Acetaminophen-induced liver injury: Molecular mechanism and treatments from natural products

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: March 27, 2023

Acetaminophen (APAP) is a widely used analgesic and antipyretic over-the-counter medicine worldwide. Hepatotoxicity caused by APAP overdose one of the leading causes acute liver failure (ALF) in US some parts Europe, limiting its clinical application. Excessive metabolism depletes glutathione increases N-acetyl-p-benzoquinoneimide (NAPQI) levels, to oxidative stress, DNA damage, cell necrosis liver, which turn leads damage. Studies have shown that natural products such as polyphenols, terpenes, anthraquinones, sulforaphane can activate hepatocyte antioxidant defense system with Nrf2 core player, reduce stress protect liver. As key enzyme metabolizing into NAPQI, cytochrome P450 enzymes are also considered be intriguing target for treatment APAP-induced injury. Here, we systematically review hepatoprotective activity molecular mechanisms found counteract hepatotoxicity APAP, providing reference information future preclinical trials products.

Language: Английский

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The Antioxidant Action of Astragali radix: Its Active Components and Molecular Basis

Molecules, Journal Year: 2024, Volume and Issue: 29(8), P. 1691 - 1691

Published: April 9, 2024

Astragali radix is a traditional medicinal herb with long history and wide application. It frequently used in prescriptions other materials to replenish Qi. According the classics of Chinese medicine, attributed properties such as Qi replenishing surface solidifying, sore healing muscle generating, inducing diuresis reduce edema. Modern pharmacological studies have demonstrated that some extracts active ingredients function antioxidants. The polysaccharides, saponins, flavonoids offer beneficial effects preventing controlling diseases caused by oxidative stress. However, there still lack comprehensive research on effective components molecular mechanisms through which exerts antioxidant activity. In this paper, we review radix; summarize content, bioavailability, mechanisms; reference for clinical application Astragalus future development novel

Language: Английский

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Protection Against Drug-Induced Liver Injuries Through Nutraceuticals via Amelioration of Nrf-2 Signaling

Journal of the American Nutrition Association, Journal Year: 2022, Volume and Issue: 42(5), P. 495 - 515

Published: June 30, 2022

Hepatotoxicity caused by the overdose of various medications is a leading cause drug-induced liver injury. Overdose drugs causes hepatocellular necrosis. Nutraceuticals are reported to prevent failure. The present article aims review protection provided medicinal plants against hepatotoxic drugs. Ayurveda considered conventional restorative arrangement in India. It consistently used for ages and still today cure hepatotoxicity focusing on antioxidant stress response pathways such as nuclear factor erythroid-2 (Nrf-2) element signaling pathway. Nrf-2 key transcription that entangles Kelch-like ECH-associating protein 1, found cell cytoplasm. Some enzymes, gamma glycine cysteine ligase (γ-GCL) heme oxygenase-1 (HO-1), expressed targeted genes. Their expression, turn, decreases stimulation hepatic macrophages induces messenger RNA (mRNA) articulation proinflammatory factors including tumor necrosis α. This will cover from mechanistic view how they stimulate interact with Nrf-2, master regulator counterbalance oxidative stress. Interestingly, therapeutic have become popular medical sector due safer yet effective supplementation prevention treatment new human diseases. contemporary study expected collect information variety traditional herbs been studied context toxicity, nutraceuticals most treatments stress-induced hepatotoxicity. They less genotoxic, lower cost, readily available. Together, exert protective effects through inhibition stress, inflammation, apoptosis. Its mechanism(s) be associated γ-GCL/HO-1 pathways.KEY TEACHING POINTSThe significant vital organ carries out metabolic activities body synthesis glycogen, formation triglycerides cholesterol, well bile.Acute failure consumption certain drugs; injury major condition.The chemopreventive activity may related reduction attenuation biosynthetic processes involved via amelioration pathway.Nrf-2 cytoplasm resulting expression genes oxygenase-1.Nutraceutical-rich phytochemicals possess high activity, which helps

Language: Английский

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Human diet‐derived polyphenolic compounds and hepatic diseases: From therapeutic mechanisms to clinical utilization

Phytotherapy Research, Journal Year: 2023, Volume and Issue: 38(1), P. 280 - 304

Published: Oct. 23, 2023

Abstract This review focuses on the potential ameliorative effects of polyphenolic compounds derived from human diet hepatic diseases. It discusses molecular mechanisms and recent advancements in clinical applications. Edible polyphenols have been found to play a therapeutic role, particularly liver injury, fibrosis, NAFLD/NASH, HCC. In regulation exhibit anti‐inflammatory antioxidant effects, primarily targeting TGF‐β, NF‐κB/TLR4, PI3K/AKT, Nrf2/HO‐1 signaling pathways. effectively reverse fibrotic process by inhibiting activation stellate cells (HSC). Furthermore, show efficacy against NAFLD/NASH lipid oxidation accumulation, mediated through AMPK, SIRT, PPARγ Moreover, several anti‐HCC activity suppressing tumor cell proliferation metastasis. inhibition involves blocking Akt Wnt signaling, as well epithelial‐mesenchymal transition (EMT). Additionally, trials nutritional evidence support notion that certain can improve disease associated metabolic disorders. However, further fundamental research are warranted validate dietary polyphenols.

Language: Английский

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Kaempferol sophoroside glucoside mitigates acetaminophen-induced hepatotoxicity: Role of Nrf2/NF-κB and JNK/ASK-1 signaling pathways

Heliyon, Journal Year: 2024, Volume and Issue: 10(10), P. e31448 - e31448

Published: May 1, 2024

APAP (Acetaminophen)-induced hepatic injury is a major public health threat that requires continuous searching for new effective therapeutics. KSG (Kaempferol-3-sophoroside-7-glucoside) kaempferol derivative was separated from plant species belonging to different genera. This study explored the protective effects of on ALI (acute liver injury) caused by overdose in mice and elucidated its possible mechanisms. The results showed pretreatment alleviated APAP-induced damage as it reduced pathological lesions well serum parameters injury. Moreover, opposed APAP-associated oxidative stress augmented antioxidants. suppressed inflammatory response decreased genetic protein expression levels cytokines. Meanwhile, enhanced mRNA level anti-inflammatory cytokine, IL-10 (interleukin-10). repressed activation NF-κB (nuclear-factor kappa-B), besides promoted Nrf2 signaling. Additionally, markedly hindered elevation ASK-1 (apoptosis-signal regulating-kinase-1) JNK (c-Jun-N-terminal kinase). Furthermore, apoptosis Bax (BCL2-associated X-protein), caspase-3 concurrent with an enhancement anti-apoptotic protein, Bcl2 liver. More thoroughly, Computational studies reveal indispensable binding affinities between Keap1 (Kelch-like ECH-associated protein-1), ASK1 (apoptosis signal-regulating kinase-1), JNK1 (c-Jun N-terminal kinase-1) distinctive tendencies selective inhibition. Taken together, our data hepatoprotective capacity against APAP-produced via modulation Nrf2/NF-κB JNK/ASK-1/caspase-3 Henceforth, could be promising candidate ALI.

Language: Английский

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Multiple Enzymes Expressed by the Gut Microbiota Can Transform Typhaneoside and Are Associated with Improving Hyperlipidemia

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Abstract The mechanism of multiple enzymes mediated drug metabolism in gut microbiota is still unclear. This study explores enzyme interaction process typhactyloside (TYP) with and its lipid‐lowering pharmacological activity. TYP, bioavailability only 2.78%, an active component Typha angustifolia L . Pushen capsules which clinically treated for hyperlipidemia. metabolic TYP identified, key involved are validated through gene knockout overexpression techniques. Through overexpressing α‐rhamnosidase (Rha) Escherichia coli , verified to metabolize into isorhamnetin‐3‐ O ‐neohesperidin (M1) ‐glucoside (M2) after removing rhamnose Rha. Besides, β‐glucosidase (Glu) confirms that generates M3 Glu glucose. Combined molecular docking, transformed generate 3,4‐dihydroxyphenylacetic acid (M4), protocatechuic (M5), 3‐hydroxyphenylacetic (M6) flavonoid reductase (Flr) chalcone isomerase (Chi). In conclusion, (Rha/Glu→Flr→Chi) identified. vivo experiments, combined use M5 also shows excellent anti‐hyperlipidemia efficacy. the first on complex activity natural flavonoids by enzymes, provide insight investigate analogous products.

Language: Английский

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Ameliorative effect of montelukast against carbon tetrachloride-induced hepatotoxicity: Targeting NLRP3 inflammasome pathway

Life Sciences, Journal Year: 2022, Volume and Issue: 304, P. 120707 - 120707

Published: June 9, 2022

Language: Английский

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Linking KATP channel activation to p-AKT/mTORC1/eEF2/BDNF axis unravels nicorandil's promise in countering acetaminophen-induced hepatic encephalopathy in mice

Life Sciences, Journal Year: 2025, Volume and Issue: 366-367, P. 123477 - 123477

Published: Feb. 20, 2025

Language: Английский

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Neem leaf extract alleviates LPS/D-GalN induced acute hepatitis in mice through its anti-inflammatory effects and activation of autophagy

Molecular Immunology, Journal Year: 2025, Volume and Issue: 180, P. 33 - 43

Published: Feb. 24, 2025

Language: Английский

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Protective Effects of Oral Pharmaceutical Solution of Fucoxanthin Against Paracetamol-Induced Liver Injury: Modulation of Drug-Metabolizing Enzymes, Oxidative Stress, and Apoptotic Pathways in Rats

Drug Development and Industrial Pharmacy, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 16

Published: Feb. 24, 2025

Paracetamol (PAC) overdose causes acute liver injury through oxidative stress, inflammation, and apoptosis. While N-acetyl cysteine (NAC) is the standard treatment, fucoxanthin (FUC), a carotenoid from brown seaweed, has shown hepatoprotective effects in animal studies, but its role PAC toxicity unclear. Compared to NAC, this study assessed potential of oral FUC solution towards PAC-induced rat's liver. was formulated as pharmaceutical characterized via UV-VIS spectroscopy. Six groups male Wistar rats each contain five which are total thirty rats: negative control (NC), positive (PC, 2 g/kg PAC), NAC (1200 mg/kg), three doses (100, 200, 500 mg/kg) for seven days, with administered on day-8. Liver tissues were analyzed gene expression, histology. clear absorbance at 433 nm. caused 30% mortality (p < 0.01 vs. others). reduced ALT (56%), AST (78%), ALP (28%), increased TP by 25% 0.001 PC). mg/kg (F500) superior, reducing (82%), (93%), (40%), increasing (35%) NAC). CYP2E1/CYP3A2 apoptosis markers, suppressed Nrf2/AMPK/AKT1. F500 improved antioxidants, apoptosis, enhanced Nrf2/AMPK pathway, downregulated 0.01). FUC, particularly mg/kg, offers significant hepatoprotection against modulating drug metabolizing enzymes enhancing antioxidant defences, warranting further research.

Language: Английский

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