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Bioactive Phytochemicals and Functional Food Ingredients in Fruits and Vegetables 2019

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: closed (31 December 2019) | Viewed by 54815

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Special Issue Editors

Dr. Francesca Giampieri

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1. Department of Clinical Sciences, Faculty of Medicine, Polytechnic University of Marche, 60131 Ancona, Italy
2. Research Group on Foods, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Isabel Torres 21, 39011 Santander, Spain
Interests: nutrition; health; disease prevention; dietary bioactive compounds; oxidative stress; aging; mitochondrial functionality; inflammation; bioenergetics
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Prof. Dr. Maurizio Battino

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Department of Odontostomatologic and Specialized Clinical Sciences, Sez-Biochimica, Faculty of Medicine, Università Politecnica delle Marche, Via Ranieri 65, 60100 Ancona, Italy
Interests: nutrition; periodontal diseases/periodontitis; oxidative stress; aging; mitochondrial function and diseases; berries (strawberry, blueberry, bilberry, cranberry, etc.); olive oil (dietary fats); honey, polyphenols; flavonoids; antioxidants, apoptosis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The importance of diet for human health and well-being has been widely recognized. Dietary guidelines around the world recommend the increased consumption of fruits and vegetables as good sources of dietary fiber, essential nutrients, and phytochemicals, to improve global health and reduce chronic disease risk. A diet rich in fruits and vegetables is indeed associated with a lower incidence of several degenerative pathologies, including obesity, diabetes, cardiovascular diseases, and cancer. In the last few years, numerous studies have demonstrated a wide range of biological properties and healthy benefits exerted by dietary phytochemicals, highlighting their beneficial role both in the prevention and in the treatment of several diseases. At the same time, functional foods have gained an enormous interest all around the world, as shown by the annual increase of their market of about 15%. Indeed, many now embrace the idea that functional foods play specific roles at different times throughout life and accept that certain foods may help to maintain a good health and prevent diseases.

The main aims of the Special Issue on "Bioactive Phytochemicals and Functional Food Ingredients in Fruits and Vegetables 2019" is to be an open forum where researchers may share their investigations and findings in this promising field and, thanks to the open access platform, increase their visibility and the chances to interact with industries and the production systems.

Prof. Dr. Maurizio Battino
Dr. Francesca Giampieri
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

nutrition
human health
dietary intake
bioactive compounds
dietary phytochemicals
natural antioxidants
nutrigenetics
nutrigenomics
inflammation
apoptosis
pharmacodynamics and pharmacokinetics of natural bioactive compounds

Related Special Issue

Bioactive Phytochemicals and Functional Food Ingredients in Fruits and Vegetables 2022 in International Journal of Molecular Sciences (33 articles)

Published Papers (11 papers)

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Editorial

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4 pages, 186 KiB

Open AccessEditorial

Bioactive Phytochemicals and Functional Food Ingredients in Fruits and Vegetables

by Francesca Giampieri and Maurizio Battino

Int. J. Mol. Sci. 2020, 21(9), 3278; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21093278 - 06 May 2020

Cited by 4 | Viewed by 3333

Abstract

Today, it is widely accepted that a plant-based diet produces wellbeing and prevents the onset of several human diseases [...] Full article

(This article belongs to the Special Issue Bioactive Phytochemicals and Functional Food Ingredients in Fruits and Vegetables 2019)

Research

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17 pages, 3489 KiB

Open AccessArticle

Tellimagrandin II, A Type of Plant Polyphenol Extracted from Trapa bispinosa Inhibits Antibiotic Resistance of Drug-Resistant Staphylococcus aureus

by Yu-Wei Chang, Wan-Chun Huang, Chun-Yu Lin, Wen-Hung Wang, Ling-Chien Hung and Yen-Hsu Chen

Int. J. Mol. Sci. 2019, 20(22), 5790; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20225790 - 18 Nov 2019

Cited by 16 | Viewed by 4333

Abstract

The emergence of methicillin-resistant Staphylococcus aureus (MRSA) has become a critical global concern. Identifying new candidates of anti-S. aureus agents is urgently required because the therapeutic strategies for infected patients are limited currently. Therefore, the present study investigated whether Tellimagrandin II (TGII), a pure compound extracted from the shells of Trapa bispinosa, exhibits antibacterial effects against MRSA. We first showed that TGII exerted potent inhibitory activity against MRSA with a minimum inhibitory concentration of 128 μg/mL. The obtained fractional inhibitory concentration suggested that TGII could alone exert antistaphylococcal activity, and TGII combined with low doses of antibiotics displayed synergistic effects against MRSA. Moreover, we found that TGII exerted bactericidal activity by reducing the expression of mecA followed by the negative regulation of the penicillin-binding protein 2a (PBP2a) of MRSA. Transmission electron microscopy (TEM) images further confirmed that TGII destroyed the integrity of the cell wall of MRSA and caused the loss of cytoplasm content. In conclusion, we evidenced the antibacterial effects of TGII against MRSA, which enables the effective dose of current antibiotics to be reduced and the predicament of drug-resistant S. aureus isolates to be overcome. Full article

(This article belongs to the Special Issue Bioactive Phytochemicals and Functional Food Ingredients in Fruits and Vegetables 2019)

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15 pages, 6816 KiB

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Quercetin Exposure Suppresses the Inflammatory Pathway in Intestinal Organoids from Winnie Mice

by Manuela Dicarlo, Gabriella Teti, Giulio Verna, Marina Liso, Elisabetta Cavalcanti, Annamaria Sila, Sathuwarman Raveenthiraraj, Mauro Mastronardi, Angelo Santino, Grazia Serino, Antonio Lippolis, Anastasia Sobolewski, Mirella Falconi and Marcello Chieppa

Int. J. Mol. Sci. 2019, 20(22), 5771; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20225771 - 16 Nov 2019

Cited by 31 | Viewed by 5240

Abstract

Inflammatory bowel diseases (IBDs) are chronic and relapsing immune disorders that result, or possibly originate, from epithelial barrier defects. Intestinal organoids are a new reliable tool to investigate epithelial response in models of chronic inflammation. We produced organoids from the ulcerative colitis murine model Winnie to explore if the chronic inflammatory features observed in the parental intestine were preserved by the organoids. Furthermore, we investigated if quercetin administration to in vitro cultured organoids could suppress LPS-induced inflammation in wild-type organoids (WT-organoids) and spontaneous inflammation in ulcerative colitis organoids (UC-organoids). Our data demonstrate that small intestinal organoids obtained from Winnie mice retain the chronic intestinal inflammatory features characteristic of the parental tissue. Quercetin administration was able to suppress inflammation both in UC-organoids and in LPS-treated WT-organoids. Altogether, our data demonstrate that UC-organoids are a reliable experimental system for investigating chronic intestinal inflammation and pharmacological responses. Full article

(This article belongs to the Special Issue Bioactive Phytochemicals and Functional Food Ingredients in Fruits and Vegetables 2019)

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16 pages, 7473 KiB

Open AccessArticle

Protective Effects of Flavone from Tamarix aphylla against CCl₄-Induced Liver Injury in Mice Mediated by Suppression of Oxidative Stress, Apoptosis and Angiogenesis

by Bishoy El-Aarag, Asmaa Khairy, Shaden A. M. Khalifa and Hesham R. El-Seedi

Int. J. Mol. Sci. 2019, 20(20), 5215; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20205215 - 21 Oct 2019

Cited by 21 | Viewed by 3620

Abstract

The current study aimed to investigate, for the first time, the beneficial effects of 3,5-dihydroxy-4′,7-dimethoxyflavone isolated from Tamarix aphylla L. against liver injury in mice. Liver injury was induced by intraperitoneal (i.p.) injection of carbon tetrachloride (CCl₄) at a dose of 0.4 mL/kg mixed in olive oil at ratio (1:4) twice a week for 6 consecutive weeks. The administration of CCl₄ caused significant histopathological changes in liver tissues while the pre-treatment with the flavone at dose of 10 and 25 mg/kg ameliorated the observed liver damages. Also, it markedly reduced hepatic malondialdehyde (MDA) level as well as increased the activities of liver superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (Gpx) compared with their recorded levels in CCl₄ model group. Moreover, the immunohistochemical analysis demonstrated the enhancement in the protein level of B-cell lymphoma-2 (Bcl-2) while the protein levels of cysteine-aspartic acid protease-3 (caspase-3), Bcl-2-associated x protein (Bax), transforming growth factor-β1 (TGF-β1) and CD31 were suppressed following the flavone treatement. These results suggest that the flavone can inhibit liver injury induced in mice owning to its impact on the oxidation, apoptotic and angiogenesis mechanisms. Further pharmacological investigations are essential to determine the effectiveness of the flavone in human. Full article

(This article belongs to the Special Issue Bioactive Phytochemicals and Functional Food Ingredients in Fruits and Vegetables 2019)

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17 pages, 2872 KiB

Open AccessArticle

Poria cocus Wolf Extract Ameliorates Hepatic Steatosis through Regulation of Lipid Metabolism, Inhibition of ER Stress, and Activation of Autophagy via AMPK Activation

by Ji-Hyun Kim, Hyun A Sim, Dae Young Jung, Eun Yeong Lim, Yun Tai Kim, Byung Joo Kim and Myeong Ho Jung

Int. J. Mol. Sci. 2019, 20(19), 4801; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20194801 - 27 Sep 2019

Cited by 63 | Viewed by 6204

Abstract

Poria cocos Wolf (PCW) is an edible, pharmaceutical mushroom with remarkable biological properties including anti-tumor, anti-inflammation, anti-oxidation, anti-ageing, and anti-diabetic effects. In the current study, we investigated the effects of PCW extract on hepatic steatosis under in vitro and in vivo conditions, and elucidated the underlying mechanisms. In this study, a mixture of HepG2 cells treated with free fatty acid (FFA)—palmitic and oleic acid—and high-fat diet (HFD)-fed obese mice were used; in this background, the triglyceride (TG) levels in HepG2 cells and mice liver were measured, and the expression levels of genes associated with lipogenesis, fatty acid oxidation, endoplasmic reticulum (ER) stress, and autophagy were determined. Treatment of HepG2 cells with FFA enhanced intracellular TG levels in HepG2 cells, but co-treatment with PCW significantly attenuated the TG levels. Notably, PCW significantly enhanced the phosphorylation of AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), and sterol regulatory element-binding protein-1c (SREBP-1c) in FFA-treated HepG2 cells. PCW downregulated the expression of lipogenesis-related genes, but upregulated the expression of genes associated with fatty acid oxidation. Further, PCW inhibited FFA-induced expression of ER stress markers and induced autophagy proteins. However, inhibition of AMPK significantly attenuated the beneficial effects of PCW in HepG2 cells. Moreover, PCW efficiently decreased HFD-induced hepatic TG accumulation in vivo and increased the phosphorylation of hepatic AMPK. Three compounds present in PCW including poricoic acid, pachymic acid, and ergosterol, significantly decreased FFA-induced increase in intracellular TG levels, consistent with increased AMPK phosphorylation, suggesting that poricoic acid, pachymic acid, and ergosterol are responsible for PCW-mediated amelioration of hepatic steatosis. Taken together, these results demonstrated that PCW ameliorates hepatic steatosis through the regulation of lipid metabolism, inhibition of ER stress, and activation of autophagy in an AMPK-dependent manner. This suggested that PCW can be potentially used for the treatment of hepatic steatosis. Full article

(This article belongs to the Special Issue Bioactive Phytochemicals and Functional Food Ingredients in Fruits and Vegetables 2019)

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17 pages, 2459 KiB

Open AccessArticle

Zerumbone Suppresses Enterotoxigenic Bacteroides fragilis Infection-Induced Colonic Inflammation through Inhibition of NF-κΒ

by Soonjae Hwang, Minjeong Jo, Ju Eun Hong, Chan Oh Park, Chang Gun Lee, Miyong Yun and Ki-Jong Rhee

Int. J. Mol. Sci. 2019, 20(18), 4560; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20184560 - 14 Sep 2019

Cited by 19 | Viewed by 4197

Abstract

Enterotoxigenic Bacteroides fragilis (ETBF) is human intestinal commensal bacterium and a potent initiator of colitis through secretion of the metalloprotease Bacteroides fragilis toxin (BFT). BFT induces cleavage of E-cadherin in colon cells, which subsequently leads to NF-κB activation. Zerumbone is a key component of the Zingiber zerumbet (L.) Smith plant and can exhibit anti-bacterial and anti-inflammatory effects. However, whether zerumbone has anti-inflammatory effects in ETBF-induced colitis remains unknown. The aim of this study was to determine the anti-inflammatory effect of orally administered zerumbone in a murine model of ETBF infection. Wild-type C57BL/6 mice were infected with ETBF and orally administered zerumbone (30 or 60 mg/kg) once a day for 7 days. Treatment of ETBF-infected mice with zerumbone prevented weight loss and splenomegaly and reduced colonic inflammation with decreased macrophage infiltration. Zerumbone treatment significantly decreased expression of IL-17A, TNF-α, KC, and inducible nitric oxide synthase (iNOS) in colonic tissues of ETBF-infected mice. In addition, serum levels of KC and nitrite was also diminished. Zerumbone-treated ETBF-infected mice also showed decreased NF-κB signaling in the colon. HT29/C1 colonic epithelial cells treated with zerumbone suppressed BFT-induced NF-κB signaling and IL-8 secretion. However, BFT-mediated E-cadherin cleavage was unaffected. Furthermore, zerumbone did not affect ETBF colonization in mice. In conclusion, zerumbone decreased ETBF-induced colitis through inhibition of NF-κB signaling. Full article

(This article belongs to the Special Issue Bioactive Phytochemicals and Functional Food Ingredients in Fruits and Vegetables 2019)

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21 pages, 4081 KiB

Open AccessArticle

Inhibition of Tyrosine-Phosphorylated STAT3 in Human Breast and Lung Cancer Cells by Manuka Honey is Mediated by Selective Antagonism of the IL-6 Receptor

by Priyanka Aryappalli, Khadija Shabbiri, Razan J. Masad, Roadha H. Al-Marri, Shoja M. Haneefa, Yassir A. Mohamed, Kholoud Arafat, Samir Attoub, Otavio Cabral-Marques, Khalil B. Ramadi, Maria J. Fernandez-Cabezudo and Basel K. al-Ramadi

Int. J. Mol. Sci. 2019, 20(18), 4340; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20184340 - 05 Sep 2019

Cited by 32 | Viewed by 5801

Abstract

Aberrantly high levels of tyrosine-phosphorylated signal transducer and activator of transcription 3 (p-STAT3) are found constitutively in ~50% of human lung and breast cancers, acting as an oncogenic transcription factor. We previously demonstrated that Manuka honey (MH) inhibits p-STAT3 in breast cancer cells, but the exact mechanism remained unknown. Herein, we show that MH-mediated inhibition of p-STAT3 in breast (MDA-MB-231) and lung (A549) cancer cell lines is accompanied by decreased levels of gp130 and p-JAK2, two upstream components of the IL-6 receptor (IL-6R) signaling pathway. Using an ELISA-based assay, we demonstrate that MH binds directly to IL-6Rα, significantly inhibiting (~60%) its binding to the IL-6 ligand. Importantly, no evidence of MH binding to two other cytokine receptors, IL-11Rα and IL-8R, was found. Moreover, MH did not alter the levels of tyrosine-phosphorylated or total Src family kinases, which are also constitutively activated in cancer cells, suggesting that signaling via other growth factor receptors is unaffected by MH. Binding of five major MH flavonoids (luteolin, quercetin, galangin, pinocembrin, and chrysin) was also tested, and all but pinocembrin could demonstrably bind IL-6Rα, partially (30–35%) blocking IL-6 binding at the highest concentration (50 μM) used. In agreement, each flavonoid inhibited p-STAT3 in a dose-dependent manner, with estimated IC₅₀ values in the 3.5–70 μM range. Finally, docking analysis confirmed the capacity of each flavonoid to bind in an energetically favorable configuration to IL-6Rα at a site predicted to interfere with ligand binding. Taken together, our findings identify IL-6Rα as a direct target of MH and its flavonoids, highlighting IL-6R blockade as a mechanism for the anti-tumor activity of MH, as well as a viable therapeutic target in IL-6-dependent cancers. Full article

(This article belongs to the Special Issue Bioactive Phytochemicals and Functional Food Ingredients in Fruits and Vegetables 2019)

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14 pages, 2008 KiB

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Pachypodol, a Methoxyflavonoid Isolated from Pogostemon cablin Bentham Exerts Antioxidant and Cytoprotective Effects in HepG2 Cells: Possible Role of ERK-Dependent Nrf2 Activation

by Eun Kyung Kim, Ji Hoon Kim, Soyeon Jeong, Yong Won Choi, Hyun Jung Choi, Chul Young Kim and Young-Mi Kim

Int. J. Mol. Sci. 2019, 20(17), 4082; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20174082 - 21 Aug 2019

Cited by 20 | Viewed by 4152

Abstract

Oxidative stress has been implicated in the pathogenesis of many diseases including chronic liver diseases. Nrf2 is a master transcriptional factor regulating the induction of cellular antioxidant defense systems. Here, the Nrf2-activating effect of the crude methanol extract of dried leaves of Pogostemon cablin Bentham was demonstrated by measuring the antioxidant response element (ARE)-driven luciferase activity and pachypodol, 4′,5-dihydroxy-3,3′,7-trimethoxyflavone, was isolated by bioactivity-guided fractionation and further separation using chromatographic techniques. To our knowledge, this is the first study to evaluate the antioxidant and cytoprotective effects of pachypodol in HepG2 cells as well as the underlying molecular mechanisms. Indeed, pachypodol protected HepG2 cells from cell death caused by tert-butylhydroperoxide-induced oxidative stress and also attenuated ROS production. The ability of pachypodol to activate Nrf2/ARE pathway was further confirmed by observing Nrf2 expression in nuclear fraction, mRNA levels of Nrf2 target antioxidants, and cellular glutathione content in HepG2 cells. Extracellular signal-regulated kinase (ERK) is one of the important kinases involved in Nrf2 activation. Pachypodol increased ERK phosphorylation and ERK inhibition by PD98059 totally abrogated the increase in ARE luciferase activity, nuclear Nrf2 accumulation and mRNA levels of antioxidant enzymes by pachypodol. In conclusion, pachypodol isolated from P. cablin can protect hepatocytes from oxidative injury, possibly mediated by enhancing endogenous antioxidant defense system through ERK-dependent Nrf2 activation. Full article

(This article belongs to the Special Issue Bioactive Phytochemicals and Functional Food Ingredients in Fruits and Vegetables 2019)

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14 pages, 2624 KiB

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Ginseng Berry Prevents Alcohol-Induced Liver Damage by Improving the Anti-Inflammatory System Damage in Mice and Quality Control of Active Compounds

by Dae Young Lee, Min-Jee Kim, Dahye Yoon, Young-Seob Lee, Geum-Soog Kim and Yung Choon Yoo

Int. J. Mol. Sci. 2019, 20(14), 3522; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20143522 - 18 Jul 2019

Cited by 15 | Viewed by 3648

Abstract

The ginseng berry contains a variety of biologically active compounds and has a higher ginsenoside content than its roots. This study focused on the hepatoprotective activity of ginseng berry extract prepared by enzyme treatment (EGB) compared to the non-enzyme-treated ginseng berry extract (GB) and quality control of EGB. The feeding effect of EGB on alcohol-induced liver damage (AILD) was investigated by measuring the serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) compared with those of EtOH-fed mice. Furthermore, cytokine levels in the culture supernatants of EGB- or GB-treated RAW 264.7 cells were determined by enzyme-linked immunosorbent assay. The developed method was applied to the simultaneous quantification of four major ginsenosides in EGB using UPLC-QTOF/MS. Treatment with EGB at a dose of 0.5 or 1 mg/mouse significantly suppressed the AST and ALT levels in mice with AILD. Enzyme-treated ginseng berry was also found to suppress the production of inflammatory mediators like nitric oxide (NO), tumor-necrosis factor-α (TNF-α), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, showing higher activity than that of GB. The amount of ginsenoside Re, F5, F3, and Rd in the EGB obtained using UPLC-QTOF/MS was 45.9, 3.3, 4.0, and 6.2 mg/g, respectively. These results suggest that EGB has a potential effect on AILD, and its hepatoprotective effect provides beneficial insights into developing new candidates for the prevention and cure of AILD. Also, this study demonstrated the utility of UPLC-QTOF/MS-based major compounds for quality control (QC) of EGB. Full article

(This article belongs to the Special Issue Bioactive Phytochemicals and Functional Food Ingredients in Fruits and Vegetables 2019)

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14 pages, 2004 KiB

Open AccessArticle

Bioavailability and In Vivo Antioxidant Activity of a Standardized Polyphenol Mixture Extracted from Brown Propolis

by Valeria Curti, Vincenzo Zaccaria, Arold Jorel Tsetegho Sokeng, Marco Dacrema, Irene Masiello, Anna Mascaro, Giuseppe D’Antona and Maria Daglia

Int. J. Mol. Sci. 2019, 20(5), 1250; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20051250 - 12 Mar 2019

Cited by 47 | Viewed by 6202

Abstract

Several lines of evidence demonstrate the antioxidant, anti-inflammatory and antimicrobial activities of propolis, mostly ascribed to its polyphenol content. However, little is known regarding the bioavailability of propolis in acute and prolonged settings of oral administration. In this study, we first determined the content of the main polyphenols in a brown propolis extract obtained using a patented extraction method (Multi Dinamic Extraction—M.E.D.) by RP-HPLC-UV-PDA-MSn analysis, followed by the bioavailability of galangin and chrysin, the most abundant polyphenols in the mixture (7.8% and 7.5% respectively), following acute (single bolus of 500 mg/kg containing about 3.65 mg of the polyphenol mixture) and prolonged (100, 250 and 500 mg/kg body for 30 days) oral administration in 30 male 8 weeks old C57BL/6 wild-type mice. In the acute setting, blood was taken at 30 s and 5, 10, 15, 20, 25, 30, 45, 60 and 120 min following the oral bolus. In the prolonged setting, blood samples were obtained after 10, 20 or 30 days of administration. At the end of treatment, expression of antioxidant enzymes (superoxyde dismutase, SOD-1; catalase, CAT; glutathione peroxidase, GSS) was evaluated in liver tissue. Following both acute and prolonged administration, neither galangin nor chrysin were detectable in the plasma of mice, whereas the glucuronide metabolite of galangine was detectable 5 min after acute administration. At the end of the prolonged treatment SOD-1 was found to have increased significantly, unlike CAT and GSS. Overall, these data suggest that oral administration of whole brown propolis extract is followed by rapid absorption and metabolization of galangin followed by adaptations of the antioxidant first line defense system. Full article

(This article belongs to the Special Issue Bioactive Phytochemicals and Functional Food Ingredients in Fruits and Vegetables 2019)

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11 pages, 2872 KiB

Open AccessArticle

Hypolipogenic Effect of Shikimic Acid Via Inhibition of MID1IP1 and Phosphorylation of AMPK/ACC

by Moon Joon Kim, Deok Yong Sim, Hye Min Lee, Hyo-Jung Lee and Sung-Hoon Kim

Int. J. Mol. Sci. 2019, 20(3), 582; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20030582 - 29 Jan 2019

Cited by 24 | Viewed by 6460

Abstract

Although shikimic acid from Illicium verum has antioxidant, antibacterial, anti-inflammatory, and analgesic effects, the effect of shikimic acid on lipogenesis has not yet been explored. Thus, in the present study, hypolipogenic mechanism of shikimic acid was examined in HepG2, Huh7 and 3T3-L1 adipocyte cells. Shikimic acid showed weak cytotoxicity in HepG2, Huh7 and 3T3-L1 cells, but suppressed lipid accumulation in HepG2, Huh7 and 3T3-L1 cells by Oil Red O staining. Also, shikimic acid attenuated the mRNA expression of de novo lipogenesis related genes such as FAS, SREBP-1c, and LXR-α in HepG2 cells by RT-PCR analysis and suppressed the protein expression of SREBP-1c and LXR-α in HepG2 and 3T3-L1 cells. It should be noted that shikimic acid activated phosphorylation of AMP-activated protein kinase (AMPK)/Aacetyl-coenzyme A carboxylase (ACC) and reduced the expression of MID1 Interacting Protein 1 (MID1IP1) in HepG2, Huh7 and 3T3-L1 cells. Conversely, depletion of MID1IP1 activated phosphorylation of AMPK, while overexpression of MID1IP1 suppressed phosphorylation of AMPK in HepG2 cells. However, AMPK inhibitor compound c did not affect the expression of MID1IP1, indicating MID1IP1 as an upstream of AMPK. Taken together, our findings suggest that shikimic acid has hypolipogenic effect in HepG2 and 3T3-L1 cells via phosphorylation of AMPK/ACC and inhibition of MID1IP1 as a potent candidate for prevention or treatment of fatty liver and hyperlipidemia. Full article

(This article belongs to the Special Issue Bioactive Phytochemicals and Functional Food Ingredients in Fruits and Vegetables 2019)

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