Flavonoids from Barnebydendron riedelii leaf extract mitigate thioacetamide-induced hepatic encephalopathy in rats : The interplay of NF-κB/IL-6 and Nrf2/HO-1 signaling pathways
Copyright © 2020 Elsevier Inc. All rights reserved..
Phytochemical investigation of the butanol fraction (BUF) derived from the 70% aqueous methanolic leaf extract of Barnebydendron riedelii led to the isolation of three flavonoid glycosides; kaempferol-3-O-α-l-rhamnopyranosyl-(1 → 6)-β-d-glucopyranoside, quercetin-3-O-α-l-rhamnopyranosyl-(1 → 6)-β-d-galactopyranoside and quercetin-3-O-α-l-rhamnopyranosyl-(1 → 6)-β-d-glucopyranoside. Docking studies were fulfilled to validate the possible bio-properties of BUF toward nuclear factorkappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2). The protective role of BUF against behavioral, biochemical, molecular, histopathological and immunohistochemical alterations in thioacetamide (TAA)-induced hepatic encephalopathy in rats was investigated. The toxicological studies indicated that BUF was safe up to 2000 mg/kg bw. Prior to TAA intoxication, rats were orally treated with either BUF at multiple doses (70, 140 and 280 mg/kg bw) or lactulose (8 mL/kg bw) for 14 consecutive days. On the 13th and the 14th day, TAA (200 mg/kg bw/day) was intraperitoneally injected. The BUF significantly improved motor impairment, ameliorated cognitive deficits and attenuated TAA-induced hepatotoxicity. Moreover, BUF controlled the inflammatory processes by suppressing the hepatic inflammatory cytokine; interleukin-6 (IL-6) as well as its pro-inflammatory mediator; NF-κB supporting the molecular docking assessment. The brain neurotransmitters; dopamine, serotonin and noradrenaline, as well as ammonia levels were improved in BUF-treated TAA-intoxicated animals in a dose-dependent manner. Furthermore, BUF administration to TAA-intoxicated rats modulated the Nrf2 and heme oxygenase 1 (HO-1) genes expression in liver and brain tissues. The histological evaluation showed that pretreatment of TAA-intoxicated rats with BUF ameliorated the degenerative effects of TAA on liver and brain tissues as well as reduced the activation of cellular apoptotic marker; caspase-3 and glial fibrillary acidic protein (GFAP+) astrocytes. In conclusion, the observed hepato-neuroprotective effect of BUF is attributed to its flavonoidal content through its modulatory effects on of NF-κB/IL-6 and Nrf2/HO-1 signaling pathways.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:105 |
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| Enthalten in: |
Bioorganic chemistry - 105(2020) vom: 20. Dez., Seite 104444 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Baraka, Sara M [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 18.03.2021 Date Revised 18.03.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bioorg.2020.104444 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM31765229X |
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| 245 | 1 | 0 | |a Flavonoids from Barnebydendron riedelii leaf extract mitigate thioacetamide-induced hepatic encephalopathy in rats |b The interplay of NF-κB/IL-6 and Nrf2/HO-1 signaling pathways |
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| 500 | |a Date Revised 18.03.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 Elsevier Inc. All rights reserved. | ||
| 520 | |a Phytochemical investigation of the butanol fraction (BUF) derived from the 70% aqueous methanolic leaf extract of Barnebydendron riedelii led to the isolation of three flavonoid glycosides; kaempferol-3-O-α-l-rhamnopyranosyl-(1 → 6)-β-d-glucopyranoside, quercetin-3-O-α-l-rhamnopyranosyl-(1 → 6)-β-d-galactopyranoside and quercetin-3-O-α-l-rhamnopyranosyl-(1 → 6)-β-d-glucopyranoside. Docking studies were fulfilled to validate the possible bio-properties of BUF toward nuclear factorkappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2). The protective role of BUF against behavioral, biochemical, molecular, histopathological and immunohistochemical alterations in thioacetamide (TAA)-induced hepatic encephalopathy in rats was investigated. The toxicological studies indicated that BUF was safe up to 2000 mg/kg bw. Prior to TAA intoxication, rats were orally treated with either BUF at multiple doses (70, 140 and 280 mg/kg bw) or lactulose (8 mL/kg bw) for 14 consecutive days. On the 13th and the 14th day, TAA (200 mg/kg bw/day) was intraperitoneally injected. The BUF significantly improved motor impairment, ameliorated cognitive deficits and attenuated TAA-induced hepatotoxicity. Moreover, BUF controlled the inflammatory processes by suppressing the hepatic inflammatory cytokine; interleukin-6 (IL-6) as well as its pro-inflammatory mediator; NF-κB supporting the molecular docking assessment. The brain neurotransmitters; dopamine, serotonin and noradrenaline, as well as ammonia levels were improved in BUF-treated TAA-intoxicated animals in a dose-dependent manner. Furthermore, BUF administration to TAA-intoxicated rats modulated the Nrf2 and heme oxygenase 1 (HO-1) genes expression in liver and brain tissues. The histological evaluation showed that pretreatment of TAA-intoxicated rats with BUF ameliorated the degenerative effects of TAA on liver and brain tissues as well as reduced the activation of cellular apoptotic marker; caspase-3 and glial fibrillary acidic protein (GFAP+) astrocytes. In conclusion, the observed hepato-neuroprotective effect of BUF is attributed to its flavonoidal content through its modulatory effects on of NF-κB/IL-6 and Nrf2/HO-1 signaling pathways | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Barnebydendron riedelii | |
| 650 | 4 | |a Hepatoprotective | |
| 650 | 4 | |a Hyperammonemia | |
| 650 | 4 | |a Neuromodulatory | |
| 650 | 7 | |a Flavonoids |2 NLM | |
| 650 | 7 | |a Glial Fibrillary Acidic Protein |2 NLM | |
| 650 | 7 | |a Interleukin-6 |2 NLM | |
| 650 | 7 | |a NF-E2-Related Factor 2 |2 NLM | |
| 650 | 7 | |a NF-kappa B |2 NLM | |
| 650 | 7 | |a Neurotransmitter Agents |2 NLM | |
| 650 | 7 | |a Plant Extracts |2 NLM | |
| 650 | 7 | |a Thioacetamide |2 NLM | |
| 650 | 7 | |a 075T165X8M |2 NLM | |
| 650 | 7 | |a Heme Oxygenase-1 |2 NLM | |
| 650 | 7 | |a EC 1.14.14.18 |2 NLM | |
| 700 | 1 | |a Saleh, Dalia O |e verfasserin |4 aut | |
| 700 | 1 | |a Ghaly, Neveen S |e verfasserin |4 aut | |
| 700 | 1 | |a Melek, Farouk R |e verfasserin |4 aut | |
| 700 | 1 | |a Gamal El Din, Amina A |e verfasserin |4 aut | |
| 700 | 1 | |a Khalil, Wagdy K B |e verfasserin |4 aut | |
| 700 | 1 | |a Said, Mahmoud M |e verfasserin |4 aut | |
| 700 | 1 | |a Medhat, Amina M |e verfasserin |4 aut | |
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