Rhubarb

Synopsis

Rhubarb (Rheum spp.) as a Dietary Supplement and Medicinal Botanical

1. Identity, Botanical Classification, and Common Preparations

Taxonomy and Species

Rhubarb is a collective name for various perennial plants of the genus Rheum L. from the Polygonaceae family. The genus comprises approximately 60 species globally. In dietary supplement and medicinal contexts, several distinct species are relevant, and their identities matter greatly because their phytochemical profiles and intended uses differ substantially.

Currently, the types of rhubarb used in traditional Chinese medicine have stabilized to three species: Rheum palmatum L., Rheum tanguticum Maxim. ex Balf., and Rheum officinale Baill. Most dietary supplements contain the roots of two specific plants that are both known as Chinese rhubarb — Rheum palmatum and Rheum officinale. Each part of the plant contains different chemicals that have different effects on the body. A fourth species, Rheum rhaponticum (Siberian or rhapontic rhubarb), is the source of the well-studied proprietary extract ERr 731®, used specifically for menopausal symptoms and discussed in detail below. Medicinal rhubarb consists of the dried rhizome and root of R. officinale Baillon or R. palmatum, of related species/hybrids grown in China (Chinese rhubarb), or of Rheum emodi or Rheum webbianum native to India, Pakistan, or Nepal (Indian rhubarb).

Rhubarb consists of the dried roots and rhizomes of Rheum palmatum L., Rheum tanguticum Maxim. ex Balf., and Rheum officinale Baill. according to the Taiwan Herbal Pharmacopeia 4th edition, or the underground parts of R. palmatum L. and R. officinale Baill. as per the European Pharmacopoeia 10.0.

Plant Morphology

The perennial herb has a conical rootstock that is fleshy and yellow inside and produces large, cordate, 7-lobed leaves 30 to 46 cm long. It is native in the regions of western China, northern Tibet, and the Mongolian Plateau. The edible stalks are up to 45 cm long and 2.5 to 5 cm in diameter, and are used in pies, jams, jellies, sauces, and juices.

Common Names and Forms

Rhubarb is also named Rhei or Dahuang (Da Huang) in traditional Chinese medicine. Other historical trade names included "Turkey rhubarb," "Russian rhubarb," and "Indian rhubarb," reflecting the routes along which the root was transported to European markets rather than any particular species.

Rhubarb is commercially available in several forms:

R. officinale (Chinese rhubarb), R. palmatum, and other anthraquinone-rich rhubarb species are predominantly administered as laxatives. They are commercially available as Radix Rhei or as components of different herbal mixtures, dietary supplements, and teas dedicated to alleviating gastrointestinal disorders and treating constipation.
Common concoctions in TCM include raw rhubarb, wine rhubarb, cooked rhubarb, and rhubarb charcoal.
A standardized proprietary root extract from R. rhaponticum, designated ERr 731®, is used in Germany and other markets specifically for the treatment of menopausal symptoms.

Petioles of edible rhubarbs such as R. rhaponticum and R. rhabarbarum are used for culinary purposes, while their underground parts are a source of herbal material.

2. Traditional and Historical Use

Traditional Chinese Medicine (TCM)

Rhubarb is one of the most ancient and important herbs in traditional Chinese medicine, and its application can be traced back to 270 BC in the Shen Nong Ben Cao Jing. In China, it is primarily utilized for medicinal purposes, ranking as one of the four principal traditional Chinese medicines. Rhubarb has been used in numerous decoctions, such as Da-Cheng-Qi-Tang and Xiao-Cheng-Qi-Tang, and in Shang-Han-Lun of Zhang-Zhong-Jing at the end of the Han Dynasty — one of the four classic Chinese medicinal literature works.

Historical records of rhubarb processing date back to the Han Dynasty, with continual innovations. Guided by Chinese medicine theory, the use of different rhubarb concoctions can enhance specific effects such as purgation to eliminate accumulation, clearing heat and toxins, cooling blood to stop hemorrhages, activating blood circulation to remove blood stasis, and inducing dampness to descend jaundice, thereby effectively treating various diseases.

TCM texts recorded rhubarb as a remedy for a remarkably broad range of conditions. It was commonly prescribed to address abdominal pain, jaundice, and dysentery, and also used externally to treat burns and infections. The Chinese also used rhubarb root as a laxative and purgative for the treatment of both constipation and diarrhea, depending upon the dosage used. Larger doses cause purging that removes toxins from the intestinal tract, while smaller doses are believed to moisten the mucous membranes of the intestines and improve their tone. The tannins that are also found in the root may eventually cause binding of the bowel.

Chinese herbalists also used rhubarb root for diseases and disorders in the upper body, including sinus and lung infections, nosebleeds, and eye infections. According to the principles of traditional Chinese medicine, rhubarb root makes the heat in the upper body discharge through the bowel.

Traditional Use in Europe and Persia

The dried roots of Chinese rhubarb became one of the most prominent items traded along the Silk Road. Imported roots of various rhubarb species were widely used in Europe for hundreds of years before the identity of the plant was eventually discovered. One of the earliest Western records appears in Dioscorides' De materia medica (50–70 CE), where it was described as Rha and recommended for conditions including stomach weakness and flatulence.

In China, it was classed as a dangerous cathartic rather than a commonplace remedy; in Europe, however, it circulated as a more tempered medicine. It has been indicated for enteritis, gastritis, constipation, and diarrhea in Persian medicine.

Rhubarb was first recorded and rated as one of the inferior remedies in the oldest Chinese herbal books, from 22 to 250 AD. Traditional uses documented across cultures include the treatment of constipation, diarrhea, fever, menstrual problems, jaundice, sores (when applied topically), ulcers, and burns.

3. Key Constituents and Active Compounds

Current literature reveals that rhubarb contains over 100 compounds, primarily including anthraquinones, tannins, stilbenes, and phenylbutanones. Thirty compounds belonging to anthraquinones, anthraquinone glucosides, dianthrones, phenylbutanones, stilbenes, flavan-3-ols, procyanidins, galloylglucoses, acylglucoses, gallic acid, and polymeric procyanidins have been analyzed quantitatively.

Anthraquinones

Anthraquinones are the main characteristic as well as pharmacodynamic ingredients of rhubarb. The proportion of anthraquinones ranges from 3 to 5% in different species. More than 30 anthraquinones have been isolated and identified from rhubarb.

These derivatives are classified into two types: free and combined. Free anthraquinones consist of compounds such as rhein, emodin, aloe-emodin, chrysophanol, and physcion. Combined anthraquinones, typically glycosides, result from the linkage of free anthraquinones with glycosyl groups, and anthrone derivatives include compounds such as sennoside A–D.

Emodin is one of the most studied individual compounds. Rhein has a variety of pharmacological effects, such as cardiocerebral protective effect, hepatoprotective effect, nephroprotective effect, anti-inflammation effect, antitumor effect, antidiabetic effect, and others. The mechanism is interrelated and complex, referring to NF-κB, PI3K/Akt/MAPK, p53, mitochondrial-mediated signaling pathway, oxidative stress signaling pathway, and so on.

Aloe-emodin, another important active compound of rhubarb, has attracted much attention due to its various effects such as cardiovascular protection, hepatoprotective activities, anti-tumor, antibacterial, antifungal, antiviral, anti-inflammatory, immune regulation, and laxative properties.

Tannins

Several pharmacological investigations have been conducted on rhubarb tannins initiating anti-diarrheagenic effects. Aloe-emodin, chrysophanol, emodin, physcion, rhein, and their glycosides are major rhubarb anthraquinones. Moreover, catechin, catechin gallate, catechin-glucopyranoside, gallic acid, and galloyl glucose are among the major rhubarb tannins. Tannins are astringent in character and are considered responsible for rhubarb's paradoxical ability to reduce diarrhea at lower doses.

Stilbenes and Hydroxystilbene Glycosides

Stilbene glycosides, including rhaponticin and the metabolite rhapontigenin, have been identified in the root. Tannins, sennosides, catechins, gallic acid, and cinnamic acid have also been identified. Lindleyin, a phytochemical with estrogenic activity, has also been described. Rhubarb is also a dietary source of resveratrol.

The estrogenic activity of R. rhaponticum has been well-documented in animal and clinical studies. It has been primarily attributed to the presence of different hydroxystilbenes and their derivatives, including rhaponticin, desoxyrhaponticin, rhapontigenin, desoxyrhapontigenin, resveratrol, and piceatannol.

Sennosides and Anthrones

Anthrones and dianthrones, also characteristic components of rhubarb, are related to purgative activity. These mainly include rheinosides A–D, palmidin A, B, C, rheidin A, B, C, and sennosidin A–F. Sennosides have strong cathartic effects through translating to anthraquinones in vivo.

Oxalic Acid

Oxalic acid is present in the leaf blades, as well as 2-methylbutanol and 4-methylhexanol. This compound is toxicologically relevant and is discussed further in the safety section.

4. Established Mechanisms of Action

Laxative and Purgative Mechanism

Anthraquinones, encompassing both derivatives and anthrone derivatives, are identified as the key characteristics and pharmacologically active compounds of rhubarb, offering effects such as laxative, anti-inflammatory, antibacterial, antiviral, and anticancer.

Free anthraquinone can upregulate VIP (vasoactive intestinal peptide) expression, promote cAMP/PKA signaling pathway transduction and CFTR expression, while inhibiting ENaC and NHE3 expression, increasing intestinal osmotic pressure and leading to diarrhea. Sennoside A can inhibit the expression of COX2 and the release of PGE2 in macrophages, thereby reducing the expression of aquaporins in the colon and inhibiting the absorption of water in the intestine, leading to diarrhea.

It is thought that anthraquinones can stimulate the nerve plexus within the mucosa and intestinal smooth muscles, promoting peristalsis. The rhubarb extractives and the anthraquinone derivatives can antagonize the adrenaline effectively, which can inhibit the contraction of the smooth muscle in an in vitro system of isolated intestine. Rhubarb effectively down-regulates the expression of AQP4 in the rat's proximal colon, and rhein/emodin can suppress AQP4 expression of LoVo cells in vitro. Sennoside A may decrease AQP3 expression in the colon to inhibit water transport from the luminal to the vascular side, leading to laxation.

Estrogenic / Selective Estrogen Receptor Modulator Activity

ERr 731 acted as a highly selective agonist for ERβ in the hypothalamus of ovariectomized rats, as well as in ERα/β cell-based reporter assays. Unlike hormone therapy, ERr 731 (a standardized botanical extract of Siberian rhubarb Rheum rhaponticum L. high in rhaponticin) acts like a selective estrogen receptor modulator for ERβ receptors and may offer a higher degree of safety while maintaining the desired efficacy profile.

Anti-inflammatory Mechanisms

Rhubarb reduces the permeability of the capillaries, inhibits the release of inflammatory cytokines and oxygen free radicals, promotes intestinal goblet cell hyperplasia, and improves microcirculation of intestinal mucosa. MAPK and PI3K-AKT parallel signaling pathways are activated, and several downstream pathways are affected, thereby eventually regulating cell cycle and apoptosis.

Renal Protective Mechanisms

Emodin decreased the gluconeogenesis of renal tubular cells and diminished the ATP content of epithelial mitochondria. Both the Na⁺/K⁺-ATPase and Ca²⁺-ATPase activities of the epithelial cell were attenuated during the administration of emodin in an in vitro study.

Hemostatic Effects

Rhubarb has a hemostatic effect and is used clinically to treat gastrointestinal bleeding. The tannin fractions are thought to contribute to this astringent, tissue-contracting action.

5. Scientific Evidence by Area of Use

5.1 Constipation and Gastrointestinal Motility

The laxative effect of rhubarb root on constipation is its best-established use and has the most supporting clinical data, though rigorous large-scale trial data in Western populations is limited.

Raw rhubarb and its formulations are utilized in treating constipation, gastrointestinal dysfunction, and intestinal obstruction. Supplementation with raw rhubarb extract has improved stool frequency and consistency in a dose-dependent manner in middle-aged constipated patients, without impacting safety indicators, thus confirming its reliability and safety for non-severe constipation cases. This therapeutic effect is likely linked to the modulation of the intestinal microbiota by raw rhubarb.

Topical application of raw rhubarb powder to the Shenque acupoint has effectively improved functional constipation in Parkinson's patients in terms of defecation frequency and stool character.

Evidence strength: Most reported clinical trials have been small and poorly designed, and in some studies, a number of different herbs were coadministered with rhubarb, making it difficult to evaluate which herb contributed to the outcomes. The mechanistic basis for laxation is well characterized at the molecular level.

5.2 Chronic Kidney Disease and Chronic Renal Failure

Rhubarb has been studied extensively in China for its potential to slow the progression of chronic renal failure (CRF), and several meta-analyses have been published.

A total of 2,786 patients were included in 34 studies for a meta-analysis. The results showed statistically significant reductions in serum creatinine (SCR) [MD = 123.57], blood urea nitrogen (BUN) [MD = −3.26, 95% CI (−4.22, −2.31)], and uric acid [MD = −42.79, 95% CI (−66.29, −19.29)]. Compared with the control group, rhubarb alone or traditional Chinese medicine compound containing rhubarb can significantly reduce serum creatinine, blood urea nitrogen, and uric acid, and increase creatinine clearance rate.

In a prospective clinical trial conducted in 151 patients with chronic renal failure, the progression rate of renal failure was slowed in patients treated with rhubarb. There was an increase in both plasma albumin and transferrin level, pointing towards improved nutritional status.

Evidence strength and limitations: There is no evidence that rhubarb is more effective than the control group in increasing hemoglobin. In addition, due to the low quality of research methodology in the included literature, it is necessary to further study high-quality literature to evaluate its efficacy and safety. Meta-analyses indicate that rhubarb may improve serum creatinine and blood urea nitrogen in patients with chronic kidney disease, although these results are limited by the methodological quality of the studies.

5.3 Menopausal Symptoms (Rheum rhaponticum / ERr 731®)

This is an important and distinct area of clinical use, driven not by anthraquinone content (which is absent in R. rhaponticum) but by the plant's estrogenic stilbene glycosides. The R. rhaponticum used in clinical studies and in the extract form of ERr 731 does not contain any emodin or aloe-emodin and thus has no laxative effects.

In Germany, the special extract ERr 731 from the roots of rhapontic rhubarb has been prescribed regularly for women with menopausal symptoms since 1993. The main compounds of ERr 731® (drug-to-extract ratio 16–26:1) are the hydroxystilbene glycosides rhaponticin and desoxyrhaponticin as well as their aglycones desoxyrhapontigenin and trans-rhapontigenin as minor constituents (both about 5%).

The clinical efficacy of ERr 731® was provided in a 12-week double-blind, placebo-controlled clinical trial in 109 perimenopausal women. The study demonstrated that in the ERr 731® group, the Menopause Rating Scale II (MRS II) total score in addition to each of the 11 MRS II criteria representing cardinal symptoms of the climacteric were significantly reduced compared to the placebo group.

Additionally, 82 subjects of this clinical trial continued intake of ERr 731® in the following 48- and 96-week open-label observational studies which demonstrated the long-term safety of ERr 731®, as no endometrial hyperplasia could be detected and no adverse events related to the study medication occurred.

ERr 731 was effective in decreasing the number and severity of hot flushes in a 12-week multicenter trial that included 109 women with climacteric complaints, a menopause rating scale total score given after 6 months of treatment in 252 women, as well as 112 perimenopausal women with menopausal symptoms followed for 12 weeks.

The supporting research included one observational study, two randomized clinical trials, two long-term (one and two years) studies, and one post-marketing study which registered approximately 200 adverse events with approximately 155 million daily doses administered.

Post-marketing surveillance data from Germany (140 million daily doses), the United States, and Canada (13 million) suggest that the extract is generally safe for consumption.

Evidence strength: The North American Menopause Society position statement for nonhormonal management of menopause-associated vasomotor symptoms (2015) states that although beneficial effects in overall symptoms have been reported with a commercial proprietary rhubarb extract preparation, more data are needed on both safety and efficacy of Siberian rhubarb (Rheum rhaponticum) for use in menopausal vasomotor symptoms (Level II). Large, randomized clinical trials are lacking.

5.4 Acute Pancreatitis

Studies from clinical trials have shown that rhubarb has beneficial effects on patients with severe acute pancreatitis (SAP) for significant improvement of gastrointestinal function and inhibition of systemic inflammation. Rhubarb inhibited the inflammatory response, improved intestinal microcirculation, and restored normal intestinal absorption, to exert the function of treating acute pancreatitis.

Rhubarb has shown benefits for treating acute pancreatitis in several Chinese meta-analyses. When administered at doses of 10 to 90 g daily via gastric tube for 3 to 14 days in combination with somatostatin or octreotide, rhubarb reduced the risk of complications such as sepsis and renal failure by 45%, shortened the duration of abdominal pain by 1.3 to 2 days, and slightly reduced hospital stay.

Evidence strength: Evidence is largely derived from Chinese clinical trials and meta-analyses, most of which use rhubarb as part of multi-herb TCM formulations. This makes it difficult to isolate rhubarb's specific contribution, and methodological quality concerns apply.

5.5 Upper Gastrointestinal Bleeding

Rhubarb has been used for conditions such as constipation, chronic renal failure, and upper gastrointestinal bleeding. Rhubarb has a hemostatic effect and is used clinically to treat gastrointestinal bleeding. A systematic review and meta-analysis evaluated spraying rhubarb powder solution under gastroscope in the treatment of acute non-varicose upper gastrointestinal bleeding, with results suggesting the approach may be beneficial, though the sample sizes included were noted as a limitation. Evidence strength: Preliminary; largely from small Chinese RCTs with significant methodological limitations.

5.6 Hyperlipidemia and Cardiovascular Risk

A growing body of evidence shows that rhubarb has excellent lipid-lowering properties and plays a vital role in the treatment of lipid metabolism disorders such as atherosclerosis. In 103 patients with atherosclerosis randomized to receive rhubarb extract for 6 months, rhubarb extract improved the lipid profile in patients with chronic renal failure compared with control. Individuals taking rhubarb reported decreased LDL compared with those taking placebo and compared with the pretreatment levels.

Treating hypercholesterolemia in men with rhubarb stalk fiber for 4 weeks lowered serum total cholesterol and low-density lipoproteins (LDL), while high-density lipoproteins remained unchanged.

Evidence strength: Preliminary. Studies are generally small and short-term. The underlying molecular mechanism appears complex: by analyzing the lipid-lowering effects and the underlying mechanism of the major ingredients of rhubarb, some active ingredients perform opposite effects in regulating the expression of lipid transporters or relative genes involved in lipid metabolism. For example, emodin can markedly facilitate the expression of PPARγ, LXRs, ABCA1, and ABCG1, whereas rhein has contrary effects, though they both downregulate lipid levels.

5.7 Antimicrobial Properties

The main chemical compositions of rhubarb include anthraquinones, anthrones, stilbenes, tannins, and polysaccharides. These compositions show extensive pharmacological activities including antimicrobial action, among others. Rhubarb is gaining global recognition beyond traditional medicine, with documented pharmacological effects including bacterial resistance.

Evidence strength: Mostly in vitro and animal data. Robust human clinical evidence for rhubarb as a standalone antimicrobial agent is lacking.

5.8 Anticancer Properties

Emodin inhibited the proliferation of tumor cells and induced apoptosis. Rhein has various pharmacological activities, such as anti-inflammatory, antitumor, antioxidant, antifibrosis, hepatoprotective, and nephroprotective activities.

Evidence strength: Preclinical only (in vitro and animal models). There are no established human clinical trials demonstrating anticancer efficacy of rhubarb or its isolated compounds in humans.

6. Body Systems Associated with Rhubarb

Gastrointestinal system: Laxative, antidiarrheal (dose-dependent), treatment of constipation, gastrointestinal bleeding, and pancreatitis.
Renal/urinary system: Potential slowing of chronic kidney disease progression; also associated with nephrotoxicity risk at high doses.
Endocrine/reproductive system: ERβ-selective estrogenic activity via stilbene constituents in R. rhaponticum; used for menopausal vasomotor symptom management.
Cardiovascular system: Preliminary evidence for lipid-lowering and anti-atherosclerotic effects via emodin, rhein, and related compounds.
Immune/inflammatory system: Inhibition of inflammatory cytokine release and modulation of NF-κB and MAPK pathways documented in laboratory studies.
Hepatic system: Dual hepatoprotective and, at high doses, hepatotoxic potential — highly dose-dependent.

7. Dosage Forms and Dosages Reported in Studies

Dried rhubarb extract 20 to 50 mg/kg daily has been used in clinical trials.

In acute pancreatitis studies, rhubarb was administered at doses of 10 to 90 g daily via gastric tube for 3 to 14 days in combination with somatostatin or octreotide.

Rhubarb extract has been evaluated in pregnancy-related hypertension at 0.75 g daily.

Rhei Rhizoma extract is taken orally at doses of 0.5–1 g each, or 1–3 g daily, in clinical practice.

For the menopausal symptoms indication, ERr 731®, an extract isolated from the roots of the Siberian rhubarb (Rheum rhaponticum), has been used regularly since the beginning of the 1990s for the treatment of women suffering from oligomenorrhea or amenorrhea. The extract has been used in clinical trials at the dose corresponding to the commercially available tablet (4 mg extract per tablet, equivalent to approximately 64–104 mg of the dried root).

Common TCM preparations include raw rhubarb, wine rhubarb, cooked rhubarb, and rhubarb charcoal, each with distinct phytochemical profiles and pharmacological emphases due to differing processing methods. Rhubarb is also available as powders, teas, tinctures, and standardized capsule/tablet supplements.

8. Safety Considerations and Drug Interactions

General Adverse Effects

Clinical trials using rhubarb extract report few adverse reactions; most relate to mild GI symptoms that resolve without treatment. Common side effects of rhubarb root may include cramping, stomach pain, diarrhea, nausea, or vomiting.

Leaf Toxicity (Oxalic Acid)

The leaf blades, but not the stalks, of rhubarb contain enough oxalic acid to cause poisoning. Consumption of rhubarb in patients with renal stones is not advised because of the oxalate content. The toxic substances — anthraquinone glycosides (possible) and oxalic acid — are found in the leaves (leaf blade) of the rhubarb plant. The stalk can be eaten. Rhubarb leaves contain high amounts of oxalic acid, which can cause health problems when eaten in higher amounts. Symptoms of toxicity include mild gastrointestinal symptoms as well as more serious problems such as kidney stones and kidney failure.

Hepatotoxicity and Nephrotoxicity

There are an increased number of concerns regarding the effectiveness and safety of rhubarb, especially after consecutive reports of adverse hepatotoxic effects and renal toxicity of anthraquinones in in vitro and in vivo studies. The U.S. Department of Health and Human Services conducted a two-year National Toxicology Program study on emodin and demonstrated the potential hepatotoxicity and nephrotoxicity of emodin on mice and rats.

The order of nephrotoxicity of the main chemical components of rhubarb is as follows: aloe-emodin > rhein > emodin > chrysophanol. Therefore, the nephrotoxicity of rhubarb is greatly reduced after concoction. The nephrotoxicity of rhubarb anthraquinones is associated with genes that improve oxidative stress, cell cycle, and nutrient metabolism pathways.

Dose control is an important factor in rhubarb anthraquinone toxicity. Electrophilic intermediates produced by emodin, aloe-emodin, and rhein in the anthraquinone components have been proven to damage the mitochondria and cause hepatocyte apoptosis in vitro. However, no hepatotoxicity in humans has been reported for rhubarb, though its most prevalent side effects are diarrhea and constipation.

Acute renal failure has been associated with long-term anthraquinone use. Rhubarb is not suitable for long-term use to avoid producing toxic and side effects.

Pregnancy and Lactation

Anthraquinones may have uterine-stimulant and genotoxic effects. Rhubarb (Rheum officinale, Rheum palmatum) root contains anthraquinones (e.g., aloe-emodin, chrysophanol, emodin, rhein), which are cathartics, and tannins, which are astringents — both categories of compounds have historically raised caution regarding use during pregnancy and breastfeeding.

Drug Interactions

Several pharmacokinetic drug interactions have been documented in laboratory and animal studies, with uncertain but potentially clinically significant implications:

Cyclosporine: Both dosages of rhubarb significantly decreased the Cmax and AUC of cyclosporine in rats. Mechanism studies indicated that rhubarb activated the functions of P-glycoprotein and CYP 3A. Rhubarb ingestion reduced the systemic exposure of cyclosporine through activating P-gp and CYP 3A. In lab studies, rhubarb decreased cyclosporine bioavailability. Clinical relevance is not yet known.
Methotrexate: In lab studies, rhubarb increased exposure to methotrexate. Clinical relevance has not been established.
CYP450 Substrate Drugs: Rhubarb may reduce the effectiveness of CYP450 substrate drugs, but clinical significance has yet to be determined.
Digoxin and Cardiac Glycosides: Potassium loss due to the laxative effect of rhubarb means it may increase the risk of low potassium levels in patients taking digoxin.
Melatonin: Lab studies suggest that using both products together may affect the way melatonin is metabolized, but clinical relevance is not yet known.

Rhei Rhizoma extract, which is taken orally at doses of 0.5–1 g each or 1–3 g daily in clinical practice, may cause pharmacokinetic herb-drug interactions in the process of intestinal and/or hepatic CYP3A-mediated drug metabolism and P-glycoprotein- and/or MRP2-mediated efflux transport in the intestine.

Contraindications and Populations Requiring Caution

Patients with arthritis, kidney problems, inflammatory bowel disease, or intestinal obstruction should refrain from consumption of medicinal rhubarb. The endometrial safety of ERr 731® has been studied, and no endometrial hyperplasia could be detected and no adverse events related to the study medication occurred in long-term observational studies — however, this applies specifically to the R. rhaponticum extract and not to anthraquinone-containing medicinal rhubarb species.

Rhein's clinical application is limited to some extent by its poor water solubility and low bioavailability.