|Pharmacological studies on Radix et Rhizoma Rhei (Da Huang) and its active component, Emodin
|Hong Kong Polytechnic University -- Dissertations.
Rhubarb -- Therapeutic use.
|Department of Applied Biology and Chemical Technology
|xviii, 158 leaves : ill. ; 30 cm.
|Cancer and hypertension are two of the most common diseases in the world. It was suggested that hypertension was associated with an increased risk of mortality from cancer. However, a better understanding of the cellular pathway and the relationship between hypertension and cancer may be helpful in elucidating more preventive and therapeutic drugs for the treatment of hypertension and cancer. Radix et Rhizoma Rhei (Da Huang) has been widely used in traditional Chinese medicines as a laxative, antiphlogistic and hemostatic herb. With high-performance liquid chromatography (HPLC) analysis, it was found that emodin (l,3,8-trihydroxy-6-methylanthraquinone) was one of the most abundant components in the Da Huang species. Emodin has been reported to have diverse biological effects such as anti-inflammatory, antibacterial, anticancer and vasorelaxant effects. However, their anticancer effect and mechanism were involved in the human lung adenocarcinoma A549 and the human breast carcinoma MCF-7 cells, and their vasorelaxant effect on aorta has not been clearly demonstrated. The purpose of this study was to investigate the anticancer effect of the Da Huang water extract, the effect of emodin on growth inhibition, apoptosis induction, and on the expression of apoptotic-related genes in MCF-7 and A549 cells and vasorelaxant effect of emodin on rats' aorta. For the anticancer study, MCF-7 and A549 cells were treated with Da Huang water extract or emodin at different dosages and time intervals. Growth inhibition was detected by MTS assay and colony formation assay, and cell apoptosis by microscopic monitoring of cell morphology, DNA fragmentation detection and Comet assays. The expression of apoptotic-related genes was detected by real-time PCR. Results showed that both Da Huang water extract or emodin had growth inhibitory effect on A549 cell and MCF-7 cell. IC50 values of Da Huang water extract on A549 cell and MCF-7 cell were 693ug/ml and 583ug/ml, respectively; IC50 values of emodin on A549 cell and MCF-7 cell were 16.85ug/ml and 7.22ug/ml, respectively. And their growth inhibitory effect was dose and time-dependent. The cell shrinkage, DNA fragmentation and DNA strand breakage were observed in both the Da Huang water extract or the emodin treated A549 and MCF-7 cells. The expression of apoptotic-related genes was modulated after emodin treatment. The results indicated that emodin induced growth inhibition and apoptosis in MCF-7 and A549 cells through modulation on expression of the apoptotic-related genes. For the antihypertensive study, the vasorelaxatant effect of emodin was demonstrated by adding emodin to phenylepherine pre-contracted rats' thoracic aorta. The nitric oxide (NO) related mechanism of emodin was investigated by adding L-NAME to exclude the involvement of NO in relaxation, the K+ channels-controlled mechanism was investigated by adding the ATP-dependent K+ channel blocker, glibenclamide, and the Ca2+-activated K+ channel blocker, tetraethyammonium. The results showed that emodin could induce relaxation on aorta partially through the K+ channels-controlled mechanism but was independent of an endothelium- and NO-related mechanism. In addition, it was shown that emodin worked as an antagonist on Ca2+ ion channel as the channel blocker, verapamil to induce relaxation. The emodin has the potential to be used as drugs for both cancer and hypertension treatment. However, it needs to be further studied in pharmaceutical, toxicological and clinical areas.
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