Rhubarb has been used as a traditional Chinese medicine since ancient times and today it
is still present in various herbal preparations. In this blog the toxicological and anti-neoplastic potentials of the main anthraquinones from Rhubarb, Rheum palmatum, will be highlighted. It is interesting to note that although the chemical structures of various anthraquinones in this plant are similar, their bioactivities are rather different.
The most abundant anthraquinone of rhubarb, emodin, was capable of inhibiting cellular proliferation, induction of apoptosis, and prevention of metastasis. These capabilities are reported to act through tyrosine kinases, phosphoinositol 3-kinase (PI3K), protein kinase C (PKC), NF-kappa B (NF-k B), and mitogen-activated protein kinase (MAPK) signaling cascades. Aloe-emodin is another major component in rhubarb found to have anti-tumor properties. Its anti-proliferative property has been demonstrated to be through the p53 and its downstream p21 pathway. Our recent proteomic study also suggests that the molecular targets of these two anthraquinones are different. However, both components were found to be able to potentiate the anti-proliferation of various chemotherapeutic agents. Rhein is the other major rhubarb anthraquinone, although less well studied. This compound could effectively inhibit the uptake of glucose in tumor cells, caused changes in membrane-associated functions and led to cell death. Interestingly, all three major rhubarb anthraquinones were reported to have in vitro phototoxic. This re-evaluation of an old remedy suggests that several bioactive anthraquinones of rhubarb possess promising anti-cancer properties and could have a broad therapeutic potential.
Most of the water-soluble components of rhubarb are readily absorbed after ingestion. This
medicinal plant is generally considered low in toxicity, but intoxication could result from over
dosage, especially of the fresh herb. Toxic symptoms include nausea, vomiting, dizziness, abdominal colic, and jaundice. Although no recent study has been conducted on the long-term effects of anthraquinones present in rhubarb, an earlier study suggested that they could lead to liver cirrhosis and hypokalemia.
A number of studies have demonstrated that the main anthraquinones of rhubarb, emodin, aloe-emodin, and rhein, inhibit the growth and proliferation of various cancer cells. Emodin has been reported to inhibit proliferation in breast, lung, cervical, colorectal, and prostate cancers cells. After comparison with other anthraquinone derivatives, such as emodin 1-O-b-D-glucoside, physcion, and physcion 1-O-b-D-glucoside, C1 and C3 position of emodin is believed to be important for the anti-tumor function. However, emodin can evoke a less or no cytotoxic effect in several normal cells, including HBL-100 cells derived from normal human breast tissue, human fibroblast-like lung WI-38 cells, and three primary cultured rat normal cells. It has also been demonstrated that emodin displays over 25-fold differential cytotoxicity against ras-transformed bronchial epithelial cells to the normal human bronchial epithelial cells. These data suggest that normal cells are more resistant to emodin-induced cytotoxicity than cancer cells. Such specificity of emodin towards malignant cells might be due to its effect targeting on some oncogene signaling transductions, which are constitutively active or amplified in cancer cells.
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