Piceid

Other Names

(E)-Piceid(E)-Polydatin3,4',5-Trihydroxystilbene-3-β-D-glucoside3,4',5-Trihydroxystilbene-3-β-monoglucoside3-Hydroxy-5-(p-hydroxystyryl)phenyl glucoside3-Hydroxy-5-[(E)-2-(4-hydroxyphenyl)ethenyl]phenyl β-D-glucopyranoside3-Hydroxy-5-[2-(4-hydroxyphenyl)ethenyl]phenyl-β-D-glucopyranoside3-O-β-D-Resveratrol-glucopyranoside4',5-Dihydroxystilben-3-yl β-D-Glucopyranosidecis-PiceidPolydatinResveratrol 3-glucosideResveratrol 3-O-glucosideResveratrol 3-O-β-D-glucopyranosideResveratrol glucosideResveratrol-3-β-mono-D-glucosidetrans-3,4',5-Trihydroxystilbene 3-O-β-D-glucosidetrans-Piceidtrans-Polydatintrans-Resveratrol 3-O-β-D-glucosidetrans-Resveratrol-3-β-D-glucosideβ-D-Glucopyranoside, 3-hydroxy-5-(2-(4-hydroxyphenyl)ethenyl)phenyl云杉新甙白藜芦醇甙白藜芦醇苷白藜芦醇葡萄糖甙虎杖甙虎杖苷

Synopsis

Piceid (Polydatin): A Comprehensive Reference Article

1. Identity and Chemical Characterization

1.1 Names and Classification

Piceid (also named polydatin, (E)-piceid, (E)-polydatin, trans-polydatin; systematic name: 3,4′,5-trihydroxystilbene-3-β-d-glucoside) is a monocrystalline compound originally isolated from the root and rhizome of Polygonum cuspidatum Sieb. It belongs to the stilbenoid class of polyphenols and is formally a stilbenoid glucoside. Its full systematic chemical name is resveratrol-3-O-β-D-glucopyranoside (3,4′,5-trihydroxystilbene-3-β-D-glucoside), and it is also known as polydatin and piceid. The CAS registry number is 27208-80-6.

Piceid (polydatin) has the molecular formula C₂₀H₂₂O₈ with a molecular weight of 390.38 g/mol and is the primary natural precursor and glycosylated form of resveratrol. It is a glucoside of resveratrol (3,4′,5-trihydroxystilbene) in which the glucoside group bound to the position C-3 substitutes a hydroxyl group, and it belongs to the stilbene phytoalexins.

Trans-piceid is the glucoside formed with trans-resveratrol, while cis-piceid is formed with cis-resveratrol. The trans isomer is generally considered the more biologically relevant and more widely studied form. The single glucose moiety attached at the 3-position of resveratrol confers significantly improved water solubility (approximately 30-fold greater than resveratrol) and enhanced stability against enzymatic oxidation and UV-light degradation.

1.2 Botanical Sources

Piceid can be found in the bark of the Sitka spruce (Picea sitchensis), which is the origin of the name "piceid," and it can also be isolated from Japanese knotweed (Reynoutria japonica).

Polydatin (piceid) was first purified from the roots and rhizomes of Polygonum cuspidatum Sieb. et Zucc. This plant, a member of the Polygonaceae family, is the richest known source of piceid and the primary botanical used for commercial extraction. The glucoside of resveratrol, piceid (3,5,4'-trihydroxystilbene-3-β-monoglucoside), has also been detected in several plant species, either with or without resveratrol, such as Eucalyptus spp., grape, and Picea spp.

Piceid (trans-3,5,4′-trihydroxystilbene-3-O-β-D-glucoside), also named polydatin, is naturally present in wine, where it is typically the most abundant stilbene, with concentrations reaching a few milligrams per liter. Red wine is considered the primary dietary source of resveratrol and piceid in Mediterranean countries.

Polydatin can also be detected in grape, peanut, hop cones, red wines, hop pellets, cocoa-containing products, chocolate products, and many daily diets. It is found in a wide range of fruits and vegetables, including grape berries, cranberries and blueberries (Vaccinium spp.), mulberries and blackberries (Morus and Rubus spp.), peanuts (Arachis hypogaea), and jackfruit (Artocarpus heterophyllus).

In grapes and grape juice, piceid is the predominant form, often present at concentrations 4- to 10-fold higher than free resveratrol. The average content of piceid was found ten times higher than that of resveratrol in Polygonum cuspidatum and red wine, making piceid the most abundant form of resveratrol in nature.

1.3 Common Forms and Preparations

Piceid is available commercially in several forms. As a dietary supplement ingredient, it is most often produced by standardized extraction from the roots and rhizomes of Polygonum cuspidatum. Production methods include direct extraction from plant material or biotransformation via microbial glucosylation of resveratrol using bacteria such as Bacillus cereus. Resveratrol can be produced from piceid by the mold Aspergillus oryzae, the mold used to make sake and soy sauce, as this fungus produces a potent beta-glucosidase.

Commercial preparations include oral capsules and tablets (standardized extracts of Polygonum cuspidatum), comicronized formulations combined with other compounds such as palmitoylethanolamide (PEA), and intravenous preparations used in clinical trials in China. Oral tablet formulations containing 200 mg PEA and 20 mg polydatin have been used in clinical studies, and for shock treatment, polydatin has been administered by diluting two 100 mg/5 mL vials into 500 mL of 0.9% NaCl injection administered as an IV infusion over 2 hours.

2. Traditional and Historical Use

2.1 Traditional Chinese Medicine

Polydatin (piceid) is a monocrystalline compound originally isolated from the root and rhizome of Polygonum cuspidatum Sieb. et Zucc. (Polygonaceae), a traditional Chinese medicine that has long been used in China as an analgesic, anti-pyretic, diuretic, and expectorant.

Polygonum cuspidatum (Polygonaceae), the root of which is included in the Chinese Pharmacopoeia under the name 'Huzhang', has a long history as a medicinal plant and vegetable. It has been used in traditional Chinese medicine for the treatment of inflammation and hyperlipemia. The Leigong paozhilun, written approximately 1,500 years ago, is the earliest ancient Chinese book recording the use of Polygonum cuspidatum as a medicine. It first appeared in Mingyi Bie Lu around 420–589 AD.

Hu Zhang can be found in Asia and North America and is used as folk medicine in countries such as Japan and Korea. In China, Hu Zhang is usually used in combination with other TCM herbs, and the therapeutic uses of those Hu Zhang-containing formulations are for treating cough, hepatitis, jaundice, amenorrhea, leucorrhea, arthralgia, burns, and snake bites.

The traditional Chinese usage of P. cuspidatum was mainly as an oral water decoction, also as a topical powder, and an ointment. P. cuspidatum is used in TCM to promote blood circulation, relieve pain, relieve coughs, dissipate phlegm, and promote choleretic action. In TCM classification, Hu Zhang is considered bitter and slightly cold in nature, and is said to enter the liver, gallbladder, and lung meridians. The richest source of piceid (polydatin) is the root of ko-jo-kon (Polygonum cuspidatum or Reynoutria japonica or Fallopia japonica), whose extracts are used in Chinese and Japanese traditional medicine for the treatment of gonococcal infection, suppurative dermatitis, tinea favosa, tinea pedis infections, hyperlipidemia, and arteriosclerosis.

2.2 Japanese and Korean Traditions

Fallopia japonica is known as Huzhang in traditional Chinese medicine and Itadori in Japanese medicine, and has been used historically for analgesic, anti-pyretic, anti-inflammatory, and anti-infective purposes. Huzhang (Japanese Knotweed) has been used in traditional Chinese medicine as well as in Japan and Korea for many years. In Japan and Korea, the plant's rhizome preparations were employed for a range of inflammatory, infectious, and cardiovascular complaints paralleling those described in Chinese texts.

3. Key Constituents and Mechanisms of Action

3.1 Structural Relationship to Resveratrol

In edible plant parts such as grapes, including juices and wine, resveratrol occurs mainly in the glycosidic form, resveratrol-3-O-β-d glucoside, called piceid or polydatin. After formation in the plant, resveratrol is modified by the addition of a hexose sugar, and the resulting component is characterized as piceid. The stilbene synthase enzyme catalyzes the conversion of one molecule of p-coumaroyl-CoA and three molecules of malonyl-CoA into 3,4′,5-trihydroxystilbene (resveratrol), the aglycone precursor.

The oral bioavailability of resveratrol is extremely low due to rapid and extensive metabolism and the consequent formation of various metabolites such as resveratrol-glucuronides and resveratrol-sulfates. Piceid's glucose moiety provides a distinct pharmacokinetic profile compared to free resveratrol. Upon ingestion, piceid undergoes hydrolysis in the gastrointestinal tract, primarily by gut microbiota such as Bifidobacterium infantis, converting it to free resveratrol for absorption. B. infantis showed the highest enzyme activity toward piceid, hydrolyzing 100% of piceid to resveratrol within 30 minutes of incubation.

Polydatin was found to be the main substance in serum after administration, hinting at its potential as a substitute for resveratrol in clinical antioxidant use. Trans-resveratrol-3-O-glucuronide is one of the two metabolites of trans-piceid in rat.

3.2 Antioxidant Mechanisms

Piceid can enhance the decomposition of H₂O₂ and dismutation of superoxide anions by increasing the availability and activity of glutathione (GSH) and superoxide dismutase (SOD), thereby reducing the damage likely to result from these free radicals. Piceid may also detoxify peroxidized lipid membranes by directly interacting with peroxidated lipids to restore them to lipid alcohols.

In the phytochemical context, it has been reported that polydatin is a potent anti-inflammatory plant secondary metabolite, beneficially promoting miR-200a expression to regulate the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor E2-related factor 2 (Nrf2) antioxidant axis. This pathway, in turn, suppresses nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation against diverse chronic inflammation-related diseases.

3.3 Anti-inflammatory Mechanisms

Polydatin's anti-inflammatory response is mainly orchestrated by extracellular-signal-regulated kinases (ERK1/2), c-Jun N-terminal kinase 1/2 (JNK1/2), and p38 protein kinases, and consequently inhibits NF-κB p65 phosphorylation and the release of inflammatory factors such as xanthine oxidase (XOD), prostaglandin E2 (PGE2), TNF-α, IL-1β, and COX-2.

Resveratrol produced on the hydrolysis of polydatin catalysed by β-glucosidase has been used as a nutraceutical targeting cyclooxygenase isoforms (COX-1 and COX-2), which are involved in the metabolism of arachidonic acid. The metabolic products of arachidonic acid — thromboxanes and prostaglandins — have roles in the inflammatory response, and upon interaction of COX-1 with resveratrol, suppression of TxA2 and TxB2 (thromboxane) in the arachidonic acid pathway was found to exhibit anti-thrombotic and anti-inflammatory activities.

3.4 SIRT1 Activation

While the pharmacological mechanisms of piceid are still not fully elucidated, it has been postulated that it acts through activation of SIRT1. Polydatin has been shown to inhibit NF-κB/NLRP3 inflammasome activation via the AMPK/SIRT1 pathway, and it has been found to have significant protective effects on diseases associated with oxidative stress by regulating SIRT1-related targets.

Polydatin treatment has been shown to reverse high-glucose-induced mitochondrial dysfunction and ROS generation by promoting SIRT1-mediated mitochondrial biogenesis and Nrf2-mediated antioxidant signaling. In experimental models of hemorrhagic shock, polydatin treatment attenuated mitochondrial dysfunction partially and inhibited expression of proapoptotic proteins, while also increasing SIRT1 activity and decreasing acetylated-p53 levels.

3.5 Anticancer Mechanisms

Polydatin possesses a broad range of biological activities including antioxidant, anti-inflammatory, anticancer, and hepatoprotective, neuroprotective, and immunostimulatory effects. At the cellular level, polydatin could effectively inhibit the migration and proliferation of ovarian cancer cells, as well as the expression of the PI3K protein. In a study of colorectal cancer, polydatin promoted apoptosis and inhibited proliferation of colorectal cancer cells by regulating the miR-382/PD-L1 axis; since miR-382 binds to the transcript of PD-L1, the overexpression of miR-382 inhibited the expression of PD-L1.

4. Scientific Evidence by Area of Use

Overview: Numerous pharmacological investigations of piceid (polydatin) mainly focus on cardiovascular effects, neuroprotection, anti-inflammatory and immunoregulatory effects, anti-oxidation, anti-tumor, and liver and lung protection. It has been isolated from Polygonum cuspidatum, but is also detected in grape, peanut, hop cones, red wines, hop pellets, cocoa-containing products, chocolate products, and many daily diets. The need to develop further clinical trials and novel delivery systems of piceid has been noted to provide new insights to researchers.

4.1 Cardiovascular and Atherosclerotic Disease

Polydatin, an active ingredient isolated from the natural medicine Polygonum cuspidatum, has been shown to have a prominent role in the treatment of cardiovascular diseases, treating atherosclerosis mainly from three aspects: anti-inflammatory activity, regulating lipid metabolism, and anti-oxidative stress.

Modern studies have confirmed that polydatin has various pharmacological effects, including anti-tumor and anti-bacterial activities, as well as protective effects on the hepatic, nervous system, cardiovascular system, and lungs, and inhibitory effects on melanogenesis. These findings are derived predominantly from preclinical (in vitro and animal) studies.

Evidence strength: Primarily preclinical. A great number of pharmacological and pharmacokinetic investigations have demonstrated that piceid has favorable therapeutic properties indicating its potential as an effective material. However, further research is needed to explore its molecular mechanisms of action and definitive target proteins. Clinical cardiovascular data in humans remain limited, and no large randomized controlled trials in cardiovascular endpoints have been reported.

4.2 Neurological Conditions and Neuroprotection

The neuroprotective properties of polydatin have been demonstrated in both cerebral ischemia and other neurodegenerative diseases. Previous studies have shown that polydatin successfully counteracts the deleterious effects of ischemic stroke in animal models. Polydatin diminishes infarct volume, reduces brain water, and improves neurologic scores in focal cerebral ischemia.

In rodent models of Parkinson's disease: co-administration of piceid orally was able to attenuate rotenone-induced motor defects in a dose-dependent manner, with 80 mg/kg dosage showing even better effect than L-levodopa (L-dopa). Similar protective effects of piceid were also observed in two additional models of PD — MPTP in mice and 6-OHDA in rats — showing corrected motor functions, SOD and MDA activities, as well as p-Akt and activated caspase-3 levels.

Another mechanism of the neuroprotective effect of polydatin is mediated by the C/EBPβ/MALAT1/CREB/PGC-1α/PPARγ signaling pathway. This process results in silencing NF-κB-associated downstream inflammatory mediators, which could alleviate cerebral infarct volume and ameliorate the integrity of the blood–brain barrier.

Evidence strength: Animal/preclinical only for Parkinson's and ischemia models. Owing to the fact that piceid is the most abundant form of resveratrol, it is largely available in non-alcoholic grape juices and is the major extracted component of a widely used traditional Chinese herbal medicine, piceid is believed to represent a new medication with modality; the Chinese FDA has approved it for multiple phase II clinical trials in China mainly for anti-shock applications. No published human clinical trials for Parkinson's disease or ischemic stroke using piceid alone have been identified in available literature.

4.3 Shock, Ischemia/Reperfusion Injury, and Multi-Organ Protection

Polydatin (piceid), a monocrystalline and polyphenolic drug isolated from Polygonum cuspidatum, is protective against mitochondrial dysfunction and has been approved for clinical trials in the treatment of shock. Several studies have shown that piceid possesses important therapeutic effects in animal models of shock. It has been reported that piceid can attenuate damage against ischemia-reperfusion injury in multiple organs, and research teams have revealed that piceid can alleviate oxidative stress and can protect mitochondria in vascular smooth muscle cells, neurons, and hepatocytes against severe shock.

In hemorrhagic shock rat models, SIRT1 activity and PGC-1α protein expression were decreased, leading to severe oxidative stress. The decreased SIRT1 activity was partially restored in the polydatin administration group, which showed reduced intestine injury and longer survival time; notably, the effect of polydatin was abolished after the addition of Ex527, a selective inhibitor of SIRT1. The results collectively suggest that polydatin is an effective SIRT1 activator for shock treatment.

Evidence strength: Phase II clinical trials in China reported for shock applications (anti-shock use), though results of those trials are not fully published in English-language literature. The bulk of supporting evidence is preclinical (animal models).

4.4 Anti-tumor and Oncology

The therapeutic and protective effects of polydatin arise from its antioxidant, anti-apoptotic, and anti-inflammatory characteristics. With more potent antioxidant and anti-inflammatory activity compared to resveratrol, polydatin has been studied for its therapeutic advantages across various pathological conditions, including diabetes, neurodegenerative disorders, rheumatoid diseases, hepatic/respiratory diseases, cardiovascular diseases, skeletal/women's disorders, gastrointestinal diseases, and infectious diseases.

Polydatin's potential in fighting cancer has been confirmed in various studies, showcasing its efficacy against cervical, nasopharyngeal, and liver cancers. The trans version of polydatin is well acknowledged in China for its significant therapeutic properties, often used as a fever reducer and painkiller.

While resveratrol showed higher inhibition capacity in cell viability than piceid, both compounds exhibited significant cytotoxicity on tumour cells at high concentrations. Moreover, polydatin has been investigated for its potential to induce cell cycle arrest and differentiation in human colorectal cancer cells.

Evidence strength: Predominantly in vitro cell culture and animal studies. No large-scale human clinical trials demonstrating anti-cancer efficacy of piceid alone have been published.

4.5 Pain Management and Endometriosis

Loi et al. assessed the effects of polydatin against chronic pelvic pain related to endometriosis in thirty symptomatic women desiring pregnancy. Patients administered 600 mg ultramicronized PEA (um-PEA) twice a day for 10 days followed by 400/40 mg co-micronized PEA/polydatin twice a day for 80 days demonstrated protective responses. The um-PEA and PEA/polydatin regimen improved pain symptoms, psychological condition, and quality of life effectively, and no adverse events were reported.

A preliminary human study also examined the combination at lower doses: four patients presenting with endometriosis-related pain intensity ≥5 (visual analogue scale) were enrolled and monitored during 3 months of treatment with oral palmitoylethanolamide 400 mg and polydatin 40 mg, twice daily for 90 days. The preliminary results indicate that all patients enrolled experienced pain relief as early as 1 month after starting treatment, and a reduction in the analgesic drugs usually employed for pain control was observed in all subjects treated.

Evidence strength: Very preliminary; small sample sizes (4–30 patients) in open-label designs. These studies used piceid in combination with palmitoylethanolamide, not as a standalone agent. Results are hypothesis-generating only.

4.6 Inflammatory Bowel Disease

Polydatin has found its way into clinical trials for the treatment of hemorrhagic shock and irritable bowel syndrome. In preclinical models, polydatin has shown efficacy against experimental colitis. A comicronized formulation of ultramicronized PEA (um-PEA) and polydatin (PEA/Pol), in which polydatin is a biological precursor of resveratrol with antioxidant activity, could have protective effects on oxidative stress produced by inflammatory processes. In a model of DNBS-induced colitis, a dose of 10 mg/kg (9 mg um-PEA + 1 mg polydatin) was evaluated. The PEA/polydatin effect could be related to a decrease in inflammatory NF-κB activation signaling and an increase in the antioxidant SIRT1/Nrf2 pathway, which represent important targets of the pharmacological action against both inflammation and oxidative stress.

Evidence strength: Predominantly animal models with some clinical trial registration for irritable bowel syndrome. Human clinical data for IBD applications are limited.

4.7 Antioxidant Activity (In Vitro Comparison with Resveratrol)

Piceid is a precursor of resveratrol. The average content of piceid was found ten times higher than that of resveratrol in Polygonum cuspidatum and red wine, and piceid was found to be the most abundant form of resveratrol in nature. In vitro antioxidant comparisons reveal that while both compounds possess significant activity, their potency profiles differ depending on the assay system.

Evidence strength: In vitro comparative studies only. No head-to-head human trials measuring antioxidant biomarkers from piceid versus resveratrol administration have been identified.

5. Body Systems Associated with Piceid Activity

Various imperative biological activities have been suggested for polydatin (piceid) toward promising therapeutic effects, including anticancer, cardioprotective, anti-diabetic, gastroprotective, hepatoprotective, neuroprotective, and anti-microbial effects, as well as health-promoting roles on the renal system, the respiratory system, rheumatoid diseases, the skeletal system, and women's health. These include:

Cardiovascular system: Atherosclerosis, lipid metabolism, platelet aggregation inhibition, blood pressure.
Nervous system: Ischemic stroke, Parkinson's disease models, blood-brain barrier integrity.
Gastrointestinal system: Ulcerative colitis, hemorrhagic shock-related intestinal injury, gastroprotection.
Hepatic system: Hepatoprotection against chemical- and alcohol-induced injury.
Renal system: Mitochondrial protection in hemorrhagic shock-related kidney injury.
Oncology: Colorectal, cervical, nasopharyngeal, liver, ovarian, and breast cancer models (preclinical).
Women's health: Endometriosis-associated pelvic pain (early human data in combination therapy).
Metabolic system: Anti-diabetic and neuroprotective effects in diabetic neuropathy models.
Immune system: Immunomodulation, anti-infective activity.

6. Dosage Forms and Reported Dosages

Piceid is reported in several dosage forms across published studies. The following dosages are reported directly from sources; they reflect study-specific use rather than any established therapeutic recommendation.

Endometriosis pain (oral, combination with PEA): Oral palmitoylethanolamide 400 mg and polydatin 40 mg, twice daily for 90 days.
Endometriosis pain (oral, combination with PEA, 30-patient study): Patients were administered 600 mg ultramicronized PEA (um-PEA) twice a day for 10 days followed by 400/40 mg co-micronized PEA/polydatin twice a day for 80 days.
Oral tablet (clinical trial registration): 200 mg PEA + 20 mg polydatin; 2 tablets per day; 12 weeks.
Shock treatment (IV, clinical trial protocol): Dilute two 100 mg/5 mL vials of polydatin into 500 mL 0.9% NaCl injection and administer as IV infusion over 2 hours; to be given as early as possible on Day 1 and once every 24 hours for an additional 4 doses.
Parkinson's disease rodent models (oral): Co-administration of piceid orally in a dose-dependent manner, with 80 mg/kg dosage showing even better effect than L-levodopa. (Animal data only.)
Preliminary human supplement range: Polydatin is generally considered well-tolerated at doses used in preliminary human studies, typically ranging from 40 to 120 mg per day, with no severe adverse events reported in short-term use.

7. Safety Considerations and Interactions

7.1 General Safety Profile

A great number of pharmacological and pharmacokinetic investigations have demonstrated that polydatin (piceid) has favorable therapeutic properties. However, further research is needed to explore its molecular mechanisms of action and definitive target proteins, and by extension, its comprehensive long-term safety profile in humans.

Polydatin is generally considered well-tolerated at doses used in preliminary human studies, typically ranging from 40 to 120 mg per day, with no severe adverse events reported in short-term use.

7.2 Potential Drug Interactions

Due to its structural similarity to resveratrol, polydatin may inhibit CYP450 enzymes (particularly CYP3A4). This mechanistic similarity raises a theoretical potential for pharmacokinetic interactions with drugs metabolized by CYP3A4, though direct clinical interaction data for piceid specifically are not yet well established. Although used for various applications, few clinical studies validate claims, and guidance regarding dosing or safety is limited.

7.3 Phytoestrogenic Considerations

As a stilbenoid with structural similarity to resveratrol, piceid may share some of resveratrol's phytoestrogenic properties. However, direct human data on estrogenic activity or interactions with hormone-modulating therapies for piceid specifically are not available in the sources reviewed.

7.4 Source-Plant Safety Concerns

Piceid is most commonly extracted from Polygonum cuspidatum, which also contains emodin and other anthraquinone compounds. Resveratrol, polydatin, quercetin, emodin, and their derivatives are the primary active phytochemical components of Polygonum cuspidatum. Standardized piceid extracts should be characterized for emodin content, as emodin has been associated with laxative effects and, in high-dose animal studies, potential genotoxicity. Consumers using whole-plant extracts rather than isolated piceid should account for these additional constituents.

7.5 Evidence Limitations

Huzhang (Japanese Knotweed) has been used in traditional Chinese medicine as well as in Japan and Korea for many years. Although used for various applications, few clinical studies validate claims, and guidance regarding dosing or safety is limited. The majority of evidence for piceid's pharmacological effects comes from in vitro cell culture studies and rodent models. Translation of these findings to human clinical outcomes requires formal well-designed randomized controlled trials, most of which have not yet been completed or published in full.

References

Health Conditions

Health conditions that Piceid may help support.

No conditions available.

Body Systems

Body systems that Piceid may help support.

No body systems available.