid-binding protein 4. These results suggest that MPCE inhibits adipogenesis by downregulating the expression levels of adipogenesis-related proteins. Therefore, the current findings demonstrate that MPCE possesses potent anti-obesity properties and could be a potential ingredient in functional food industries.

• Food Science and Preservation
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• v.18 no.5
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• pp.755-763
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• 2011

This study was conducted to monitor the quality characteristics Citrus unshiu ethanolic extracts by a response surface methodology. In extraction conditions based on the central composite design with variations in ethanol concentration (0~100%), extraction temperature($35\sim95^{\circ}C$), and ratio of solvent to sample(20 mL/g). The maximum value of yield was 36.31% at $93.18^{\circ}C$, 67.13% of ethanol concentration. The extraction yield and total polyphenol content were improved with the increase of ethanol concentration than extraction temperature. Total flavonoid content was improved with the increase of extraction temperature than ethanol concentration. The coefficients of determinations($R^2$) were 0.8646(p<0.1) and 0.9153(p<0.05) in electron donating ability and hesperidin content, respectively. Estimated conditions for the maximized extraction including yield, total polyphenol content, total flavonoid content, electron donating ability, and hesperidin content were 55~73% in ethanol concentration, $89\sim95^{\circ}C$ in extraction temperature, and 20 mL/g in ratio of solvent to sample.