Gallic Acid Attenuates Dimethylnitrosamine-Induced Liver Fibrosis by Alteration of Smad Phosphoisoform Signaling in Rats

Chen, Yuxin; Zhou, Ziping; Mo, Qigui; Zhou, Gao; Wang, You-Wei

doi:10.1155/2018/1682743

Cited by 15 publications

(12 citation statements)

References 40 publications

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“…Among those inflammatory cytokines involved in liver fibrosis, TGF- β 1 appears to be the most important one. In our previous study, we proved that GA in medium and high doses could significantly reduce TGF- β 1 and hydroxyproline in rats with liver fibrosis [32], which is consistent with the results found in this study. Cheng et al provided a prospect that silencing of TGF- β 1 by siRNA and shRNA might be an efficient approach against liver fibrosis [33].…”

Section: Resultssupporting

confidence: 92%

Active Constituent in the Ethyl Acetate Extract Fraction of Terminalia bellirica Fruit Exhibits Antioxidation, Antifibrosis, and Proapoptosis Capabilities In Vitro

Chen

Zhou

et al. 2019

Oxidative Medicine and Cellular Longevity

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Terminalia bellirica (Gaertn.) Roxb. fruit (TBF) is a widely planted traditional medicinal herb in Tibet. We aimed to determine the most active substance-enriched extract by comparing the in vitro antioxidant activities of different extract fractions of TBF that were subsequently extracted by petroleum ether, chloroform, ethyl acetate, and n-butanol after initial extraction by 95% ethanol. The main compounds of the ethyl acetate extract fraction (EF) were analyzed via HPLC-MS. Gallic acid (GA) was obtained from EF to determine in vitro antifibrotic activity based on the traditional usage of TBF. After HSC-T6 cells were incubated with GA, extracellular secreted levels of fibrosis-associated cytokines, such as collagen I, collagen III, TGF-β1, and hydroxyproline, were estimated by ELISA. Gene and protein expressions of PDGFR, CTGF, NF-κB, MMP-2, TIMP-1, TIMP-2, α-SMA, and the Bcl-2/Bax family were determined by quantitative PCR and western blot. The proapoptotic effect of GA was further investigated by annexin V-PI and TUNEL staining. These results indicate that EF has prominent in vitro antioxidant activity among four extract fractions, and its main component, GA, manifests antifibrosis activity and its potential mechanism of action includes inhibition of cytokine secretion and collagen synthesis, as well as proapoptosis of HSCs.

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Section: Resultssupporting

confidence: 92%

Active Constituent in the Ethyl Acetate Extract Fraction of Terminalia bellirica Fruit Exhibits Antioxidation, Antifibrosis, and Proapoptosis Capabilities In Vitro

Chen

Zhou

et al. 2019

Oxidative Medicine and Cellular Longevity

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“…These results support its ability to regulate the antioxidant enzymes activities and inhibit lipid peroxidation. Many studies have demonstrated its hepatoprotective effects [49,50,51].…”

Section: Discussionmentioning

confidence: 99%

Antioxidant Activity of Graptopetalum paraguayense E. Walther Leaf Extract Counteracts Oxidative Stress Induced by Ethanol and Carbon Tetrachloride Co-Induced Hepatotoxicity in Rats

et al. 2019

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(1) Background: Graptopetalum paraguayense E. Walther is a traditional Chinese herbal medicine. In our previous study, 50% ethanolic G. paraguayense extracts (GE50) demonstrated good antioxidant activity. (2) Methods: To investigate the hepatoprotective effects of GE50 on ethanol and carbon tetrachloride (CCl4) co-induced hepatic damage in rats, Sprague–Dawley rats were randomly divided into five groups (Control group; GE50 group, 0.25 g/100 g BW; EC group: Ethanol + CCl4, 1.25 mL 50% ethanol and 0.1 mL 20% CCl4/100 g BW; EC + GE50 group: Ethanol + CCl4 + GE50; EC + silymarin group: ethanol + CCl4 + silymarin, 20 mg/100 g BW) for six consecutive weeks. (3) Results: Compared with the control group, EC group significantly elevated the serum aspartate aminotransferase (AST), alanine aminitransferase (ALT), and lactate dehydrogenase (LDH). However, GE50 or silymarin treatment effectively reversed these changes. GE50 had a significant protective effect against ethanol + CCl4 induced lipid peroxidation and increased the levels of glutathione (GSH), vitamin C, E, total antioxidant status (TAS), and the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and glutathione S-transferases (GST). Furthermore, in EC focal group, slight fat droplet infiltration was observed in the livers, while in the GE50 or silymarin treatment groups, decreased fat droplet infiltration. HPLC phytochemical profile of GE50 revealed the presence of gallic acid, flavone, genistin, daidzin, and quercetin. (4) Conclusions: The hepatoprotective activity of GE50 is proposed to occur through the synergic effects of its chemical component, namely, gallic acid, flavone, genistin, daidzin, and quercetin. Hence, G. paraguayense can be used as a complementary and alternative therapy in the prevention of alcohol + CCl4-induced liver injury.

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“…11,12 Gallic acid (3, 4, 5-trihydroxybenzoic acid, GA), is one of the abundant natural phenolic acids in human diets, 13 which possesses a broad range of biological activities, including antioxidant, anti-inflammatory, antimutagenic, and anticancer properties. 14,15 Furthermore, GA has shown promising antifibrotic activity in vitro 16 and in experimental animals [15][16][17] owing to its robust antioxidant and anti-inflammatory properties, 15 in addition to its ability to suppress the activation 16,17 and induce apoptosis of aHSCs. 16 However, its efficacy and therapeutic applicability are hindered by its low bioavailability as it is poorly absorbed and subjected to extensive metabolism with rapid clearance, which results in low plasma concentration.…”

Section: Introductionmentioning

confidence: 99%

<p>Zein/Phospholipid Composite Nanoparticles for Successful Delivery of Gallic Acid into aHSCs: Influence of Size, Surface Charge, and Vitamin A Coupling</p>

Radwan¹,

El-Maadawy²,

Yousry³

et al. 2020

IJN

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Purpose Zein/phospholipid composite nanoparticles (CNPs) were developed as a delivery platform for gallic acid (GA), a polyphenolic compound with reported preclinical antifibrotic activities. However, the therapeutic applicability of GA is hampered owing to its low bioavailability and rapid clearance. Accordingly, we developed GA-loaded CNPs. The effect of their size, surface charge and targeting strategies was investigated and optimized, with the aim of enhancing their ability to deliver GA to the activated hepatic stellate cells (aHSCs) in order to suppress hepatic fibrosis progression. Methods Different CNP systems were prepared and characterized with regard to their particle size, zeta potential, and GA entrapment efficiency (EE%). Also, they were statistically optimized via response surface methodology. The optimized systems were investigated with regard to their in vitro GA release, in vitro efficacy on aHSCs, and in vivo biodistribution in healthy rats. Results The GA-loaded cationic CNPs coupled with vitamin A (GA-CACNP/VA; 192 nm) showed high GA EE% (60% w/w), highest cellular internalization via active targeting, and more selective hepatic distribution, relative to free GA solution, GA-loaded anionic, and GA-loaded cationic systems. Furthermore, GA-CACNP/VA markedly triggered the apoptosis of aHSCs, repressed collagen deposition, and inhibited HSCs’ activation to a lesser extent. Conclusion The GA-CACNP/VA was shown to be a promising candidate for specific and controlled delivery of GA to aHSCs, which may provide an effective antifibrotic therapeutic approach.

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Gallic Acid Attenuates Dimethylnitrosamine-Induced Liver Fibrosis by Alteration of Smad Phosphoisoform Signaling in Rats

Cited by 15 publications

References 40 publications

Active Constituent in the Ethyl Acetate Extract Fraction of Terminalia bellirica Fruit Exhibits Antioxidation, Antifibrosis, and Proapoptosis Capabilities In Vitro

Active Constituent in the Ethyl Acetate Extract Fraction of Terminalia bellirica Fruit Exhibits Antioxidation, Antifibrosis, and Proapoptosis Capabilities In Vitro

Antioxidant Activity of Graptopetalum paraguayense E. Walther Leaf Extract Counteracts Oxidative Stress Induced by Ethanol and Carbon Tetrachloride Co-Induced Hepatotoxicity in Rats

<p>Zein/Phospholipid Composite Nanoparticles for Successful Delivery of Gallic Acid into aHSCs: Influence of Size, Surface Charge, and Vitamin A Coupling</p>

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