Emodin induces apoptosis through caspase 3-dependent pathway in HK-2 cells
Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing, China. Toxicology
(Impact Factor: 3.62).
04/2007; 231(2-3):120-8. DOI: 10.1016/j.tox.2006.11.064
Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is a major constituent of rhubarb. Although it has been claimed to have a wild spectrum of therapeutic value, its side effects, especially in human kidney cells have not been well characterized. In the present study, we treated human proximal tubular epithelial cell line HK-2 cells with emodin in vitro and evaluated its toxic effects with cell viability, cell cycle phases and induction of apoptosis/necrosis and activity of caspase 3. The proliferation of HK-2 cells was inhibited by emodin in a dose- and time-dependent manner. Cell cycle analysis revealed that HK-2 cells were locked in G1 phase by emodin as for 12h. Apoptosis was supported by the Annexin V/propidium iodide (PI) assay and the occurrence of a sub-G1 peak. Emodin caused an increase in caspase 3-like activities and a caspase 3 inhibitor, Ac-DEVD-CHO, attenuated the apoptosis. These results suggested that HK-2 cells are sensitive to emodin-induced cytotoxic effects, which are mediated through the induction of apoptosis in caspase 3-dependent pathway.
Available from: Surrinder Lattoo
- "R. emodi finds an extensive use in Ayurvedic and other traditional medical systems, like homeopathic, Tibetan, Unani and Chinese systems (Bhatia et al., 2011). Extracts from the roots, bark and leaves of rhubarb have been used as a laxative since ancient times and presently are widely used in various herbal preparations (Wang et al., 2007). The major phytoconstituents reported from the plant include anthraquinones (emodin, aloe-emodin, chrysophanol, rhein, physcion) and stilbenes, and their respective glycoside derivatives . "
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ABSTRACT: Rheum emodi (Polygonaceae), a multipurpose medicinal herb is a rich repository of pharmacologically active secondary metabolites known as anthraquinones. The present study entails HPLC quantitation and in vitro activity of four major constituents and the extracts of R. emodi. The anthraquinone glycosides were more abundant than their aglycone constituents viz. emodin and chrysophanol. MTT assay was used to assess the in vitro antiproliferative activity of anthraquinones and extracts on four cancer cell lines namely MIAPaCa-2, HCT-116, MCF-7 and T47D. The cytotoxicity was more obvious on MIAPaCa-2. Further, the study of mechanism of action involving cell cycle analysis and determination of mitochondrial membrane potential (MMP) loss was also investigated. The extracts significantly reduced cell viability by inducing apoptosis/necrosis and cell cycle arrest with concurrent loss of MMP (∆ψm) in a concentration dependent manner. The methanolic extract of rhizome (SPL5) with the least IC50 value (25 μg/ml) showed a significant increase in the percentage of apoptotic/necrotic cells (42.3% at 100 μg/ml) compared to that of vehicle treated cells (11.6%). These cellular manifestations corresponded remarkably with a decrease in integrity of the mitochondrial membrane. In conclusion, SPL5 with emodin and chrysophanol as the preponderant constituents exhibited considerable antiproliferative activity possibly by reducing cell viability and stirring up ∆ψm loss.
Available from: Linfang Huang
- "Among these materials, several anthraquinone derivatives, including emodin, chrysophanol, rhein, aloe-emodin, and physcion, as well as their corresponding glucosides, have been identified as important bioactive components, and reported to exhibit a variety of pharmacological effects, such as purgative , anti-inflammatory , anticancer , nephric protection , hepatic protection , antimicrobial and hemostasis activities [11, 12]. Several reports have appeared in the literature, however, suggesting that the rhubarb components of R. palmatum have an adverse impact on liver and kidney function, as well as causing gastrointestinal reactions [13–15], and some of the anthraquinone and tannin compounds present in R. palmatum have been reported to be toxic . R. palmatum has been subjected to the standard processing technologies used in TCM reduce the toxicity of the raw material, as well as alleviating any symptoms of decanta and celialgia, and the resulting material has been used in clinical practice for hundreds of years R. palmatum wine, prepared R. palmatum, and charred R. palmatum have been well documented in the Chinese Pharmacopoeia as therapeutic materials , whereas the use of vinegar R. palmatum has been recorded in the standardized processing of traditional Chinese medicine (version 1988) . "
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ABSTRACT: The long term use of Rheum palmatum for the treatment of diseases associated with chronic hepatitis and renal failure can lead to liver and kidney damage. To reduce the toxicity of R. palmatum and alleviate any symptoms of decanta and celialgia, the raw material has been subjected to a specific process prior to its use for hundreds of years. Despite its extensive use in medicine, very little is currently known about the nature of the components present in this material in terms of their efficacy and overall toxicity, and the effect that processing has on the levels of these components in the processed material. The aim of this investigation was to explore potential differences in the chemical markers between batches of raw and processed R. palmatum and to develop a deeper understanding of the underlying mechanisms responsible for the enhanced efficacy and reduced toxicity of the processed material.
Raw and processed R. palmatum samples were analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) coupled with multivariate statistical analysis using principal component analysis (PCA) and orthogonal partial least square discriminant analysis (OPLS-DA).
The emodin-8-O-glucoside, emodin-O-glucoside, catechin-glucopyranoside, gallic acid-3-O-glucoside, torachrysone, and chrysophanol dimethyl ether were rapidly explored as representative markers to distinguish for the first time between the raw and processed R. palmatum material. Among the potential chemical markers, Emodin-8-O-glucoside and gallic acid-3-O-glucoside were determined to be the best markers for the raw and processed R. palmatum.
UPLC/Q-TOF-MS with multivariate statistical analysis represents an efficient method for exploring the chemical markers in the raw and processed R. palmatum material, as well as investigating the mechanisms associated with the processing, quality control, and safe application of R. palmatum.
Available from: Priyanka Dhar
- "Apoptosis, as well as antitumor action, has been demonstrated and Rhubarb extract has been suggested as an adjunct to chemotherapy. Antiangiogenic action of Rhubarb has also been shown (Srinivas et al., 2007; Huang et al., 2007; Wang et al., 2007; Cai et al., 2008; Cui et al., 2008 and Lin et al., 2003). It has been used in cases of GI bleeds to eliminate extravasated blood (Jiao et al., 1980 and Srinivas et al., 2007). "
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ABSTRACT: In recent years, a numerous studies had been conducted in all over the world to explore the traditional medicinal system as a resource of complementary and alternative medicine. The Indian indigenous drugs from the medicinal plants also have great importance, both professional and economical point of view. Rheum webbianum Royle commonly known as Rhubarb, is an important medicinal plant, belonging to the family Polygonaceae. It is commonly used for the management of renal function disorders, hyperlipidemia, cancer and improves the memory in senile patients. R. webbianum, R. speciformae, R. tibetana and R. orcroftianum are the commonly found species in cold arid zones of India. The Rheum species contains a number of anthraquinone derivatives. The free anthraquinones viz. rhein, emodin, aloe-emodin, physcion, and chrysophamol are present in nearly all species. Stilbene glycosides, including rhaponticin and the metabolite rhapontigenin, have been identified in the root. Tannins, sennosides, catechins, gallic acid, and cinnaminic acid have been identified. Keeping in view the utility of this plant in certain herbal products and traditional medicine, conservation and sustainable utilization of this rare species is the urgent need of present hour. This will not only provide raw material but also provide resource generation for economic development for the local population in the cold arid high altitude regions of Ladakh Himalaya.
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