Aucubin Attenuates Liver Ischemia-Reperfusion Injury by Inhibiting the HMGB1/TLR-4/NF-κB Signaling Pathway, Oxidative Stress, and Apoptosis

Zhang, Shilong; Feng, Zanjie; Gao, Weidong; Duan, Yuling; Fan, Guoxin; Geng, Xin; Wu, Bo; Li, Kai; Liu, Kangwei; Peng, Cijun

doi:10.3389/fphar.2020.544124

Cited by 43 publications

(37 citation statements)

References 57 publications

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“…UCP2 is found in the mitochondria and functions by controlling ROS in lipid metabolism. Actually, the physiological function of UCP2 is still controversial and, for example, one study showed protective effects of UCP2 induction after liver ischemiareperfusion injury in obese mice [30]. However, several studies using the same animal model as in our study pointed out increases in UCP2 expression in obese subjects or in animals with a metabolic disorder in response to a high-fat diet [31,32].…”

Section: Discussionmentioning

confidence: 57%

Protective Effects of Sesamol against Liver Oxidative Stress and Inflammation in High-Fat Diet-Induced Hepatic Steatosis

Zheng

Song

et al. 2021

Nutrients

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Chronic high-fat diet (HFD) is associated with the onset and progression of hepatic steatosis, and oxidative stress is highly involved in this process. The potential role of sesamol (SEM) against oxidative stress and inflammation at the transcriptional level in a mice model of hepatic steatosis is not known. In this study, we aimed to investigate the scavenging effects of SEM towards reactive oxygen generated by lipid accumulation in the liver of obese mice and to explore the mechanisms of protection. Markers of oxidative stress, vital enzymes involved in stimulating oxidative stress or inflammation, and nuclear transcription of Nrf2 were examined. Our results showed that SEM significantly inhibited the activity of the HFD-induced hepatic enzymes CYP2E1 and NOX2, associated with oxidative stress generation. Additionally, SEM reversed HFD-induced activation of NF-κB, a redox-sensitive transcription factor, and attenuated the expression of hepatic TNF-α, a proinflammatory molecule. Moreover, SEM enhanced HFD-induced hepatic Nrf2 nuclear transcription and increased the levels of its downstream target genes Ho1 and Nqo1, which indicated antiinflammation and antioxidant properties. Our study suggests that chronic HFD led to hepatic steatosis, while SEM exhibited protective effects on the liver by counteracting the oxidative stress and inflammation induced by HFD. The underlying mechanism might involve multiple pathways at the transcriptional level; the antioxidant defense mechanism was in partly mediated by the upregulation of Nrf2.

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Section: Discussionmentioning

confidence: 57%

Protective Effects of Sesamol against Liver Oxidative Stress and Inflammation in High-Fat Diet-Induced Hepatic Steatosis

Zheng

Song

et al. 2021

Nutrients

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“…As a common complication in liver resection and transplantation, IRI has been associated with diverse and complex mechanisms, such as activation of TLRs and the innate immune response [ 21 , 33 ]. Recently, some studies have confirmed the critical role of the gut flora in hepatic IRI [ 7 – 9 ].…”

Section: Discussionmentioning

confidence: 99%

Antibiotic pretreatment attenuates liver ischemia–reperfusion injury by Farnesoid X receptor activation

et al. 2022

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Prophylactic antibiotics (Abx) are used before liver surgery, and the influence of antibiotic pretreatment on hepatic ischemia–reperfusion injury (IRI) remains unclear. Hence, we explored the impact of Abx pretreatment on hepatic IRI in the present work. The gut microbiota has an essential role in hepatic bile acid (BA) metabolism, and we assumed that depletion of the gut microbiota could affect the composition of hepatic BAs and affect liver IRI. The IRI model demonstrated that Abx pretreatment attenuated liver IRI by alleviating cell apoptosis, reducing the inflammatory response, and decreasing the recruitment of CCR2+ monocytes. Mechanistically, Abx pretreatment reshaped the gut microbiota, especially decreasing the relative abundance of Firmicutes and increasing the relative abundance of Clostridium, which were related to the transformation of BAs and were consistent with the altered bile acid species (unconjugated BAs, especially UDCA). These altered BAs are known FXR agonists and lead to the activation of the farnesoid X receptor (FXR), which can directly bind to the FXR response element (FXRE) harbored in the TLR4 promoter and further suppress downstream mitogen-activated protein kinase (MAPK) and nuclear kappa B (NF-κB) pathways. Meanwhile, the CCL2–CCR2 axis was also involved in the process of FXR activation, as we confirmed both in vivo and in vitro. Importantly, we proved the importance of FXR in mice and clinical occlusion samples, which were inversely correlated with liver injury. Taken together, our study identified that Abx pretreatment before liver resection was a beneficial event by activating FXR, which might become a potential therapeutic target in treating liver injury.

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“…As reported by these authors, most of these nonvolatile glycoside compounds exhibit numerous therapeutic properties. As shown by Zhang et al [ 130 ], aucubin has anti-inflammatory, antioxidative, and antiapoptotic properties and is able to reduce the degree of liver ischemia–reperfusion injury significantly. In turn, the results reported by Zhou et al [ 131 ] indicate an inhibitory effect of aucubin on the proliferation and differentiation of fibroblasts, thereby providing protection against pulmonary fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Histochemical and Phytochemical Analysis of Lamium album subsp. album L. Corolla: Essential Oil, Triterpenes, and Iridoids

et al. 2021

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The aim of this study was to conduct a histochemical analysis to localize lipids, terpenes, essential oil, and iridoids in the trichomes of the L. album subsp. album corolla. Morphometric examinations of individual trichome types were performed. Light and scanning electron microscopy techniques were used to show the micromorphology and localization of lipophilic compounds and iridoids in secretory trichomes with the use of histochemical tests. Additionally, the content of essential oil and its components were determined using gas chromatography-mass spectrometry (GC-MS). Qualitative analyses of triterpenes carried out using high-performance thin-layer chromatography (HPTLC) coupled with densitometric detection, and the iridoid content expressed as aucubin was examined with spectrophotometric techniques. We showed the presence of iridoids and different lipophilic compounds in papillae and glandular and non-glandular trichomes. On average, the flowers of L. album subsp. album yielded 0.04 mL/kg of essential oil, which was dominated by aldehydes, sesquiterpenes, and alkanes. The extract of the L. album subsp. album corolla contained 1.5 × 10−3 ± 4.3 × 10−4 mg/mL of iridoid aucubin and three triterpenes: oleanolic acid, β-amyrin, and β-amyrin acetate. Aucubin and β-amyrin acetate were detected for the first time. We suggest the use of L. album subsp. album flowers as supplements in human nutrition.

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Aucubin Attenuates Liver Ischemia-Reperfusion Injury by Inhibiting the HMGB1/TLR-4/NF-κB Signaling Pathway, Oxidative Stress, and Apoptosis

Cited by 43 publications

References 57 publications

Protective Effects of Sesamol against Liver Oxidative Stress and Inflammation in High-Fat Diet-Induced Hepatic Steatosis

Protective Effects of Sesamol against Liver Oxidative Stress and Inflammation in High-Fat Diet-Induced Hepatic Steatosis

Antibiotic pretreatment attenuates liver ischemia–reperfusion injury by Farnesoid X receptor activation

Histochemical and Phytochemical Analysis of Lamium album subsp. album L. Corolla: Essential Oil, Triterpenes, and Iridoids

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