Erica multiflora extract rich in quercetin-3-O-glucoside and kaempferol-3-O-glucoside alleviates high fat and fructose diet-induced fatty liver disease by modulating metabolic and inflammatory pathways in Wistar rats

Khlifi, Rihab; Dhaouefi, Zaineb; Toumia, Imène Ben; Lahmar, Aida; Sioud, Fairouz; Bouhajeb, Rim; Bellalah, Ahlem; Chekir‐Ghedira, Leila

doi:10.1016/j.jnutbio.2020.108490

Cited by 35 publications

(23 citation statements)

References 77 publications

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“…Also of current interest, molecular docking studies of 33 molecules predicted rutin as the strongest contender in binding the active site of the SARS-CoV-2 main 3C-L protease for inhibiting viral replication and potentially treating the COVID-19 pandemic ( 52 ). Antilipotoxicity and antiviral activities by rutin are not unprecedented ( 53 – 56 ), albeit not used to date to inform new uses of traditional medicine. Our results thus broaden the therapeutic potential and applications of P. insularum in Samoan traditional medicine.…”

Section: Discussionmentioning

confidence: 99%

Functional genomics and metabolomics advance the ethnobotany of the Samoan traditional medicine “matalafi”

Molimau-Samasoni

Woolner

Foliga³

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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The leaf homogenate of Psychotria insularum is widely used in Samoan traditional medicine to treat inflammation associated with fever, body aches, swellings, wounds, elephantiasis, incontinence, skin infections, vomiting, respiratory infections, and abdominal distress. However, the bioactive components and underlying mechanisms of action are unknown. We used chemical genomic analyses in the model organism Saccharomyces cerevisiae (baker’s yeast) to identify and characterize an iron homeostasis mechanism of action in the traditional medicine as an unfractionated entity to emulate its traditional use. Bioactivity-guided fractionation of the homogenate identified two flavonol glycosides, rutin and nicotiflorin, each binding iron in an ion-dependent molecular networking metabolomics analysis. Translating results to mammalian immune cells and traditional application, the iron chelator activity of the P. insularum homogenate or rutin decreased proinflammatory and enhanced anti-inflammatory cytokine responses in immune cells. Together, the synergistic power of combining traditional knowledge with chemical genomics, metabolomics, and bioassay-guided fractionation provided molecular insight into a relatively understudied Samoan traditional medicine and developed methodology to advance ethnobotany.

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Section: Discussionmentioning

confidence: 99%

Functional genomics and metabolomics advance the ethnobotany of the Samoan traditional medicine “matalafi”

Molimau-Samasoni

Woolner

Foliga³

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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“…Persicaria glabra has been investigated for its antiinflammatory, analgesic, and antirheumatic activities. Compounds 1, 17, 29, and 30 the methanol leaf extract of E. multiflora prevented obesity using metabolic syndrome modulation, decreasing inflammation, and enhancing the activities of antioxidant enzymes (Khlifi et al, 2020).…”

Section: Saadatmandi Et Al Investigated the Activity Of Compounds 1 11mentioning

confidence: 99%

“…The extract also reduced TNF‐α and IL‐6, liver MDA content, and increased the activities of SOD, CAT, and GPx. Generally, the methanol leaf extract of E. multiflora prevented obesity using metabolic syndrome modulation, decreasing inflammation, and enhancing the activities of antioxidant enzymes (Khlifi et al, 2020).…”

Section: O‐glycoside Derivatives Of Quercetinmentioning

confidence: 99%

O‐Glycosidequercetin derivatives: Biological activities, mechanisms of action, and structure–activity relationship for drug design, a review

Alizadeh

Ebrahimzadeh

2021

Phytotherapy Research

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Quercetin as a valuable natural flavonoid has shown extensive biological activities, including anticancer, antioxidant, antibacterial, antiinflammatory, anti-Alzheimer, antifungal, antiviral, antithalassemia, iron chelation, antiobesity, antidiabetic, antihypertension, and antiphospholipase A2 (PLA2) activities, by the modulation of various targets and signaling pathways that have attracted much attention. However, the low solubility and poor bioavailability of quercetin have limited its applications; therefore, the researchers have tried to design and synthesize many new derivatives of quercetin through different strategies to modify quercetin restrictions and improve its biological activities. This review categorized the O-glycoside derivatives of Quercetin into two main classes, 3-O-glycoside and other O-glycoside derivatives. Also, it studied biological activities, structure-activity relationship (SAR), and the action mechanism of O-glycoside quercetin derivatives. Overall, we summarized past and present research for discovering new potent lead compounds. Highlights• Quercetin is a natural flavonoid with a valuable scaffold.• O-Glycoside quercetin derivatives represents broad-spectrum biological activities.• The structure-activity relationship investigation is discussed after modifying the scaffold of quercetin.• This review can help researchers to rationally design/develop various drugs.

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“…It was found that treatment of quercetin attenuated the fatty acid uptake, trafficking-related gene expression, and lipid peroxidation in nonalcoholic steatohepatitis of MCD-induced mice [ 31 ]. The extract rich in quercetin glucoside improved metabolic syndrome and possessed liver-protective effect by reducing the inflammatory cytokines and oxidative stress [ 32 ]. Actually, we have also tested the sub-subfractions of F1.…”

Section: Discussionmentioning

confidence: 99%

Abelmoschus esculentus subfractions ameliorate hepatic lipogenesis and lipid uptake via regulating dipeptidyl peptidase-4—With improving insulin resistance

Peng

Ker

et al. 2022

PLoS ONE

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Nonalcoholic fatty liver disease (NAFLD) is recognized as the liver component of metabolic syndrome. The regulation of hepatic lipid should be emphasized to prevent accompanying illness. As AMP-activated protein kinase (AMPK) and sterol regulatory element binding protein (SREBP) regulate lipid metabolism, CD36 and fatty acid synthase (FAS) promote lipid uptake and lipogenesis respectively, while acetyl-CoA carboxylase (ACC) is an indicator of negative feedback. The increase of IRS-1 phosphorylation at the residue ser307 (p-ser307-IRS-1) and decrease of p-ser473-Akt (p-Akt) are viewed as the insulin resistance markers, and our previous reports suggested dipeptidyl peptidase-4 (DPP-4) mediates insulin resistance, the crucial factor of metabolic syndrome. Abelmoschus esculentus (AE) fruit is well-known for its antidiabetic utility. We had isolated several AE subfractions by successive steps, and found that F1 and F2 were especially valid in suppressing DPP-4 signaling. Since little is known if AE works on NAFLD, now we first attempt to investigate whether AE is useful to attenuate hepatic lipogenesis and lipid uptake in liver cells, along with improving the metabolic targets. We demonstrated that AE subfractions attenuated the hepatic lipid accumulation induced by free fatty acids. Treatment of AE alleviated FAS and returned the level of p-ser79-ACC (p-ACC). Although F1 was more effective on AMPK, F2 seemed more stable to attenuate SREBP-1. Moreover, as fatty acids stimulated the expression of CD36, F2 showed a superior effect to down-regulate the lipid uptake. Both AE subfractions reduced the generation of ROS, decreased the level of p-ser307-IRS-1, and restored the expression of p-Akt. Moreover, treatment of DPP-4 inhibitor linagliptin revealed that, AE could prevent the hepatic lipogenesis, oxidative burden, and the related insulin resistance via downregulating DPP-4. In conclusion, the present investigation revealed that AE, especially F2, is potential to be developed as adjuvant to prevent NAFLD.

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Erica multiflora extract rich in quercetin-3-O-glucoside and kaempferol-3-O-glucoside alleviates high fat and fructose diet-induced fatty liver disease by modulating metabolic and inflammatory pathways in Wistar rats

Cited by 35 publications

References 77 publications

Functional genomics and metabolomics advance the ethnobotany of the Samoan traditional medicine “matalafi”

Functional genomics and metabolomics advance the ethnobotany of the Samoan traditional medicine “matalafi”

O‐Glycosidequercetin derivatives: Biological activities, mechanisms of action, and structure–activity relationship for drug design, a review

Abelmoschus esculentus subfractions ameliorate hepatic lipogenesis and lipid uptake via regulating dipeptidyl peptidase-4—With improving insulin resistance

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