Apigenin protects mice against 3,5-diethoxycarbonyl-1,4-dihydrocollidine-induced cholestasis

Zheng, Shihong; Cao, Peichang; Yin, Zequn; Wang, Xuerui; Chen, Yuanli; Yu, Maoyun; Xu, Baocai; Liao, Chenzhong; Duan, Yajun; Zhang, Shuang; Han, Jihong; Yang, Xiaoxiao

doi:10.1039/d0fo02910f

Cited by 21 publications

(23 citation statements)

References 43 publications

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“…Cell viability was detected using MTT assay [ 26 ]. After washing with PBS 3 times and incubating in DMSO (150 mL/well) for 15 min, the optical density at a wavelength of 550 nm was read by a microplate reader (BioTek Instruments, Winooski, VT, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Total RNA was extracted and stored at −80 °C; IL-1β and TNF-α mRNA levels were analyzed by qRT-PCR. Similarly, after extraction, total cellular proteins were stored at −20 °C and used to determine iNOS, COX-2, p38, p-p38, JNK, p-JNK, ERK, p-ERK, and SOD1 protein expression by Western blotting as described previously [ 26 ]. To analyze NF-κB translocation, RAW264.7 cells were cultured on coverslips in a 48-well plate.…”

Section: Methodsmentioning

confidence: 99%

“…Liver sections were subjected to DHE staining to determine the ROS levels as described and photographed with a fluorescence microscope (Leica, Wetzlar, Hesse-Darmstadt, German) [ 26 ].…”

Section: Methodsmentioning

confidence: 99%

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Discovery of Novel Pterostilbene Derivatives That Might Treat Sepsis by Attenuating Oxidative Stress and Inflammation through Modulation of MAPKs/NF-κB Signaling Pathways

et al. 2021

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Sepsis remains one of the most common life-threatening illnesses that is characterized by a systemic inflammatory response syndrome (SIRS) and usually arises following severe trauma and various septic infections. It is still in urgent need of new effective therapeutic agents, and chances are great that some candidates can be identified that can attenuate oxidative stress and inflammatory responses. Pterostilbene, which exerts attractive anti-oxidative and anti-inflammatory activities, is a homologue of natural polyphenolic derivative of resveratrol. Starting from it, we have made several rounds of rational optimizations. Firstly, based on the strategy of pharmacophore combination, indanone moiety was introduced onto the pterostilbene skeleton to generate a novel series of pterostilbene derivatives (PIF_1–PIF_16) which could possess both anti-oxidative and anti-inflammatory activities for sepsis treatment. Then, all target compounds were subjected to their structure–activity relationships (SAR) screening of anti-inflammatory activity in mouse mononuclear macrophage RAW264.7 cell line, and their cytotoxicities were determined after. Finally, an optimal compound, PIF_9, was identified. It decreased the mRNA levels of lipopolysaccharide (LPS)-induced interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX2). We also found that the anti-inflammatory effects might be contributed by its suppression on the nuclear factor-κB (NF-κB) and MAPKs signaling pathway. Moreover, PIF_9 also demonstrated potent anti-oxidative activity in RAW264.7 macrophages and the sepsis mouse model. Not surprisingly, with the benefits mentioned above, it ameliorated LPS-induced sepsis in C57BL/6J mice and reduced multi-organ toxicity. Taken together, PIF_9 was identified as a potential sepsis solution, targeting inflammation and oxidative stress through modulating MAPKs/NF-κB.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Discovery of Novel Pterostilbene Derivatives That Might Treat Sepsis by Attenuating Oxidative Stress and Inflammation through Modulation of MAPKs/NF-κB Signaling Pathways

et al. 2021

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“…Cholestasis, which is defined as the impairment of bile flow with the accumulation of toxic bile acids (BAs), is widely known as a common acute liver injury. 1,2 Cholestasis further causes serious issues, including hepatitis, cirrhosis, or even liver failure without proper treatment. 3,4 Cytotoxicity and apoptosis that are induced by toxic hydrophobic BAs are regarded as the major causes of cholestasis.…”

Section: Introductionmentioning

confidence: 99%

Combination of resveratrol and luteolin ameliorates α-naphthylisothiocyanate-induced cholestasis by regulating the bile acid homeostasis and suppressing oxidative stress

Wang

Ran

et al. 2022

Food Funct.

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“…Wang et al [ 14 ] found that Glechoma hederacea could reduce inflammation by down-regulating the expression of NF-κB and reducing the expression of α-SMA and TGF-β to inhibit fibrosis caused by cholestasis. Moreover, apigenin can inhibit DDC-induced cholestasis and fibrosis by reducing inflammation, and down-regulating the expression of TGF-β and α-SMA [ 15 ]. Bile duct transporters also play an important role in bile metabolism, and the expression of bile salt export pump (BSEP) and multidrug resistance-associated protein2 (MRP2) is closely related to the tubular transport of bile acids [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Protective Effect of Rhus chinensis Mill. Fruits on 3,5-Diethoxycarbonyl-1,4-Dihydrocollidine-Induced Cholestasis in Mice via Ameliorating Oxidative Stress and Inflammation

et al. 2022

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This study focused on the preventive effects of the extracts of Rhus chinensis Mill. (RCM) fruits on cholestasis induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) in mice. The results showed that RCM extracts could significantly ameliorate DDC-induced cholestasis via multiple mechanisms, including (1) alleviating liver damage via enhancing antioxidant capacity, such as increasing the contents of glutathione, superoxide dismutase, and catalase and inhibiting the levels of malondialdehyde; (2) preventing liver inflammation by suppressing NF-κB pathway and reducing proinflammatory cytokines secretion (e.g., tumor necrosis factor-α, interleukin-1β, and interleukin-6); (3) inhibiting liver fibrosis and collagen deposition by regulating the expression of transforming growth factor-β and α-smooth muscle actin; (4) modulating abnormal bile acid metabolism through increasing the expression of bile salt export pump and multidrug resistance-associated protein 2. This study was the first to elucidate the potential preventive effect of RCM extracts on DDC-induced cholestasis in mice from multiple pathways, which suggested that RCM fruits could be considered as a potential dietary supplement to prevent cholestasis.

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Apigenin protects mice against 3,5-diethoxycarbonyl-1,4-dihydrocollidine-induced cholestasis

Abstract: Apigenin prevented the DDC-induced abnormal lipid metabolism, liver damage and liver fibrosis by reducing inflammation and oxidative stress. Apigenin might be a potential drug for the treatment of cholestatic liver diseases.

Cited by 21 publications

References 43 publications

Discovery of Novel Pterostilbene Derivatives That Might Treat Sepsis by Attenuating Oxidative Stress and Inflammation through Modulation of MAPKs/NF-κB Signaling Pathways

Discovery of Novel Pterostilbene Derivatives That Might Treat Sepsis by Attenuating Oxidative Stress and Inflammation through Modulation of MAPKs/NF-κB Signaling Pathways

Combination of resveratrol and luteolin ameliorates α-naphthylisothiocyanate-induced cholestasis by regulating the bile acid homeostasis and suppressing oxidative stress

Protective Effect of Rhus chinensis Mill. Fruits on 3,5-Diethoxycarbonyl-1,4-Dihydrocollidine-Induced Cholestasis in Mice via Ameliorating Oxidative Stress and Inflammation

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