Protective effects of trans-2,3,5,4′-tetrahydroxystilbene 2-O-β-<scp>d</scp>-glucopyranoside on liver fibrosis and renal injury induced by CCl4via down-regulating p-ERK1/2 and p-Smad1/2

Long, Tao; Wang, Liwen; Yang, Yiwen; Li, Yuan; Zhao, Hui; Chang, Chia‐Che; Yang, Guliang; Ho, Chi‐Tang; Li, Shiming

doi:10.1039/c9fo01010f

Cited by 22 publications

(14 citation statements)

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“…The MEK/ERK pathway participates in the regulation of liver injury [ 27 , 28 ] by modulating both cell apoptosis [ 29 ] and autophagy [ 31 ], and interestingly, researchers notice that ASP regulates the MEK/ERK pathway in osteoarthritis chondrocytes [ 26 ], which were validated by our data that DB inactivated the MEK/ERK pathway in the chondrocytes, which were reactivated by co-treating cells with ASP, suggesting that ASP activated the MEK/ERK pathway in DB-treated hepatocytes. In addition, based on the published data [ 26 ], we evidenced that ASP promoted cell autophagy in DB-treated hepatocytes by activating the MEK/ERK pathway.…”

Section: Discussionmentioning

confidence: 99%

“…The MEK/ERK signaling pathway is closely associated with liver injury [ 27 , 28 ], which involves in regulating both cell apoptosis [ 29 , 30 ] and autophagy [ 31 ]. For example, Fu et al find that activation of the MEK/ERK pathway ameliorates hypoxic/ischemic-induced bone mesenchymal stem cell apoptosis [ 29 ], and Wang et al evidence that MEK/ERK-induced autophagy contributes to cell survival in IPEC-J2 cells with Ochratoxin A exposure [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

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Angelica sinensis polysaccharide (ASP) attenuates diosbulbin-B (DB)-induced hepatotoxicity through activating the MEK/ERK pathway

Liu

Zheng

et al. 2021

Bioengineered

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Diosbulbin-B (DB) is a promising therapeutic drug for cancer treatment; however, DB-induced hepatotoxicity seriously limits its clinical utilization. Based on this, the present study investigated whether the Angelica sinensis extract, angelica sinensis polysaccharide (ASP), was effective to attenuate DB-induced cytotoxicity in hepatocytes. The primary hepatocytes were isolated from rats and cultured in vitro, which were subsequently treated with high-dose DB (100 μM) and ASP (12 μg/ml) to establish the DB-induced hepatotoxicity models. MTT assay and flow cytometry (FCM) were performed to evaluate cell viability, and the results showed that high-dose DBinduced cell apoptosis and inhibition of proliferation were reversed by co-treating cells with ASP, which were supported by our Western Blot assay data that ASP upregulated Cyclin D1 and CDK2 to abrogate high-dose DB-induced cell cycle arrest. In addition, ASP exerted its regulating effects on cell autophagy, and we found that ASP increased LC3B-II/I ratio and Atg5, but decreased p62 to activate the autophagy flux. Of note, the MEK/ERK pathway could be activated by ASP in the DB-treated hepatocytes, and the protective effects of ASP on high-dose DB-induced hepatocyte death were abolished by co-treating cells with the autophagy inhibitor (3-methyladenine, 3-MA) and MEK/ERK selective inhibitor (SCH772984). Moreover, blockage of the MEK/ERK pathway suppressed cell autophagy in the hepatocytes co-treated with ASP and high-dose DB. Taken together, this in vitro study illustrated that ASP activated the MEK/ERK pathway mediated autophagy to suppress high-dose DB-induced hepatotoxicity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Angelica sinensis polysaccharide (ASP) attenuates diosbulbin-B (DB)-induced hepatotoxicity through activating the MEK/ERK pathway

Liu

Zheng

et al. 2021

Bioengineered

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“…Detailed materials and methods used herein are provided in Supplementary Material 1, unless otherwise indicated below. RES and its analogues PTE, oxyresveratrol (ORES), acetyl- trans -resveratrol (ARES), and trans -2,3,5,4′-tetrahydroxystilbene-2- O -glucoside (TSG) (Figure ) were obtained as previously described. , Mouse BV-2 microglial cells (China Center for Type Culture Collection, Wuhan, China) were maintained at 37 °C and a 5% CO 2 atmosphere in Dulbecco’s modified Eagle’s medium (DMEM) added with 10% fetal bovine serum (FBS) and 1% streptomycin–penicillin.…”

Section: Methodsmentioning

confidence: 99%

Effects of Selected Resveratrol Analogues on Activation and Polarization of Lipopolysaccharide-Stimulated BV-2 Microglial Cells

Wang

Zhao

Wang

et al. 2020

J. Agric. Food Chem.

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Increasing health-promoting effects of resveratrol and its molecular structural analogues have been discovered, and the acting mechanism has been explored. However, the activity comparison of such compounds in targeting macrophage-related inflammation associated with neurodegenerative diseases remains untouched. In this study, we evaluated the activation and polarization transition of lipopolysaccharide (LPS)-stimulated BV-2 mouse microglial macrophages exposed to resveratrol (RES) and its analogues pterostilbene (PTE), oxyresveratrol (ORES), acetyl-trans-resveratrol (ARES), and trans-2,3,5,4′-tetrahydroxystilbene-2-O-glucopyranoside (TSG). At 10 μM, all of the five stilbene compounds have effectively suppressed the LPS-stimulated BV-2 cell release of proinflammatory mediators such as NO, TNF-α, iNOS, IL-1β, and IL-6. Mechanism study elucidated that they exert anti-inflammatory effects through MAPKs (ERK1/2, JNK, and p38) and NF-κB signaling pathways. Further investigation in treating BV-2 cells with resveratrol and its analogues revealed the reversal of LPS-induced phenotype molecules from M1 (iNOS, IL-1β, IL-6, and CD86) to M2 (Arg1, CD163, and IL-10) subtypes, manifesting that these five stilbenes suppressed inflammation through modulating the polarized phenotypes of BV-2 microglia. Most importantly, PTE demonstrated the most potent inhibitory activity among these five stilbene compounds. Therefore, this study not only highlights microglia-induced inflammatory responses as a potential therapeutic target but also suggests future insights in considering the options of nutraceutical development for resveratrol and its analogues.

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“…MMPs are involved in the degradation of the extracellular matrix, as well as the processing of growth factors, cytokines, chemokines, adhesion molecules, and several other enzymes [ 30 , 31 ]. Several studies have shown that MMP2 and MMP9 are associated with liver fibrosis and that trans-THSG impeded fibrosis-associated extracellular matrix remodeling by inhibiting the transcription of MMP2 and MMP9 [ 32 , 33 ]. In our study, immunoblotting and IHC for MMP2 and MMP9 was used to investigate hyperlipidemia-induced fibrosis in renal tissue.…”

Section: Discussionmentioning

confidence: 99%

Effect of Thymoquinone on Renal Damage Induced by Hyperlipidemia in LDL Receptor-Deficient (LDL-R-/-) Mice

Zhang

et al. 2022

BioMed Research International

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Hyperlipidemia is a well-established risk factor for kidney injury, which can lead to chronic kidney disease (CKD). Thymoquinone (TQ) is one of the most active ingredients in Nigella sativa seeds. It has various beneficial properties, including antioxidant and anti-inflammatory activities. TQ also exerts positive effects on doxorubicin- (DOX-) induced nephropathy and ischemia-reperfusion-induced kidney injury in rats. Therefore, in this study, we investigated the possible protective effects of TQ against kidney injury in low-density lipoprotein receptor-deficient (LDL-R-/-) mice. Eight-week-old male LDL-R-/- mice were randomly divided into the following three groups: normal diet (ND group), high-fat diet (HFD group), and HFD combined with TQ (HFD+TQ group). The mice were fed the same diet for eight weeks. After eight weeks, we performed serological analysis of the mice in all three groups. We histologically analyzed the kidney tissue and also investigated the expression of proinflammatory cytokines in the kidney tissue. Metabolic characteristics, including total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and creatinine (CRE) levels, were lower in the LDL-R-/- HFD+TQ mice than in the HFD mice. Periodic acid-Schiff (PAS) and Masson’s trichrome staining revealed excessive lipid deposition and collagen accumulation in the kidneys of the LDL-R-/- HFD mice, which were significantly reduced in the LDL-R-/- HFD+TQ mice. Furthermore, macrophages and levels of proinflammatory cytokines were lower in the kidney tissues of the LDL-R-/- HFD+TQ mice than in those of the LDL-R-/- HFD mice. Moreover, profibrosis- and oxidative stress-related protein expression was lower in the kidney tissues of the LDL-R-/- HFD+TQ mice than in those of the LDL-R-/- HFD mice. These results indicate that TQ may be a potential therapeutic agent for kidney damage caused by hyperlipidemia.

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Protective effects of trans-2,3,5,4′-tetrahydroxystilbene 2-O-β-d-glucopyranoside on liver fibrosis and renal injury induced by CCl₄via down-regulating p-ERK1/2 and p-Smad1/2

Abstract: Both as a food and an herbal plant, Polygonum multiflorum (PM) has long been used in food and prescriptions for several centuries in Southeast Asia.

Cited by 22 publications

References 28 publications

Angelica sinensis polysaccharide (ASP) attenuates diosbulbin-B (DB)-induced hepatotoxicity through activating the MEK/ERK pathway

Angelica sinensis polysaccharide (ASP) attenuates diosbulbin-B (DB)-induced hepatotoxicity through activating the MEK/ERK pathway

Effects of Selected Resveratrol Analogues on Activation and Polarization of Lipopolysaccharide-Stimulated BV-2 Microglial Cells

Effect of Thymoquinone on Renal Damage Induced by Hyperlipidemia in LDL Receptor-Deficient (LDL-R-/-) Mice

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Protective effects of trans-2,3,5,4′-tetrahydroxystilbene 2-O-β-d-glucopyranoside on liver fibrosis and renal injury induced by CCl4via down-regulating p-ERK1/2 and p-Smad1/2

Abstract: Both as a food and an herbal plant, Polygonum multiflorum (PM) has long been used in food and prescriptions for several centuries in Southeast Asia.

Cited by 22 publications

References 28 publications

Angelica sinensis polysaccharide (ASP) attenuates diosbulbin-B (DB)-induced hepatotoxicity through activating the MEK/ERK pathway

Angelica sinensis polysaccharide (ASP) attenuates diosbulbin-B (DB)-induced hepatotoxicity through activating the MEK/ERK pathway

Effects of Selected Resveratrol Analogues on Activation and Polarization of Lipopolysaccharide-Stimulated BV-2 Microglial Cells

Effect of Thymoquinone on Renal Damage Induced by Hyperlipidemia in LDL Receptor-Deficient (LDL-R-/-) Mice

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Protective effects of trans-2,3,5,4′-tetrahydroxystilbene 2-O-β-d-glucopyranoside on liver fibrosis and renal injury induced by CCl₄via down-regulating p-ERK1/2 and p-Smad1/2