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Umsumarng S, Semmarath W, Arjsri P, Srisawad K, Intanil I, Jamjod S, Prom-u-thai C, Dejkriengkraikul P. Anthocyanin-Rich Fraction from Kum Akha Black Rice Attenuates NLRP3 Inflammasome-Driven Lung Inflammation In Vitro and In Vivo. Nutrients 2025; 17:1186. [PMID: 40218944 PMCID: PMC11990836 DOI: 10.3390/nu17071186] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2025] [Revised: 03/25/2025] [Accepted: 03/27/2025] [Indexed: 04/14/2025] Open
Abstract
BACKGROUND/OBJECTIVES Chronic lower respiratory tract inflammation can result from exposure to bacterial particles, leading to the activation of the NLRP3 inflammasome pathway. These effects may cause irreversible respiratory damage, contributing to persistent lung injury and chronic obstructive pulmonary disease (COPD), as observed in long COVID or bacterial pneumonia in older adults' patients. Given its profound impact, the NLRP3 inflammasome has emerged as a key therapeutic target for mitigating aberrant inflammatory responses. METHODS In this study, we investigated the anti-inflammatory effects of Kum Akha black rice, a functional food, on the attenuation of NLRP3 inflammasome pathway using lipopolysaccharide-induced A549 lung epithelial cells and a C57BL/6NJcl mouse model. The anthocyanin-rich fraction from Kum Akha black rice germ and bran extract (KA1-P1) was obtained using a solvent-partitioned extraction technique. RESULTS KA1-P1 exhibited a high anthocyanin content (74.63 ± 1.66 mg/g extract) as determined by the pH differential method. The HPLC analysis revealed cyanidin-3-O-glucoside (C3G: 45.58 ± 0.48 mg/g extract) and peonidin-3-O-glucoside (P3G: 6.92 ± 0.29 mg/g extract) as its anthocyanin's active compounds. Additionally, KA1-P1 demonstrated strong antioxidant activity, as assessed by DPPH and ABTS assays. KA1-P1 (12.5-100 μg/mL) possessed inhibitory effects on LPS + ATP-induced A549 lung cells inflammation through the significant suppressions of NLRP3, IL-6, IL-1β, and IL-18 mRNA levels and the inhibition of cytokine secretions in a dose-dependent manner (p < 0.05). Mechanistic analysis revealed that KA1-P1 downregulated key proteins in the NLRP3 inflammasome pathway (NLRP3, ASC, pro-caspase-1, and cleaved-caspase-1). Furthermore, in vivo studies demonstrated that KA1-P1 significantly diminished LPS-induced lower respiratory inflammation in C57BL/6NJcl mice, as evidenced by the reduced bronchoalveolar lavage fluid and blood levels of inflammatory cytokines (IL-6, IL-1β, and IL-18) and diminished histopathological inflammatory lung lesions. CONCLUSIONS Overall, our findings suggest that the anti-inflammatory properties of KA1-P1 may support its application as a functional supplement or promote the consumption of pigmented rice among the elderly to mitigate chronic lower respiratory tract inflammation mediated by the NLRP3 inflammasome pathway.
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Affiliation(s)
- Sonthaya Umsumarng
- Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai 50100, Thailand;
- Lanna Rice Research Center, Chiang Mai University, Chiang Mai 50200, Thailand; (S.J.); (C.P.-u.-t.)
| | - Warathit Semmarath
- Akkhraratchakumari Veterinary College, Walailak University, Nakhon Si Thammarat 80160, Thailand;
- Centre for One Health, Walailak University, Nakhon Si Thammarat 80160, Thailand
| | - Punnida Arjsri
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (P.A.); (K.S.); (I.I.)
| | - Kamonwan Srisawad
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (P.A.); (K.S.); (I.I.)
- Anticarcinogenesis and Apoptosis Research Cluster, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Intranee Intanil
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (P.A.); (K.S.); (I.I.)
| | - Sansanee Jamjod
- Lanna Rice Research Center, Chiang Mai University, Chiang Mai 50200, Thailand; (S.J.); (C.P.-u.-t.)
- Department of Plant and Soil Sciences, Faculty of Agriculture, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Chanakan Prom-u-thai
- Lanna Rice Research Center, Chiang Mai University, Chiang Mai 50200, Thailand; (S.J.); (C.P.-u.-t.)
| | - Pornngarm Dejkriengkraikul
- Lanna Rice Research Center, Chiang Mai University, Chiang Mai 50200, Thailand; (S.J.); (C.P.-u.-t.)
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (P.A.); (K.S.); (I.I.)
- Anticarcinogenesis and Apoptosis Research Cluster, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
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2
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Li J, Guo C, Yang X, Xie W, Mi W, Hua C, Tang C, Wang H. Effects of natural products on macrophage immunometabolism: A new frontier in the treatment of metabolic diseases. Pharmacol Res 2025; 213:107634. [PMID: 39889866 DOI: 10.1016/j.phrs.2025.107634] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 01/20/2025] [Accepted: 01/27/2025] [Indexed: 02/03/2025]
Abstract
Immunometabolic variations in macrophages critically influence their differentiation into pro-inflammatory or anti-inflammatory phenotypes, thereby contributing to immune homeostasis, defense against infection, and tissue repair. Dysregulation of macrophage immunometabolism has been closely implicated in several metabolic diseases, including obesity, type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), hypertension, atherosclerosis, and gout, which positions macrophages as potential therapeutic targets. Recently, several natural products that target macrophage metabolic pathways have shown significant efficacy in managing metabolic diseases; however, a systematic review of these findings has yet to be conducted. This study consolidates natural products with immunoregulatory properties, including flavonoids, phenols, terpenoids, and naphthoquinones, which can alleviate chronic inflammation associated with metabolic disorders by modulating macrophage metabolic pathways, such as aerobic glycolysis, oxidative phosphorylation (OXPHOS), and fatty acid oxidation (FAO). This review aims to elucidate the metabolic regulation of the immune system, analyze metabolic alterations in macrophage associated with metabolic diseases, and summarize the beneficial roles of natural products in immunometabolism, providing novel insights for the prevention and therapeutic management of metabolic diseases.
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Affiliation(s)
- Jiani Li
- Beijing Academy of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Chen Guo
- Beijing Academy of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Xiaofei Yang
- Beijing University of Chinese Medicine, Beijing 100029, China
| | - Weinan Xie
- Beijing University of Chinese Medicine, Beijing 100029, China
| | - Wenjing Mi
- Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Chenglong Hua
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Cheng Tang
- Beijing Academy of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
| | - Han Wang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China.
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3
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Escobedo A, Avalos-Flores L, Mojica L, Lugo-Cervantes E, Gschaedler A, Alcazar M. Native Mexican black bean purified anthocyanins fractionated by high-performance counter-current chromatography modulate inflammatory pathways. Food Chem 2024; 458:140216. [PMID: 38970958 DOI: 10.1016/j.foodchem.2024.140216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Revised: 06/07/2024] [Accepted: 06/22/2024] [Indexed: 07/08/2024]
Abstract
In addition to their pigment properties, the potential health benefits of anthocyanins have made them a subject of interest in recent years. This study aimed to obtain purified anthocyanin fractions from native Mexican black bean cultivars using Amberlite XAD-7 resin column and HPCCC and evaluate their anti-inflammatory properties using RAW 264.7 cells. The major anthocyanins in the purified anthocyanin fractions were delphinidin 3-glucoside (61.8%), petunidin 3-glucoside (25.2%), and malvidin 3-glucoside (12.2%). Purified anthocyanin fractions at 12.5 μg/mL effectively prevented LPS-induced ERK1/ERK2 phosphorylation and reduced the protein expression of COX-2 and mRNA expression of iNOS. Results showed that purified anthocyanin fractions have the potential to modulate the inflammatory response by inhibiting the production of pro-inflammatory mediators through the ERK1/ERK2 and NF-κB pathways. This study suggests that anthocyanins from black beans could be used as a natural strategy to help modulate inflammation-associated diseases.
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Affiliation(s)
- Alejandro Escobedo
- Food Technology, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco (CIATEJ), A.C., Camino Arenero #1227, Col. El Bajío, 45019 Zapopan, Mexico
| | - Lucero Avalos-Flores
- Food Technology, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco (CIATEJ), A.C., Camino Arenero #1227, Col. El Bajío, 45019 Zapopan, Mexico
| | - Luis Mojica
- Food Technology, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco (CIATEJ), A.C., Camino Arenero #1227, Col. El Bajío, 45019 Zapopan, Mexico
| | - Eugenia Lugo-Cervantes
- Food Technology, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco (CIATEJ), A.C., Camino Arenero #1227, Col. El Bajío, 45019 Zapopan, Mexico
| | - Anne Gschaedler
- Industrial Biotechnology, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco (CIATEJ), A.C., Camino Arenero #1227, Col. El Bajío, 45019 Zapopan, Mexico
| | - Montserrat Alcazar
- Food Technology, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco (CIATEJ), A.C., Camino Arenero #1227, Col. El Bajío, 45019 Zapopan, Mexico.
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Talib WH, Baban MM, Bulbul MF, Al-Zaidaneen E, Allan A, Al-Rousan EW, Ahmad RHY, Alshaeri HK, Alasmari MM, Law D. Natural Products and Altered Metabolism in Cancer: Therapeutic Targets and Mechanisms of Action. Int J Mol Sci 2024; 25:9593. [PMID: 39273552 PMCID: PMC11394730 DOI: 10.3390/ijms25179593] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 08/27/2024] [Accepted: 08/30/2024] [Indexed: 09/15/2024] Open
Abstract
Cancer is characterized by uncontrolled cell proliferation and the dysregulation of numerous biological functions, including metabolism. Because of the potential implications of targeted therapies, the metabolic alterations seen in cancer cells, such as the Warburg effect and disruptions in lipid and amino acid metabolism, have gained attention in cancer research. In this review, we delve into recent research examining the influence of natural products on altered cancer metabolism. Natural products were selected based on their ability to target cancer's altered metabolism. We identified the targets and explored the mechanisms of action of these natural products in influencing cellular energetics. Studies discussed in this review provide a solid ground for researchers to consider natural products in cancer treatment alone and in combination with conventional anticancer therapies.
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Affiliation(s)
- Wamidh H Talib
- Faculty of Allied Medical Sciences, Applied Science Private University, Amman 11931, Jordan
- Faculty of Health and Life Sciences, Inti International University, Nilai 71800, Negeri Sembilan, Malaysia
| | - Media Mohammad Baban
- Department of Clinical Pharmacy and Therapeutics, Applied Science Private University, Amman 11931, Jordan
| | - Mais Fuad Bulbul
- Department of Clinical Pharmacy and Therapeutics, Applied Science Private University, Amman 11931, Jordan
| | - Esraa Al-Zaidaneen
- Department of Clinical Pharmacy and Therapeutics, Applied Science Private University, Amman 11931, Jordan
| | - Aya Allan
- Department of Clinical Pharmacy and Therapeutics, Applied Science Private University, Amman 11931, Jordan
| | - Eiman Wasef Al-Rousan
- Department of Clinical Pharmacy and Therapeutics, Applied Science Private University, Amman 11931, Jordan
| | - Rahaf Hamed Yousef Ahmad
- Department of Clinical Pharmacy and Therapeutics, Applied Science Private University, Amman 11931, Jordan
| | - Heba K Alshaeri
- Department of Pharmacology, Faculty of Medicine, King Abdul-Aziz University, Rabigh 25724, Saudi Arabia
| | - Moudi M Alasmari
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Jeddah 21423, Saudi Arabia
- King Abdullah International Medical Research Centre (KAIMRC), Jeddah 22233, Saudi Arabia
| | - Douglas Law
- Faculty of Health and Life Sciences, Inti International University, Nilai 71800, Negeri Sembilan, Malaysia
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5
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Zhu L, Cao F, Hu Z, Zhou Y, Guo T, Yan S, Xie Q, Xia X, Yuan H, Li G, Luo F, Lin Q. Cyanidin-3-O-Glucoside Alleviates Alcoholic Liver Injury via Modulating Gut Microbiota and Metabolites in Mice. Nutrients 2024; 16:694. [PMID: 38474822 DOI: 10.3390/nu16050694] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2024] [Revised: 02/21/2024] [Accepted: 02/24/2024] [Indexed: 03/14/2024] Open
Abstract
Alcoholic liver disease (ALD) is primarily caused by long-term excessive alcohol consumption. Cyanidin-3-O-glucoside (C3G) is a widely occurring natural anthocyanin with multiple biological activities. This study aims to investigate the effects of C3G isolated from black rice on ALD and explore the potential mechanism. C57BL/6J mice (male) were fed with standard diet (CON) and Lieber-DeCarli liquid-fed (Eth) or supplemented with a 100 mg/kg/d C3G Diet (Eth-C3G), respectively. Our results showed that C3G could effectively ameliorate the pathological structure and liver function, and also inhibited the accumulation of liver lipids. C3G supplementation could partially alleviate the injury of intestinal barrier in the alcohol-induced mice. C3G supplementation could increase the abundance of Norank_f_Muribaculaceae, meanwhile, the abundances of Bacteroides, Blautia, Collinsella, Escherichia-Shigella, Enterococcus, Prevotella, [Ruminococcus]_gnavus_group, Methylobacterium-Methylorubrum, Romboutsia, Streptococcus, Bilophila, were decreased. Spearman's correlation analysis showed that 12 distinct genera were correlated with blood lipid levels. Non-targeted metabolic analyses of cecal contents showed that C3G supplementation could affect the composition of intestinal metabolites, particularly bile acids. In conclusion, C3G can attenuate alcohol-induced liver injury by modulating the gut microbiota and metabolites, suggesting its potential as a functional food ingredient against alcoholic liver disease.
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Affiliation(s)
- Lingfeng Zhu
- National Engineering Laboratory for Deep Process of Rice and Byproducts, Hunan Key Laboratory of Grain-Oil Deep Process and Quality Control, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha 410004, China
- Hunan Agricultural Product Processing Institute, Hunan Academy of Agricultural Sciences, Changsha 410125, China
| | - Fuliang Cao
- College of Forestry, Nanjing Forestry University, Nanjing 210037, China
| | - Zuomin Hu
- National Engineering Laboratory for Deep Process of Rice and Byproducts, Hunan Key Laboratory of Grain-Oil Deep Process and Quality Control, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha 410004, China
| | - Yaping Zhou
- National Engineering Laboratory for Deep Process of Rice and Byproducts, Hunan Key Laboratory of Grain-Oil Deep Process and Quality Control, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha 410004, China
| | - Tianyi Guo
- National Engineering Laboratory for Deep Process of Rice and Byproducts, Hunan Key Laboratory of Grain-Oil Deep Process and Quality Control, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha 410004, China
| | - Sisi Yan
- National Engineering Laboratory for Deep Process of Rice and Byproducts, Hunan Key Laboratory of Grain-Oil Deep Process and Quality Control, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha 410004, China
| | - Qiutao Xie
- Hunan Agricultural Product Processing Institute, Hunan Academy of Agricultural Sciences, Changsha 410125, China
| | - Xinxin Xia
- Hunan Agricultural Product Processing Institute, Hunan Academy of Agricultural Sciences, Changsha 410125, China
| | - Hongyan Yuan
- Hunan Agricultural Product Processing Institute, Hunan Academy of Agricultural Sciences, Changsha 410125, China
| | - Gaoyang Li
- Hunan Academy of Agricultural Sciences, Changsha 410125, China
| | - Feijun Luo
- National Engineering Laboratory for Deep Process of Rice and Byproducts, Hunan Key Laboratory of Grain-Oil Deep Process and Quality Control, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha 410004, China
| | - Qinlu Lin
- National Engineering Laboratory for Deep Process of Rice and Byproducts, Hunan Key Laboratory of Grain-Oil Deep Process and Quality Control, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha 410004, China
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6
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Cho Y, Han HT, Kim TR, Sohn M, Park YS. Immunostimulatory activity of Lactococcus lactis LM1185 isolated from Hydrangea macrophylla. Food Sci Biotechnol 2023; 32:497-506. [PMID: 36911332 PMCID: PMC9992465 DOI: 10.1007/s10068-022-01199-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Revised: 10/15/2022] [Accepted: 10/25/2022] [Indexed: 11/14/2022] Open
Abstract
The lactic acid bacteria, Lactococcus lactis subsp. lactis LM1185 was isolated from Hydrangea macrophylla. Strain LM1185 showed 50.5% of acid tolerance at pH 2.5 for 2 h and 30.4% of 0.3% (w/v) bile salt tolerance for 24 h. The antioxidant activity of this strain was measured at 99.4% of 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activity. When RAW 264.7 macrophage cells were treated with strain LM1185, there was no observed cytotoxicity. This strain showed high nitric oxide production and mRNA expression levels of cytokines such as tumor necrosis factor-α and inducible nitric oxide synthase (iNOS). The nuclear factor-kB signaling pathway was activated by this strain resulting in the production of iNOS and cyclooxygenase-2 determined by western blotting. The present results indicated that L. lactis subsp. lactis LM1185 could be used as potential probiotics and may play a crucial role in the immunostimulatory effect on macrophages. Supplementary Information The online version contains supplementary material available at 10.1007/s10068-022-01199-5.
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Affiliation(s)
- Yoonjeong Cho
- Department of Food Science and Biotechnology, Gachon University, Seongnam, 13120 Republic of Korea
| | - Hyeon Tak Han
- Center for Research and Development, LACTOMASON, Jinju, 52840 Republic of Korea
| | - Tae-rahk Kim
- Center for Research and Development, LACTOMASON, Jinju, 52840 Republic of Korea
| | - Minn Sohn
- Center for Research and Development, LACTOMASON, Jinju, 52840 Republic of Korea
| | - Young-Seo Park
- Department of Food Science and Biotechnology, Gachon University, Seongnam, 13120 Republic of Korea
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7
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Thongnak L, Jaruan O, Pengrattanachot N, Promsan S, Phengpol N, Sutthasupha P, Jaikumkao K, Sriyotai W, Mahatheeranont S, Lungkaphin A. Resistant starch from black rice, Oryza sativa L. var. ameliorates renal inflammation, fibrosis and injury in insulin resistant rats. Phytother Res 2023; 37:935-948. [PMID: 36379906 DOI: 10.1002/ptr.7675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Revised: 10/07/2022] [Accepted: 10/20/2022] [Indexed: 11/17/2022]
Abstract
It has recently been reported that black rice (BR) extract has anti-obesity, anti-diabetic, and anti-osteoporosis effects. It has been shown to reduce obese-related kidney dysfunction in animal models. This study aimed to investigate the effect of resistant starch from BR (RS) on renal inflammation, oxidative stress, and apoptosis in obese insulin resistant rats. Male Wistar rats were divided into six groups: normal diet (ND), ND treated with 150 mg of RS (NDRS150), high-fat (HF) diet, HF treated with 100 and 150 mg of RS (HFRS100), (HFRS150), and HF treated with metformin as a positive control. Insulin resistance was shown in the HF rats by glucose intolerance, increased insulin, total area under the curve of glucose and homeostasis model assessment of insulin resistance and dyslipidemia. The resulting metabolic disturbance in the HF rats caused renal inflammation, fibrosis and apoptosis progressing to kidney injury and dysfunction. Prebiotic RS including anthocyanin from BR at doses of 100 and 150 mg ameliorated insulin resistance, dyslipidemia and liver injury. Treatment with RS reduced TGF-β fibrotic and apoptotic pathways by inhibition of NF-κB and inflammatory cytokines which potentially restore kidney damage and dysfunction. In conclusion, prebiotic RS from BR ameliorated obesity induced renal injury and dysfunction by attenuating inflammatory, fibrotic, and apoptotic pathways in insulin resistant rats induced by HF.
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Affiliation(s)
- Laongdao Thongnak
- Renal Transporters and Molecular Signaling Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.,Princess Srisavangavadhana College of Medicine, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Onanong Jaruan
- Renal Transporters and Molecular Signaling Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Nattavadee Pengrattanachot
- Renal Transporters and Molecular Signaling Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Sasivimon Promsan
- Renal Transporters and Molecular Signaling Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Nichakorn Phengpol
- Renal Transporters and Molecular Signaling Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Prempree Sutthasupha
- Renal Transporters and Molecular Signaling Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Krit Jaikumkao
- Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand
| | - Woraprapa Sriyotai
- Department of Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai, Thailand.,Center of Excellence for Innovation in Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai, Thailand
| | - Sugunya Mahatheeranont
- Department of Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai, Thailand.,Center of Excellence for Innovation in Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai, Thailand
| | - Anusorn Lungkaphin
- Renal Transporters and Molecular Signaling Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.,Functional Foods for Health and Disease, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.,Functional Food Research Center for Well-Being, Chiang Mai University, Chiang Mai, Thailand
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8
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Notarte KI, Quimque MTJ, Macaranas IT, Khan A, Pastrana AM, Villaflores OB, Arturo HC, Pilapil IV DYH, Tan SMM, Wei DQ, Wenzel-Storjohann A, Tasdemir D, Yen CH, Ji SY, Kim GY, Choi YH, Macabeo APG. Attenuation of Lipopolysaccharide-Induced Inflammatory Responses through Inhibition of the NF-κB Pathway and the Increased NRF2 Level by a Flavonol-Enriched n-Butanol Fraction from Uvaria alba. ACS OMEGA 2023; 8:5377-5392. [PMID: 36816691 PMCID: PMC9933231 DOI: 10.1021/acsomega.2c06451] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Accepted: 01/18/2023] [Indexed: 05/12/2023]
Abstract
Pathologic hyperreactive inflammatory responses occur when there is excessive activation of a proinflammatory NF-κB pathway and a reduced cytoprotective NRF2 cascade. The noncytotoxic, highly selective COX-2 inhibitory flavonol-enriched butanol fraction (UaB) from Uvaria alba (U. alba) was investigated for its inflammatory modulating potential by targeting NF-κB activation and NRF2 activity. Enzyme-linked immunosorbent assay was initially performed to measure levels of proinflammatory mediators [nitric oxide (NO), prostaglandin E2, and reactive oxygen species (ROS)] and cytokines [tumor necrosis factor-alpha (TNF-α), IL-1β, and IL-6], followed by reverse transcription-polymerase chain reaction and western blotting to determine mRNA and protein expression, respectively. Using immunofluorescence staining combined with western blot analysis, the activation of NF-κB was further investigated. NRF2 activity was also measured using a luciferase reporter assay. UaB abrogated protein and mRNA expressions of inducible nitric oxide synthase (iNOS), COX-2, TNF-α, IL-1β, and IL-6 in RAW 264.7 macrophages, thereby suppressing the production of proinflammatory mediators and cytokines. This was further validated when a concentration-dependent decrease in NO and ROS production was observed in zebrafish (Danio rerio) larvae. UaB also increased NRF2 activity in HaCaT/ARE cell line and attenuated NF-κB activation by inhibiting the nuclear translocation of transcription factor p65 in RAW 264.7 macrophages. Nontargeted LC-MS analysis of UaB revealed the presence of the flavonols quercitrin (1), quercetin (2), rutin (3), kaempferol (4), and kaempferol 3-O-rutinoside (5). Molecular docking indicates that major flavonol aglycones have high affinity toward COX-2 NSAID-binding sites, TNF-α, and TNF-α converting enzyme, while the glycosylated flavonoids showed strong binding toward iNOS and IKK-all possessing dynamic stability when performing molecular dynamics simulations at 140 ns. This is the first report to have elucidated the mechanistic anti-inflammatory potential of the Philippine endemic plant U. alba.
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Affiliation(s)
- Kin Israel
R. Notarte
- Laboratory
of Organic Reactivity, Discovery and Synthesis (LORDS), Research Center
for Natural and Applied Sciences, University
of Santo Tomas, España, 1015Manila, Philippines
- Department
of Pathology, Johns Hopkins University School
of Medicine, Baltimore, Maryland21218, United
States
| | - Mark Tristan J. Quimque
- Laboratory
of Organic Reactivity, Discovery and Synthesis (LORDS), Research Center
for Natural and Applied Sciences, University
of Santo Tomas, España, 1015Manila, Philippines
- Chemistry
Department, College of Science and Mathematics, Mindanao State University - Iligan Institute of Technology, Tibanga, 9200Iligan City, Philippines
| | - Imee T. Macaranas
- Faculty
of Medicine and Surgery, University of Santo
Tomas, España, 1008Manila, Philippines
| | - Abbas Khan
- Department
of Bioinformatics and Biostatistics, State Key Laboratory of Microbial
Metabolism, Shanghai Jiao Tong University, 800 Dongchuan Road Shanghai, Minhang
District, Shanghai200240, China
| | - Adriel M. Pastrana
- Faculty
of Medicine and Surgery, University of Santo
Tomas, España, 1008Manila, Philippines
| | - Oliver B. Villaflores
- Laboratory
of Phytochemistry, Research Center for Natural and Applied Sciences, University of Santo Tomas, España, 1015Manila, Philippines
| | - Hans Christian
P. Arturo
- Laboratory
of Organic Reactivity, Discovery and Synthesis (LORDS), Research Center
for Natural and Applied Sciences, University
of Santo Tomas, España, 1015Manila, Philippines
| | - Delfin Yñigo H. Pilapil IV
- Laboratory
of Organic Reactivity, Discovery and Synthesis (LORDS), Research Center
for Natural and Applied Sciences, University
of Santo Tomas, España, 1015Manila, Philippines
| | - Sophia Morgan M. Tan
- Laboratory
of Organic Reactivity, Discovery and Synthesis (LORDS), Research Center
for Natural and Applied Sciences, University
of Santo Tomas, España, 1015Manila, Philippines
| | - Dong-Qing Wei
- Department
of Bioinformatics and Biostatistics, State Key Laboratory of Microbial
Metabolism, Shanghai Jiao Tong University, 800 Dongchuan Road Shanghai, Minhang
District, Shanghai200240, China
| | - Arlette Wenzel-Storjohann
- GEOMAR
Centre for Marine Biotechnology (GEOMAR-Biotech), Research Unit Marine
Natural Product Chemistry, GEOMAR Helmholtz Centre for Ocean Research
Kiel, 24106Kiel, Germany
| | - Deniz Tasdemir
- GEOMAR
Centre for Marine Biotechnology (GEOMAR-Biotech), Research Unit Marine
Natural Product Chemistry, GEOMAR Helmholtz Centre for Ocean Research
Kiel, 24106Kiel, Germany
- Faculty
of Mathematics and Natural Sciences, Kiel
University, 24118Kiel, Germany
| | - Chia-Hung Yen
- National
Natural Product Libraries and High-Throughput Screening Core Facility, Kaohsiung Medical University, Kaohsiung80708, Taiwan
| | - Seon Yeong Ji
- Department
of Biochemistry, Dongeui University College
of Korean Medicine, 52-57,
Yangjeong-ro, Busanjin-gu, Busan47227Republic of Korea
| | - Gi-Young Kim
- Department
of Marine Life Science, Jeju National University, 102 Jejudaehak-ro, Jeju-si, Jeju Special Self-Governing Province63243, Republic of Korea
| | - Yung Hyun Choi
- Department
of Biochemistry, Dongeui University College
of Korean Medicine, 52-57,
Yangjeong-ro, Busanjin-gu, Busan47227Republic of Korea
| | - Allan Patrick G. Macabeo
- Laboratory
of Organic Reactivity, Discovery and Synthesis (LORDS), Research Center
for Natural and Applied Sciences, University
of Santo Tomas, España, 1015Manila, Philippines
- ;
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9
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Mapoung S, Semmarath W, Arjsri P, Thippraphan P, Srisawad K, Umsumarng S, Phromnoi K, Jamjod S, Prom-u-Thai C, Dejkriengkraikul P. Comparative analysis of bioactive-phytochemical characteristics, antioxidants activities, and anti-inflammatory properties of selected black rice germ and bran ( Oryza sativa L.) varieties. Eur Food Res Technol 2023; 249:451-464. [PMID: 36246093 PMCID: PMC9547098 DOI: 10.1007/s00217-022-04129-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 09/23/2022] [Accepted: 09/24/2022] [Indexed: 12/01/2022]
Abstract
Black rice has numerous health benefits and one of the well-known functional foods throughout the world. To encourage the increasing trend of the consumer interest in health-promoting functional foods, special varieties of rice have been developed offering greater nutrient values and exhibiting biological activities that are beneficial to the consumer. In this study, we aimed to evaluate the associations of the phytochemical contents, antioxidants, and anti-inflammatory properties among eight selected black rice germ and bran extracts (BR extracts) from 4 non-glutinous and 4 glutinous rice varieties. Accordingly, glutinous BR extracts possessed higher degree of Cyanidin-3-O-glucoside (C3G), Peonidin-3-O-glucoside (P3G) contents, antioxidant and anti-inflammatory properties than the non-glutinous BR extracts. Pearson's correlation indicated that the amount of C3G in the BR extracts had a strong positive association with the antioxidant properties (DPPH; r = 0.846, ABTS; r = 0.923, and FRAP; r = 0.958, p < 0.01). While P3G exhibited a strong positive association with the anti-inflammatory properties (r value = 0.717 and 0.797 for IL-6 and TNF-α inhibition, respectively, p < 0.05). Lastly, the principal component analysis (PCA) categorized the black rice varieties into three groups: Group A with high C3G content and superior antioxidant properties, Groups B with a high amount of P3G and potent anti-inflammatory properties, and Group C with a lower amount of phytochemical contents and less potent bioactivities. Overall, the outcomes of this study could provide vital information to food industries in selecting the variety of black rice for the functional food based on the anthocyanin contents that could benefit to consumers for new normal healthy lifestyle.
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Affiliation(s)
- Sariya Mapoung
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand ,Center for Research and Development of Natural Products for Health, Chiang Mai University, Chiang Mai, Thailand
| | - Warathit Semmarath
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand ,Center for Research and Development of Natural Products for Health, Chiang Mai University, Chiang Mai, Thailand ,Akkraratchkumari Veterinary College, Walailak University, Nakhon Si Thammarat, 80160 Thailand
| | - Punnida Arjsri
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand ,Center for Research and Development of Natural Products for Health, Chiang Mai University, Chiang Mai, Thailand
| | - Pilaiporn Thippraphan
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand ,Center for Research and Development of Natural Products for Health, Chiang Mai University, Chiang Mai, Thailand
| | - Kamonwan Srisawad
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand ,Anticarcinogenesis and Apoptosis Research Cluster, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Sonthaya Umsumarng
- Center for Research and Development of Natural Products for Health, Chiang Mai University, Chiang Mai, Thailand ,Division of Veterinary Preclinical Sciences, Department of Veterinary Biosciences and Veterinary Public Health, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Kanokkarn Phromnoi
- Division of Biochemistry, School of Medical Sciences, University of Phayao, Phayao, Thailand
| | - Sansanee Jamjod
- Lanna Rice Research Center, Chiang Mai University, Chiang Mai, Thailand
| | | | - Pornngarm Dejkriengkraikul
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand ,Center for Research and Development of Natural Products for Health, Chiang Mai University, Chiang Mai, Thailand ,Anticarcinogenesis and Apoptosis Research Cluster, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand ,Lanna Rice Research Center, Chiang Mai University, Chiang Mai, Thailand
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10
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Xu H, Dai ZH, He GL, Cai HC, Chen XY, Chen YL, Xu C, Sheng SR. Gamma-oryzanol alleviates intervertebral disc degeneration development by intercepting the IL-1β/NLRP3 inflammasome positive cycle. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 102:154176. [PMID: 35660354 DOI: 10.1016/j.phymed.2022.154176] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 05/04/2022] [Accepted: 05/14/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND Intervertebral disc degeneration (IVDD) is a highly prevalent musculoskeletal disorder characterized by a local inflammatory response associated with the IL-1β/NLRP3 inflammasome positive feedback loop. Rice bran-derived gamma-oryzanol (Ory) as a sterol ferulate has attracted much attention due to its powerful anti-inflammatory, hypoglycemic and hypolipidemic health effects. As a clinical pharmaceutical for autonomic disorders, Ory's role in musculoskeletal degenerative disease remains unknown. PURPOSE This study aims to validate the role of Ory in IVDD and explore the potential mechanism. STUDY DESIGN Establishing the in vitro and in vivo IVDD models to detect the protective effect and molecular mechanism of Ory. METHOD The anti-ECM degradation, antioxidant and anti-NLRP3 inflammasome activation effects of Ory on IL-1β-stimulated nucleus pulposus (NP) cells were assessed by immunoblotting and immunofluorescence, etc. MRI, S-O staining and immunohistochemistry were performed to estimate the effects of Ory administration on acupuncture-mediated IVDD in rats at imaging and histological levels. RESULTS Ory treatment inhibited IL-1β-mediated ECM degradation, oxidative stress and NLRP3 inflammasome activation in NP cells. By interfering with NF-κB signaling and ROS overproduction, Ory interrupted IL-1β/NLRP3-inflammasome positive cycle. In vivo experiments showed that Ory delayed acupuncture-mediated IVDD development. CONCLUSION Our results support the potential application of Ory as a therapeutic compound for IVDD.
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Affiliation(s)
- Hui Xu
- Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejian 325000, China
| | - Zi-Han Dai
- Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejian 325000, China
| | - Gao-Lu He
- Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejian 325000, China
| | - Han-Chen Cai
- Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejian 325000, China
| | - Xuan-Yang Chen
- Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejian 325000, China
| | - Yan-Lin Chen
- Department of Orthopaedics Surgery, Lishui Central Hospital and Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang 323000, China.
| | - Cong Xu
- Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejian 325000, China.
| | - Sun-Ren Sheng
- Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejian 325000, China.
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11
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Anti-inflammaging effects of black soybean and black rice mixture extract by reprogramming of mitochondrial respirations in murine macrophages. J Funct Foods 2022. [DOI: 10.1016/j.jff.2022.105114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
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12
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Wu CF, Wu CY, Lin CF, Liu YW, Lin TC, Liao HJ, Chang GR. The anticancer effects of cyanidin 3-O-glucoside combined with 5-fluorouracil on lung large-cell carcinoma in nude mice. Biomed Pharmacother 2022; 151:113128. [PMID: 35609368 DOI: 10.1016/j.biopha.2022.113128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 05/11/2022] [Accepted: 05/13/2022] [Indexed: 11/16/2022] Open
Abstract
The haskap (Lonicera caerulea L., Caprifoliaceae) berry has been widely used in traditional medicine in Kuril Islands, Russia, Japan, and China. Cyanidin-3-O-glucoside (C3G) is the most abundant anthocyanin in haskap berries, and C3G induces antiproliferative pharmacological activity in various cancer cells. However, no study has investigated its anti-lung large-cell carcinoma (LCC) pharmacological role. Therefore, this study determined whether C3G alone or C3G combined with 5-fluorouracil (5-FU) inhibits human lung LCC. We determined the tumor growth, apoptosis, inflammation, and metastasis in the H661 lung LCC lines xenografted into BALB/c nude mice. The mice were administered saline (control), 5-FU, C3G, or both C3G and 5-FU. Relative to the control mice, those treated with C3G alone or both C3G and 5-FU exhibited impaired tumor growth; increased tumor apoptosis; decreased inflammatory cytokine levels (e.g., IL-1β, TNF-α, C-reactive protein, and IL-6); decreased inflammation-related factors, including cyclooxygenase-2 protein and nuclear factor-κB (NF-κB) mRNA; increased inhibition of NF-κB kinase α mRNA; and downregulated metastasis-related factors, such as transforming growth factor-β, CD44, epidermal growth factor receptor, and vascular endothelial growth factor. In addition, C3G alone or combined with 5-FU affected the expression of the tumor microenvironment-related factors Ki67, CD45, PDL1, and CD73. Compared with the mice treated with 5-FU or C3G alone, those treated with both C3G and 5-FU exhibited significantly impaired tumor growth, decreased tumor sizes, and increased tumor inhibition. This in vivo study demonstrated that C3G alone or combined with 5-FU may impair the growth of lung LCC and inhibit tumorigenesis. The findings indicate that C3G alone or C3G combined with 5-FU may be beneficial for treating human lung LCC.
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Affiliation(s)
- Ching-Feng Wu
- Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Chang Gung Memorial Hospital, Linkou, 5 Fuxing Street, Guishan District, Taoyuan 33305, Taiwan; Department of Medicine, College of Medicine, Chang Gung University, Guishan, 259 Wenhua 1st Road, Taoyuan 33302, Taiwan.
| | - Ching-Yang Wu
- Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Chang Gung Memorial Hospital, Linkou, 5 Fuxing Street, Guishan District, Taoyuan 33305, Taiwan; Department of Medicine, College of Medicine, Chang Gung University, Guishan, 259 Wenhua 1st Road, Taoyuan 33302, Taiwan.
| | - Chuen-Fu Lin
- Department of Veterinary Medicine, College of Veterinary Medicine, National Pingtung University of Science and Technology, 1 Shuefu Road, Neipu, Pingtung 912301, Taiwan.
| | - Yi-Wen Liu
- Department of Microbiology, Immunology and Biopharmaceuticals, College of Life Sciences, National Chiayi University, 300 Syuefu Road, Chiayi 60004, Taiwan.
| | - Tzu-Chun Lin
- Department of Veterinary Medicine, National Chiayi University, 580 Xinmin Road, Chiayi 60054, Taiwan.
| | - Huei-Jyuan Liao
- Department of Veterinary Medicine, National Chiayi University, 580 Xinmin Road, Chiayi 60054, Taiwan.
| | - Geng-Ruei Chang
- Department of Veterinary Medicine, National Chiayi University, 580 Xinmin Road, Chiayi 60054, Taiwan.
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13
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Cyanidin-3-O-glucoside and Peonidin-3-O-glucoside-Rich Fraction of Black Rice Germ and Bran Suppresses Inflammatory Responses from SARS-CoV-2 Spike Glycoprotein S1-Induction In Vitro in A549 Lung Cells and THP-1 Macrophages via Inhibition of the NLRP3 Inflammasome Pathway. Nutrients 2022; 14:nu14132738. [PMID: 35807916 PMCID: PMC9268823 DOI: 10.3390/nu14132738] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 06/27/2022] [Accepted: 06/28/2022] [Indexed: 02/06/2023] Open
Abstract
Black rice is a functional food that is high in anthocyanin content, primarily C3G and P3G. It possesses nutraceutical properties that exhibit a range of beneficial effects on human health. Currently, the spike glycoprotein S1 subunit of SARS-CoV-2 (SP) has been reported for its contribution to pathological inflammatory responses in targeting lung tissue and innate immune cells during COVID-19 infection and in the long-COVID phenomenon. Our objectives focused on the health benefits of the C3G and P3G-rich fraction of black rice germ and bran (BR extract) on the inhibition of inflammatory responses induced by SP, as well as the inhibition of NF-kB activation and the NLRP3 inflammasome pathway in an in vitro model. In this study, BR extract was identified for its active anthocyanins, C3G and P3G, using the HPLC technique. A549-lung cells and differentiated THP-1 macrophages were treated with BR extract, C3G, or P3G prior to exposure to 100 ng/mL of SP. Their anti-inflammatory properties were then determined. BR extract at concentrations of 12.5−100 μg/mL exhibited anti-inflammation activity for both A549 and THP-1 cells through the significant suppression of NLRP3, IL-1β, and IL-18 inflammatory gene expressions and IL-6, IL-1β, and IL-18 cytokine secretions in a dose-dependent manner (p < 0.05). It was determined that both cell lines, C3G and P3G (at 1.25−10 μg/mL), were compatibly responsible for the significant inhibition of SP-induced inflammatory responses for both gene and protein levels (p < 0.05). With regard to the anti-inflammation mechanism, BR extract, C3G, and P3G could attenuate SP-induced inflammation via counteraction with NF-kB activation and downregulation of the inflammasome-dependent inflammatory pathway proteins (NLRP3, ASC, and capase-1). Overall, the protective effects of anthocyanins obtained from black rice germ and bran can be employed in potentially preventive strategies that use pigmented rice against the long-term sequelae of COVID-19 infection.
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14
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Anthocyanins in Red Jasmine Rice (Oryza sativa L.) Extracts and Efficacy on Inhibition of Herpes Simplex Virus, Free Radicals and Cancer Cell. Nutrients 2022; 14:nu14091905. [PMID: 35565872 PMCID: PMC9101121 DOI: 10.3390/nu14091905] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Revised: 04/26/2022] [Accepted: 04/28/2022] [Indexed: 12/10/2022] Open
Abstract
Rice is one of the most important food crops in many countries, with nutritional value and health benefits. In this study, the ethanolic and aqueous extracts of red jasmine rice from Chiang Mai, Thailand were examined for their anthocyanins and phenolic contents. The antioxidant and antiviral activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), as well as anticancer activity, were investigated. The total anthocyanins content of 708.03 ± 11.56 mg Cy-3-glc equivalent/g extract, determined from the ethanolic extract, was higher than the aqueous extract. However, the aqueous extract showed the highest total phenolic compound of 81.91 ± 0.51 mg GAE/g extract. In addition, the ethanolic extract demonstrated higher antioxidant activity than aqueous extract using DPPH, ABTS, and FRAP assays by 28.91 ± 3.26 mg GAE/g extract, 189.45 ± 11.58 mg 24 TEAC/g extract, and 3292.46 ± 259.64 g FeSO4/g extract, respectively. In the antiviral assay, it was found that the ethanolic extract of red jasmine rice could inhibit HSV-1 more effectively than HSV-2 when treated before, during, and after the viral attachment on Vero cells, with 50% effective doses of 227.53 ± 2.41, 189.59 ± 7.76, and 192.62 ± 2.40 µg/mL, respectively. The extract also demonstrated the highest reduction of HSV-1 particles at 4 h after treatment and the inhibition of HSV-1 replication. The ethanolic extract exhibited a higher toxicity level than the aqueous extract, as well as the potential to induce DNA fragmentation by intrinsic and extrinsic apoptosis pathways on the Caco-2 cells. These findings suggest that red jasmine rice extract demonstrates nutritional value and biological activity on HSV, free radicals, and cancer cell inhibition.
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15
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Gonçalves AC, Flores-Félix JD, Coutinho P, Alves G, Silva LR. Zimbro ( Juniperus communis L.) as a Promising Source of Bioactive Compounds and Biomedical Activities: A Review on Recent Trends. Int J Mol Sci 2022; 23:3197. [PMID: 35328621 PMCID: PMC8952110 DOI: 10.3390/ijms23063197] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 03/11/2022] [Accepted: 03/15/2022] [Indexed: 02/01/2023] Open
Abstract
Plant-derived products and their extracted compounds have been used in folk medicine since early times. Zimbro or common juniper (Juniperus communis) is traditionally used to treat renal suppression, acute and chronic cystitis, bladder catarrh, albuminuria, leucorrhea, and amenorrhea. These uses are mainly attributed to its bioactive composition, which is very rich in phenolics, terpenoids, organic acids, alkaloids, and volatile compounds. In the last few years, several studies have analyzed the huge potential of this evergreen shrub, describing a wide range of activities with relevance in different biomedical discipline areas, namely antimicrobial potential against human pathogens and foodborne microorganisms, notorious antioxidant and anti-inflammatory activities, antidiabetic, antihypercholesterolemic and antihyperlipidemic effects, and neuroprotective action, as well as antiproliferative ability against cancer cells and the ability to activate inductive hepato-, renal- and gastroprotective mechanisms. Owing to these promising activities, extracts and bioactive compounds of juniper could be useful for the development of new pharmacological applications in the treatment of several acute and chronic human diseases.
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Affiliation(s)
- Ana C. Gonçalves
- CICS-UBI—Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilhã, Portugal; (A.C.G.); (J.D.F.-F.); (P.C.); (G.A.)
| | - José David Flores-Félix
- CICS-UBI—Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilhã, Portugal; (A.C.G.); (J.D.F.-F.); (P.C.); (G.A.)
| | - Paula Coutinho
- CICS-UBI—Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilhã, Portugal; (A.C.G.); (J.D.F.-F.); (P.C.); (G.A.)
- CPIRN-UDI/IPG—Center of Potential and Innovation of Natural Resources, Research Unit for Inland Development (UDI), Polytechnic Institute of Guarda, 6300-559 Guarda, Portugal
| | - Gilberto Alves
- CICS-UBI—Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilhã, Portugal; (A.C.G.); (J.D.F.-F.); (P.C.); (G.A.)
| | - Luís R. Silva
- CICS-UBI—Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilhã, Portugal; (A.C.G.); (J.D.F.-F.); (P.C.); (G.A.)
- CPIRN-UDI/IPG—Center of Potential and Innovation of Natural Resources, Research Unit for Inland Development (UDI), Polytechnic Institute of Guarda, 6300-559 Guarda, Portugal
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16
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Gonçalves AC, Costa AR, Flores-Félix JD, Falcão A, Alves G, Silva LR. Anti-Inflammatory and Antiproliferative Properties of Sweet Cherry Phenolic-Rich Extracts. Molecules 2022; 27:268. [PMID: 35011501 PMCID: PMC8747005 DOI: 10.3390/molecules27010268] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 12/28/2021] [Accepted: 12/30/2021] [Indexed: 12/18/2022] Open
Abstract
Cherries have largely been investigated due to their high content in phenolics in order to fully explore their health-promoting properties. Therefore, this work aimed to assess, for the first time, the anti-inflammatory potential of phenolic-targeted fractions of the Saco cherry, using RAW 264.7 macrophages stimulated with lipopolysaccharide. Additionally, the cytotoxic effects on gastric adenocarcinoma (AGS), neuroblastoma (SH-SY5Y) and normal human dermal fibroblast (NHDF) cells were evaluated, as well as the ability to protect these cellular models against induced oxidative stress. The obtained data revealed that cherry fractions can interfere with cellular nitric oxide (NO) levels by capturing NO radicals and decreasing inducible nitric oxide synthase and cyclooxygenase-2 expression. Furthermore, it was observed that all cherry fractions exhibited dose-dependent cytotoxicity against AGS cells, presenting cytotoxic selectivity for these cancer cells when compared to SH-SY5Y and NHDF cells. Regarding their capacity to protect cancer cells against oxidative injury, in most assays, the total cherry extract was the most effective. Overall, this study reinforces the idea that sweet cherries can be incorporated into new pharmaceutical products, smart foods and nutraceuticals.
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Affiliation(s)
- Ana C. Gonçalves
- CICS-UBI—Health Sciences Research Centre, University of Beira Interior, 6201-001 Covilhã, Portugal; (A.C.G.); (A.R.C.); (J.D.F.-F.); (G.A.)
- CIBIT—Coimbra Institute for Biomedical Imaging and Translational Research, University of Coimbra, 3004-531 Coimbra, Portugal;
| | - Ana R. Costa
- CICS-UBI—Health Sciences Research Centre, University of Beira Interior, 6201-001 Covilhã, Portugal; (A.C.G.); (A.R.C.); (J.D.F.-F.); (G.A.)
| | - José D. Flores-Félix
- CICS-UBI—Health Sciences Research Centre, University of Beira Interior, 6201-001 Covilhã, Portugal; (A.C.G.); (A.R.C.); (J.D.F.-F.); (G.A.)
| | - Amílcar Falcão
- CIBIT—Coimbra Institute for Biomedical Imaging and Translational Research, University of Coimbra, 3004-531 Coimbra, Portugal;
- Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, 3004-531 Coimbra, Portugal
| | - Gilberto Alves
- CICS-UBI—Health Sciences Research Centre, University of Beira Interior, 6201-001 Covilhã, Portugal; (A.C.G.); (A.R.C.); (J.D.F.-F.); (G.A.)
| | - Luís R. Silva
- CICS-UBI—Health Sciences Research Centre, University of Beira Interior, 6201-001 Covilhã, Portugal; (A.C.G.); (A.R.C.); (J.D.F.-F.); (G.A.)
- CPIRN-UDI/IPG, Center of Potential and Innovation of Natural Resources, Research Unit for Inland Development (UDI), Polytechnic Institute of Guarda, 6300-559 Guarda, Portugal
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Kim SA, Lee CY, Mitra A, Kim H, Woo BY, Hong YD, Noh JK, Yi DK, Kim HG, Cho JY. Anti-Inflammatory Effects of Huberia peruviana Cogn. Methanol Extract by Inhibiting Src Activity in the NF-κB Pathway. PLANTS (BASEL, SWITZERLAND) 2021; 10:plants10112335. [PMID: 34834697 PMCID: PMC8619548 DOI: 10.3390/plants10112335] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Revised: 10/25/2021] [Accepted: 10/27/2021] [Indexed: 06/13/2023]
Abstract
There is a growing need to develop anti-inflammatory drugs to regulate inflammatory responses. An extract of Huberia peruviana Cogn. had the best inhibitory effect on nitric oxide (NO) production in screening process undertaken in our laboratory. However, the anti-inflammatory effect of Huberia peruviana Cogn. methanol extract (Hp-ME) has not been studied. In this study, the anti-inflammatory effect of Hp-ME was assessed by using an NO assay, RT-PCR, luciferase reporter gene activity assay, western blotting assay, HCl/EtOH-induced acute gastritis model, and LPS-induced acute lung injury model. The phytochemical components of Hp-ME were determined through LC-MS/MS analysis. When RAW264.7 and HEK293T cells were treated with Hp-ME, NO production was decreased dose-dependently without cytotoxicity and the mRNA levels of iNOS, COX-2, and TNF-α were decreased. In a luciferase assay, the activity of transcription factors, NF-κB in TRIF or MyD88-overexpressing HEK293T cells was extremely reduced by Hp-ME. The western blotting analysis indicated that Hp-ME has anti-inflammatory effects by inhibiting the phosphorylation of Src. Hp-ME showed anti-inflammatory effects on in vivo models of HCl/EtOH-induced gastritis and LPS-induced acute lung injury. LC-MS/MS revealed that Hp-ME contains several anti-inflammatory flavonoids. The final findings of this study imply that Hp-ME could be used as an anti-inflammatory drug in several inflammatory diseases.
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Affiliation(s)
- Seung A Kim
- Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Korea; (S.A.K.); (C.Y.L.); (H.K.)
| | - Chae Young Lee
- Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Korea; (S.A.K.); (C.Y.L.); (H.K.)
| | - Ankita Mitra
- Research Institute of Biomolecule Control and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Korea;
| | - Haeyeop Kim
- Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Korea; (S.A.K.); (C.Y.L.); (H.K.)
| | - Byoung Young Woo
- AMOREPACIFIC R&D Center, Yongin 17074, Korea; (B.Y.W.); (Y.D.H.)
| | - Yong Deog Hong
- AMOREPACIFIC R&D Center, Yongin 17074, Korea; (B.Y.W.); (Y.D.H.)
| | - Jin Kyoung Noh
- Instituto de BioEconomia, El Batan, Quito 170135, Ecuador;
| | - Dong-Keun Yi
- International Biological Material Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Korea;
| | - Han Gyung Kim
- Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Korea; (S.A.K.); (C.Y.L.); (H.K.)
- Research Institute of Biomolecule Control and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Korea;
| | - Jae Youl Cho
- Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Korea; (S.A.K.); (C.Y.L.); (H.K.)
- Research Institute of Biomolecule Control and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Korea;
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Efficacy of black rice extract on obesity in obese postmenopausal women: a 12-week randomized, double-blind, placebo-controlled preliminary clinical trial. ACTA ACUST UNITED AC 2021; 28:1391-1399. [PMID: 34547006 DOI: 10.1097/gme.0000000000001862] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
OBJECTIVES Postmenopausal obesity is a paramount health concern among older women. Black rice is a well-known pigmented rice variety with a higher anthocyanin content. Both in vitro and in vivo studies have demonstrated the effects of black rice on obesity. The present study aimed to investigate the effects of black rice extract (BRE) on obesity among obese postmenopausal women from Korea. METHODS This was a 12-week, randomized, double-blind, placebo-controlled preliminary clinical trial. The participants were postmenopausal women who had stopped menstruating for more than a year. Specifically, 105 participants were randomly assigned to the BRE (1 g/d) or placebo (maltodextrin, 1 g/d) group. RESULTS Eighty-eight participants completed the study, 47 in the intervention group and 41 in the placebo group. At the study endpoint, dual-energy x-ray absorptiometry assessment showed that the BRE group had a significantly lower trunk fat (P = 0.04), total fat (P = 0.04), and total body fat percentage (P = 0.04) than did the placebo group. The body fat percentage (P = 0.04) was lower in the BRE group with marginal significance, and there were no significant differences in anthropometric measures such as weight, body mass index, waist circumference, or waist-to-hip ratio estimated by bioelectrical impedance analysis. CONCLUSION BRE supplementation for 12 weeks seems to be effective in reducing fat accumulation in postmenopausal women.
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Lee S, Ha J, Park J, Kang E, Jeon SH, Han SB, Ningsih S, Paik JH, Cho S. Antioxidant and Anti-Inflammatory Effects of Bischofia javanica (Blume) Leaf Methanol Extracts through the Regulation of Nrf2 and TAK1. Antioxidants (Basel) 2021; 10:antiox10081295. [PMID: 34439543 PMCID: PMC8389227 DOI: 10.3390/antiox10081295] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 08/12/2021] [Accepted: 08/13/2021] [Indexed: 11/16/2022] Open
Abstract
Bischofia javanica (Blume) has been traditionally used to treat inflammatory diseases such as tonsillitis and ulcers throughout Asia, including China, Indonesia, and the Philippines: however, the molecular mechanisms by which B. javanica exerts its antioxidant and anti-inflammatory properties remain largely unknown. In this study, we analyzed the antioxidant and anti-inflammatory mechanisms of methanol extracts of B. javanica leaves (MBJ) in vitro and in vivo. MBJ decreased nitric oxide (NO) production and the expression of pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, in lipopolysaccharide (LPS)-treated RAW 264.7 cells. The observed suppression of inflammatory responses by MBJ was correlated with an inhibition of the nuclear factor-κB (NF-κB) and the mitogen-activated protein kinase (MAPK) pathways. Additionally, MBJ induced nuclear translocation of the nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor that upregulates the expression of anti-inflammatory and antioxidant genes. Furthermore, MBJ exhibited antioxidant and anti-inflammatory effects in an acute hepatitis mouse model. In conclusion, our results confirm the medicinal properties of B. javanica, and therefore MBJ could be applied to improve inflammatory and redox imbalances in different types of pathologies.
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Affiliation(s)
- Sewoong Lee
- Laboratory of Molecular and Pharmacological Cell Biology, College of Pharmacy, Chung-Ang University, Seoul 06974, Korea; (S.L.); (J.H.); (J.P.); (E.K.)
| | - Jain Ha
- Laboratory of Molecular and Pharmacological Cell Biology, College of Pharmacy, Chung-Ang University, Seoul 06974, Korea; (S.L.); (J.H.); (J.P.); (E.K.)
| | - Jiyoung Park
- Laboratory of Molecular and Pharmacological Cell Biology, College of Pharmacy, Chung-Ang University, Seoul 06974, Korea; (S.L.); (J.H.); (J.P.); (E.K.)
| | - Eunjeong Kang
- Laboratory of Molecular and Pharmacological Cell Biology, College of Pharmacy, Chung-Ang University, Seoul 06974, Korea; (S.L.); (J.H.); (J.P.); (E.K.)
| | - Sung-Hyun Jeon
- Biomedical Mass Spectrometry Lab, College of Pharmacy, Chung-Ang University, Seoul 06974, Korea; (S.-H.J.); (S.B.H.)
| | - Sang Beom Han
- Biomedical Mass Spectrometry Lab, College of Pharmacy, Chung-Ang University, Seoul 06974, Korea; (S.-H.J.); (S.B.H.)
| | - Sri Ningsih
- Center for Pharmaceutical and Medical Technology, Deputy for Agroindustrial Technology and Biotechnology, The Agency for the Assessment and Application of Technology (BPPT), Jl. Raya Puspiptek, Kota Tangerang Selatan 15310, Banten, Indonesia;
| | - Jin Hyub Paik
- International Biological Material Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Korea;
| | - Sayeon Cho
- Laboratory of Molecular and Pharmacological Cell Biology, College of Pharmacy, Chung-Ang University, Seoul 06974, Korea; (S.L.); (J.H.); (J.P.); (E.K.)
- Correspondence: ; Tel.: +82-2-820-5595; Fax: +82-2-816-7338
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Platonova EY, Shaposhnikov MV, Lee HY, Lee JH, Min KJ, Moskalev A. Black chokeberry (Aronia melanocarpa) extracts in terms of geroprotector criteria. Trends Food Sci Technol 2021. [DOI: 10.1016/j.tifs.2021.06.020] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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Saenjum C, Pattananandecha T, Nakagawa K. Antioxidative and Anti-Inflammatory Phytochemicals and Related Stable Paramagnetic Species in Different Parts of Dragon Fruit. Molecules 2021; 26:molecules26123565. [PMID: 34200974 PMCID: PMC8230633 DOI: 10.3390/molecules26123565] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 06/07/2021] [Accepted: 06/07/2021] [Indexed: 01/29/2023] Open
Abstract
In this study, we investigated the antioxidant and anti-inflammatory phytochemicals and paramagnetic species in dragon fruit using high-performance liquid chromatography (HPLC) and electron paramagnetic resonance (EPR). HPLC analysis demonstrated that dragon fruit is enriched with bioactive phytochemicals, with significant variations between each part of the fruit. Anthocyanins namely, cyanidin 3-glucoside, delphinidin 3-glucoside, and pelargonidin 3-glucoside were detected in the dragon fruit peel and fresh red pulp. Epicatechin gallate, epigallocatechin, caffeine, and gallic acid were found in the dragon fruit seed. Additionally, 25–100 mg × L−1 of dragon fruit pulp and peel extracts containing enrichment of cyanidin 3-glucoside were found to inhibit the production of reactive oxygen species (ROS), reactive nitrogen species (RNS), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in cell-based studies without exerted cytotoxicity. EPR primarily detected two paramagnetic species in the red samples. These two different radical species were assigned as stable radicals and Mn2+ (paramagnetic species) based on the g-values and hyperfine components. In addition, the broad EPR line width of the white peel can be correlated to a unique moiety in dragon fruit. Our EPR and HPLC results provide new insight regarding the phytochemicals and related stable intermediates found in various parts of dragon fruit. Thus, we suggest here that there is the potential to use dragon fruit peel, which contains anthocyanins, as a natural active pharmaceutical ingredient.
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Affiliation(s)
- Chalermpong Saenjum
- Cluster of Excellence on Biodiversity-Based Economic and Society (B.BES-CMU), Chiang Mai University, Chiang Mai 50200, Thailand;
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand
- Correspondence: (C.S.); (K.N.); Tel.: +66-53-94-4312 (C.S.); +81-172-39-5921 (K.N.)
| | - Thanawat Pattananandecha
- Cluster of Excellence on Biodiversity-Based Economic and Society (B.BES-CMU), Chiang Mai University, Chiang Mai 50200, Thailand;
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Kouichi Nakagawa
- Division of Regional Innovation, Graduate School of Health Sciences, Hirosaki University, 66-1 Hon-Cho, Hirosaki 036-8564, Japan
- Correspondence: (C.S.); (K.N.); Tel.: +66-53-94-4312 (C.S.); +81-172-39-5921 (K.N.)
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Arundina I, Diyatri I, Surboyo MD, Monica E, Afanda NM. Growth factor stimulation for the healing of traumatic ulcers with liquid rice hull smoke. J Taibah Univ Med Sci 2021; 16:431-439. [PMID: 34140871 PMCID: PMC8178683 DOI: 10.1016/j.jtumed.2021.01.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Revised: 01/02/2021] [Accepted: 01/10/2021] [Indexed: 10/29/2022] Open
Abstract
OBJECTIVE The healing process of a traumatic ulcer requires growth factors to rebuild the lost tissue after the inflammatory process has been completed. Liquid rice hull smoke (LR-HS) has shown unique anti-inflammatory properties. This study analyses the role of LR-HS in growth factor stimulation for the healing of traumatic ulcers, such as fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and collagen type 1 (COL-1) expression. METHODS We obtained LR-HS from the pyrolysis of rice hulls. Traumatic ulcers were created in the labial fornix incisive inferior of Wistar rats and treated with LR-HS once a day for 3, 5, and 7 days. The control group was treated with sterile water. Each animal was sacrificed after treatment, and its labial fornix incisive inferior tissues were biopsied and immunohistochemically stained to examine FGF, VEGF, PDGF, and COL-1 expression. RESULT The treatment of traumatic ulcers with LR-HS showed an increase in FGF, VEGF, PDGF, and COL-1 expression. VEGF expression increased under LR-HS treatment compared with the control 7-day treatment groups (p < 0.000). FGF and COL-1 expression increased under LR-HS treatment compared with the control 5- and 7-day treatment groups (p < 0.000). PDGF expression increased after treatment with LR-HS for 3, 5, and 7 days (p < 0.000). CONCLUSION This study has demonstrated that LR-HS can induce the expression of growth factors during the healing of a traumatic ulcer using immunohistochemical staining. We suggest that LR-HS can be used as a herbal medicine for oral ulcer therapy.
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Affiliation(s)
- Ira Arundina
- Department of Oral Biology, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Indeswati Diyatri
- Department of Oral Biology, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Meircurius D.C. Surboyo
- Department of Oral Medicine, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Elita Monica
- Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
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Qiu T, Sun Y, Wang X, Zheng L, Zhang H, Jiang L, Zhu X, Xiong H. Drum drying-and extrusion-black rice anthocyanins exert anti-inflammatory effects via suppression of the NF-κB /MAPKs signaling pathways in LPS-induced RAW 264.7 cells. FOOD BIOSCI 2021. [DOI: 10.1016/j.fbio.2020.100841] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Dash R, Mitra S, Ali MC, Oktaviani DF, Hannan MA, Choi SM, Moon IS. Phytosterols: Targeting Neuroinflammation in Neurodegeneration. Curr Pharm Des 2021; 27:383-401. [PMID: 32600224 DOI: 10.2174/1381612826666200628022812] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2019] [Accepted: 05/02/2020] [Indexed: 11/22/2022]
Abstract
Plant-derived sterols, phytosterols, are well known for their cholesterol-lowering activity in serum and their anti-inflammatory activities. Recently, phytosterols have received considerable attention due to their beneficial effects on various non-communicable diseases, and recommended use as daily dietary components. The signaling pathways mediated in the brain by phytosterols have been evaluated, but little is known about their effects on neuroinflammation, and no clinical studies have been undertaken on phytosterols of interest. In this review, we discuss the beneficial roles of phytosterols, including their attenuating effects on inflammation, blood cholesterol levels, and hallmarks of the disease, and their regulatory effects on neuroinflammatory disease pathways. Despite recent advancements made in phytosterol pharmacology, some critical questions remain unanswered. Therefore, we have tried to highlight the potential of phytosterols as viable therapeutics against neuroinflammation and to direct future research with respect to clinical applications.
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Affiliation(s)
- Raju Dash
- Department of Anatomy, Dongguk University College of Medicine, 123 Dongdae-ro, Gyeongju 38066, Korea
| | - Sarmistha Mitra
- Plasma Bioscience Research Center, Plasma Bio-display, Kwangwoon University, Seoul-01897, Korea
| | - Md Chayan Ali
- Department of Biotechnology and Genetic Engineering, Islamic University, Kushtia-7003, Bangladesh
| | - Diyah Fatimah Oktaviani
- Department of Anatomy, Dongguk University College of Medicine, 123 Dongdae-ro, Gyeongju 38066, Korea
| | - Md Abdul Hannan
- Department of Anatomy, Dongguk University College of Medicine, 123 Dongdae-ro, Gyeongju 38066, Korea
| | - Sung Min Choi
- Department of Pediatrics, Dongguk University College of Medicine, Gyeongju-38066, Korea
| | - Il Soo Moon
- Department of Anatomy, Dongguk University College of Medicine, 123 Dongdae-ro, Gyeongju 38066, Korea
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Hong SM, Kang MC, Jin M, Lee TH, Lim BO, Kim SY. Fermented blueberry and black rice containing Lactobacillus plantarum MG4221: a novel functional food for particulate matter (PM 2.5)/dinitrochlorobenzene (DNCB)-induced atopic dermatitis. Food Funct 2021; 12:3611-3623. [PMID: 33900308 DOI: 10.1039/d0fo02966a] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Particulate matter (PM2.5) is a risk factor for the deterioration of atopic dermatitis (AD) and certain constituents of PM2.5 can induce inflammation via oxidative stress. Natural functional foods, including antioxidative blueberry and black rice, can be the best alternative for the development of AD therapy. Thus, we investigated whether PM2.5 regulated the expression of proinflammatory cytokines involved in the progression of AD and further investigated the improvement effect of fermented blueberry and black rice extract (FBBBR) containing Lactobacillus plantarum MG4221 in vitro and in vivo. The FBBBR treatment significantly ameliorated skin inflammation compared with the control treatments via regulation of the mitogen-activated protein kinase (MAPK)/nuclear factor-κB (NF-κB) pathways in PM2.5-treated HaCaT cells. In PM2.5/dinitrochlorobenzene (DNCB)-treated NC/Nga mice, the oral administration of FBBBR significantly decreased transepidermal water loss and erythema, the incidence of scratching behavior, and the production of serum immunoglobin E and T helper 2-associated cytokine and, similar to dexamethasone treatment, up-regulated the protein expression of filaggrin and involucrin in skin tissue. Syringic acid and kuromanin, standard compounds found in FBBBR, significantly decreased the interleukin (IL)-1β, IL-6 and IL-8 levels in PM2.5-treated HaCaT cells. Therefore, we can suggest that FBBBR may serve as an important functional food for AD.
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Affiliation(s)
- Seong Min Hong
- College of Pharmacy, Gachon University, #191, Hambakmoero, Yeonsu-gu, Incheon 21936, Republic of Korea.
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Masuelli L, Benvenuto M, Focaccetti C, Ciuffa S, Fazi S, Bei A, Miele MT, Piredda L, Manzari V, Modesti A, Bei R. Targeting the tumor immune microenvironment with "nutraceuticals": From bench to clinical trials. Pharmacol Ther 2020; 219:107700. [PMID: 33045254 DOI: 10.1016/j.pharmthera.2020.107700] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/30/2020] [Indexed: 02/06/2023]
Abstract
The occurrence of immune effector cells in the tissue microenvironment during neoplastic progression is critical in determining tumor growth outcomes. On the other hand, tumors may also avoid immune system-mediated elimination by recruiting immunosuppressive leukocytes and soluble factors, which coordinate a tumor microenvironment that counteracts the efficiency of the antitumor immune response. Checkpoint inhibitor therapy results have indicated a way forward via activation of the immune system against cancer. Widespread evidence has shown that different compounds in foods, when administered as purified substances, can act as immunomodulators in humans and animals. Although there is no universally accepted definition of nutraceuticals, the term identifies a wide category of natural compounds that may impact health and disease statuses and includes purified substances from natural sources, plant extracts, dietary supplements, vitamins, phytonutrients, and various products with combinations of functional ingredients. In this review, we summarize the current knowledge on the immunomodulatory effects of nutraceuticals with a special focus on the cancer microenvironment, highlighting the conceptual benefits or drawbacks and subtle cell-specific effects of nutraceuticals for envisioning future therapies employing nutraceuticals as chemoadjuvants.
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Affiliation(s)
- Laura Masuelli
- Department of Experimental Medicine, University of Rome "Sapienza", Viale Regina Elena 324, 00161 Rome, Italy
| | - Monica Benvenuto
- Saint Camillus International University of Health and Medical Sciences, via di Sant'Alessandro 8, 00131 Rome, Italy; Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy
| | - Chiara Focaccetti
- Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy; Department of Human Science and Promotion of the Quality of Life, San Raffaele University Rome, Via di Val Cannuta 247, 00166 Rome, Italy
| | - Sara Ciuffa
- Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy
| | - Sara Fazi
- Department of Experimental Medicine, University of Rome "Sapienza", Viale Regina Elena 324, 00161 Rome, Italy
| | - Arianna Bei
- Medical School, University of Rome "Tor Vergata", 00133 Rome, Italy
| | - Martino Tony Miele
- Department of Experimental Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy
| | - Lucia Piredda
- Department of Biology, University of Rome "Tor Vergata", Via della Ricerca Scientifica 1, 00133 Rome, Italy
| | - Vittorio Manzari
- Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy
| | - Andrea Modesti
- Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy
| | - Roberto Bei
- Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy; CIMER, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy.
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Gil TY, Jin BR, Hong CH, Park JH, An HJ. Astilbe Chinensis ethanol extract suppresses inflammation in macrophages via NF-κB pathway. BMC Complement Med Ther 2020; 20:302. [PMID: 33028307 PMCID: PMC7542915 DOI: 10.1186/s12906-020-03073-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Accepted: 09/07/2020] [Indexed: 12/23/2022] Open
Abstract
Background Macrophages play a crucial role in inflammation. Astilbe chinensis is one of perennial herbs belonging to the genus Astilbe. Plants in the genus have been used for pain, headaches, arthralgia, and chronic bronchitis. However, the effect of A.chinensis on inflammation remains unclear. To study the anti-inflammatory action of A.chinensis ethanol extract (ACE), we investigated the effect of ACE on the production of pro-inflammatory mediators and cytokines in macrophages. Methods We evaluated the effectiveness of ACE in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and thioglycollate (TG)-elicited peritoneal macrophages from male C57BL/6 mice. We measured the levels of pro-inflammatory mediators and cytokines, and examined the anti-inflammatory actions of ACE on nuclear factor κB (NF-κB) pathway in the macrophages. Western blot analysis and immunofluorescence microscopy were used to determine protein level and translocation, respectively. Results ACE suppressed the output of nitric oxide (NO), prostaglandin E2 (PGE2), and pro-inflammatory cytokines in stimulated macrophages via inhibiting the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins. ACE suppressed mRNA expression of pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α). We examined the efficacies of ACE on NF-κB activation by measuring the expressions including IκB kinase (IKK), inhibitor of κB (IκB), and nuclear p65 proteins. In addition, the inhibition of NF-κB p65’s translocation was determined with immunofluorescence assay. Conclusion Our findings manifested that ACE inhibited LPS or TG-induced inflammation by blocking the NF-κB signaling pathway in macrophages. It indicated that ACE is a potential therapeutic mean for inflammation and related diseases.
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Affiliation(s)
- Tae-Young Gil
- Department of Pharmacology, College of Korean Medicine, Sangji University, 83, Sangjidae-gil, Wonju-si, Gangwon-do, 26339, Republic of Korea
| | - Bo-Ram Jin
- Department of Pharmacology, College of Korean Medicine, Sangji University, 83, Sangjidae-gil, Wonju-si, Gangwon-do, 26339, Republic of Korea
| | - Chul-Hee Hong
- Department of Korean Medicine Ophthalmology & Otolaryngology & Dermatology, College of Korean Medicine, Sangji University, 83, Sangjidae-gil, Wonju-si, Gangwon-do, 26339, Republic of Korea
| | | | - Hyo-Jin An
- Department of Pharmacology, College of Korean Medicine, Sangji University, 83, Sangjidae-gil, Wonju-si, Gangwon-do, 26339, Republic of Korea.
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Lee AY, Choi JM, Lee YA, Shin SH, Cho EJ. Beneficial effect of black rice ( Oryza sativa L. var. japonica ) extract on amyloid β-induced cognitive dysfunction in a mouse model. Exp Ther Med 2020; 20:64. [PMID: 32963594 DOI: 10.3892/etm.2020.9192] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2019] [Accepted: 05/29/2020] [Indexed: 12/29/2022] Open
Abstract
Alzheimer's disease (AD) is an age-dependent progressive neurodegenerative disease, resulting in memory loss and cognitive dysfunction. The accumulation of amyloid β (Aβ) has been identified as the most important risk factor for AD. Black rice (BR; Oryza sativa L. var. japonica), which is widely consumed in Asia, is a good source of bioactive compounds including anthocyanins. Therefore, the aim of the present study was to evaluate the protective effect of BR extracts against Aβ25-35-induced memory impairment in an in vivo AD mouse model. After intracerebroventricular injection of Aβ25-35, mice were treated with BR extract supplementation for 14 days. Memory and cognition function were evaluated over this period in both treated and untreated animals using T-maze, novel object recognition and Morris water maze tests. After behavioral tests, malondialdehyde (MDA) and nitric oxide (NO) concentrations in brain, liver and kidney tissues were analyzed. Mice treated with Aβ25-35 had impaired memory and cognitive function; however, mice administered BR extract (100 mg/kg/day) demonstrated an improvement in cognition and memory function compared with the Aβ25-35-injected control group. Furthermore, injection of Aβ25-35 significantly increased MDA and NO generation in the brain, liver and kidney of mice. However, the group administered with BR extract had significantly inhibited lipid peroxidation and NO generation in the brain, liver and kidney. In addition, the protective effect of BR on lipid peroxidation and NO production by Aβ25-35 was stronger in the brain compared with other tissues. Collectively, these findings suggested that BR supplementation may prevent memory and cognition deficits caused by Aβ25-35-induced oxidative stress.
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Affiliation(s)
- Ah Young Lee
- Department of Food Science, Gyeongnam National University of Science and Technology, Jinju 52725, Republic of Korea
| | - Ji Myung Choi
- Department of Food Science and Nutrition, Research Institute of Ecology, Pusan National University, Busan 46241, Republic of Korea
| | - Young A Lee
- Department of Food Science and Nutrition, Catholic University of Daegu, Gyeongsan 38430, Republic of Korea
| | - Seon Hwa Shin
- Department of Food Science and Nutrition, Research Institute of Ecology, Pusan National University, Busan 46241, Republic of Korea
| | - Eun Ju Cho
- Department of Food Science and Nutrition, Research Institute of Ecology, Pusan National University, Busan 46241, Republic of Korea
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Dharmawansa KS, Hoskin DW, Rupasinghe HPV. Chemopreventive Effect of Dietary Anthocyanins against Gastrointestinal Cancers: A Review of Recent Advances and Perspectives. Int J Mol Sci 2020; 21:ijms21186555. [PMID: 32911639 PMCID: PMC7554903 DOI: 10.3390/ijms21186555] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Revised: 08/28/2020] [Accepted: 09/02/2020] [Indexed: 12/14/2022] Open
Abstract
Anthocyanins are a group of dietary polyphenols, abundant mainly in fruits and their products. Dietary interventions of anthocyanins are being studied extensively related to the prevention of gastrointestinal (GI) cancer, among many other chronic disorders. This review summarizes the hereditary and non-hereditary characteristics of GI cancers, chemistry, and bioavailability of anthocyanins, and the most recent findings of anthocyanin in GI cancer prevention through modulating cellular signaling pathways. GI cancer-preventive attributes of anthocyanins are primarily due to their antioxidative, anti-inflammatory, and anti-proliferative properties, and their ability to regulate gene expression and metabolic pathways, as well as induce the apoptosis of cancer cells.
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Affiliation(s)
- K.V. Surangi Dharmawansa
- Department of Plant, Food, and Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS B2N 5E3, Canada;
| | - David W. Hoskin
- Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 4R2, Canada;
- Department of Microbiology and Immunology, and Department of Surgery, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 4R2, Canada
| | - H. P. Vasantha Rupasinghe
- Department of Plant, Food, and Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS B2N 5E3, Canada;
- Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 4R2, Canada;
- Correspondence: ; Tel.: +1-902-893-6623
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Arundina I, Diyatri I, Kusumaningsih T, Surboyo MDC, Monica E, Afanda NM. The Role of Rice Hull Liquid Smoke in the Traumatic Ulcer Healing. Eur J Dent 2020; 15:33-38. [PMID: 32777835 PMCID: PMC7902118 DOI: 10.1055/s-0040-1714445] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Objective
The aim of this study was to prove the role of rice hull liquid smoke (RH-LS) on lymphocytes, macrophages, fibroblasts, interleukin 6 (IL-6), and transforming growth factor β (TGF-β) expression during traumatic ulcer healing.
Materials and Methods
The RH-LS was obtained from the pyrolysis process. Traumatic ulcers were made 10 mm along the labial fornix incisive inferior of Wistar rat using a round stainless-steel blade. In control group, traumatic ulcers were treated using sterile water, and meanwhile in experimental group were treated using RH-LS once a day for 3, 5, and 7 days. After treatment, animal was terminated and their labial fornix incisive inferior tissues were biopsy and stained using hematoxylin and eosin staining to determine lymphocytes, macrophages, and fibroblasts. The IL-6 and TGF-β expressions were analyzed used immunohistochemistry staining.
Result
The lymphocytes, macrophages, and fibroblasts were higher in the RH-LS group for 3-, 5-, and 7-day treatment (
p
< 0.05). The IL-6 expression was higher only in the 5-day treatment, and the TGF-β expression was higher in the 3- and 7-day treatment.
Conclusion
The RH-LS able to accelerated the traumatic ulcer healing by increasing the number of lymphocytes, macrophages, fibroblasts, IL-6, and TGF-β expression.
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Affiliation(s)
- Ira Arundina
- Department of Oral Biology, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Indeswati Diyatri
- Department of Oral Biology, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Tuti Kusumaningsih
- Department of Oral Biology, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
| | | | - Elita Monica
- Undergraduate Student, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Novitasari Mira Afanda
- Undergraduate Student, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
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Speciale A, Saija A, Bashllari R, Molonia MS, Muscarà C, Occhiuto C, Cimino F, Cristani M. Anthocyanins As Modulators of Cell Redox-Dependent Pathways in Non-Communicable Diseases. Curr Med Chem 2020; 27:1955-1996. [PMID: 30417771 DOI: 10.2174/0929867325666181112093336] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2018] [Revised: 10/22/2018] [Accepted: 11/04/2018] [Indexed: 12/15/2022]
Abstract
Chronic Noncommunicable Diseases (NCDs), mostly represented by cardiovascular diseases, diabetes, chronic pulmonary diseases, cancers, and several chronic pathologies, are one of the main causes of morbidity and mortality, and are mainly related to the occurrence of metabolic risk factors. Anthocyanins (ACNs) possess a wide spectrum of biological activities, such as anti-inflammatory, antioxidant, cardioprotective and chemopreventive properties, which are able to promote human health. Although ACNs present an apparent low bioavailability, their metabolites may play an important role in the in vivo protective effects observed. This article directly addresses the scientific evidences supporting that ACNs could be useful to protect human population against several NCDs not only acting as antioxidant but through their capability to modulate cell redox-dependent signaling. In particular, ACNs interact with the NF-κB and AP-1 signal transduction pathways, which respond to oxidative signals and mediate a proinflammatory effect, and the Nrf2/ARE pathway and its regulated cytoprotective proteins (GST, NQO, HO-1, etc.), involved in both cellular antioxidant defenses and elimination/inactivation of toxic compounds, so countering the alterations caused by conditions of chemical/oxidative stress. In addition, supposed crosstalks could contribute to explain the protective effects of ACNs in different pathological conditions characterized by an altered balance among these pathways. Thus, this review underlines the importance of specific nutritional molecules for human health and focuses on the molecular targets and the underlying mechanisms of ACNs against various diseases.
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Affiliation(s)
- Antonio Speciale
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
| | - Antonella Saija
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
| | - Romina Bashllari
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
| | - Maria Sofia Molonia
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
| | - Claudia Muscarà
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.,"Prof. Antonio Imbesi" Foundation, University of Messina, Messina, Italy
| | - Cristina Occhiuto
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
| | - Francesco Cimino
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
| | - Mariateresa Cristani
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
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32
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Kamalian A, Sohrabi Asl M, Dolatshahi M, Afshari K, Shamshiri S, Momeni Roudsari N, Momtaz S, Rahimi R, Abdollahi M, Abdolghaffari AH. Interventions of natural and synthetic agents in inflammatory bowel disease, modulation of nitric oxide pathways. World J Gastroenterol 2020; 26:3365-3400. [PMID: 32655263 PMCID: PMC7327787 DOI: 10.3748/wjg.v26.i24.3365] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Revised: 05/09/2020] [Accepted: 06/04/2020] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD) refers to a group of disorders characterized by chronic inflammation of the gastrointestinal (GI) tract. The elevated levels of nitric oxide (NO) in serum and affected tissues; mainly synthesized by the inducible nitric oxide synthase (iNOS) enzyme; can exacerbate GI inflammation and is one of the major biomarkers of GI inflammation. Various natural and synthetic agents are able to ameliorate GI inflammation and decrease iNOS expression to the extent comparable with some IBD drugs. Thereby, the purpose of this study was to gather a list of natural or synthetic mediators capable of modulating IBD through the NO pathway. Electronic databases including Google Scholar and PubMed were searched from 1980 to May 2018. We found that polyphenols and particularly flavonoids are able to markedly attenuate NO production and iNOS expression through the nuclear factor κB (NF-κB) and JAK/STAT signaling pathways. Prebiotics and probiotics can also alter the GI microbiota and reduce NO expression in IBD models through a broad array of mechanisms. A number of synthetic molecules have been found to suppress NO expression either dependent on the NF-κB signaling pathway (i.e., dexamethasone, pioglitazone, tropisetron) or independent from this pathway (i.e., nicotine, prednisolone, celecoxib, β-adrenoceptor antagonists). Co-administration of natural and synthetic agents can affect the tissue level of NO and may improve IBD symptoms mainly by modulating the Toll like receptor-4 and NF-κB signaling pathways.
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Affiliation(s)
- Aida Kamalian
- Department of Medicine, Tehran University of Medical Sciences, Tehran 1417614411, Iran
| | - Masoud Sohrabi Asl
- Department of Medicine, Tehran University of Medical Sciences, Tehran 1417614411, Iran
| | - Mahsa Dolatshahi
- Department of Medicine, Tehran University of Medical Sciences, Tehran 1417614411, Iran
- Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran 1417614411, Iran
| | - Khashayar Afshari
- Department of Medicine, Tehran University of Medical Sciences, Tehran 1417614411, Iran
| | - Shiva Shamshiri
- Department of Traditional Pharmacy, School of Persian Medicine, Tehran University of Medical Sciences, Tehran 1417614411, Iran
| | - Nazanin Momeni Roudsari
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran 1941933111, Iran
| | - Saeideh Momtaz
- Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Tehran 1417614411, Iran
- Toxicology and Diseases Group (TDG), Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), and Department of Toxicology and Pharmacology, School of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran
- Gastrointestinal Pharmacology Interest Group, Universal Scientific Education and Research Network, Tehran 1417614411, Iran
| | - Roja Rahimi
- Department of Traditional Pharmacy, School of Persian Medicine, Tehran University of Medical Sciences, Tehran 1417614411, Iran
| | - Mohammad Abdollahi
- Toxicology and Diseases Group (TDG), Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), and Department of Toxicology and Pharmacology, School of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran
| | - Amir Hossein Abdolghaffari
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran 1941933111, Iran
- Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Tehran 1417614411, Iran
- Toxicology and Diseases Group (TDG), Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), and Department of Toxicology and Pharmacology, School of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran
- Gastrointestinal Pharmacology Interest Group, Universal Scientific Education and Research Network, Tehran 1417614411, Iran
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran
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Fakhri S, Khodamorady M, Naseri M, Farzaei MH, Khan H. The ameliorating effects of anthocyanins on the cross-linked signaling pathways of cancer dysregulated metabolism. Pharmacol Res 2020; 159:104895. [PMID: 32422342 DOI: 10.1016/j.phrs.2020.104895] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2020] [Revised: 04/13/2020] [Accepted: 05/05/2020] [Indexed: 12/25/2022]
Abstract
Cancer cells underlie the dysregulated metabolism of carbohydrate, lipid and protein and thereby, employ interconnected cross-linked signaling pathways to supply adequate energy for growth and related biosynthetic procedures. In the present study, a comprehensive review of cancer metabolism and anthocyanin's effect was conducted using the existing electronic databases, including Medline, PubMed, Scopus, and Web of Science, as well as related articles in the field. Such keywords as "cancer", and "cancer metabolism" in the title/abstract/keyword and all the "anthocyanins" in the whole text were used. Data were collected without time restriction until February 2020. The results indicated the involvement of several signaling pathways, including inflammatory PI3K/Akt/mTOR pathway, Bax/Bcl-2/caspases as apoptosis modulators, and NF-κB/Nrf2 as oxidative stress mediators in the cancer dysregulated metabolism. Compelling studies have shown that targeting these pathways, as critical hallmarks of cancer, plays a critical role in combating cancer dysregulated metabolism. The complexity of cancer metabolism signaling pathways, along with toxicity, high costs, and resistance to conventional drugs urge the need to investigate novel multi-target agents. Increasing evidence has introduced plant-derived secondary metabolites as hopeful anticancer candidates which target multiple dysregulated cross-linked pathways of cancer metabolism. Amongst these metabolites, anthocyanins have demonstrated positive anticancer effects by targeting inflammation, oxidative stress, and apoptotic signaling pathways. The current study revealed the cross-linked signaling pathways of cancer metabolism, as well as the promising pharmacological mechanisms of anthocyanins in targeting the aforementioned signaling mediators. To overcome the pharmacokinetic limitations of anthocyanins in cancer treatment, their interactions with gut microbiota and the need to develop related nano-formulations were also considered.
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Affiliation(s)
- Sajad Fakhri
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran.
| | - Minoo Khodamorady
- Department of Organic Chemistry, Faculty of Chemistry, Razi University, Kermanshah, 67149-67346, Iran.
| | - Maryam Naseri
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran.
| | - Mohammad Hosein Farzaei
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran.
| | - Haroon Khan
- Department of Pharmacy, Abdul Wali Khan University Mardan, 23200, Pakistan.
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Seesen M, Semmarath W, Yodkeeree S, Sapbamrer R, Ayood P, Malasao R, Ongprasert K, Chittrakul J, Siviroj P, Limtrakul (Dejkriengkraikul) P. Combined Black Rice Germ, Bran Supplement and Exercise Intervention Modulate Aging Biomarkers and Improve Physical Performance and Lower-Body Muscle Strength Parameters in Aging Population. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:E2931. [PMID: 32340343 PMCID: PMC7215642 DOI: 10.3390/ijerph17082931] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Revised: 04/15/2020] [Accepted: 04/20/2020] [Indexed: 12/25/2022]
Abstract
Aging is a time-dependent functional decline in muscle mass and strength, which is reflected in poor physical performances, hormonal imbalance, and development of chronic low-grade inflammation. This study aimed to assess the effectiveness of black rice germ, bran supplement, and exercise program either alone or in combination for 24 weeks on the aging biomarkers (C-reactive protein, Interleukin-6, Insulin-like growth factor-1, and CD4:CD8 T cell ratio) physical performance, muscle strength parameters (walking speed, sit-to-stand time, grip strength) among Thai aging population. A total of 120 healthy volunteers aged 65-74 years were assigned to the exercise group (EX), black rice germ, and bran supplement (BR) group or the combination of BR and EX group (BR + EX). Over the course of the 24-week intervention, compared with baseline data (T0), the combined BR + EX intervention significantly decreased the inflammatory biomarkers (C-reactive protein and interleukin-6 levels, both p < 0.05 vs. T0) and significantly increased the insulin-like growth factor-1 levels (p < 0.001 vs. T0). Significant improvement in physical performance and muscle strength were also observed in the combined BR + EX group (decrease in sit-to-stand time and gait speed over the 24-week intervention, both p < 0.05 vs. T0, and trend toward grip strength improvement at p = 0.088 vs. T0). Overall, our results indicated a synergistic effect towards the combined intervention with the sustainable improvement in physical performances, lower-body muscle strength, and the modulation of both inflammatory and endocrine biomarkers. This study could encourage older adults to change their lifestyles to improve healthy aging and longevity.
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Affiliation(s)
- Mathuramat Seesen
- Department of Community Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (M.S.); (R.S.); (P.A.); (R.M.); (K.O.); (J.C.)
| | - Warathit Semmarath
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (W.S.); (S.Y.)
- Center for Research and Development of Natural Products for Health, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Supachai Yodkeeree
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (W.S.); (S.Y.)
- Center for Research and Development of Natural Products for Health, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Ratana Sapbamrer
- Department of Community Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (M.S.); (R.S.); (P.A.); (R.M.); (K.O.); (J.C.)
| | - Pisittawoot Ayood
- Department of Community Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (M.S.); (R.S.); (P.A.); (R.M.); (K.O.); (J.C.)
| | - Rungnapa Malasao
- Department of Community Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (M.S.); (R.S.); (P.A.); (R.M.); (K.O.); (J.C.)
| | - Krongporn Ongprasert
- Department of Community Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (M.S.); (R.S.); (P.A.); (R.M.); (K.O.); (J.C.)
| | - Jiraporn Chittrakul
- Department of Community Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (M.S.); (R.S.); (P.A.); (R.M.); (K.O.); (J.C.)
| | - Penprapa Siviroj
- Department of Community Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (M.S.); (R.S.); (P.A.); (R.M.); (K.O.); (J.C.)
| | - Pornngarm Limtrakul (Dejkriengkraikul)
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (W.S.); (S.Y.)
- Center for Research and Development of Natural Products for Health, Chiang Mai University, Chiang Mai 50200, Thailand
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35
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Callcott ET, Blanchard CL, Snell P, Santhakumar AB. The anti-inflammatory and antioxidant effects of pigmented rice consumption in an obese cohort. Food Funct 2020; 10:8016-8025. [PMID: 31750484 DOI: 10.1039/c9fo02261a] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
The development of lifestyle diseases in the obese has been attributed to higher levels of inflammation and free radical mediated oxidative stress. The antioxidant and anti-inflammatory properties of polyphenols in pigmented rice varieties could have potential to neutralize oxidative stress and modulate inflammatory responses in the obese. A cross-over dietary intervention human clinical trial was conducted with three pigmented rice varieties chosen from previous chemical and in vitro antioxidant and anti-inflammatory screening. Obese (n = 22, BMI > 30) sedentary participants consumed one cup of pigmented rice (Reiziq (brown), Purple (purple) and Yunlu29 (red)). Blood samples were collected prior consumption (baseline) and at set time points of 30 minutes, 1 hour, 2 hours and 4 hours post rice consumption. The collected blood samples were analysed for antioxidant and inflammatory biomarkers. Total antioxidant activity increased (p < 0.001) at the 1 hour time point by 40.3% post purple rice consumption. The red rice variety, Yunlu29 increased antioxidant activity at the 30 minute (p < 0.001) and 1 hour (p < 0.01) time point by 29.5% and 21.2% respectively. Lipid peroxidation biomarker, malondialdehyde (MDA), decreased (p < 0.05) at the 30 minute time point by 6.8% post purple rice consumption. At the 4 hour time point MDA levels was significantly reduced (p < 0.001) by the red rice variety Yunlu29, by 9.6%. Pro-inflammatory cytokine, interleukin-10 (IL-10), was significantly (p < 0.0001) reduced by 3.1% 30 minutes post purple rice consumption. In contrast, Yunlu29 (red) reduced interleukin-6 levels by 13.6% and 11.0% at the 30 minute and 1 hour time points respectively. Both the purple (p < 0.01) and red (p < 0.001) varieties significantly reduced interleukin-12p70 concentrations at 30 minutes by 8.7% and 10.3% respectively. Reiziq (brown) did not affect any of the biomarkers analysed in this study. The outcomes of this study highlight that polyphenols found in pigmented rice may play a key role in targeting specific therapeutic pathways in obesity-related oxidative stress and inflammation.
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Affiliation(s)
- Esther T Callcott
- Australian Research Council (ARC) Industrial Transformation Training Centre for Functional Grains, Graham Centre for Agricultural Innovation, Charles Sturt University, Wagga Wagga, New South Wales 2650, Australia
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36
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Verma DK, Srivastav PP. Bioactive compounds of rice (Oryza sativa L.): Review on paradigm and its potential benefit in human health. Trends Food Sci Technol 2020. [DOI: 10.1016/j.tifs.2020.01.007] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
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37
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Arulselvan P, Santhanam R, Muniandy K, Gothai S, Shaari K, Senthilkumar P, Ganesan P. Anti-inflammatory activity of Zanthoxylum rhetsa bark fractions via suppression of nuclear factor-kappa B in lipopolysaccharide-stimulated macrophages. Pharmacogn Mag 2020. [DOI: 10.4103/pm.pm_486_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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38
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39
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Joo SH, Hahn C, Lim HK, Yoon KD, Yoon SH, Lee CU. An Exploration of the Oryza sativa L. Cyanidin-3-glucoside on the Cognitive Function in Older Adults with Subjective Memory Impairment. Psychiatry Investig 2019; 16:759-765. [PMID: 31558689 PMCID: PMC6801312 DOI: 10.30773/pi.2019.06.17] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2019] [Accepted: 06/17/2019] [Indexed: 11/29/2022] Open
Abstract
OBJECTIVE Cyanidin-3-glucoside (C3G), is a component of anthocyanin, have been considered to positively influence cognition and be beneficial for the prevention and treatment of dementia. We aimed to assess the safety and efficacy of cyanidin-3-glucoside-rich Oryza sativa L. (black rice) extract on cognitive function. METHODS A 12-weeks double-blind randomized, placebo controlled trial assessed safety and cognitive outcomes in participants with subjective memory impairment (n=48) following consumption of 6 black rice extract capsules or a placebo. Cognitive function was assessed using the ADAS-cog and the CERAD-K. Subjective memory impairment also assessed. Safety was assessed by hematologic blood test, urine analysis, and participant reports of adverse events. RESULTS There was significant improvement on subjective memory in intervention group. There was no statistically significant difference in objective cognitive outcomes following 12 weeks of consuming black rice extract. ADAS-cog scores, however, trended toward improvement in the intervention group compared to the placebo group. There was no adverse event. CONCLUSION Although significant improvement in objective cognitive function was not proved, we found that C3G-rich Oryza sativa L. extract improves subjective memory in this study. Therefore the results may be informative of the possible effectiveness of the C3G-rich Oryza sativa L. on cognitive function.
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Affiliation(s)
- Soo Hyun Joo
- Department of Psychiatry, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.,Catholic Agro-Medical Center, The Catholic University of Korea, Seoul, Republic of Korea
| | - Changtae Hahn
- Department of Psychiatry, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Daejeon, Republic of Korea.,Catholic Agro-Medical Center, The Catholic University of Korea, Seoul, Republic of Korea
| | - Hyun Kook Lim
- Department of Psychiatry, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.,Catholic Agro-Medical Center, The Catholic University of Korea, Seoul, Republic of Korea
| | - Kee Dong Yoon
- College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon, Republic of Korea.,Catholic Agro-Medical Center, The Catholic University of Korea, Seoul, Republic of Korea
| | - Shin Hee Yoon
- Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.,Catholic Agro-Medical Center, The Catholic University of Korea, Seoul, Republic of Korea
| | - Chang Uk Lee
- Department of Psychiatry, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.,Catholic Agro-Medical Center, The Catholic University of Korea, Seoul, Republic of Korea
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40
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Semmarath W, Seesen M, Yodkeeree S, Sapbamrer R, Ayood P, Malasao R, Siviroj P, Limtrakul Dejkriengkraikul P. The Association between Frailty Indicators and Blood-Based Biomarkers in Early-Old Community Dwellers of Thailand. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2019; 16:ijerph16183457. [PMID: 31533354 PMCID: PMC6765843 DOI: 10.3390/ijerph16183457] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Revised: 09/12/2019] [Accepted: 09/13/2019] [Indexed: 12/29/2022]
Abstract
Thailand has officially reached the status of an "aged society" and become the developing country with the 2nd largest proportion of senior citizens in Southeast Asia. A cross-sectional study of 526 early-old community dwellers was conducted for the Fried frailty phenotype assessment, This included five indicators: Weakness, slowness, physical activity, exhaustion, and weight loss. C-reactive protein (CRP), interleukin-6 (IL-6), insulin-like growth factor-1, and CD4+:CD8+ Ratio which serve as blood-based biomarkers of frailty. The prevalence of frailty and pre-frail in this population was found to be 15% and 69.6% respectively and was higher among women than men. Frail (n = 58) and non-frail (n = 60) participants were evaluated for the associations between the frail indicators and the blood-based biomarkers. Serum levels of IL-6 and CRP from frail group were significantly elevated when compared with the non-frail counterparts (p = 0.044 and 0.033, respectively), and were significantly associated with the frailty status with an Odd RatioIL-6 [OR] of 1.554-fold (95% confidence interval [CI], 1.229-1.966) and an ORCRP of 1.011-fold (95 CI, 1.006-1.016). Decreased hand-grip strength was the only frailty indicator that was significantly associated with both inflammatory biomarkers, (ORIL-6 of 1.470-fold and ORCRP of 1.008-fold). Our study is the first to assess the frailty status among the early-old population in Thailand. These findings will encourage general practitioners to combine frailty indicators and serum biomarkers as early detection tools for at-risk older adults to achieve the goal of healthy aging.
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Affiliation(s)
- Warathit Semmarath
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
- Center for Research and Development of Natural Products for Health, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Mathuramat Seesen
- Department of Community Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Supachai Yodkeeree
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
- Center for Research and Development of Natural Products for Health, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Ratana Sapbamrer
- Department of Community Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Pisittawoot Ayood
- Department of Community Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Rungnapa Malasao
- Department of Community Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Penprapa Siviroj
- Department of Community Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Pornngarm Limtrakul Dejkriengkraikul
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
- Center for Research and Development of Natural Products for Health, Chiang Mai University, Chiang Mai 50200, Thailand.
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Cho YH, Lim SY, Rehman A, Farooq M, Lee DJ. Characterization and quantification of γ-oryzanol in Korean rice landraces. J Cereal Sci 2019. [DOI: 10.1016/j.jcs.2019.05.019] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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42
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Kuo HCD, Wu R, Li S, Yang AY, Kong AN. Anthocyanin Delphinidin Prevents Neoplastic Transformation of Mouse Skin JB6 P+ Cells: Epigenetic Re-activation of Nrf2-ARE Pathway. AAPS JOURNAL 2019; 21:83. [PMID: 31254216 DOI: 10.1208/s12248-019-0355-5] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Accepted: 06/17/2019] [Indexed: 12/11/2022]
Abstract
Redox imbalance is a major contributor to the pathogenesis of melanoma and nonmelanoma skin cancer. Activation of the nuclear factor E2-related factor 2 (Nrf2) antioxidant responsive element (ARE) pathway is an intrinsic defense mechanism against oxidative stress. Flavonoids such as anthocyanidins, which are found abundantly in fruits and vegetables, have been shown to activate Nrf2. However, the epigenetic and genetic mechanisms by which anthocyanidins modulate the Nrf2-ARE pathway remain poorly understood in the context of skin cancer. In this study, delphinidin, one of the most potent and abundant anthocyanidins in berries, significantly inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced neoplastic cell transformation in mouse epidermal JB6 P+ cells by 69.4 to 99.4%. The mechanism was elucidated based on observations of increased ARE-driven luciferase activity and elevated mRNA and protein expression of Nrf2 downstream genes, such as heme oxygenase-1 (Ho-1), in JB6 P+ cells. Activation of the Nrf2-ARE pathway was correlated with demethylation of 15 CpG sites in the mouse Nrf2 promoter region between nt - 1226 and - 863 from the transcription start site. The reduced CpG methylation ratio in the Nrf2 promoter region was consistent with observed decreases in the protein expression of DNA methyltransferases 1 (DNMT1), DNMT3a, and class I/II histone deacetylases (HDACs). Overall, our results suggest that delphinidin, an epigenetic demethylating agent of the Nrf2 promoter, can activate the Nrf2-ARE pathway, which can be applied as a potential skin cancer chemopreventive agent.
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Affiliation(s)
- Hsiao-Chen Dina Kuo
- Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, New Jersey, 08854, USA.,Center for Phytochemical Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA
| | - Renyi Wu
- Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, New Jersey, 08854, USA.,Center for Phytochemical Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA
| | - Shanyi Li
- Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, New Jersey, 08854, USA.,Center for Phytochemical Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA
| | - Anne Yuqing Yang
- Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, New Jersey, 08854, USA.,Center for Phytochemical Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA
| | - Ah-Ng Kong
- Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, New Jersey, 08854, USA. .,Center for Phytochemical Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA.
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43
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Dokkaew A, Punvittayagul C, Insuan O, Limtrakul Dejkriengkraikul P, Wongpoomchai R. Protective Effects of Defatted Sticky Rice Bran Extracts on the Early Stages of Hepatocarcinogenesis in Rats. Molecules 2019; 24:molecules24112142. [PMID: 31174320 PMCID: PMC6600176 DOI: 10.3390/molecules24112142] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Revised: 05/26/2019] [Accepted: 06/04/2019] [Indexed: 12/31/2022] Open
Abstract
Use of natural products is one strategy to lessen cancer incidence. Rice bran, especially from colored rice, contains high antioxidant activity. Cancer chemopreventive effects of hydrophilic purple rice bran extract (PRBE) and white rice bran extract (WRBE) on carcinogen-induced preneoplastic lesion formation in livers of rats were investigated. A 15-week administration of PRBE and WRBE did not induce hepatic glutathione S-transferase placental form (GST-P) positive foci formation as the biomarker of rat hepatocarcinogenesis. PRBE and WRBE at 500 mg/kg body weight significantly decreased number and size of GST-P positive foci in diethylnitrosamine (DEN)-initiated rats. The number of proliferating nuclear antigen positive hepatocytes were also reduced in preneoplastic lesions in both PRBE and WRBE fed DEN-treated rats. Notably, the inhibitory effect on GST-P positive foci formation induced by DEN during the initiation stage was found only in rats treated by PRBE for five weeks. Furthermore, PRBE attenuated the expression of proinflammatory cytokines involving genes including TNF-α, iNOS, and NF-κB. PBRE contained a higher number of anthocyanins and other phenolic compounds and vitamin E. PRBE might protect DEN-induced hepatocarcinogenesis in rats via attenuation of cellular inflammation and cell proliferation. Anthocyanins and other phenolic compounds, as well as vitamin E, might play a role in cancer chemopreventive activity in rice bran extract.
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Affiliation(s)
- Aphisit Dokkaew
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
| | - Charatda Punvittayagul
- Research Affairs, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai 50100, Thailand.
- Functional Food Research Center for Well-being, Chiang Mai University, Chiang Mai 50200, Thailand.
| | - Orapin Insuan
- Department of Medical Technology, School of Allied Health Sciences, University of Phayao, Phayao 56000, Thailand.
| | - Pornngarm Limtrakul Dejkriengkraikul
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
- Anticarcinogenesis and Apoptosis Research Cluster, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
| | - Rawiwan Wongpoomchai
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
- Functional Food Research Center for Well-being, Chiang Mai University, Chiang Mai 50200, Thailand.
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Owolabi IO, Chakree K, Takahashi Yupanqui C. Bioactive components, antioxidative and anti‐inflammatory properties (on RAW 264.7 macrophage cells) of soaked and germinated purple rice extracts. Int J Food Sci Technol 2019. [DOI: 10.1111/ijfs.14148] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Affiliation(s)
- Iyiola Oluwakemi Owolabi
- Interdisciplinary Graduate School of Nutraceutical and Functional Food (IGS‐NFF) Prince of Songkla University Hat‐Yai Songkhla 90112 Thailand
| | - Korawan Chakree
- Interdisciplinary Graduate School of Nutraceutical and Functional Food (IGS‐NFF) Prince of Songkla University Hat‐Yai Songkhla 90112 Thailand
| | - Chutha Takahashi Yupanqui
- Interdisciplinary Graduate School of Nutraceutical and Functional Food (IGS‐NFF) Prince of Songkla University Hat‐Yai Songkhla 90112 Thailand
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Upanan S, Yodkeeree S, Thippraphan P, Punfa W, Wongpoomchai R, Limtrakul Dejkriengkraikul P. The Proanthocyanidin-Rich Fraction Obtained from Red Rice Germ and Bran Extract Induces HepG2 Hepatocellular Carcinoma Cell Apoptosis. Molecules 2019; 24:molecules24040813. [PMID: 30813458 PMCID: PMC6412498 DOI: 10.3390/molecules24040813] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Revised: 02/20/2019] [Accepted: 02/20/2019] [Indexed: 02/03/2023] Open
Abstract
This study aims to determine the anti-carcinogenic effects of the proanthocyanidin-rich fraction (PRFR) obtained from red rice germ and bran extract on HepG2 cells. The PRFR obtained from red rice germ and bran extract could reduce the cell viability of HepG2 cells as shown by the IC50 value at 20 µg/mL. Notably, PRFR concentrations at 20 and 40 µg/mL significantly increased the number of cells in the G2/M phase from 25.7% ± 1.4%in the control group to 36.2% ± 3.4% (p < 0.01) and 48.9% ± 2.6% (p < 0.0001), respectively, suggesting that the cells were arrested in this phase, which was confirmed by the reduction of survival proteins, including cyclin B1 and cdc25. Moreover, the PRFR at 20 and 40 µg/mL could induce cell death via the apoptosis cascade, indicated by the percentage of total apoptotic cells from 9.9% ± 3.1% in the control group to 41.1 ± 3.9 (p < 0.0001) and 82.2% ± 5.8% (p < 0.0001), respectively. This was clarified by increasing apoptotic proteins (such as cleaved PARP-1, cleaved caspase-8 and cleaved caspase-3) and decreasing anti-apoptotic protein survivin without p53 alterations. These results demonstrated that the PRFR obtained from red rice germ and bran extract could inhibit cell proliferation and induce cell apoptosis in HepG2 cells via survivin, which could potentially serve as a new target for cancer therapeutics making it an excellent "lead candidate" molecule for in vivo proof-of concept studies.
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Affiliation(s)
- Supranee Upanan
- Anticarcinogenesis and Apoptosis Research Cluster, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
| | - Supachai Yodkeeree
- Anticarcinogenesis and Apoptosis Research Cluster, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
| | - Pilaiporn Thippraphan
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
| | - Wanisa Punfa
- Anticarcinogenesis and Apoptosis Research Cluster, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
| | - Rawiwan Wongpoomchai
- Anticarcinogenesis and Apoptosis Research Cluster, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
| | - Pornngarm Limtrakul Dejkriengkraikul
- Anticarcinogenesis and Apoptosis Research Cluster, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
- Center for Research and Development of Natural Products for Health, Chiang Mai University, Chiang Mai 50200, Thailand.
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Kim DO, Byun JE, Seong HA, Yoon SR, Choi I, Jung H. Thioredoxin-interacting protein-derived peptide (TN13) inhibits LPS-induced inflammation by inhibiting p38 MAPK signaling. Biochem Biophys Res Commun 2018; 507:489-495. [DOI: 10.1016/j.bbrc.2018.11.069] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2018] [Accepted: 11/12/2018] [Indexed: 12/13/2022]
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Anti-inflammatory and wound healing properties of polyphenolic extracts from strawberry and blackberry fruits. Food Res Int 2018; 121:453-462. [PMID: 31108769 DOI: 10.1016/j.foodres.2018.11.059] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2018] [Revised: 11/16/2018] [Accepted: 11/26/2018] [Indexed: 12/27/2022]
Abstract
The polyphenolic profiles by HPLC-TOF-MS of strawberry 'San Andreas' and blackberry 'Black Satin' crude extracts (CE) were analyzed. Anthocyanin-enriched fractions (AEFs) and proanthocyanidin-enriched fractions (PEFs) were prepared, and all samples were probed for in vitro anti-inflammatory and wound healing effects in a LPS-stimulated RAW 264.7 macrophage model and in a skin fibroblast migration and proliferation assay, respectively. Blackberry samples exhibited higher ROS reduction than strawberry's (up to 50% ROS suppression). Berries CEs exhibited 20% inhibition in Cox-2 gene expression, while AEFs and PEFs were inactive at the same concentration. Strawberry AEF and PEF were more active against IL-1β and IL-6 gene expressions than the similar fractions from blackberry, where PEF was more active than AEF (75% suppression by strawberry PEF). Moreover, berry PEFs were the active polyphenol fraction against iNOS gene expression (50% and 65% gen suppression by strawberry and blackberry PEF, respectively), mirroring results of NO synthesis suppression. The cell migration potential of berry polyphenolics was associated with anthocyanins. AEFs showed fibroblast migration around 50% of that registered for the positive control. Results obtained in this work highlight the anti-inflammatory properties of berry polyphenolics, especially due to proanthocyanidins. Moreover, promising results were obtained about the effects of berry anthocyanins on wound healing.
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48
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Callcott ET, Blanchard CL, Oli P, Santhakumar AB. Pigmented Rice‐Derived Phenolic Compounds Reduce Biomarkers of Oxidative Stress and Inflammation in Human Umbilical Vein Endothelial Cells. Mol Nutr Food Res 2018; 62:e1800840. [DOI: 10.1002/mnfr.201800840] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Revised: 10/16/2018] [Indexed: 11/09/2022]
Affiliation(s)
- Esther T. Callcott
- Australian Research Council Industrial Transformation Training Centre for Functional Grains Graham Centre for Agricultural Innovation Charles Sturt University Wagga Wagga New South Wales 2650 Australia
- School of Biomedical Sciences Charles Sturt University Wagga Wagga New South Wales 2650 Australia
| | - Christopher L. Blanchard
- Australian Research Council Industrial Transformation Training Centre for Functional Grains Graham Centre for Agricultural Innovation Charles Sturt University Wagga Wagga New South Wales 2650 Australia
- School of Biomedical Sciences Charles Sturt University Wagga Wagga New South Wales 2650 Australia
| | - Prakash Oli
- New South Wales Department of Primary Industries Yanco Agricultural Institute Private Mail Bag Yanco New South Wales 2703 Australia
| | - Abishek B. Santhakumar
- Australian Research Council Industrial Transformation Training Centre for Functional Grains Graham Centre for Agricultural Innovation Charles Sturt University Wagga Wagga New South Wales 2650 Australia
- School of Biomedical Sciences Charles Sturt University Wagga Wagga New South Wales 2650 Australia
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Tamura H, Maekawa T, Domon H, Hiyoshi T, Yonezawa D, Nagai K, Ochiai A, Taniguchi M, Tabeta K, Maeda T, Terao Y. Peptides from rice endosperm protein restrain periodontal bone loss in mouse model of periodontitis. Arch Oral Biol 2018; 98:132-139. [PMID: 30485826 DOI: 10.1016/j.archoralbio.2018.11.021] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2018] [Revised: 11/16/2018] [Accepted: 11/19/2018] [Indexed: 12/31/2022]
Abstract
OBJECTIVE Food-derived peptides have been reported to exhibit antibacterial activity against periodontal pathogenic bacteria. However, no effect has been shown on inflammation and bone resorption in periodontal pathology. The overall objective of the current study was to investigate how rice peptides influence biological defense mechanisms against periodontitis-induced inflammatory bone loss, and identify their novel functions as a potential anti-inflammatory drug. DESIGN The expression of inflammatory and osteoclast-related molecules was examined in mouse macrophage-derived RAW 264.7 cell cultures using qPCR. Subsequently, the effect of these peptides on inflammatory bone loss in mouse periodontitis was examined using a mouse model of tooth ligation. Briefly, periodontal bone loss was induced for 7 days in mice by ligating the maxillary second molar and leaving the contralateral tooth un-ligated (baseline control). The mice were microinjected daily with the peptide in the gingiva until the day before euthanization. One week after the ligation, TRAP-positive multinucleated cells (MNCs) were enumerated from five random coronal sections of the ligated sites in each mouse. RESULTS Rice peptides REP9 and REP11 significantly inhibited transcription activity of inflammatory and osteoclast-related molecules. Local treatment with the rice peptides, in mice subjected to ligature-induced periodontitis, inhibited inflammatory bone loss, explaining the decreased numbers of osteoclasts in bone tissue sections. CONCLUSION Therefore, these data suggested that the rice peptides possess a protective effect against periodontitis.
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Affiliation(s)
- Hikaru Tamura
- Division of Microbiology and Infectious Diseases, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan; Research Center for Advanced Oral Science, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan; Division of Periodontology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Tomoki Maekawa
- Division of Microbiology and Infectious Diseases, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan; Research Center for Advanced Oral Science, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Hisanori Domon
- Division of Microbiology and Infectious Diseases, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan; Research Center for Advanced Oral Science, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Takumi Hiyoshi
- Division of Microbiology and Infectious Diseases, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan; Division of Periodontology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Daisuke Yonezawa
- Research Center for Advanced Oral Science, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan; Division of Oral Science for Health Promotion, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Kosuke Nagai
- Division of Microbiology and Infectious Diseases, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Akihito Ochiai
- Department of Materials Science and Technology, Graduate School of Science and Technology, Niigata University, Niigata, Japan
| | - Masayuki Taniguchi
- Department of Materials Science and Technology, Graduate School of Science and Technology, Niigata University, Niigata, Japan
| | - Koichi Tabeta
- Division of Periodontology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Takeyasu Maeda
- Research Center for Advanced Oral Science, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Yutaka Terao
- Division of Microbiology and Infectious Diseases, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan; Research Center for Advanced Oral Science, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
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50
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Magni G, Marinelli A, Riccio D, Lecca D, Tonelli C, Abbracchio MP, Petroni K, Ceruti S. Purple Corn Extract as Anti-allodynic Treatment for Trigeminal Pain: Role of Microglia. Front Cell Neurosci 2018; 12:378. [PMID: 30455630 PMCID: PMC6230559 DOI: 10.3389/fncel.2018.00378] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Accepted: 10/03/2018] [Indexed: 12/15/2022] Open
Abstract
Natural products have attracted interest in the search for new and effective analgesics and coadjuvant approaches to several types of pain. It is in fact well known that many of their active ingredients, such as anthocyanins (ACNs) and polyphenols, can exert potent anti-inflammatory actions. Nevertheless, their potential beneficial effects in orofacial painful syndromes have not been assessed yet. Here, we have evaluated the preventive effect of an ACN-enriched purple corn extract against the development of orofacial allodynia, in comparison with isogenic yellow corn extract containing only polyphenols. Orofacial allodynia developed following induction of temporomandibular joint (TMJ) inflammation in male rats, due to the injection of Complete Freund’s Adjuvant (CFA), and was evaluated by von Frey filaments. Animals drank purple or yellow corn extracts or water starting from 11 days before induction of inflammation and up to the end of the experiment 3 days later. To highlight possible additive and/or synergic actions, some animals also received the anti-inflammatory drug acetyl salicylic acid (ASA). In parallel with the evaluation of allodynia, we have focused our attention on the activation of microglia cells in the central nervous system (CNS), as it is well-known that they significantly contribute to neuronal sensitization and pain. Our data demonstrate that purple corn extract is as effective as ASA in preventing the development of orofacial allodynia, and only partial additive effect is observed when the two agents are co-administered. Yellow corn exerted no effect. Multiple mechanisms are possibly involved in the action of purple corn, including reduction of trigeminal macrophage infiltration and the shift of microglia cell polarization to an anti-inflammatory phenotype. In fact, in rats receiving yellow corn or water microglia cells show thick, short cell processes typical of activated cells. Conversely, thinner and longer microglia cell processes are observed in the brainstem of animals drinking purple corn extract; shape changes are accompanied by a reduction in the expression of pro-inflammatory molecules and increased production of anti-inflammatory mediators. Administration of purple corn extracts therefore represents a possible low-cost and easy way to reduce trigeminal-associated pain in various pathological conditions also thanks to the modulation of microglia reactivity.
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Affiliation(s)
- Giulia Magni
- Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy
| | | | - Daniele Riccio
- Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy
| | - Davide Lecca
- Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy
| | - Chiara Tonelli
- Department of Biosciences, Università degli Studi di Milano, Milan, Italy
| | - Maria P Abbracchio
- Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy
| | - Katia Petroni
- Department of Biosciences, Università degli Studi di Milano, Milan, Italy
| | - Stefania Ceruti
- Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy
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