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Emodin is moderately cytotoxic and can inhibit the growth of many cell types by interfering with the cell cycle, possibly by stimulating the expression of p53 and p21. Alternatively, it may do this by creating DNA strand breaks and/or non-covalently binding to DNA and inhibiting the catalytic activity of topoisomerase II. It may also induce apoptosis by inhibiting the electron transport chain, producing reactive oxygen species. Emodin is a strong inhibitor of tyrosine-protein kinase Lck and other tyrosine kinase receptors, which likely contributes to its growth suppressing activity. It may act as a chemopreventive agent by activating DNA repair machinery. Emodin can also inhibit metastasis by interfering with the activity of matrix metalloproteinases, either directly or through through inhibition of focal adhesion kinase, mitogen-activated protein kinase, and RAC-alpha serine/threonine-protein kinase activation, and partial inhibition of transcription factor AP-1 and nuclear factor NF-kappa-B (NF-kB) transcriptional activities. Emodin exerts its purgative effects by acting directly or indirectly on colon epithelial cells. This activates the underlying smooth muscle cells, leading to muscle contractility. Possible mechanisms for this effect includes enhancing the hormone motilin, activating muscarinic receptors by triggering the release of acetylcholine, stimulating the protein kinase C-alpha pathway for increased calcium sensibility, inhibiting the secretion of the hormone somatostatin, increasing fluid electrolyte accumulation in the distal ileum and colon, and inhibiting the activity of Na+/K+-ATPase and/or potassium channels. Emodin's antiinflammatory action is due to its specific inhibition of the transcription factor NF-kB. It also regulates angiogenesis by inhibiting the enzymes casein kinase II and nitric oxide synthase and has shown potent estrogen receptor binding affinity. Emodin can induce the microsomal enzyme cytochrome P-450 1A1, perpetuating its own metabolic activation. (A3043, A3044, A3045, A3046, A3047, A3048, A3049, A3050, A3051, A3052, A3053, A3054)

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical. [http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=518-82-1]

Emodin

TR-493: Toxicology and Carcinogenesis Studies of Emodin (CASRN 518-82-1) in F344/N Rats and B6C3F1 Mice (Feed Studies) (2001 )

05/21/99

No Evidence

Equivocal Evidence

Equivocal Evidence

/LABORATORY ANIMALS: Acute Exposure/ This compound has caused gastrointestinal effects in experimental animals.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ ... The effect of emodin on hepatic fibrosis in rats /was investigated/. The rat hepatic fibrosis model was induced by the subcutaneous injection of 40% CCl4 (twice a week for 6 weeks) dissolved in olive oil. The emodin-treated rats were treated with low-dose, intermediate-dose and high-dose emodin (20, 40 and 80 mg/kg body weight, once a day for 42 days) dissolved in 0.5% sodium carboxymethylcellulose (CMC), except receiving CCl4. Control group received only olive oil and 0.5% CMC... Compared with model group, the emodin-treated rats showed (1) liver functions were improved, alanine transaminase (ALT) and alkaline phosphatase (AKP) were obviously reduced, and total protein (TP) and albumin (ALB) were significantly increased; (2) serum hyaluronic acid and laminin were markedly reduced; (3) liver hydroxyproline was significantly decreased; (4) the degrees of fibrosis were reduced. The changes of parameters mentioned above were significant (P < 0.05 or P < 0.01). Emodin has effect on hepatic fibrosis in rats. The hepatoprotective of emodin /SRP: may effect liver fibrosis/.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ ... Emodin and cassiamin B /were examined as cancer chemopreventive agents/ ... These compounds exhibited the remarkable anti-tumor promoting effect on two-stage carcinogenesis test of mouse skin tumors induced by 7,12-dimethylbenz[a]anthracene as an initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as a promoter by both topical application. Furthermore, emodin exhibited potent inhibitory activity on two-stage carcinogenesis test of mouse skin tumors induced by nitric oxide donor, (+/-)-(E)-methyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexeneamide as an initiator and TPA as a promoter.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ EMOD /emodin/ was administered in feed to timed-mated Sprague-Dawley (CD) rats (0, 425, 850, and 1,700 ppm; gestational day (gd) 6 to 20), and Swiss albino (CD-1) mice (0, 600, 2,500; or 6,000 ppm; gd 6 to 17). Ingested dose was 0, 31, 57, and 80-144 mg EMOD/kg/day (rats) and 0, 94, 391, and 1,005 mg EMOD/kg/day (mice). ...There were no maternal deaths; discolored, soft or loose feces were observed at the high dose in mice. In rats, maternal body wt decreased at the high dose (gd 9, 12); wt gain was reduced at the mid (gd 6-9) and high dose (gd 6-9; 6-20). Maternal body wt (gestation) and wt gain (corrected for gravid uterine weight (GUW)) exhibited a decreasing trend. In mice, maternal body wt and wt gain decreased at the high dose. Prenatal mortality, live litter size, fetal sex ratio, and morphological development were unaffected in both rats and mice. At the high dose, rat average fetal body wt/litter was unaffected, but was significantly reduced in mice. The rat maternal LOAEL was 1,700 ppm based on maternal body weight and weight gain; the NOAEL was 850 ppm. The rat developmental toxicity NOAEL was greater than 1,700 ppm; a LOAEL for rat developmental toxicity was not established. In mice, the maternal toxicity LOAEL was 6,000 ppm based on reduction of maternal body wt and wt gain; the NOAEL was 2,500 ppm. The developmental toxicity LOAEL was 6000 ppm, based on reduction of fetal body wt; the NOAEL was 2,500 ppm.

SKIN CONTACT: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment.

INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. IMMEDIATELY call a physician and be prepared to transport the victim to a hospital even if no symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Respirator Recommendation.

EYE CONTACT: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

INGESTION: If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Generally, the induction of vomiting is NOT recommended outside of a physician's care due to the risk of aspirating the chemical into the victim's lungs. However, if the victim is conscious and not convulsing and if medical help is not readily available, consider the risk of inducing vomiting because of the high toxicity of the chemical ingested. Ipecac syrup ... may be used in such an emergency. IMMEDIATELY transport the victim to a hospital. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

Medicine (cathartic)

This compound is used as a cathartic and a dye intermediate.

Emodin is a mycotoxin and naturally occurring anthraquinone present in the roots and barks of numerous plants, such as rhubarb. It is an active ingredient of Chinese herbs, including Rheum officinale and Polygonam cuspidatum. Emodin is also produced as a secondary metabolite by molds and lichens such as Aspergillus wentii. It has been used as a laxative and also investigated as a potential chemotherapeutic drug. (A3043)