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Artemisia annua Extract Attenuate Doxorubicin-Induced Hepatic Injury via PI-3K/Akt/Nrf-2-Mediated Signaling Pathway
Karim Samy El-Said1, Ahmed S Haidyrah2, Maysa A Mobasher3
1Biochemistry Division, Chemistry Department, Faculty of Science, Tanta University, Tanta 31527, Egypt.
Abstract:
Doxorubicin (DOX), which is used to treat cancer, has harmful effects that limit its therapeutic application. Finding preventative agents to thwart DOX-caused injuries is thus imperative. Artemisia annua has numerous biomedical uses. This study aims to investigate the attenuative effect of Artemisia annua leaf extract (AALE) treatment on DOX-induced hepatic toxicity in male rats. A phytochemical screening of AALE was evaluated. Forty male rats were used; G1 was a negative control group, G2 was injected with AALE (150 mg/kg) intraperitoneally (i.p) daily for a month, 4 mg/kg of DOX was given i.p to G3 once a week for a month, and G4 was injected with DOX as G3 and with AALE as G2. Body weight changes and biochemical, molecular, and histopathological investigations were assessed. The results showed that AALE contains promising phytochemical constituents that contribute to several potential biomedical applications. AALE mitigated the hepatotoxicity induced by DOX in rats as evidenced by restoring the alterations in the biochemical parameters, antioxidant gene expression, and hepatic histopathological alterations in rats. Importantly, the impact of AALE against the hepatic deterioration resulting from DOX treatment is through activation of the PI-3K/Akt/Nrf-2 signaling, which in turn induces the antioxidant agents.
Insights
Artemisia annua leaf extract (AALE) can protect against liver damage caused by the cancer drug Doxorubicin (DOX). AALE treatment in rats reduced DOX-induced hepatotoxicity by activating antioxidant pathways.
Area of Science:
- Pharmacology
- Toxicology
- Natural Products Chemistry
Background:
- Doxorubicin (DOX) is a vital chemotherapy agent with dose-limiting hepatotoxicity.
- Identifying protective agents against DOX-induced liver injury is crucial for improving cancer therapy.
- Artemisia annua, known for its medicinal properties, has potential therapeutic applications.
Purpose of the Study:
- To evaluate the protective effects of Artemisia annua leaf extract (AALE) against Doxorubicin-induced hepatic toxicity in male rats.
- To investigate the underlying molecular mechanisms of AALE's protective action.
Main Methods:
- Phytochemical screening of AALE was performed.
- Male rats were divided into four groups: control, AALE-treated, DOX-treated, and DOX + AALE-treated.
- Assessment included body weight changes, biochemical markers, antioxidant gene expression, and histopathological analysis.
Main Results:
- AALE possesses significant phytochemical constituents with potential biomedical benefits.
- AALE treatment significantly mitigated DOX-induced hepatotoxicity, normalizing biochemical parameters and improving liver histology.
- AALE administration restored antioxidant gene expression in DOX-treated rats.
Conclusions:
- Artemisia annua leaf extract demonstrates a protective effect against Doxorubicin-induced liver injury in rats.
- The protective mechanism involves the activation of the PI-3K/Akt/Nrf-2 signaling pathway, leading to enhanced antioxidant defense.
- AALE shows promise as a supportive therapeutic agent to reduce chemotherapy-related liver damage.
