Tetrahydrocurcumin and octahydrocurcumin, the primary and final hydrogenated metabolites of curcumin, possess superior hepatic-protective effect against acetaminophen-induced liver injury: Role of CYP2E1 and Keap1-Nrf2 pathway

Luo, Dandan; Chen, Jinfen; Liu, Jingjing; Xie, Jianhui; Zhang, Zhenbiao; Gu, Jiangyong; Zhuo, Jian-Yi; Huang, Song; Su, Zi‐Ren; Sun, Zhang‐Hua

doi:10.1016/j.fct.2018.11.012

Cited by 65 publications

(60 citation statements)

References 35 publications

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“…Similar to the results of the current study, metabolites of curcumin, including tetrahydrocurcumin and octahydrocurcumin, greatly enhance the translation of Nrf2 to the target gene HO-1 by activating the Keap1-Nrf2 pathway and inhibiting expression of CYP2E1. is indicates that curcumin has excellent liver protective and antioxidant e ects [34]. erefore, we conclude that QGD may also show hepatoprotective e ects by activating the Nrf2-Keap1 signaling pathway and inhibiting CYP2E1.…”

Section: Evidence-based Complementary and Alternative Medicinementioning

confidence: 66%

CCl₄-Induced Liver Injury Was Ameliorated by Qi-Ge Decoction through the Antioxidant Pathway

Peng

Zhou

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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Qi-Ge decoction (QGD), which is derived from the Huangqi Gegen decoction, contains three traditional Chinese herbs: Astragalus membranaceus (Huangqi), Pueraria lobata (Gegen), and Citri Reticulatae Blanco Pericarpium (Chenpi). Gastric mucosal damage caused by ethanol was prevented and alleviated by QGD. However, the role of QGD in protecting the liver from toxins has not been reported. High-performance liquid chromatography with diode-array detection was used to qualitatively analyze QGD. Positive control (silymarin 100 mg/kg/day), QGD (20, 10, or 5 g/kg/day), and Nrf2 inhibitor brusatol (0.4 mg/kg/2 d) were administered to rats for 7 days, and then, liver injury was induced by injecting 2 mL/kg 25% CCl4. After 24 h, blood and liver were collected for analysis and evaluation. QGD was found to contain 12 main components including calycosin, puerarin, and hesperidin. QGD treatment significantly reduced liver damage and decreased serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase activities. QGD increased superoxide dismutase and catalase activities, and glutathione levels, but decreased malondialdehyde levels in livers from CCl4-treated rats. Compared to rats treated with CCl4 alone, after QGD administration, mRNA and protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 were increased, while those of Kelch-like ECH-related protein 1 (Keap1) and cytochrome P450 (CYP)2E1 were decreased. However, these improvements in QGD were reversed by brusatol. In conclusion, QGD can achieve its hepatoprotective effect through an antioxidant mechanism by activating the Nrf2 pathway.

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Section: Evidence-based Complementary and Alternative Medicinementioning

confidence: 66%

CCl₄-Induced Liver Injury Was Ameliorated by Qi-Ge Decoction through the Antioxidant Pathway

Peng

Zhou

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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“…Inclusion of curcumin at both steps demonstrated increased yield, better morphology and integrity, enhanced basal and stimulated insulin secretion, as well as induction of Hsp70 and HO-1 [68]. While the study did not directly discuss the activation of Nrf2/Keap1, we infer its role given that curcumin is metabolized into THC, a confirmed activator [65].…”

Section: Preservation: Dynamic Temperature Stress On Islet Cellsmentioning

confidence: 87%

“…They found that THC-treated cells had 1.3-fold greater glucose sensitivity and produced B-cell lymphoma 2 (BCL2) (antiapoptotic) along with protective caspase proteins [64]. Although at the time of the study it was established that THC increased glutathione (GSH) (a low molecular weight antioxidant), Luo et al have recently demonstrated that this occurs specifically through the Nrf2/Keap1 pathway [65]. THC causes Nrf2 to translocate into the nucleus, and induce glutamate cysteine ligase (GCL), which is a key determinant of GSH synthesis [66].…”

Section: Isolation: Metabolic Challengesmentioning

confidence: 99%

Potential Benefits of Nrf2/Keap1 Targeting in Pancreatic Islet Cell Transplantation

López

Lau

et al. 2020

Antioxidants

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Permanent pancreatic islet cell destruction occurs in type 1 diabetes mellitus (T1DM) through the infiltration of inflammatory cells and cytokines. Loss of β-cell integrity secondary to oxidation leads to an inability to appropriately synthesize and secrete insulin. Allogenic islet cell transplantation (ICT) has risen as a therapeutic option to mitigate problematic hypoglycemia. Nevertheless, during the process of transplantation, islet cells are exposed to oxidatively caustic conditions that severely decrease the islet cell yield. Islet cells are at a baseline disadvantage to sustain themselves during times of metabolic stress as they lack a robust anti-oxidant defense system, glycogen stores, and vascularity. The Nrf2/Keap1 system is a master regulator of antioxidant genes that has garnered attention as pharmacologic activators have shown a protective response and a low side effect profile. Herein, we present the most recently studied Nrf2/Keap1 activators in pancreas for application in ICT: Dh404, dimethyl fumarate (DMF), and epigallocatechin gallate (EGCG). Furthermore, we discuss that Nrf2/Keap1 is a potential target to ameliorate oxidative stress at every step of the Edmonton Protocol.

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“…THC possessed better hepatoprotective effects and antioxidant activities in case of liver injury than the parent compound curcumin. The activity was mediated via inhibition of CYP2E1 and activation of the Keap1-Nrf2 anti-oxidation pathway [ 58 ]. In one of the studies, THC found to be the most potent compound in vitro in arachidonic acid-induced blood platelet aggregation when compared with curcumin, bisdemethoxycurcumin, and demethoxycurcumin [ 59 ].…”

Section: Functions Of Reduced Metabolites Of Curcuminmentioning

confidence: 99%

Reductive metabolites of curcumin and their therapeutic effects

Pandey

Chaturvedi

Mishra

et al. 2020

Heliyon

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Tetrahydrocurcumin and octahydrocurcumin, the primary and final hydrogenated metabolites of curcumin, possess superior hepatic-protective effect against acetaminophen-induced liver injury: Role of CYP2E1 and Keap1-Nrf2 pathway

Cited by 65 publications

References 35 publications

CCl₄-Induced Liver Injury Was Ameliorated by Qi-Ge Decoction through the Antioxidant Pathway

CCl₄-Induced Liver Injury Was Ameliorated by Qi-Ge Decoction through the Antioxidant Pathway

Potential Benefits of Nrf2/Keap1 Targeting in Pancreatic Islet Cell Transplantation

Reductive metabolites of curcumin and their therapeutic effects

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Tetrahydrocurcumin and octahydrocurcumin, the primary and final hydrogenated metabolites of curcumin, possess superior hepatic-protective effect against acetaminophen-induced liver injury: Role of CYP2E1 and Keap1-Nrf2 pathway

Cited by 65 publications

References 35 publications

CCl4-Induced Liver Injury Was Ameliorated by Qi-Ge Decoction through the Antioxidant Pathway

CCl4-Induced Liver Injury Was Ameliorated by Qi-Ge Decoction through the Antioxidant Pathway

Potential Benefits of Nrf2/Keap1 Targeting in Pancreatic Islet Cell Transplantation

Reductive metabolites of curcumin and their therapeutic effects

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Product

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CCl₄-Induced Liver Injury Was Ameliorated by Qi-Ge Decoction through the Antioxidant Pathway

CCl₄-Induced Liver Injury Was Ameliorated by Qi-Ge Decoction through the Antioxidant Pathway