Desoxyrhaponticin

Other Names

(2S,3R,4S,5S,6R)-2-(3-hydroxy-5-((E)-4-methoxystyryl)phenoxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol(2S,3R,4S,5S,6R)-2-[3-hydroxy-5-[(E)-2-(4-methoxyphenyl)ethenyl]phenoxy]-6-(hydroxymethyl)oxane-3,4,5-triol(E)-4'-Methoxy-5-(β-D-glucopyranosyloxy)stilbene-3-ol2-[3-Hydroxy-5-[(E)-2-(4-methoxyphenyl)ethenyl]phenoxy]-6-(hydroxymethyl)oxane-3,4,5-triol3,5-Dihydroxy 4'-methoxystilbene 3-glucoside3,5-DIHYDROXY-4'-METHOXYSTILBENE 3-O-BETA-D-GLUCOSIDE3,5-Dihydroxy-4'-methoxystilbene 3-O-β-D-glucoside3-(β-D-glucopyranosyloxy)-5-[(E)-2-(4-methoxyphenyl)ethenyl]phenol3-(β-D-Glucopyranosyloxy)-5-[(E)-2-(4-methoxyphenyl)vinyl]phenol3-Hydroxy-5-[(E)-2-(4-methoxyphenyl)ethenyl]phenyl β-D-glucopyranosideDeoxyrhaponticinDeoxyrhapontigenin O-glucosideDeoxyrhapontinRhapontin, deoxy-trans-Desoxyrhaponticinβ-D-Glucopyranoside, 3-hydroxy-5-[(1E)-2-(4-methoxyphenyl)ethenyl]phenylβ-D-Glucopyranoside, 3-hydroxy-5-[2-(4-methoxyphenyl)ethenyl]phenyl, (E)-

Synopsis

Desoxyrhaponticin: A Comprehensive Reference Article

1. Identity: Chemical Names, Botanical Sources, and Common Forms

1.1 Chemical Identity

Desoxyrhaponticin is a naturally occurring stilbene glycoside predominantly found in the roots of rhubarb (Rheum species). It is chemically classified as a derivative of rhaponticin, and its structure is characterized by a glucose moiety attached to a stilbene backbone, which contributes to its biological activity and pharmacological significance.

The compound's systematic chemical name is 3,5-dihydroxy-4′-methoxystilbene 3-O-β-D-glucoside. Its molecular formula is C₂₁H₂₄O₈. Its CAS registry number is 30197-14-9. Desoxyrhaponticin is classified as a stilbenoid and a glycoside. Structurally, desoxyrhapontigenin — the aglycone form of desoxyrhaponticin produced after deglycosylation — is a 4′-methoxy derivative of resveratrol. This means desoxyrhaponticin shares the core trans-stilbene scaffold with resveratrol, differing primarily in the methoxylation at the 4′ position of the B-ring and, in its glycosidic form, in the attachment of a β-D-glucopyranose unit at the 3-position.

1.2 Botanical Sources

Desoxyrhaponticin is a stilbene glycoside primarily found in the roots of Rheum species (rhubarb). More specifically, desoxyrhaponticin is a natural product found in Veratrum dahuricum, Rheum palmatum, and other organisms. It has also been isolated from Rheum undulatum, Rheum tanguticum, Rheum rhabarbarum, and Rheum tataricum. Three stilbenes — rhaponticin, desoxyrhaponticin, and resveratroloside — have been isolated and characterized from the ethanol extract of roots and rhizomes of Rheum tataricum L., growing in Central Asia. The structure of desoxyrhaponticin was confirmed by X-ray diffraction analyses in that study.

The most commercially and clinically significant source of desoxyrhaponticin is Rheum rhaponticum L. (rhapontic rhubarb, Siberian rhubarb). R. rhaponticum L., commonly known as rhapontic or Siberian rhubarb, originates from Central Asia and was introduced into Europe in the 17th century. Within the root of this species, rhaponticin — a glucoside of rhapontigenin — constitutes the primary stilbene, often comprising over 90% of the extract's stilbene content, while desoxyrhaponticin, its demethylated analog, occurs in smaller amounts.

1.3 Related Compounds and the ERr 731 Extract

Desoxyrhaponticin is most extensively studied not in isolation, but as a key constituent of the proprietary standardized dry root extract known as ERr 731®. The standardized extract ERr 731® (drug-to-extract ratio 16–26:1, with calcium oxide-to-water 1:38 (mass/mass) as extraction solvent) consists mainly of rhaponticin and desoxyrhaponticin and small amounts of the aglycones trans-rhapontigenin and desoxyrhapontigenin (both together about 5%).

The extract from roots of rhubarb mainly consists of rhaponticin and desoxyrhaponticin, which are converted to the resveratrol-like aglycones rhapontigenin and desoxyrhapontigenin by the microbiome. This biotransformation is important because the aglycones — particularly desoxyrhapontigenin — are thought to be the pharmacologically active forms following intestinal metabolism.

1.4 Common Forms and Preparations

In scientific research, desoxyrhaponticin is obtained as a high-purity (≥98% by HPLC) botanical reference material, typically isolated from rhubarb roots. The primary extraction method involves extracting desoxyrhaponticin from rhubarb roots using solvents like ethanol or methanol, a method that preserves the compound's natural configuration. Chemical synthesis in the laboratory may involve the modification of simpler stilbene derivatives through glycosylation reactions, although this approach is less common due to the complexity and cost involved.

In commercial supplement contexts, desoxyrhaponticin is not typically sold in isolation. Rather, it is found as part of standardized plant extract formulations based on Rheum rhaponticum root. In Germany, the ERr 731 extract has been marketed under several trade names including Phytoestrol N, Phyto-Strol, Phyto-Strol Loges, and femi-loges, while in the United States, Canada, and South Africa it was marketed as Estrovera, with introduction in the United States occurring in 2009. In clinical trials, ERr 731 has been administered as an enteric-coated tablet, with the tablet taken once daily.

2. Traditional and Historical Use

2.1 Traditional Chinese Medicine

The genus Rheum has an exceptionally long history of medicinal use. Rhubarb (also named Rhei or Dahuang), one of the most ancient and important herbs in traditional Chinese medicine (TCM), belongs to the Rheum L. genus from the Polygonaceae family, and its application can be traced back to 270 BC in the Shen Nong Ben Cao Jing. Rhubarb has long been used as an antibacterial, anti-inflammatory, anti-fibrotic and anticancer medicine in China. Rhubarb and its wide range of uses were first documented in the Divine Husbandman's Classic of Materia Medica, which was written during the later Han Dynasty, around 200 AD.

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. Common concoctions include raw rhubarb, wine rhubarb, cooked rhubarb and rhubarb charcoal. The active compounds of rhubarb are known to promote defecation, exhibit antibacterial and anti-inflammatory properties, regulate coagulation, protect the digestive system, and possess anti-tumor activities. 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.

In ancient China, rhubarb root was taken to try to cure stomach ailments and as a cathartic (an agent used to relieve constipation), and used as a poultice for fevers and edema (swelling caused by fluid retention in the body tissues).

It is important to note that the medicinal species historically used in TCM — primarily R. palmatum, R. tanguticum, and R. officinale — are rich in anthraquinone glycosides responsible for the laxative effect. These differ from R. rhaponticum (Siberian rhubarb), which is comparatively richer in stilbene glycosides including rhaponticin and desoxyrhaponticin. The compound desoxyrhaponticin itself was not identified or named in traditional systems; traditional applications referred to the whole dried root or rhizome under the collective material terms.

2.2 European and Asian Trade History

The dried roots of Chinese rhubarb became one of the most prominent items traded along the Silk Road. Rhubarb occurs in commerce under various names: Russian, Turkey, East Indian and Chinese; the geographical source of all species is the same, but the commercial names of the drug indicated only the route by which it formerly reached the European market.

In the Shennong bencao jing (25–220 CE), the oldest surviving Chinese materia medica, rhubarb was classified under 'low herbs' (下品) which included strong, often poisonous, substances. To Europeans, rhubarb's appeal lay in its cleansing properties, which aligned neatly with humoral theory. The Dutch physician Herman Boerhaave (1668–1738) classed rhubarb as a gentle purgative, often prepared by soaking powdered rhubarb in ale. The common Rheum rhaponticum and Rheum undulatum, otherwise known as 'false rhubarb,' served as less potent substitutes before the introduction of 'true rhubarb' to Britain in 1762 by James Mounsey.

Before the seventeenth century, rhubarb species were utilized medicinally in traditional Chinese herbal medicine. Traditional uses include the treatment of constipation, diarrhea, fever, menstrual problems, jaundice, sores (when applied topically), ulcers, and burns.

2.3 Tibetan and Central Asian Use

Rheum tanguticum Maxim., a source of desoxyrhaponticin, is a Chinese traditional nutritional food from the Tibetan region. In Tibetan and Central Asian traditions, rhubarb species were incorporated both as foodstuffs and as components of medicinal preparations, particularly for digestive and inflammatory conditions. The identification of desoxyrhaponticin as an isolable phytochemical within these plants, however, is a development of modern analytical chemistry rather than traditional knowledge.

3. Key Constituents, Structural Relationships, and Mechanisms of Action

3.1 Position within the Stilbene Class

Desoxyrhaponticin belongs to the stilbene class of polyphenols. Desoxyrhapontigenin (its aglycone) is a 4′-methoxy derivative of resveratrol, while rhapontigenin is a 3′-hydroxy-4′-methoxy derivative of resveratrol. As a glycoside, desoxyrhaponticin differs from its aglycone (desoxyrhapontigenin) by the presence of the β-D-glucopyranose attached at the 3-hydroxyl of the stilbene backbone. Choi et al. isolated stilbenoids rhaponticin, rhapontigenin, isorhaponticin, desoxyrhaponticin, desoxyrhapontigenin, and resveratrol from rhubarb (Rheum undulatum) and tested them for their anti-inflammatory effect.

3.2 Biotransformation to the Active Aglycone

A central pharmacological concept for desoxyrhaponticin is that the intact glycoside has limited direct bioavailability and acts largely as a prodrug. After ingestion, large amounts of the aglycones might be released due to deglycosylation of rhaponticin and desoxyrhaponticin by intestinal bacteria. ERr 731 may exert its biological effects via selective binding to, and activation of, ER-β without acting on ER-α. Thus, the gut microbiome plays a key role in determining the pharmacological activity of desoxyrhaponticin in vivo.

3.3 Selective Estrogen Receptor-β (ERβ) Agonism

The most extensively characterized mechanism of the ERr 731 extract — and by implication of its major constituents rhaponticin and desoxyrhaponticin — is selective agonism at the estrogen receptor-β subtype. Experimental studies had demonstrated that both the extract and its individual constituents — rhaponticin and desoxyrhaponticin, with small amounts of aglycones rhapontigenin and desoxyrhapontigenin — have exhibited selective estrogen receptor (ER)-β agonistic activity as well as a lack of ER-α affinity. The ERr 731 extract, as well as its individual compounds, have been demonstrated to act as potent, selective ERβ agonists in human endometrial cells, without significant ERα effects.

The selective ERβ activity may explain the anxiolytic effects of the extract. In tissues where both ER-α and ER-β are expressed, ER-β may function as a negative regulator of ER-α, offering relief of menopausal symptoms, as well as protection against inflammation and proliferation.

3.4 Fatty Acid Synthase (FASN) Inhibition

The primary mechanism of action of desoxyrhaponticin in the context of cancer research is believed to be its inhibition of fatty acid synthase (FASN) in cancer cells. By hindering fatty acid production, it disrupts the cell's ability to build membranes and maintain energy homeostasis, ultimately leading to apoptosis (programmed cell death). Desoxyrhaponticin (DC) and rhaponticin (RC), two stilbene glycosides from rhubarb, could be considered as promising FAS inhibitors. Both DC and RC could inhibit intracellular FAS activity and downregulate FAS expression in human breast cancer MCF-7 cells.

3.5 Inhibition of Glucose Uptake and Transport

Desoxyrhaponticin has been investigated as a major stilbene in rhubarb as a glucose uptake inhibitor. It was demonstrated to inhibit glucose uptake in rabbit intestinal membrane vesicles as well as in rat everted gut sleeves, with IC₅₀ values of 148.3 and 30.9 μM, respectively. Kinetics studies revealed that desoxyrhaponticin is a competitive inhibitor of glucose uptake in both systems. The in vivo antidiabetic action of this compound can be explained, in part at least, by inhibition of glucose transport in the small intestine and inhibition of glucose reabsorption in the kidney.

3.6 Antioxidant Activity and Nrf2 Pathway

Studies using the aglycone form (desoxyrhapontigenin) — which, as noted, is the metabolic product of desoxyrhaponticin — have characterized antioxidant mechanisms. Six stilbene derivatives isolated from Rheum undulatum L. were assessed for their antioxidative potential. In the tert-butylhydroperoxide-induced RAW 264.7 macrophage cell line, desoxyrhapontigenin was the most potent component that reduced intracellular reactive oxygen species (ROS) and peroxynitrite. In response to desoxyrhapontigenin, the mRNA expression levels of antioxidant enzymes were up-regulated. An electrophoretic mobility shift assay (EMSA) confirmed that desoxyrhapontigenin promoted the DNA binding of Nrf2 and increased the expression of antioxidant proteins and enzymes regulated by Nrf2. Further investigation utilizing specific inhibitors of Akt, p38, JNK and ERK demonstrated that the phosphatidylinositol 3-kinase (PI3K)/Akt pathway mediates HO-1 expression.

3.7 Anti-Inflammatory Mechanisms

Six stilbenes (rhaponticin, rhapontigenin, isorhaponticin, desoxyrhaponticin, desoxyrhapontigenin and resveratrol) isolated from the R. rhabarbarum rhizome reduced the reactive oxygen species production in RAW 264.7 macrophages.

At the level of the aglycone, the anti-inflammatory mechanisms are well characterized. To determine the anti-inflammatory effects, LPS-induced RAW 264.7 macrophages were treated with different concentrations of six stilbene derivatives. The results indicated that desoxyrhapontigenin (at 10, 30 and 50 μM concentrations) significantly inhibited nitric oxide (NO) production, nuclear factor kappa B (NF-κB) activation, the protein expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression. Desoxyrhapontigenin also produced dose-dependent inhibition of LPS-induced activation of NF-κB and AP-1. Moreover, desoxyrhapontigenin inhibited the protein expression of myeloid differentiation primary response gene 88 (MyD88), IκB kinase (IKK) phosphorylation and the degradation of IκBα.

Prior studies revealed that stilbene compounds of rhubarb possess anti-inflammatory activity, but studies have also addressed whether desoxyrhaponticin can regulate the polarization of macrophages to exert anti-inflammatory effects, with investigations designed to assess its underlying mechanism.

4. Scientific Evidence by Area of Use

4.1 Menopausal Symptoms

4.1.1 Mechanistic Basis

The mechanistic rationale for using desoxyrhaponticin-containing extracts in menopause rests on selective ERβ agonism. The mechanism of action of ERr 731 has not been fully elucidated. After ingestion, large amounts of the aglycones might be released due to deglycosylation of rhaponticin and desoxyrhaponticin by intestinal bacteria. ERr 731 may exert its biological effects via selective binding to, and activation of, ER-β without acting on ER-α.

4.1.2 Pivotal Randomized Controlled Trial (Heger et al., 2006)

The objective was to investigate the efficacy and safety of the special extract ERr 731 from the roots of Rheum rhaponticum compared to placebo in perimenopausal women with climacteric complaints. The design was a multicenter, prospective, randomized, double-blind, placebo-controlled clinical trial in which 109 women with climacteric complaints received either one enteric-coated tablet of ERr 731 (n = 54) or placebo (n = 55) daily for 12 weeks. By 12 weeks, the Menopause Rating Scale II (MRS II) total score and each MRS II symptom significantly decreased in the ERr 731 group compared to the placebo group (P < 0.0001). After 4 weeks, ERr 731 also significantly decreased the number and severity of hot flushes. Compared to placebo, ERr 731 significantly reduces the occurrence and severity of climacteric complaints in perimenopause. It is also safe and well tolerated.

At 12 weeks, the ERr 731 group had a significant reduction in total MRS II score, as well as significant decreases in all 11 individual symptom scores compared with placebo (p < 0.001). No abnormalities in safety parameters such as breast tissue, endometrium, hormones, liver enzymes, body weight, and blood pressure were noted.

4.1.3 Confirmation Trial (Kaszkin-Bettag et al., 2009)

In a previous study, the special extract ERr 731 of Rheum rhaponticum significantly reduced vasomotor and other menopausal symptoms associated with perimenopause. A confirmatory multicenter, randomized, placebo-controlled clinical trial enrolled 112 perimenopausal women with menopausal symptoms, receiving either one enteric-coated tablet of ERr 731 (n = 56) or placebo (n = 56) daily for 12 weeks. The primary outcome criterion was the change in the Menopause Rating Scale (MRS) total score from day 0 to day 84, with other efficacy assessments including number and severity of hot flushes, individual MRS symptoms, and safety parameters. By 12 weeks, ERr 731 caused a highly significant reduction of the MRS total score from 27.0 ± 4.7 points to 12.4 ± 5.3 points.

4.1.4 Long-Term Observational Data

Additionally, 82 subjects of this clinical trial continued intake of ERr 731® in 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.

The efficacy of ERr 731®, a commercially available extract isolated from Rheum rhaponticum, in terms of menopausal complaints like hot flushes, depression, anxiety and vaginal dryness has been proven in a two-year clinical study.

4.1.5 Systematic Review and Meta-Analysis (2024)

ERr 731® is a standardized extract from Rheum rhaponticum root that has been clinically studied for its role in reducing menopausal symptoms. A systematic review and meta-analysis aimed to evaluate the efficacy of ERr 731® supplementation in alleviating the severity of menopausal symptoms, searching across three online databases up to March 2023 and evaluating study quality by the Physiotherapy Evidence Database scale. After screening and evaluation, four high-quality studies (a total of 390 participants; ERr 731® group: 193 participants; control group: 197 participants) were included in the meta-analysis. The results showed that ERr 731® supplementation significantly reduced the Menopause Rating Scale score (MD: –15.12; P < 0.001), compared with control therapy. The current review provides evidence that ERr 731® supplementation is effective in reducing menopause symptoms.

4.1.6 Evaluation in Non-Western Populations

The clinical efficacy of ERr 731 has been shown in the western population; however, this extract had not previously been evaluated in Indian perimenopausal women until an interim analysis study, published as a PMC article from 2021, examined its use in that demographic, assessing MRS II total scores, endometrial thickness, blood pressure, glycemic status, lipid profile, and high-sensitivity C-reactive protein levels.

4.1.7 Evidence Strength Assessment (Menopausal Symptoms)

The evidence for ERr 731 (containing desoxyrhaponticin as a major constituent alongside rhaponticin) for menopausal symptom relief is among the strongest available for any botanical in this indication. Two independent multicenter, double-blind, placebo-controlled RCTs, long-term open-label observational data out to 96 weeks, a formal systematic review and meta-analysis, and post-marketing safety surveillance all converge on a consistent finding of symptomatic efficacy without endometrial or breast tissue abnormalities. Limitations include that no trials have directly compared ERr 731 to hormone replacement therapy in a head-to-head design, most trials were conducted by or with industry-linked investigators, and the specific contribution of desoxyrhaponticin versus rhaponticin to clinical outcomes cannot be disentangled from the mixed-extract studies.

4.2 Antidiabetic / Glucose Regulation Effects

4.2.1 In Vitro Evidence

Desoxyrhaponticin was demonstrated to inhibit glucose uptake in rabbit intestinal membrane vesicles as well as in rat everted gut sleeves, with IC₅₀ values of 148.3 and 30.9 μM, respectively. Kinetics studies revealed that desoxyrhaponticin is a competitive inhibitor of glucose uptake in both systems. Moreover, desoxyrhaponticin could reduce glucose uptake in the intestinal membrane vesicles of both normal and diabetic rats.

4.2.2 In Vivo Animal Evidence

Under the inhibition of desoxyrhaponticin, uptake of glucose in both the intestinal and renal membrane vesicles of normal rats was no different from that of the diabetic rats. The IC₅₀ values of the uptake inhibition in the renal membrane vesicles of normal and diabetic rats were 118.8 and 115.7 μM, respectively. In a type 2 diabetic animal model in which rats were treated with streptozotocin at the neonatal stage, postprandial hyperglycemia was significantly suppressed by oral administration of this compound (300 mg/kg body weight). These results suggest that desoxyrhaponticin is an agent potentially effective in controlling postprandial hyperglycemia in diabetes.

4.2.3 Evidence Strength Assessment (Diabetes/Glucose)

The antidiabetic evidence for desoxyrhaponticin is entirely preclinical (in vitro and rodent models). No human clinical trials have investigated desoxyrhaponticin in isolation for diabetes or glycemic control. The identified dosage in the animal study (300 mg/kg body weight, orally) is very high relative to any conceivable human supplementation dose. This area of research is preliminary and cannot form the basis of any clinical recommendation at this stage.

4.3 Anticancer / Antiproliferative Effects

4.3.1 Fatty Acid Synthase Inhibition in Breast Cancer Cells

Desoxyrhaponticin (DC) and rhaponticin (RC), two stilbene glycosides from rhubarb, could be considered as promising FAS inhibitors. Both DC and RC could inhibit intracellular FAS activity and downregulate FAS expression in human breast cancer MCF-7 cells. The apoptotic effect of DC on human cancer cells was announced for the first time in this study. Since FAS plays a key role in the biosynthesis pathway of fatty acids in cancer cells, these findings suggest that DC has potential applications in the prevention and treatment of cancer.

4.3.2 Endoplasmic Reticulum Stress and Apoptosis (Aglycone)

Research on the aglycone desoxyrhapontigenin, the principal metabolic product of desoxyrhaponticin, has explored additional anticancer mechanisms. Activation of endoplasmic reticulum stress–mediated apoptosis pathway represents the mechanism of action of deoxyrhapontigenin-induced cytotoxic effects in human breast cancer cells. Deoxyrhapontigenin, a natural analog of resveratrol, has already been reported to have antidiabetic and anti-inflammatory activities.

4.3.3 Evidence Strength Assessment (Anticancer)

All anticancer data for desoxyrhaponticin are from cell-line (in vitro) studies, predominantly in MCF-7 human breast cancer cells, and from animal models. There are no human clinical trials. The cell-culture IC₅₀ concentrations required for FASN inhibition may not be pharmacologically achievable in vivo at safe doses. This area is early-stage, hypothesis-generating preclinical research only.

4.4 Anti-Inflammatory and Antioxidant Effects

As described in the mechanisms section, the in vitro anti-inflammatory evidence for desoxyrhaponticin and its aglycone is relatively consistent across multiple research groups, spanning reduction of ROS in macrophages, suppression of NF-κB and MAPK signaling, downregulation of iNOS, COX-2, and pro-inflammatory cytokines, and upregulation of the cytoprotective Nrf2/HO-1 axis. In the LPS-induced in vivo lung inflammation model, pretreatment with desoxyrhapontigenin markedly ameliorated LPS-induced lung inflammation and histological changes.

The anti-inflammatory evidence for desoxyrhaponticin specifically (as opposed to the aglycone) at the in vivo level is more limited. Rhapontici Radix, the herb from which these compounds are derived, has been used in traditional medicine in East Asia and has been shown to have various beneficial effects. Treatment with the ethanolic root extract significantly inhibited the secretion of NO and inflammatory cytokines in RAW 264.7 cells and mouse peritoneal macrophages without cytotoxicity. The extract strongly suppressed the expression of iNOS and COX-2 and induced HO-1 expression. It also prevented nuclear translocation of NF-κB by inhibiting the phosphorylation and degradation of IκBα. Furthermore, the phosphorylation of MAPKs was significantly inhibited. These findings suggest that the extract may operate as an effective anti-inflammatory agent.

All available data on anti-inflammatory and antioxidant effects remain preclinical (cell culture and animal studies). No human clinical trials have been designed specifically to test the anti-inflammatory properties of desoxyrhaponticin in isolation.

5. Body Systems and Health Areas Associated with Desoxyrhaponticin

Endocrine / Reproductive System: Selective ERβ agonism supports the established clinical use of the containing extract for menopausal and climacteric symptoms, including vasomotor symptoms (hot flushes), anxiety, sleep disturbance, and vaginal dryness. The compound and its aglycone lack significant ERα agonism, which is considered relevant to the avoidance of endometrial proliferation.
Metabolic / Glycemic Regulation: Competitive inhibition of intestinal and renal glucose transporters (SGLT-like mechanisms) has been demonstrated in vitro and in diabetic rodent models, suggesting potential relevance to post-prandial blood glucose management, though no human data exist.
Oncology (Preclinical): FASN inhibition and induction of apoptosis via endoplasmic reticulum stress have been demonstrated in breast cancer cell lines. All such evidence is preclinical.
Immune / Inflammatory: Suppression of NF-κB, MAPK, and related pro-inflammatory cascades; induction of antioxidant Nrf2/HO-1 signaling; reduction of nitric oxide, TNF-α, IL-6, and other cytokines in macrophage models.
Cardiovascular (Indirect): Inflammation, endothelial dysfunction, and alterations in blood physiology are key factors contributing to atherosclerosis and other cardiovascular disorders. The anti-inflammatory properties of rhubarb stilbenes including desoxyrhaponticin have been examined in the context of endothelial cell inflammatory response, though no direct human cardiovascular outcome data exist for desoxyrhaponticin specifically.

6. Dosage Forms and Reported Dosages

The following dosages are reported in the cited scientific literature. They pertain primarily to the standardized extract ERr 731® as a whole, within which desoxyrhaponticin is a component alongside rhaponticin.

Clinical trials (ERr 731 extract, perimenopausal symptoms): A multicenter, prospective, randomized, double-blind, placebo-controlled clinical trial administered one enteric-coated tablet of ERr 731 or placebo daily for 12 weeks. The product label dose for the commercially marketed product Estrovera was reported as effective at 4 mg daily, with noticeable results in just 4 weeks. This 4 mg figure represents the total standardized extract (ERr 731) per tablet, standardized to its stilbene glycoside content. The relative proportions of rhaponticin and desoxyrhaponticin within this dose are not individually specified in the available clinical literature reviewed.
Animal model (antidiabetic): In a type 2 diabetic animal model, postprandial hyperglycemia was significantly suppressed by oral administration of desoxyrhaponticin at 300 mg/kg body weight. No human equivalent dose has been established.
In vitro glucose transport (IC₅₀ values): Desoxyrhaponticin inhibited glucose uptake in rabbit intestinal membrane vesicles and in rat everted gut sleeves, with IC₅₀ values of 148.3 and 30.9 μM, respectively. The IC₅₀ values of the uptake inhibition in the renal membrane vesicles of normal and diabetic rats were 118.8 and 115.7 μM, respectively.
In vitro anti-inflammatory (aglycone form): Desoxyrhapontigenin at 10, 30 and 50 μM concentrations significantly inhibited nitric oxide production, NF-κB activation, COX-2 and iNOS expression in LPS-stimulated macrophages.

7. Safety Considerations and Interactions

7.1 Clinical Safety Profile of the Containing Extract (ERr 731)

The pivotal 12-week, placebo-controlled, randomized trial with perimenopausal women (N = 109) reported no differences between the extract and a placebo in the gynecological findings (e.g., endometrial biopsies and bleeding) and in the laboratory safety parameters. The trial also found that no adverse events had been classified as being related to the extract.

A second 12-week, placebo-controlled, randomized trial in perimenopausal women (N = 112) reported a similar safety profile and found that no serious adverse events had occurred. A long-term observational clinical study of 81 women who received ERr 731 for 96 weeks found no changes in gynecological findings or laboratory safety parameters and no adverse events related to use of ERr 731.

In a 6-month, open-label clinical evaluation conducted at 70 German gynecological practices with 252 menopausal women who were taking ERr 731, only 1 adverse event was documented. The gynecologist assessed it as not being causally related to the extract.

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.

7.2 Endometrial Safety

A specific preclinical concern with any estrogenically active compound is the potential for endometrial proliferation, which is associated with risk of endometrial hyperplasia and cancer. A recent preclinical study excluded unwanted side effects on the endometrium by showing a lack of stimulation of proliferation marker genes by ERr 731® or its constituents in the 3-day uterotrophic assay. ERr 731 did not stimulate a uterotrophic response in the uterotrophic assay with ovariectomized rats nor stimulate or modulate the expression of genes associated with proliferation. In combination with estradiol (E2), ERr 731 reduced the E2-induced uterine growth stimulation, which suggests a potentially protective, anti-proliferative interaction in the uterus when co-present with estrogen. This is consistent with the known anti-proliferative role of ERβ as a negative modulator of ERα-driven proliferation.

7.3 Drug Interactions

Studies indicate that desoxyrhaponticin may interact with medications such as anticoagulants (e.g., warfarin), potentially enhancing their effects, attributed to the laxative properties associated with rhubarb preparations. This interaction concern applies to rhubarb-derived preparations generally and is not specifically characterized for desoxyrhaponticin in isolation in the published peer-reviewed literature reviewed. The compound's interaction with human serum albumin suggests it may influence drug bioavailability and distribution in the body. The clinical significance of albumin binding for desoxyrhaponticin specifically has not been quantified in human pharmacokinetic studies.

7.4 Oxalic Acid and Species-Specific Caution

Rhubarb is considered relatively safe when consumed in moderation; however, caution is advised due to its oxalic acid content, which can lead to kidney issues if consumed excessively. This safety note applies to whole rhubarb preparations and is most relevant to high-dose ingestion of leaves (which contain far higher oxalate levels than the roots). Standardized root extracts such as ERr 731 are processed to contain specific stilbene glycoside fractions and do not carry the same oxalate burden as crude whole-leaf preparations.

7.5 Evidence Limitations and Research Gaps

The vast majority of pharmacological data for desoxyrhaponticin as an isolated compound derive from in vitro and animal studies. Human clinical trials have investigated the standardized multi-component extract ERr 731, not desoxyrhaponticin in isolation. The contribution of desoxyrhaponticin specifically — as opposed to rhaponticin, the aglycones, or other trace constituents — to the observed clinical effects in menopausal symptom trials cannot be determined from the available literature. Formal pharmacokinetic data in humans (absorption, distribution, metabolism, elimination, bioavailability) for desoxyrhaponticin alone are not available in the published literature reviewed.

The mechanism of action of ERr 731 has not been fully elucidated. Furthermore, in contrast to the clinical effectiveness of ERr 731®, little was known about the molecular mechanism of the extract or its potential metabolites at the time several key mechanistic studies were undertaken, and this picture remains incomplete. Future research isolating the individual contributions of rhaponticin and desoxyrhaponticin to the clinical outcomes of ERr 731 would be valuable.

References

Health Conditions

Health conditions that Desoxyrhaponticin may help support.

No conditions available.

Body Systems

Body systems that Desoxyrhaponticin may help support.

No body systems available.