Objective:

2

To explore the prophylactic and therapeutic effects of

Alhagi maurorum

ethanolic extract (AME) in concanavalin A (Con A)-induced hepatitis (CIH) as well as possible underlying mechanisms.

Methods:

2

Polyphenols in AME were characterized using high performance liquid chromatography (HPLC). Swiss albino mice were divided into 4 groups. Normal group received intravenous phosphate-buffered saline (PBS); Con A group received 40 mg/kg intravenous Con A. Prophylaxis group administered 300 mg/(kg • d) AME orally for 5 days before Con A intervention. Treatment group received intravenous Con A then administered 300 mg/kg AME at 30 min and 3 h after Con A intervention. After 24 h of Con A injection

hepatic injury

oxidative stress

and inflammatory mediators were assessed. Histopathological examination and markers of apoptosis

inflammation

and CD4

+

cell infiltration were also investigated.

Results:

2

HPLC analysis revealed that AME contains abundant polyphenols with pharmacological constituents

such as ellagic acid

gallic acid

ferulic acid

methylgallate

and naringenin. AME alleviated Con A-induced hepatic injury

as manifested by a significant reduction in alanine aminotransferase

aspartate aminotransferase and alkaline phosphatase (

P

<

0.01). Additionally

the antioxidant effect of AME was revealed by a significant reduction in oxidative stress markers (nitric oxide and malondialdehyde) and restored glutathione (

P

<

0.01). The levels of proinflammatory cytokines (tumor necrosis factor-α

interferon-γ

and interleukin-6) and c-Jun N-t

erminal kinase (JNK) activity were reduced (

P

<

0.01). Histopathological examination of liver tissue showed that AME significantly ameliorated necrotic and inflammatory lesions induced by Con A (

P

<

0.01). Moreover

AME reduced the expression of nuclear factor kappa B

pro-apoptotic protein (Bax)

caspase-3

and CD4

+

T cell hepatic infiltration (

P

<

0.01). The expression of anti-apoptotic protein Bcl-2 was increased (

P

<

0.01).

Conclusions:

2

AME has hepatoprotective and ameliorative effects in CIH mice. These beneficial effects are likely due to the anti-inflammatory

antioxidant

and anti-apoptotic effects of the clinically important polyphenolic content. AME could be a novel and promising hepatoprotective agent for managing immune-mediated hepatitis.