الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Medicinal plants play an important role in the treatment of different diseases because of their content of biologically active phytochemicals. Clinical trials have been conducted on medicinal plants for many years, and there has often been a correlation between the traditional uses of medicinal plants and the biological activities of their chemical constituents.
Medicinal plant therapy is widely used across the world on a constantly growing basis. Currently, it is estimated that over 50% of the available drugs are somehow derived from medicinal plants. The global trend of synthetic compounds has turned to herbal drugs, which we can refer to as a return to nature.
The Viburnum tinus (V.tinus) is an evergreen shrub widely distributed in Southern Europe, especially in Mediterranean regions as a member of the Viburnum genus which is very popular among medicinal plants. It has valuable phytochemicals such as polyphenols (e.g. chlorogenic acid), triterpenoids (e.g. oleanolic acid), flavonoids, coumarins, and iridoids and it has been used in
folk medicine as neuroprotective, hepatoprotective, sedative, and spasmolytic treatment.
Chlorogenic acid (CGA) is naturally occurring phenolic compound that have been shown to help with hypertension, hyperglycemia, antimicrobial, antitumor, memory enhancement, weight management, and other conditions. Further, it is also reported to have anticancer, antioxidant, and anti-inflammatory activities.
Oleanolic acid (OA) is a biologically active pentacyclic triterpenoid that has several beneficial properties, including antioxidant, anti-inflammatory, antiviral, anti-diabetic, and inhibits tumor growth in tumor- bearing animals, such as those with breast cancer.
The Viburnum tinus leaves were collected and dried then extracted with different organic solvent to obtained different extracts e.g. crude, chloroform, n-Hexane and methanolic. The phytochemical constituents screening as flavonoids and saponins are highly concentrated in the n- Hexane extract followed by methanolic, chloroform, and finally crude extract. While tannins, phenolic compounds and terpenoids were concentrated in the chloroform extract which used further in the isolation of active constituents as oleanolic and chlorogenic acid using chromatographic techniques.
In the current work the biological activities of Viburnum tinus different extracts in addition to isolated oleanolic and chlorogenic acid as anti-inflammatory, antiviral, anticancer and apoptotic therapeutic agents were evaluated in vitro.
The current study showed the activity of different extracts in the inhibition of proteinase activity, protein denaturation inhibition, and increased membrane stabilization with minor toxicity on RBCs in addition to inhibitory effect on inflammatory cytokine e.g. interferon gamma as the following order: n-Hexane > methanol > chloroform > crude suggested due to its content of flavonoids and saponins which reported to have anti- inflammatory activity.
The isolated chlorogenic and oleanolic acid showed a highly anti-inflammatory effect as protein denaturation inhibition, proteinase inhibitor, membrane stabilization In addition to inhibition of the INF- γ level comparing to its authentic commercial chlorogenic and oleanolic acid sample.
The current work demonstrated that the V.tinus leaves different extracts exhibits a significant anti-proliferative activity against different cancerous cell
lines in the following order: liver (HepG2)> breast (MCF7)> colorectal (CaCO2).
from all extracts the n-Hexane is the most active one due to its high content of phenolic compounds and terpenoids which affect cell proliferation.
In the current work, the methanolic extract has the highest selective index (SI) on liver carcinoma (HepG2), followed by crude extract and chloroform, and n-Hexane having the lowest, while methanol has the highest selective index in colorectal (CaCO2), followed by n-Hexane, crude extract, and chloroform, while n-Hexane has the highest selective index against breast (MCF7) followed by chloroform, crude extract, and finally methanol. All of the extracts have a greater SI, indicating that various extracts have distinct anticancer effectiveness on various cell types.
The effectiveness of V.tinus leaves different extracts on malignant cell line is accomplished through the induction of apoptosis and cell death to evaluate exactly how active agents behave to allow understanding how they can be used to treat cancer. In this work, n-Hexane is the most active extract which appears on cell morphology and confirmed by DNA laddering as HepG2 extracted DNA after 48 hours incubation found fragmented in multiplex of
150 bp followed by methanol, chloroform and finally crude.
The relative quantification of BAX gene expression increased, while BCL-2 was inhibited in the following order: n-Hexane, methanol, chloroform, and crude. The BAX/BCL-2 ratio of the different extracts by time of treatment revealed (increased) susceptibility to apoptosis.
In the current work, the isolated (OA.I) showed cytotoxic effect against different cancerous cell lines as the following order HepG2>MCF7>CaCO2 and cell cycle arrested at G0/G1 phase and Annexin V-FITC analysis on HepG2 cells showed induction of apoptosis as increase level of early (25%) and late (12%) apoptotic cells after 24 hours of treatment, while the isolated CGA.I exhibits cytotoxic effect on cancerous cell lines as the following order MCF7>HepG2>CaCO2 and cell cycle arrested at G0/G1 phase and Annexin V-FITC analysis on HepG2 cells showed induction apoptosis as increase level of early (15%) and late (10%) apoptotic cells after 24 hours of treatment.
The isolated OA.I and CGA.I showed significant increase in BAX level expression and significant decrease in BCL-2 expression level compared to normal cell line with non-significance with their authentic samples of OA
and CGA, these data confirmed that OA.I and CGA.I have apoptotic activity on cancerous cell lines.
In this work, the n-Hexane extract showed the highest antiviral effect against VSV viral replication it based on its highest content of specific phytochemicals as iridoids, alkaloids, terpenes, and flavonoids. The isolated oleanolic acid (OA.I) exhibits the second highest antiviral activity on VSV replication in this work with highly significant increase from its authentic sample. The isolated chlorogenic acid exhibits the third highest antiviral activity on VSV replication in this work with non-significant increase from its authentic sample.