دورية أكاديمية
Kaempferol sophoroside glucoside mitigates acetaminophen-induced hepatotoxicity: Role of Nrf2/NF-κB and JNK/ASK-1 signaling pathways.
| العنوان: | Kaempferol sophoroside glucoside mitigates acetaminophen-induced hepatotoxicity: Role of Nrf2/NF-κB and JNK/ASK-1 signaling pathways. |
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| المؤلفون: | Mohamed GA; Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia., El-Agamy DS; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt., Abdallah HM; Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia., Sindi IA; Department of Biology, Faculty of Science, King Abdulaziz University, Jeddah, 21589, Saudi Arabia., Almogaddam MA; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Gezira, Wad Madani, 21111, Sudan., Alzain AA; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Gezira, Wad Madani, 21111, Sudan., Andijani YS; Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Al-Madinah Al-Munawwarah, 30078, Saudi Arabia., Ibrahim SRM; Department of Chemistry, Preparatory Year Program, Batterjee Medical College, Jeddah, 21442, Saudi Arabia.; Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut, 71526, Egypt. |
| المصدر: | Heliyon [Heliyon] 2024 May 17; Vol. 10 (10), pp. e31448. Date of Electronic Publication: 2024 May 17 (Print Publication: 2024). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Ltd Country of Publication: England NLM ID: 101672560 Publication Model: eCollection Cited Medium: Print ISSN: 2405-8440 (Print) Linking ISSN: 24058440 NLM ISO Abbreviation: Heliyon Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: London : Elsevier Ltd, [2015]- |
| مستخلص: | 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) is a kaempferol derivative that was separated from plant species belonging to different genera. This study explored the protective effects of KSG on ALI (acute liver injury) caused by APAP overdose in mice and elucidated its possible mechanisms. The results showed that KSG pretreatment alleviated APAP-induced hepatic damage as it reduced hepatic pathological lesions as well as the serum parameters of liver injury. Moreover, KSG opposed APAP-associated oxidative stress and augmented hepatic antioxidants. KSG suppressed the inflammatory response as it decreased the genetic and protein expression as well as the levels of inflammatory cytokines. Meanwhile, KSG enhanced the mRNA expression and level of anti-inflammatory cytokine, IL-10 (interleukin-10). KSG repressed the activation of NF-κB (nuclear-factor kappa-B), besides it promoted the activation of Nrf2 signaling. Additionally, KSG markedly hindered the elevation of ASK-1 (apoptosis-signal regulating-kinase-1) and JNK (c-Jun-N-terminal kinase). Furthermore, KSG suppressed APAP-induced apoptosis as it decreased the level and expression of Bax (BCL2-associated X-protein), and caspase-3 concurrent with an enhancement of anti-apoptotic protein, Bcl2 in the liver. More thoroughly, Computational studies reveal indispensable binding affinities between KSG and Keap1 (Kelch-like ECH-associated protein-1), ASK1 (apoptosis signal-regulating kinase-1), and JNK1 (c-Jun N-terminal protein kinase-1) with distinctive tendencies for selective inhibition. Taken together, our data showed the hepatoprotective capacity of KSG against APAP-produced ALI via modulation of Nrf2/NF-κB and JNK/ASK-1/caspase-3 signaling. Henceforth, KSG could be a promising hepatoprotective candidate for ALI. Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2024 The Authors.) |
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| فهرسة مساهمة: | Keywords: Acetaminophen; Acute liver injury; Drug discovery; Health and wellbeing; Hepatotoxicity; Industrial development; Kaempferol-3-sophoroside-7-glucoside; Life on land |
| تواريخ الأحداث: | Date Created: 20240530 Latest Revision: 20240531 |
| رمز التحديث: | 20240531 |
| مُعرف محوري في PubMed: | PMC11133934 |
| DOI: | 10.1016/j.heliyon.2024.e31448 |
| PMID: | 38813141 |
| قاعدة البيانات: | MEDLINE |
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