Rhubarb is a group of plants that belong to the genus Rheum in the family Polygonaceae. They are herbaceous perennial plants growing from short, thick rhizomes. They have large leaves that are somewhat triangular, with long fleshy petioles.
They have small flowers grouped in large compound leafy greenish-white to rose-red inflorescences.
Although the leaves are toxic, various parts of the plants have medicinal and culinary uses. The traditional Chinese pharmacopeia features rhubarb (as a laxative).
TOXICITY
Rhubarb leaves contain poisonous substances, including oxalic acid which is a nephrotoxic and corrosive acid that is present in many plants. The
LD50 (median lethal dose) for pure oxalic acid in rats is about 375 mg/kg body weight, or about 25 grams for a 65 kg (~140 lb) human. (Other sources give a much higher oral
LDLo (lowest published lethal dose) of 600 mg/kg.) While the oxalic acid content of rhubarb leaves can vary, a typical value is about 0.5%, so a rather unlikely 5 kg of the extremely sour leaves would have to be consumed to reach an
LD50 of oxalic acid. Cooking the leaves with soda can make them more poisonous by producing soluble oxalates. However, the leaves are believed to contain also an additional, unidentified toxin, which might be an anthraquinone glycoside (also known as senna glycosides).
MEDICINE
Rhubarb can be used as a strong
laxative. Its roots have been used as a laxative for at least 5,000 years.
PURGATIVE ACTION
The purgative activity of RH appears to be due to rhein and the sennoside components [14]. Sennoside content correlated highly with laxative activity, whereas the correlation between anthraquinone content and laxative activity was low. Studies on the oxidized products of sennosides suggest that the sennosides act predominantly on large intestine motility after their degradation by colonic microorganisms. The mechanism appears to be hydrolysis of sennosides by microbial b-glycosidase in a stepwise fashion to sennidins A & B, which are then reduced to rheinanthrone, the laxative principle. The active principles of RH seem to act by stimulating Auerbach's plexus or the submucosal nerve plexus. Other investigators found that RH increased the water content of the large intestine, producing a watery stool. Interestingly, small doses of RH (0.05-0.3g/kg) in some patients can be used to treat diarrhea or may increase constipation. At these dosage levels, it is thought that the effect of the tannins in binding stool overcomes the laxative effect. It may also be due to the differences in gut flora and consequent metabolites. Certain species contain more tannins than others, for example R. palmatum contains about 11% tannin, whereas other species range from 4-7%.
The roots and stems are rich in anthraquinones, such as emodin and rhein. These substances are cathartic and laxative, which explains the sporadic use of rhubarb as a dieting aid.
The rhizomes ('roots') contain stilbenoid compounds (including rhaponticin), which seem to lower blood glucose levels in diabetic mice
In the petioles, the amount of oxalic acid is much lower, only about 2-2.5% of the total acidity, which is dominated by malic acid.This means the raw stalks may not be hazardous, although the tart taste of raw stalks is so strong as to be unpalatable to many.
Rhubarb,2012
ANTHRAQUINONE
Anthraquinone is an organic compound whose structure serves as a basic building block for a number of naturally occurring plant pigments. The compound is used in the production of dyes and as a catalyst for the production of wood pulp. Anthraquinone is also an effective goose repellent – the birds experience an unpleasant intestinal reaction after eating grass that is treated with the compound.
Chemical Structure of Anthraquinone:
Two-year toxicity tests conducted by the National Toxicology Program have raised serious concerns about the safety of anthraquinone. According to the
NTP report on anthraquinone released in February 2004, the test results showed clear evidence of liver carcinogenicity in laboratory animals that consumed feed containing the compound. The researchers also found evidence of non-cancerous lesions in other organs, along with possible effects on the endocrine system.
In September 2007, the California Environmental Protection Agency added anthraquinone to the list of chemicals known to cause cancer. The public listing of known cancer-causing agents is required by the Safe Drinking Water and Toxic Enforcement Act, commonly known as Proposition 65.1 The agency based its listing on the National Toxicology Program’s formal identification of anthraquinone as a carcinogen in laboratory animals.
Back in 1998, the compound was approved by the
U.S. Environmental Protection Agency for use as a non-lethal goose repellent in terrestrial areas near airports, commercial and industrial sites, and developed urban areas.2 The
EPA conducted a review of anthraquinone following a request by Environmental Biocontrol International to approve the use of the compound. Based on studies submitted by the company, the
U.S. EPA concluded that the overall toxicological risk to humans from exposure to anthraquinone was considered negligible. For more information on the findings and conclusions of the
EPA review, please see the Anthraquinone Fact Sheet
National Institutes of Health,Anthraquinone,2007
Anthraquinone, also called anthracenedione or dioxoanthracene is an aromatic organic compound with formula
C14H8O2. Several isomers are possible, each of which can be viewed as a quinone derivative. The term anthraquinone, however, almost invariably refers to one specific isomer, 9,10-anthraquinone (IUPAC: 9,10-dioxoanthracene) wherein the keto groups are located on the central ring. It is a building block of many dyes and is used in bleaching pulp for papermaking. It is a yellow highly crystalline solid, poorly soluble in water but soluble in hot organic solvents. For instance, it is almost completely insoluble in ethanol near room temperature but 2.25 g will dissolve in 100 g of boiling ethanol.
ANTI-CANCER PROPERTIES OF ANTHRAQUINONES FROM RHUBARB
Rhubarb has been used as a traditional Chinese medicine since ancient times and today it is still present in various herbal preparations. In this review 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-kappaB), 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.
Anti-cancer properties of anthraquinones from rhubarb,2007
Antineoplastic effect
Emodin was found to be a strong inhibitor of respiration in Ehrlich ascites carcinoma cells [10]. This was also observed in leukemia
L1210 cells. Emodin strongly inhibited the oxidation and dehydrogenation of some amino acids and intermediate metabolites of glucose in Ehrlich ascites carcinoma cells. At 50mg/ml emodin inhibited the oxidation and dehydrogenation of lactic acid in these cells by 87 & 91% respectively. It was further reported that the anthraquinone derivatives rhein, emodin and aloe emodin had an in vivo inhibitory effect against
P388 leukemia in mice. Their survival time was markedly increased and the ascites volume and tumor cell number were decreased. In general, it is thought that the antineoplastic activity of RH is mainly due to the inhibition of oxidation and dehydrogenation of the cancer cells.
ANTI-ANGIOGENIC PROPERTIES
ETHNOPHARMACOLOGICAL RELEVANCE: Rhubarb root (Dahuang) is often included as an ingredient in traditional Chinese compound prescriptions for the treatment of inflammatory diseases. This application may possibly be mediated through anti-angiogensis and thus would shed light on its potential value in cancer therapy.
AIM OF THE STUDY: To elucidate the anti-angiogenic properties of rhubarb root, we tested the inhibitory effects of different fractions and a series of anthraquinone derivatives against vessel formation in zebrafish embryos.
MATERIALS AND METHODS: The 95% ethanol extract and four subsequent fractions (n-hexane, ethyl acetate, n-butanol and aqueous fractions) of rhubarb root and five anthraquinone derivatives were investigated on zebrafish model by quantitative endogenous alkaline phosphatase assay and staining assay.
RESULTS:
Ethyl acetate fraction showed the strongest inhibition of vessel formation by 52%. Three anthraquinones (aloe-emodin, emodin and rhein) displayed potent anti-angiogenic activities.
CONCLUSIONS:
The angiogenic properties of rhubarb root may partly account for its use in inflammatory diseases. The anthraquinones with acidic or polar, hydrophilic substitution at C-6 or C-3 positions played a substantial role in inhibiting angiogenesis. The value of the zebrafish angiogenic model is further supported.
Anti-angiogenic effects of rhubarb and its anthraquinone derivatives,2009
TRANS-RESVERATROL ALONE AND HYDROXYSTILBENES OF RHUBARB (RHEUM RHAPONTICUM L.) ROOT REDUCE LIVER DAMAGE INDUCED BY CHRONIC ETHANOL ADMINISTRATION
The hepatoprotective effects and pharmacokinetics of trans-resveratrol and hydroxystilbenes of the garden rhubarb (Rheum rhaponticum
L., R. rhaponticum) root ethanol extract were studied. Ethanol was administered to male
BALB/c mice for 35 days in an inhalation chamber. During this time vehicle, trans-resveratrol (20 mg/kg per day) or R. rhaponticum extract was intraperitoneally (i.p.) administered and mice were sacrificed for the collection of liver and blood. In an additional experiment, the level of parent compounds and metabolites was estimated in the blood after acute i.p. administration of trans-resveratrol or R. rhaponticum extract. The levels of hydroxystilbenes, their metabolites and fatty acid oxy-metabolites (oxylipins) were studied by LC-tandem
DAD-MS/MS. Ethanol induced hepatotoxicity, as evidenced by histological changes and accumulation of oxylipins in the blood. Both trans-resveratrol and R. rhaponticum extract reduced the extent of these changes. The pharmacokinetics of trans-resveratrol was characterized by a rapid removal from the blood and metabolism to sulfates and glucuronides. After the administration of R. rhaponticum extract, in addition to trans-resveratrol glucoside and its metabolites, several other hydroxystilbenes were found. Inhibition of oxidation of polyunsaturated fatty acids is proposed as a basis of the hepatoprotective effect of both trans-resveratrol and R. rhaponticum extract.
Trans-resveratrol alone and hydroxystilbenes of rhubarb (Rheum rhaponticum L.) root reduce liver damage induced by chronic ethanol administration: a comparative study in mice,2009
AQUEOUS EXTRACT OF RHUBARB STABILIZES VULNERABLE ATHEROSCLEROTIC PLAQUES DUE TO DEPRESSION OF INFLAMMATION AND LIPID ACCUMULATION
The study evaluated the effect of the traditional Chinese medicine rhubarb on the stability of atherosclerotic plaque. Atherosclerotic lesions were induced in rabbits through balloon injury with a high-cholesterol diet and then were divided into a control group, a rhubarb group and a simvastatin group. At week 24 recombinant-p53 adenoviruses were locally delivered to the atherosclerotic plaques. At week 26 plaque rupture was triggered by the intra-arterial Chinese Russell's viper venom and histamine. Serological, ultrasonographic, pathologic, immunohistochemical and gene expression studies were performed. The results showed that the incidence of plaque rupture in the rhubarb group and the simvastatin group was significantly lower than that in the control group (42.86% and 35.71% versus 80.00%, both p < 0.05). Serum
TC, LDL-C (p < 0.05-0.01),
IMT (both p < 0.01), PA (both p < 0.01), PB (%) (both p < 0.01) and the mRNA and protein expressions of
TLR2, TLR4 and NF-kappaB (p < 0.05, 0.01, respectively) in the rhubarb group and the simvastatin group were significantly lower than those in the control group. In contrast,
AIIc% (both p < 0.05) in the two treatment groups were significantly higher than those in the control group. These results suggest that rhubarb has antiatherosclerotic and plaque-stabilizing properties due to antiinflammation and lipid-lowering effects.
Aqueous extract of rhubarb stabilizes vulnerable atherosclerotic plaques due to depression of inflammation and lipid accumulation,2008
Hypertension during pregnancy
Shanghai Medical University conducted a double blind study with processed rhubarb (low dose of 0.75g/day) in pregnant women at risk of pregnancy-induced hypertension (PIH). Rhubarb (140 cases) and placebo (125 cases) was given to women at risk of
PIH consecutively from the 28th week of gestation to delivery, with another 68 pregnant women as control. In the treated group, 5.7% of the women developed
PIH, whereas in the untreated group 20.8% developed
PIH. This result was statistically significant (P<0.01). The mechanism of this apparent protection may be related to the inhibition of Plasminogen activator inhibitor (PAI), plasma Fibronectin (Fn), and decreased damage to the vascular endothelium. Interestingly, the tannin components of RH have also been found to have
ACE-inhibiting actions.
In summary, for its chemical component, rhubarb has many important medical effects. Many of these have already to be study
