Rhein

Rhein at a Glance

Rhein is an anthraquinone aglycone of rhubarb, yellow dock and senna — and, uniquely among the plant anthraquinones, it has a licensed pharmaceutical identity.

Rhein is the active metabolite of diacerein, an approved osteoarthritis drug that works by inhibiting interleukin-1beta. That prodrug relationship gives rhein something no other compound in this class has: genuine human clinical data, generated through a regulated medicine rather than a supplement.

Rhein, Diacerein and the Two Regulatory Identities

The same molecule occupies two entirely different regulatory worlds, and which one a claim comes from decides how much it is worth.

As a plant constituent, rhein is an unregulated anthraquinone in rhubarb, yellow dock, senna and Cassia, with no dose, no product and no human trial of its own.

As a drug, rhein is the active moiety of diacerein (diacetylrhein) — a licensed symptomatic slow-acting osteoarthritis medicine in the EU and elsewhere, never approved by the FDA. Diacerein is essentially completely deacetylated before and at first pass, so rhein is the only species reaching the circulation in meaningful quantity ^{1Reference 1Nicolas P et al. · 1998ReviewClinical pharmacokinetics of diacerein — reviewView study →}. Everything human known about this molecule was generated inside that regulated pathway.

That is a genuine advantage over every other plant anthraquinone: real randomised trials, meta-analyses, a Cochrane review, measured pharmacokinetics and a regulator’s assessment of harm. It is also a trap. The diacetyl ester is what makes the human numbers work. Diacerein reaches roughly 35–56% oral bioavailability depending on formulation ^{1Reference 1Nicolas P et al. · 1998ReviewClinical pharmacokinetics of diacerein — reviewView study →}; isolated plant rhein has poor aqueous solubility and low oral absorption ^{8Reference 8Fu Y et al. · 2024ReviewRhein: An Updated Review Concerning Its Biological Activity, Pharmacokinetics, Structure Optimization, and Future Pharmaceutical Applications — reviewView study →}. The favourable exposure belongs to the delivery form, not to the molecule as a plant supplies it.

And the regulated pathway generated a negative body of evidence as much as a positive one. Earlier meta-analyses found a small benefit in osteoarthritis ^{3,5Reference 3Rintelen B et al. · 2006Meta-analysisA meta-analysis of controlled clinical studies with diacerein in the treatment of osteoarthritis — meta-analysisView study →Reference 5Bartels EM et al. · 2010Meta-analysisSymptomatic efficacy and safety of diacerein in the treatment of osteoarthritis: a meta-analysis of randomized placebo-controlled trials — meta-analysisView study →}; the 2014 Cochrane review judged it minimal-to-none against placebo ^{4Reference 4Fidelix TS et al. · 2014Meta-analysisDiacerein for osteoarthritis — meta-analysisView study →}; diarrhoea is the dominant harm; and a 2014 EU referral over gastrointestinal and liver toxicity left the drug restricted rather than withdrawn. A herbal product cannot borrow the positive half of that record and leave the rest.

Why Rhein Is Not the Laxative

Rhubarb and senna are among the strongest plant laxatives in use, rhein is one of their major anthraquinones, and the inference between those two facts is wrong.

The purgative action belongs to the anthraquinone glycosides — sennosides and anthraquinone-O-glucosides — which are not absorbed in the small intestine and survive to the colon. There, bacterial enzymes cleave and reduce them to the corresponding anthrones, and it is rhein-anthrone that alters water and electrolyte transport and drives motility ^{12Reference 12Wang D et al. · 2021ReviewPharmacokinetics of Anthraquinones from Medicinal Plants — reviewView study →}. Free rhein, absorbed upstream in the oxidised anthraquinone form, is a weak stand-alone laxative; it alters intestinal ion transport in rodent epithelium ^{9Reference 9Tsai JC et al. · 2004AnimalEffect of ethanol extracts of three Chinese medicinal plants with laxative properties on ion transport of the rat intestinal epithelia — rat in vivo animal modelView study →}, but that is not the mechanism the herbs work by.

The general rule is the same one that runs through this whole family: the reduced anthrones are active and the oxidised anthraquinones are quiet. It is why chrysophanol is a weak laxative while its anthrone chrysarobin is biologically aggressive, and why a rhubarb preparation’s purgative strength tracks its glycoside content rather than its free-aglycone content.

Two practical consequences. A rhein result obtained by injecting or feeding the pure aglycone says nothing about a laxative herb. And a person taking diacerein is taking rhein systemically, which is why their commonest adverse effect is still diarrhoea — the molecule reaches the colon by a different route and the class effect follows it there.

What It's Used For

Rhein is an anthraquinone aglycone — a sibling of emodin — found in rhubarb, yellow dock, senna and Cassia ^{13,14Reference 13Qian H et al. · 2024ReviewRumex crispus L.: A comprehensive review on botany, traditional uses, phytochemistry, pharmacology, and safety — reviewView study →Reference 14Vasas A et al. · 2015ReviewThe Genus Rumex: Review of traditional uses, phytochemistry and pharmacology — reviewView study →}, usually bound in the intact plant as glycosides or sennoside dianthrones. What sets it apart from the other plant anthraquinones is a drug connection: rhein is the active metabolite of diacerein (diacetylrhein), a licensed slow-acting osteoarthritis drug, so it uniquely carries human clinical data by proxy ^{1Reference 1Nicolas P et al. · 1998ReviewClinical pharmacokinetics of diacerein — reviewView study →}.

Two caveats frame all of it. First, every human result is for diacerein, not isolated plant-derived rhein — and even for diacerein the osteoarthritis benefit is small and disputed ^{4Reference 4Fidelix TS et al. · 2014Meta-analysisDiacerein for osteoarthritis — meta-analysisView study →}.

Second, isolated rhein has poor aqueous solubility and low oral absorption; the favorable human pharmacokinetics belong to the diacerein delivery form ^{8Reference 8Fu Y et al. · 2024ReviewRhein: An Updated Review Concerning Its Biological Activity, Pharmacokinetics, Structure Optimization, and Future Pharmaceutical Applications — reviewView study →}.

Evidence by IndicationStrength of support · Beta

01Osteoarthritis (via diacerein)Shaky42%Human RCTs/meta-analyses of diacerein, contested ^{3,4,5Reference 3Rintelen B et al. · 2006Meta-analysisA meta-analysis of controlled clinical studies with diacerein in the treatment of osteoarthritis — meta-analysisView study →Reference 4Fidelix TS et al. · 2014Meta-analysisDiacerein for osteoarthritis — meta-analysisView study →Reference 5Bartels EM et al. · 2010Meta-analysisSymptomatic efficacy and safety of diacerein in the treatment of osteoarthritis: a meta-analysis of randomized placebo-controlled trials — meta-analysisView study →}

02Anti-inflammatory (IL-1β)Shaky30%Ex-vivo cartilage/synovial mechanism ^{6Reference 6Martel-Pelletier J · 2010ReviewEffects of diacerein at the molecular level in the osteoarthritis disease process — reviewView study →}

03Diabetic nephropathy / renalShaky28%Animal meta-analysis + one human RCT (negative on primary) ^{10,11,2Reference 10Hu HC et al. · 2019Meta-analysisA Significant Association Between Rhein and Diabetic Nephropathy in Animals: A Systematic Review and Meta-Analysis — systematic reviewView study →Reference 11Zhang Q et al. · 2017AnimalRhein reverses Klotho repression via promoter demethylation and protects against kidney and bone injuries in mice with chronic kidney disease — mouse modelView study →Reference 2Piovesan F et al. · 2017RCTEffect of diacerein on renal function and inflammatory cytokines in participants with type 2 diabetes mellitus and chronic kidney disease: a randomized controlled trialView study →}

04AnticancerShaky20%Preclinical only ^{7Reference 7Henamayee S et al. · 2020ReviewTherapeutic Emergence of Rhein as a Potential Anticancer Drug: A Review of Its Molecular Targets and Anticancer Properties — reviewView study →}

05Laxative (class)Shaky16%Anthraquinone class; free rhein a weak contributor ^{9,12Reference 9Tsai JC et al. · 2004AnimalEffect of ethanol extracts of three Chinese medicinal plants with laxative properties on ion transport of the rat intestinal epithelia — rat in vivo animal modelView study →Reference 12Wang D et al. · 2021ReviewPharmacokinetics of Anthraquinones from Medicinal Plants — reviewView study →}

Mechanisms

Pharmacokinetics

Load-bearing, with a key distinction: rhein is relatively well absorbed for an anthraquinone, but the human data describe rhein delivered as diacerein, not free plant rhein. Diacerein is essentially completely deacetylated to rhein before and at first pass, so rhein is the only species reaching the circulation in meaningful amounts ^{1Reference 1Nicolas P et al. · 1998ReviewClinical pharmacokinetics of diacerein — reviewView study →}; absolute bioavailability is roughly 35–56% depending on formulation (food delays but slightly increases absorption), plasma protein binding is ~99% and non-saturable, and rhein is glucuronidated (~60%) and sulfated (~20%) with a steady-state half-life of ~7–8 hours ^{1Reference 1Nicolas P et al. · 1998ReviewClinical pharmacokinetics of diacerein — reviewView study →}. The free-aglycone caveat is decisive: isolated rhein itself has poor aqueous solubility and low oral absorption, so much of the favorable human pharmacokinetics is attributable to the diacerein form ^{8Reference 8Fu Y et al. · 2024ReviewRhein: An Updated Review Concerning Its Biological Activity, Pharmacokinetics, Structure Optimization, and Future Pharmaceutical Applications — reviewView study →}.

Clinical Trials

There are no clinical trials of isolated, plant-derived rhein — the human evidence is entirely diacerein: positive-but-modest OA meta-analyses ^{3,5Reference 3Rintelen B et al. · 2006Meta-analysisA meta-analysis of controlled clinical studies with diacerein in the treatment of osteoarthritis — meta-analysisView study →Reference 5Bartels EM et al. · 2010Meta-analysisSymptomatic efficacy and safety of diacerein in the treatment of osteoarthritis: a meta-analysis of randomized placebo-controlled trials — meta-analysisView study →}, the skeptical 2014 Cochrane review ^{4Reference 4Fidelix TS et al. · 2014Meta-analysisDiacerein for osteoarthritis — meta-analysisView study →}, and a diabetic-CKD RCT that was negative on its primary endpoints ^{2Reference 2Piovesan F et al. · 2017RCTEffect of diacerein on renal function and inflammatory cytokines in participants with type 2 diabetes mellitus and chronic kidney disease: a randomized controlled trialView study →}. Potency of the isolated molecule or of the raw herb should not be inferred from these prodrug trials.

Last checked: September 2026.

Isolate vs. Plant Studies

Rhein has three evidence layers and they do not stack.

The drug layer is human, randomised and regulated — and it is diacerein, not rhein: the OA meta-analyses ^{3,5Reference 3Rintelen B et al. · 2006Meta-analysisA meta-analysis of controlled clinical studies with diacerein in the treatment of osteoarthritis — meta-analysisView study →Reference 5Bartels EM et al. · 2010Meta-analysisSymptomatic efficacy and safety of diacerein in the treatment of osteoarthritis: a meta-analysis of randomized placebo-controlled trials — meta-analysisView study →}, the Cochrane review ^{4Reference 4Fidelix TS et al. · 2014Meta-analysisDiacerein for osteoarthritis — meta-analysisView study →} and the diabetic-CKD trial ^{2Reference 2Piovesan F et al. · 2017RCTEffect of diacerein on renal function and inflammatory cytokines in participants with type 2 diabetes mellitus and chronic kidney disease: a randomized controlled trialView study →} all dosed the diacetyl prodrug. Rhein is what the body makes from it, which is a strong basis for talking about rhein systemically and no basis at all for talking about a rhubarb product.

The isolate layer is preclinical and reasonably clean. The IL-1β work in cartilage ^{6Reference 6Martel-Pelletier J · 2010ReviewEffects of diacerein at the molecular level in the osteoarthritis disease process — reviewView study →}, the Klotho promoter-demethylation finding ^{11Reference 11Zhang Q et al. · 2017AnimalRhein reverses Klotho repression via promoter demethylation and protects against kidney and bone injuries in mice with chronic kidney disease — mouse modelView study →} and the anticancer cell work ^{7Reference 7Henamayee S et al. · 2020ReviewTherapeutic Emergence of Rhein as a Potential Anticancer Drug: A Review of Its Molecular Targets and Anticancer Properties — reviewView study →} all used purified rhein at stated concentrations, and the animal diabetic-nephropathy literature has been meta-analysed as such ^{10Reference 10Hu HC et al. · 2019Meta-analysisA Significant Association Between Rhein and Diabetic Nephropathy in Animals: A Systematic Review and Meta-Analysis — systematic reviewView study →}. The recurring discount is solubility: rhein’s in-vitro potencies assume free-drug concentrations its own physical chemistry makes hard to reach from an oral aglycone dose ^{8Reference 8Fu Y et al. · 2024ReviewRhein: An Updated Review Concerning Its Biological Activity, Pharmacokinetics, Structure Optimization, and Future Pharmaceutical Applications — reviewView study →}.

The plant layer transfers almost nothing. Rhubarb, yellow dock and senna are used as laxatives, and that action is glycoside- and anthrone-driven rather than rhein-driven (see above). Rhein is a large share of the free-anthraquinone fraction — about 43% of a representative rhubarb extract, against ~27% emodin and ~1.5% chrysophanol ^{15Reference 15Li P et al. · 2017AnimalPharmacokinetics and pharmacodynamics of rhubarb anthraquinones extract in normal and disease rats — rat pharmacokinetic animal modelView study →} — but a large share of the wrong fraction. Where whole plants have been studied, as with Rumex crispus, the results belong to extracts containing several anthraquinones ^{13,14Reference 13Qian H et al. · 2024ReviewRumex crispus L.: A comprehensive review on botany, traditional uses, phytochemistry, pharmacology, and safety — reviewView study →Reference 14Vasas A et al. · 2015ReviewThe Genus Rumex: Review of traditional uses, phytochemistry and pharmacology — reviewView study →}.

So the best human evidence describes a pharmaceutical, the mechanism work describes an isolate, and the plants describe something else again.

Its Role in Plants

Rhein is a polyketide, built by condensing acetate units into a folded chain that cyclises to the anthracene skeleton and is then oxidised — the same route that makes emodin, chrysophanol and physcion, which is why the four appear together wherever any of them appears. Rhein is the most oxidised of the set: it carries a carboxylic acid at C-3 where chrysophanol has a methyl group, which is what makes it more polar, more water-soluble as a salt, and more readily conjugated.

In the living plant almost none of it is free. Rheum and Senna store it as glycosides and dianthrones — sennoside A and B are two rhein anthrone units joined and doubly glucosylated — which keeps the reactive anthrone locked up until gut bacteria release it. That storage form is not only a safety mechanism for the plant; it is what makes these plants purgatives rather than irritants, because the release happens in the colon rather than the stomach.

The anthraquinones are pigments and defences at once: yellow-orange, strongly UV-absorbing, antimicrobial and antifeedant. Rhubarb’s root colour and its purgative action are the same chemistry seen from two directions.

Prevalence in Nature

Rhein is a Polygonaceae and Fabaceae molecule — rhubarb (Rheum spp.), yellow dock and the other docks (Rumex), senna (Senna spp.) and Cassia — and it is nearly always bound rather than free ^{13,14Reference 13Qian H et al. · 2024ReviewRumex crispus L.: A comprehensive review on botany, traditional uses, phytochemistry, pharmacology, and safety — reviewView study →Reference 14Vasas A et al. · 2015ReviewThe Genus Rumex: Review of traditional uses, phytochemistry and pharmacology — reviewView study →}.

Where it is quantified, it is abundant within its fraction: rhein made up roughly 43% of the free anthraquinones of a representative rhubarb extract, the largest single share, against ~27% emodin, ~1.5% chrysophanol and smaller amounts of aloe-emodin and physcion ^{15Reference 15Li P et al. · 2017AnimalPharmacokinetics and pharmacodynamics of rhubarb anthraquinones extract in normal and disease rats — rat pharmacokinetic animal modelView study →}. But “free anthraquinone fraction” is a laboratory preparation. In the intact root the same molecule is present chiefly as glucosides and, in senna, as the sennoside dianthrones, so free-aglycone content depends entirely on how the material was extracted and how long it was stored.

Unlike emodin and chrysophanol, rhein does not turn up in the survey of ordinary vegetables and herbal liquors — that work found emodin, chrysophanol and physcion in lettuce, beans, peas and liquors, with physcion predominating, and rhein was not among the anthraquinones screened for ^{16Reference 16Mueller SO et al. · 1999In vitroOccurrence of emodin, chrysophanol and physcion in vegetables, herbs and liquorsView study →}. Dietary rhein exposure outside the laxative herbs is not characterised.

Major Natural Sources

Source	Family	Part	Form	Notes
Rhubarb (Rheum spp.)	Polygonaceae	Rhizome	Glucosides; free aglycone on extraction	~43% of the free-anthraquinone fraction 15Reference 15Li P et al. · 2017AnimalPharmacokinetics and pharmacodynamics of rhubarb anthraquinones extract in normal and disease rats — rat pharmacokinetic animal modelView study →
Senna (Senna spp.)	Fabaceae	Leaf, pod	Sennoside dianthrones	Two rhein-anthrone units, doubly glucosylated
Yellow dock (Rumex crispus)	Polygonaceae	Root	Glycosides	With emodin, chrysophanol, physcion 13,14Reference 13Qian H et al. · 2024ReviewRumex crispus L.: A comprehensive review on botany, traditional uses, phytochemistry, pharmacology, and safety — reviewView study →Reference 14Vasas A et al. · 2015ReviewThe Genus Rumex: Review of traditional uses, phytochemistry and pharmacology — reviewView study →
Cassia spp.	Fabaceae	Leaf, pod	Glycosides	The senna chemistry under an older genus name

Discovery & Synthesis

Rhein is named for the rhubarb genus, Rheum, and like its siblings it emerged from the long nineteenth-century effort to work out what made rhubarb root purgative — a question that ran from the 1830s through to the end of the century without being settled, because the active forms are the unstable anthrones rather than the crystalline anthraquinones that chemists could actually isolate. Alexander Tschirch, the founder of modern pharmacognosy, was still publishing notes on rhubarb’s active constituents in 1899 ^{17Reference 17Tschirch A · 1899Notiz über den Rhabarber und seine wirksamen BestandteileView study →}. The precise first isolation of rhein is not well documented in the accessible literature.

Structures came in the following decade, as part of the anthraquinone chemistry that Graebe and Liebermann’s 1868 alizarin synthesis had made industrially important: Jowett and Potter settled chrysophanic acid and emodin in 1903 ^{18Reference 18Jowett HAD · 1903The constitution of chrysophanic acid and of emodinView study →}, and the hydroxy-methyl-anthraquinone series was mapped over the following thirty years.

The modern chapter is pharmaceutical. Acetylating rhein’s two phenolic hydroxyls gives diacerein, a prodrug with far better handling properties, which was developed as a slow-acting osteoarthritis drug and licensed in Europe — the only member of this molecular family to become a regulated medicine ^{1Reference 1Nicolas P et al. · 1998ReviewClinical pharmacokinetics of diacerein — reviewView study →}. Manufacture of rhein itself is by extraction from rhubarb or Cassia material, partly as a feedstock for diacerein synthesis and partly as a reference standard.

Patents: not yet researched.

Toxicity & Safety

Almost everything known about rhein’s safety comes from diacerein, the licensed drug it is the active metabolite of — and that record is heavy enough to matter: frequent dose-related diarrhea, a hepatotoxicity signal, and an EU restriction that keeps the drug away from older patients and anyone with liver disease.

Safety at a Glance

⚠️ Moderate toxicityLiver riskDrug interactions

• Hepatotoxicity signal. Raised transaminases and cases of acute liver injury; contraindicated in current or prior liver disease.
• Diarrhea is the dominant harm. Frequent, dose-related and sometimes severe — the top adverse effect across every diacerein trial.
• Under EU regulatory restriction. Not recommended over 65, start at half dose, stop if diarrhea occurs. Not FDA-approved in the US.
• Not recommended in pregnancy or breastfeeding. See the box below.
• Stimulant-laxative class concerns. Electrolyte loss, dependence with chronic use, pseudomelanosis coli.
• Additive interactions. Other laxatives and co-administered hepatotoxic drugs are the practical concerns.

Full Safety & Interactions Detail

Rhein’s safety profile is dominated by its behaviour as diacerein, and that record is heavy enough to carry the caution here on its own. Diarrhoea is the dominant adverse effect — frequent, dose-related and sometimes severe, consistently the top harm across the OA meta-analyses and the Cochrane review ^{4Reference 4Fidelix TS et al. · 2014Meta-analysisDiacerein for osteoarthritis — meta-analysisView study →}.

Diacerein also carries a hepatotoxicity signal (raised transaminases and cases of acute liver injury). Following a French-initiated referral over gastrointestinal and liver toxicity, the EMA in 2014 kept diacerein’s benefit–risk positive but restricted: it is not recommended in patients ≥65 years, should be started at half dose (50 mg/day) and stopped if diarrhea occurs, and is contraindicated in current or prior liver disease with liver monitoring advised (it is not FDA-approved in the US). As an anthraquinone it also sits inside the stimulant-laxative class concerns — electrolyte loss, dependence with chronic use, melanosis coli — and inside the EU restriction on hydroxyanthracene derivatives in food and supplements. That class material is written up once, on emodin; what belongs to rhein specifically is the diacerein record above: dose-related diarrhoea as the dominant harm, a hepatotoxicity signal, and a regulator’s restriction rather than a withdrawal. The high but non-saturable protein binding makes displacement interactions unlikely ^{1Reference 1Nicolas P et al. · 1998ReviewClinical pharmacokinetics of diacerein — reviewView study →}; the practical interaction concerns are additive diarrhea (other laxatives) and co-administered hepatotoxic drugs.

Pregnancy & Lactation

⚠ Avoid in pregnancy⚠ Avoid while breastfeeding

Avoid. Anthraquinone metabolites including rhein are excreted into breast milk ^{12Reference 12Wang D et al. · 2021ReviewPharmacokinetics of Anthraquinones from Medicinal Plants — reviewView study →}, stimulant anthraquinones are generally advised against in pregnancy and lactation, and diacerein has inadequate human pregnancy safety data — not recommended in either.

Dosage

There is no established or safe dose for isolated plant-derived rhein, and nothing here is a recommendation. The only figures with a regulatory basis belong to the prodrug.

Each 50 mg of diacerein delivers roughly one molar equivalent of rhein — but that is a restricted prescription medicine with monitoring requirements, not a supplement dose, and isolated plant rhein would not produce the same exposure from the same weight ^{1,8Reference 1Nicolas P et al. · 1998ReviewClinical pharmacokinetics of diacerein — reviewView study →Reference 8Fu Y et al. · 2024ReviewRhein: An Updated Review Concerning Its Biological Activity, Pharmacokinetics, Structure Optimization, and Future Pharmaceutical Applications — reviewView study →}. These are doses studied in research and used under regulation, and are not a personal recommendation.

References

1. Nicolas P, Tod M, Padoin C, et al. (1998). Clinical pharmacokinetics of diacerein — review. Clinical Pharmacokinetics. https://pubmed.ncbi.nlm.nih.gov/9839088/
2. Piovesan F, Tres GS, Moreira LB, et al. (2017). Effect of diacerein on renal function and inflammatory cytokines in participants with type 2 diabetes mellitus and chronic kidney disease: a randomized controlled trial. PLoS One. https://pubmed.ncbi.nlm.nih.gov/29049415/
3. Rintelen B, Neumann K, Leeb BF (2006). A meta-analysis of controlled clinical studies with diacerein in the treatment of osteoarthritis — meta-analysis. Archives of Internal Medicine. https://pubmed.ncbi.nlm.nih.gov/17000948/
4. Fidelix TS, Macedo CR, Maxwell LJ, et al. (2014). Diacerein for osteoarthritis — meta-analysis. Cochrane Database of Systematic Reviews. https://pubmed.ncbi.nlm.nih.gov/24515444/
5. Bartels EM, Bliddal H, Schøndorff PK, et al. (2010). Symptomatic efficacy and safety of diacerein in the treatment of osteoarthritis: a meta-analysis of randomized placebo-controlled trials — meta-analysis. Osteoarthritis and Cartilage. https://pubmed.ncbi.nlm.nih.gov/19857509/
6. Martel-Pelletier J, Pelletier JP (2010). Effects of diacerein at the molecular level in the osteoarthritis disease process — review. Therapeutic Advances in Musculoskeletal Disease. https://pubmed.ncbi.nlm.nih.gov/22870441/
7. Henamayee S, Banik K, Sailo BL, et al. (2020). Therapeutic Emergence of Rhein as a Potential Anticancer Drug: A Review of Its Molecular Targets and Anticancer Properties — review. Molecules. https://pubmed.ncbi.nlm.nih.gov/32408623/
8. Fu Y, Yang L, Liu L, et al. (2024). Rhein: An Updated Review Concerning Its Biological Activity, Pharmacokinetics, Structure Optimization, and Future Pharmaceutical Applications — review. Pharmaceuticals. https://pubmed.ncbi.nlm.nih.gov/39770507/
9. Tsai JC, Tsai S, Chang WC (2004). Effect of ethanol extracts of three Chinese medicinal plants with laxative properties on ion transport of the rat intestinal epithelia — rat in vivo animal model. Biological & Pharmaceutical Bulletin. https://pubmed.ncbi.nlm.nih.gov/14758025/
10. Hu HC, Zheng LT, Yin HY, et al. (2019). A Significant Association Between Rhein and Diabetic Nephropathy in Animals: A Systematic Review and Meta-Analysis — systematic review. Frontiers in Pharmacology. https://pubmed.ncbi.nlm.nih.gov/31920660/
11. Zhang Q, Liu L, Lin W, et al. (2017). Rhein reverses Klotho repression via promoter demethylation and protects against kidney and bone injuries in mice with chronic kidney disease — mouse model. Kidney International. https://pubmed.ncbi.nlm.nih.gov/27692562/
12. Wang D, Wang XH, Yu X, et al. (2021). Pharmacokinetics of Anthraquinones from Medicinal Plants — review. Frontiers in Pharmacology. https://pubmed.ncbi.nlm.nih.gov/33935728/
13. Qian H, Jia Y, Zheng K, et al. (2024). Rumex crispus L.: A comprehensive review on botany, traditional uses, phytochemistry, pharmacology, and safety — review. International Immunopharmacology. https://pubmed.ncbi.nlm.nih.gov/39520965/
14. Vasas A, Orbán-Gyapai O, Hohmann J (2015). The Genus Rumex: Review of traditional uses, phytochemistry and pharmacology — review. Journal of Ethnopharmacology. https://pubmed.ncbi.nlm.nih.gov/26384001/
15. Li P, Lu Q, Jiang W, et al. (2017). Pharmacokinetics and pharmacodynamics of rhubarb anthraquinones extract in normal and disease rats — rat pharmacokinetic animal model. Biomedicine & Pharmacotherapy. https://pubmed.ncbi.nlm.nih.gov/28475921/
16. Mueller SO, Schmitt M, Dekant W, et al. (1999). Occurrence of emodin, chrysophanol and physcion in vegetables, herbs and liquors. Genotoxicity and anti-genotoxicity of the anthraquinones and of the whole plants — in vitro. Food and Chemical Toxicology. https://pubmed.ncbi.nlm.nih.gov/10456676/
17. Tschirch A (1899). Notiz über den Rhabarber und seine wirksamen Bestandteile. Archiv der Pharmazie. https://doi.org/10.1002/ardp.18992370808
18. Jowett HAD, Potter CE (1903). The constitution of chrysophanic acid and of emodin. Journal of the Chemical Society, Transactions. https://doi.org/10.1039/ct9038301327

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