Water extract from Herpetospermum pedunculosum attenuates oxidative stress and ferroptosis induced by acetaminophen via regulating Nrf2 and NF-κB pathways

Li, Jintao; Lu, Qiuxia; Peng, Meihao; Liao, Jiaqing; Zhang, Bowen; Yang, Di; Huang, Peng; Yang, Yixi; Zhao, Qi; Han, Bo; Li, Jian

doi:10.1016/j.jep.2022.116069

Cited by 12 publications

(13 citation statements)

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“…4 D, Dataset S4 ). Previous researches have suggested that the most important hepatoprotective compounds in H. pedunculosum are lignans, primarily dehydrodiconiferyl alcohol, herpetrione, herpetin, herpetetrone and herpetotriol [ 9 , 33 ]. Most of these species-specific lignans were found in YM seeds but not in GM seeds (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…The dried ripe seeds of H. pedunculosum ( Herpetospermum caudigerum Wall), with “Se-ji-mei-duo” in Tibet or Chinese name “Bo-Leng-Gua-Zi,” are frequently used for the treatment of “Chiba” diseases caused by liver dysfunction, such as jaundice, hepatitis, cholecystitis [ 1 ]. Modern pharmacological studies have indicated that H. caudigerum contains a variety of bioactive lignans, such as herpetin, herpetfluorenone, and herpetone [ 2 , 3 ], which are mainly responsible for their anti-infammatory [ 1 ], anti-fatigue [ 4 ], anti-hepatitis B virus [ 5 ], anti-cholestatic [ 6 ], and hepatoprotective activities [ 7 – 9 ] ascribed to them. The use of H. pedunculosum in medicine has led to an increasing trend of using this plant as the main ingredient in various medications, such as the “Shi-wei-di-da” capsule, “twenty-five flavors-big soup” pills, and “Jiu-wei-Niu-huang” pills [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…Modern pharmacological studies have indicated that H. caudigerum contains a variety of bioactive lignans, such as herpetin, herpetfluorenone, and herpetone [ 2 , 3 ], which are mainly responsible for their anti-infammatory [ 1 ], anti-fatigue [ 4 ], anti-hepatitis B virus [ 5 ], anti-cholestatic [ 6 ], and hepatoprotective activities [ 7 – 9 ] ascribed to them. The use of H. pedunculosum in medicine has led to an increasing trend of using this plant as the main ingredient in various medications, such as the “Shi-wei-di-da” capsule, “twenty-five flavors-big soup” pills, and “Jiu-wei-Niu-huang” pills [ 9 ]. However, the active ingredients of medicinal plants are generally present at a lower content.…”

Section: Introductionmentioning

confidence: 99%

“…However, the active ingredients of medicinal plants are generally present at a lower content. Recent studies on H. pedunculosum have primarily focused on exploring its active ingredients and pharmacological mechanisms [ 9 – 11 ]. However, the mechanisms involved in lignan biosynthesis and regulation in H. pedunculosum have not yet been elucidated.…”

Section: Introductionmentioning

confidence: 99%

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Integrative analysis of the metabolome and transcriptome provides insights into the mechanisms of lignan biosynthesis in Herpetospermum pedunculosum (Cucurbitaceae)

Zhu,

Chen,

Sun

et al. 2024

BMC Genomics

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Background Herpetospermum pedunculosum (Ser.) C. B. Clarke is a traditional Chinese herbal medicine that heavily relies on the lignans found in its dried ripe seeds (Herpetospermum caudigerum), which have antioxidant and hepatoprotective functions. However, little is known regarding the lignan biosynthesis in H. pedunculosum. In this study, we used metabolomic (non-targeted UHPLC-MS/MS) and transcriptome (RNA-Seq) analyses to identify key metabolites and genes (both structural and regulatory) associated with lignan production during the green mature (GM) and yellow mature (YM) stages of H. pedunculosum. Results The contents of 26 lignan-related metabolites and the expression of 30 genes involved in the lignan pathway differed considerably between the GM and YM stages; most of them were more highly expressed in YM than in GM. UPLC-Q-TOF/MS confirmed that three Herpetospermum-specific lignans (including herpetrione, herpetotriol, and herpetin) were found in YM, but were not detected in GM. In addition, we proposed a lignan biosynthesis pathway for H. pedunculosum based on the fundamental principles of chemistry and biosynthesis. An integrated study of the transcriptome and metabolome identified several transcription factors, including HpGAF1, HpHSFB3, and HpWOX1, that were highly correlated with the metabolism of lignan compounds during seed ripening. Furthermore, functional validation assays revealed that the enzyme 4-Coumarate: CoA ligase (4CL) catalyzes the synthesis of hydroxycinnamate CoA esters. Conclusion These results will deepen our understanding of seed lignan biosynthesis and establish a theoretical basis for molecular breeding of H. pedunculosum.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Integrative analysis of the metabolome and transcriptome provides insights into the mechanisms of lignan biosynthesis in Herpetospermum pedunculosum (Cucurbitaceae)

Zhu,

Chen,

Sun

et al. 2024

BMC Genomics

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“…Through the Fenton reaction, cytosolic iron overload can result in toxic ROS production, which may exacerbate the oxidative stress-induced damage caused by APAP 12,53 . The metallothionein, SLC7A11, is part of System Xc -; therefore, inhibiting its expression can reduce the GSH activity.…”

Section: Discussionmentioning

confidence: 99%

GAS1 Promotes Ferroptosis of Liver Cells in Acetaminophen-Induced Acute Liver Failure

Tao,

Xue,

Wang

et al. 2023

Int. J. Med. Sci.

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Purpose: Acute liver failure (ALF) is a clinically fatal disease that leads to the rapid loss of normal liver function. Acetaminophen (APAP) is a leading cause of drug-induced ALF. Ferroptosis, defined as iron-dependent cell death associated with lipid peroxide accumulation, has been shown to be strongly associated with APAP-induced liver injury. Growth arrest-specific 1 (GAS1) is a growth arrest-specific gene, which is closely related to the inhibition of cell growth and promotion of apoptosis. However, the functional role and underlying mechanism of GAS1 in APAP-induced ferroptosis remain unknown. Methods: We established liver-specific overexpression of GAS1 (GAS1 AAV8-OE) mice and the control (GAS1 ) mice by tail vein injection of male mice with adeno-associated virus. APAP at 500 mg/kg was intraperitoneally injected into these two groups of mice to induce acute liver failure. The shRNA packaged by the lentivirus inhibits GAS1 gene expression in human hepatoma cell line HepaRG (HepaRG-shNC and HepaRG-shGAS1-2) and primary hepatocytes of mice with liver-specific overexpression of GAS1 were isolated and induced by APAP in vitro to further investigate the regulatory role of GAS1 in APAP-induced acute liver failure. Results: APAP-induced upregulation of ferroptosis, levels of lipid peroxides and reactive oxygen species, and depletion of glutathione were effectively alleviated by the ferroptosis inhibitor, ferrostatin-1, and downregulation of GAS1 expression. GAS1 overexpression promoted ferroptosis-induced lipid peroxide accumulation via p53, inhibiting its downstream target, solute carrier family 7 member 11. Conclusion: Collectively, our findings suggest that GAS1 overexpression plays a key role in aggravating APAP-induced acute liver injury by promoting ferroptosis-induced accumulation of lipid peroxides.

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Chronic hypoxia drives the occurrence of ferroptosis in liver of fat greening (Hexagrammos otakii) by activating HIF-1α and promoting iron production

Gao,

Wu,

Zhan

et al. 2024

Ecotoxicology and Environmental Safety

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Water extract from Herpetospermum pedunculosum attenuates oxidative stress and ferroptosis induced by acetaminophen via regulating Nrf2 and NF-κB pathways

Cited by 12 publications

References 54 publications

Integrative analysis of the metabolome and transcriptome provides insights into the mechanisms of lignan biosynthesis in Herpetospermum pedunculosum (Cucurbitaceae)

Integrative analysis of the metabolome and transcriptome provides insights into the mechanisms of lignan biosynthesis in Herpetospermum pedunculosum (Cucurbitaceae)

GAS1 Promotes Ferroptosis of Liver Cells in Acetaminophen-Induced Acute Liver Failure

Chronic hypoxia drives the occurrence of ferroptosis in liver of fat greening (Hexagrammos otakii) by activating HIF-1α and promoting iron production

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