الفهرس 
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Abstract
Acute liver injury is caused by multiple factors, such as hepatic viruses, excessive alcohol consumption and hepatotoxins (for example, paracetamol, flutamide and carbon tetrachloride). This injury leads to down-regulation of hepatic enzymes. It is well known that treatment of liver diseases involves antiviral drugs, vaccines, and many other treatments which are thought to have adverse side effects thus safer and more effective drugs are in urgent need. In recent years, focus has shifted towards traditional herbal medicine products for their efficacy and high safety profile in treatment of liver diseases. Moreover, herbs cost much less than prescriptions medication.
Roots, seeds, fruits, leaves, flowers, stem and bark of plants can all constitute herbal medicines. The medicinal value of these plants lies in their phytochemical components which produce definite and various physiological actions on human body. Some of the most important of these components are flavonoids and phenolic compounds. Hyphaene thebaica (HT) is used in the treatment of hypertension, bilharzias and is considered a haematinic agent. Moreover, the aqueous extract of the doum fruit showed an antioxidant activity, this is due to their substantial amount of water soluble phenolic contents.
The current study investigates the molecular, biochemical and physiological effects of HT seeds ethanolic crude extract on the normal male albino rats as well as the effect on the acute liver injury induced by CCl4 pretreatment in male albino rats.
Preliminary toxicological study was performed to determine the half lethal dose (LD50) of HT seeds’ ethanolic crude extract y using thirty male albino rats divided into five (5) groups; six animals each,. The animals received the extract in different doses ranged from 100-1600 mg/kg BW for 14 days. There were no death in the treated animals; hence the lethal dose (LD50) of the extract was not calculated.
Eighty male albino rats were divided into 10 groups for determination of hematological, biochemical, antioxidant, molecular and histological assays after their scarification as follows:
group 1: Rats didn’t receive any treatment
group 2: Rats were injected intraperitoneally with olive oil at 1 ml/Kg BW, vehicle control group, for 21 days.
Groups (3, 4 and 5): normal, non-treated, rats only injected orally with HT crude ethanolic extract at 100 mg/ Kg BW, 200 mg/ Kg BW and 400 mg/ Kg BW, respectively, for 21 days.
Groups 6: Positive control group, in which rats only injected intraperitoneally with CCl4 at 1 ml/Kg BW, dissolved in olive oil (V/V) every 72 hours for two weeks
Groups (7, 8 and 9):CCl4-pretreated rats injected intraperitoneally as group 6 for the same period of time, followed by daily oral treatment with the extract at 100 mg/Kg BW, 200 mg/Kg BW and 400 mg/Kg BW doses respectively for 21 days.
group 10: Reference drug group in which rats were injected intraperitoneally for the same period of time, followed by daily oral treatment with silymarin (100 mg/Kg BW) for 21 days.
The obtained results can be summarized as follow:
A-Effect of oral treatment of HT seeds’ ethanolic crude extract on normal albino rats
Oral treatment with HT seeds’ ethanolic crude extract caused significant improvement/increase (P ≤ 0.05) for the body weight gain, liver weigh, liver index, WBCs, RBCs count and Hb concentration in addition to significant decrease (P ≤ 0.05) in the level of cholesterol and triglycerides after oral administration of the moderate dose (200 mg/Kg BW) and the highest dose (400 mg/Kg BW) to CCl4-nontreated animals when compared with negative control group. Moreover, all doses ( 100 mg/Kg BW, 200 mg/Kg BW and 400 mg/Kg BW) did not show any significant change in liver, kidney function tests and platelets count.
B-Effect of intraperitoneal injection of CCl4 on male albino rats
When the animals were injected intraperitoneally with CCl4, there was an observable elevation in WBCs count and liver enzymes (ALT, AST, GGT, ALP and LDH) levels as well as elevation in the levels of oxidative stress biomarkers including NO and MDA contents of the liver as. On the other hand, the observable reduction in liver proteins as albumin and total protein. Furthermore, the harmful reductions of antioxidative stress enzymes as (GSH, SOD and CAT). Also, the histopathological studies a disturbed tissue profile when compared with the negative group.
C- Effect of oral treatment of HT seeds’ ethanolic crude extract on CCl4-pretreated animals
1- Oral treatment with the extract induced the body weight gain in addition to reducing the liver weight and liver index for CCl4-pretreated animals when compared with CCl4 positive control group.
2- Oral treatment with crude extract reduced white blood cells count (WBCs). Moreover, it induced hemoglobin (Hb) concentration, red blood cells count (RBCs) and platelets count especially those treated with 400 mg/Kg BW and 200 mg/Kg BW but there was non-significant change in these parameters in the animals treated with 100 mg/Kg BW of the extract when compared with CCl4 positive control group.
3- The activity of AST, ALT, GGT, ALP and LDH enzymes.in addition to creatinine, urea, cholesterol and triglycerides levels had observable and significant decreased under the treatment with the three different doses of the extract. Furthermore, these doses could restore the levels of albumin and total protein in the CCl4-pretreated animals when compared with CCl4 positive control group.
4-The antioxidant levels had significantly affected by the extract. For example, the MDA levels and the T.NO levels in the liver had a high significant reduction by the different doses of the extract. In contrast, the liver CAT, GSH and SOD levels showed high significant increases in CCl4-injured livers after treatment with the three different doses of the extract when compared with CCl4 positive control group.
Regarding the histopathological study, there was an improvement in the liver and the kidney tissues caused by different doses treatment by extract, especially the highest dose, when compared with CCl4 positive control group.
The in vitro as well as the molecular experiments in this study may interpret the mechanism by which the different treatments improved the hepatic morphology and function. The real time polymerase chain reaction (PCR) results indicated that the extract treatment may stimulate apoptotic cell death in the liver tissues in a dose-dependent fashion by upregulating BAX expression rather than Bcl2 downregulation.
Conclusion
All in all, treating the normal animals with varied range of doses of HT did not negatively affect the animals but enhanced the antioxidant capacity of the animals; liver. Moreover, HT showed an appreciated therapeutic efficacy for the different damage/injury by CCl4 and for the human cancer cells as well. Mechanistic experiment showed the HT kills cells by apoptosis. These results may open the gate for further study to identify the exact mechanism and the effective compound in these seeds in the future.