1. What Is Urolithin B?
Urolithin B (Uro B; IUPAC: 3-hydroxy-6H-dibenzo[b,d]pyran-6-one) is a gut microbiota-derived phenolic metabolite belonging to the urolithin family — a class of benzocoumarins produced through the microbial biotransformation of ellagitannins and ellagic acid found in pomegranates, berries, walnuts, and oak-aged red wine. Unlike Urolithin A — which carries four hydroxyl groups and is best known for mitophagy activation — Urolithin B has a single hydroxyl group at position 3, giving it distinct physicochemical and pharmacological properties including greater lipophilicity, enhanced blood-brain barrier (BBB) penetration, and a multi-target mechanism centered on NF-κB suppression, AMPK activation, and androgen receptor-mediated mTORC1 signaling.
First structurally characterized as a urinary metabolite, Urolithin B was historically overlooked in favor of the more hydroxylated urolithins. However, landmark studies by Rodriguez et al. (2017, J Cachexia Sarcopenia Muscle) and Chen et al. (2021, Front Pharmacol) have since established Urolithin B as a standalone bioactive entity with distinct therapeutic potential in muscle wasting, neurodegeneration, and inflammatory disease — independent of its precursor ellagitannins.
Gut Microbiota Origin
Produced by colonic bacteria (Gordonibacter, Ellagibacter) from dietary ellagitannins; generation depends on individual gut microbiome composition (metabotype).
Dietary Sources
Pomegranate (Punica granatum), strawberries, red raspberries, walnuts, oak-aged red wine, and almonds — all rich in ellagitannin precursors.
BBB Penetrant
In silico and in vivo validated to cross the blood-brain barrier — a property absent in parent ellagitannins and limited in Urolithin A.
2. Physicochemical Specifications
| Parameter | Specification |
|---|---|
| CAS Number | 1139-83-9 |
| IUPAC Name | 3-Hydroxy-6H-dibenzo[b,d]pyran-6-one |
| Synonym(s) | 3-Hydroxyurolithin; Uro B; 3-Hydroxy-6H-benzo[c]chromen-6-one; NSC 94726 |
| Empirical Formula | C₁₃H₈O₃ |
| Molecular Weight | 212.20 g/mol |
| Chemical Class | Benzocoumarin (dibenzo-α-pyrone); polyphenol; urolithin |
| Appearance | White to pale beige powder; pale yellow to yellow solid |
| Purity | ≥99% (HPLC), identity confirmed by NMR & LC-MS |
| Melting Point | 255–256°C |
| Density | 1.395±0.06 g/cm³ (predicted) |
| Solubility | DMSO: ~249 mg/mL (sonication recommended); DMSO: 5 mg/mL (clear, warmed); Ethanol: ~12 mg/mL; Water: nearly insoluble (0.093 g/L at 25°C) |
| LogP | ~3.1 (predicted; moderate lipophilicity) |
| pKa | ~7.9–8.3 (phenolic –OH, predicted; deprotonated at physiological pH) |
| λmax | ~305 nm (UV-Vis, MeOH) |
| InChI Key | WXUQMTRHPNOXBV-UHFFFAOYSA-N |
| SMILES | C1=CC=C2C(=C1)C3=C(C=C(C=C3)O)OC2=O |
| Storage (Powder) | −20°C, protected from light and moisture, 36 months |
| Storage (Solution) | −80°C, 12 months; −20°C, 1 month (DMSO stock) |
3. Mechanism of Action
Urolithin B exerts its biological effects through a multi-target, multi-pathway pharmacological profile — distinct from the primarily mitophagy-focused mechanism of Urolithin A. Its single phenolic hydroxyl group confers enhanced lipophilicity and membrane permeability, enabling access to intracellular targets across multiple tissue compartments including the CNS.
3.1 NF-κB / Inflammatory Signaling (Primary Anti-Inflammatory Axis)
Urolithin B is one of the most well-characterized natural-product inhibitors of the canonical NF-κB pathway. It suppresses IκB kinase (IKK)-mediated phosphorylation of IκBα, preventing its ubiquitination and proteasomal degradation. Stabilized IκBα retains NF-κB (p65/p50) in the cytoplasm, blocking its nuclear translocation and transcriptional activation of pro-inflammatory target genes including TNF-α, IL-6, IL-1β, and COX-2.
Phosphorylation
Degradation
Translocation
↓ IL-6
↓ IL-1β
⊘ = Urolithin B inhibits this step | Red = suppressed Green = outcome
3.2 AMPK Activation & Metabolic Regulation
Urolithin B enhances AMP-activated protein kinase (AMPK) phosphorylation, shifting cellular metabolism toward catabolic and energy-conserving programs. This AMPK activation simultaneously suppresses anabolic pathways driven by Akt, ERK1/2, and JNK — creating a dual-pronged anti-inflammatory and metabolic regulatory effect. The AMPK activation is particularly relevant in hepatic tissue, where it coordinates with PPARα repression and Nrf2 activation (see Section 3.3) to restore metabolic homeostasis.
3.3 Keap1/Nrf2 Antioxidant Axis & Hepatoprotection
In cholestatic liver injury models, Urolithin B activates the Keap1/Nrf2 pathway, leading to upregulation of heme oxygenase-1 (HO-1) and restoration of oxidant/antioxidant balance. Simultaneously, it suppresses PPARα expression while reducing serum transaminases (ALT, AST), alkaline phosphatase (ALP), and total bilirubin — demonstrating coordinated hepatoprotection through Nrf2 activation, NF-κB suppression, and PPARα modulation.
3.4 Androgen Receptor / mTORC1 — Skeletal Muscle Hypertrophy
In a landmark study, Rodriguez et al. (2017) demonstrated that Urolithin B (15 μM, 24 h) increases C2C12 myotube diameter by ~25%, enhances myoblast fusion (differentiation), and promotes protein synthesis while simultaneously repressing the ubiquitin-proteasome pathway. The mechanism involves a crosstalk between the androgen receptor (AR) and mTORC1 signaling, partially mediated through AMPK. In vivo, a continuous 28-day infusion (10 μg/day) induced significant hypertrophy of tibialis anterior, gastrocnemius, and quadriceps muscles in mice and attenuated denervation-induced muscle atrophy — effects not observed with Urolithin A at equivalent doses.
Receptor
(p-rpS6 ↑,
p-eEF2 ↓)
Synthesis ↑
Pathway
Degradation ↓
Net effect: muscle hypertrophy (increased myotube diameter + reduced atrophy markers)
3.5 PI3K/Akt — Neuroprotection & Cognitive Function
Urolithin B crosses the blood-brain barrier (validated by both in silico prediction and in vivo tissue distribution) and protects neurons through the PI3K/Akt pathway. In D-galactose-induced brain aging models, Urolithin B activated ERK and PI3K signaling, leading to Akt and p44/42 MAPK phosphorylation, reduced cytochrome c release from mitochondria, and inhibited JNK-mediated apoptosis. These effects translated to significantly improved performance in Morris water maze and passive avoidance tests — demonstrating functional cognitive preservation. The compound also reduced advanced glycation end products (AGEs) accumulation and elevated Cu,Zn-SOD and catalase activities in brain tissue.
3.6 HMGB1-TLR4-NF-κB — Gut Barrier & Intestinal Immunity
In the intestinal epithelium, Urolithin B suppresses the HMGB1-TLR4 signaling axis, reducing IRAK4, TRAF6, IKK-β, and NF-κB p65 expression. This pathway underlies its ability to attenuate intestinal barrier injury, reshape gut microbiota composition (increasing beneficial genera while reducing pathobionts), and restore mucosal immune homeostasis in aging models.
3.7 Aromatase Inhibition & Hormonal Modulation
Urolithin B inhibits aromatase (CYP19A1), the enzyme responsible for converting androgens to estrogens. This property, combined with its AR agonism in muscle, positions Urolithin B as a unique tool for studying tissue-selective androgen/estrogen balance — with potential implications for conditions involving aromatase dysregulation.
3.8 Summary of Key Targets
| Target / Pathway | Effect | Functional Consequence | Key Reference |
|---|---|---|---|
| NF-κB (IκBα stabilization) | ↓ Inhibition | Anti-inflammatory (↓ TNF-α, IL-6, IL-1β) | Multiple in vitro/in vivo |
| AMPK | ↑ Activation | Metabolic regulation; suppresses ERK/JNK/Akt | BV2 microglia studies |
| Keap1/Nrf2 → HO-1 | ↑ Activation | Antioxidant defense; hepatoprotection | Cholestatic liver injury, 2025 |
| Androgen Receptor / mTORC1 | ↑ Activation | Muscle hypertrophy; protein synthesis ↑ | Rodriguez et al., 2017 |
| Ubiquitin-Proteasome | ↓ Inhibition | Reduced muscle protein degradation | Rodriguez et al., 2017 |
| PI3K/Akt (neuronal) | ↑ Activation | Neuronal survival; cognitive preservation | Chen et al., 2021 |
| JNK (neuronal apoptosis) | ↓ Inhibition | Reduced cytochrome c release; anti-apoptotic | Chen et al., 2021 |
| HMGB1-TLR4 (intestinal) | ↓ Inhibition | Gut barrier protection; microbiota reshaping | Chen et al., 2021 (Food Funct) |
| Aromatase (CYP19A1) | ↓ Inhibition | Androgen/estrogen balance modulation | Sigma-Aldrich bioactivity profile |
| PPARα (hepatic) | ↓ Repression | Hepatoprotective metabolic shift | Cholestatic liver injury, 2025 |
4. Core Advantages
4.1 Urolithin B vs Urolithin A — Structural & Functional Distinction
Though both are ellagitannin-derived urolithins, Urolithin B and Urolithin A differ fundamentally in hydroxylation pattern, mechanism, and biological output. Understanding these differences is critical for experimental design.
| Parameter | Urolithin B (UB) | Urolithin A (UA) |
|---|---|---|
| Hydroxyl Groups | 1 (position 3) | 4 (positions 3, 8, 9, 10) |
| CAS Number | 1139-83-9 | 1143-70-0 |
| Molecular Formula | C₁₃H₈O₃ | C₁₃H₈O₆ |
| Molecular Weight | 212.20 | 228.20 |
| Lipophilicity (LogP) | ~3.1 (more lipophilic) | ~2.6 |
| Water Solubility | ~0.093 g/L | Poor |
| BBB Penetration | Yes (validated) | Limited |
| Primary Mechanism | NF-κB ↓ / AMPK ↑ / AR-mTORC1 | Mitophagy (PINK1/Parkin) / SIRT1 |
| Muscle Effect | Hypertrophy (AR-mTORC1) + anti-atrophy | Endurance / mitochondrial quality |
| Neuroprotection | PI3K/Akt anti-apoptotic; anti-AGEs | Mitophagy; Aβ clearance; SIRT1 |
| Anti-inflammatory | NF-κB (IκBα stabilization) — primary | NLRP3 inflammasome; secondary to mitophagy |
| Aromatase Inhibition | Yes | Not reported |
4.2 Why Choose Urolithin B Over Urolithin A?
Superior BBB Penetration
Single hydroxyl group lowers polarity; validated to cross BBB where parent ellagitannins and UA cannot. Ideal CNS research tool.
Muscle Hypertrophy — Not Mitophagy
AR-mTORC1 driven protein synthesis and ubiquitin-proteasome suppression; unmatched by UA for muscle anabolism studies.
IκBα-Stabilized NF-κB Blockade
Mechanistically distinct from UA's NLRP3 inhibition; broader anti-inflammatory coverage across TNF-α, IL-6, IL-1β axes.
Aromatase Modulation
CYP19A1 inhibition not shared by UA; enables tissue-level androgen/estrogen balance studies in muscle, prostate, and adipose.
Hepatoprotective Triad
Simultaneous Keap1/Nrf2 activation + NF-κB suppression + PPARα modulation — coordinated liver protection validated in cholestatic injury.
Gut Barrier + Microbiome
HMGB1-TLR4 suppression reshapes microbiota composition and restores mucosal immunity — a mechanism absent in UA's profile.
5. Research & Formulation Applications
Sarcopenia & Muscle Wasting
AR-mTORC1 mediated myotube hypertrophy (diameter +25%), protein synthesis enhancement, ubiquitin-proteasome suppression. Validated in denervation atrophy models. Key reference: Rodriguez et al. 2017.
Alzheimer's & Brain Aging
BBB penetrant, PI3K/Akt-mediated neuronal survival, JNK apoptosis inhibition, AGEs reduction, and cognitive preservation (Morris water maze validated). Crosses BBB where UA cannot. Key reference: Chen et al. 2021.
Cholestatic Liver Injury
Triple mechanism (Keap1/Nrf2 ↑ + NF-κB ↓ + PPARα ↓); reduces ALT, AST, ALP, total bilirubin; normalizes hepatic architecture. Validated in ANIT-induced CLI model, 2025.
Intestinal Barrier & Immunity
HMGB1-TLR4-NF-κB downregulation; gut microbiota reshaping (beneficial genera enrichment); mucosal immune restoration in D-galactose aging model. Key reference: Chen et al. 2021, Food Funct.
IAPP / Diabetes Research
Dual mechanism against IAPP proteotoxicity: direct amyloid aggregation inhibition + autophagy induction (comparable to rapamycin). Reduces mitochondrial ROS, restores β-cell proliferation. Key reference: PMC9797523, 2023.
Anti-Proliferative Studies
Inhibits LNCaP prostate cancer cell proliferation; additive effect with bicalutamide; suppresses HCC growth via Wnt/β-catenin inactivation. Additive anti-proliferative with AR antagonists.
Microglial & Systemic Inflammation
NF-κB/AP-1 dual suppression in LPS-stimulated BV2 microglia; AMPK upregulation with concurrent Akt/JNK/ERK downregulation. Broad-spectrum anti-inflammatory reference compound.
Reference Inhibitor & Tool Compound
Well-characterized NF-κB/AMPK modulator for HTS assay validation, hit confirmation, and mechanistic benchmarking in inflammation, metabolism, and neurodegeneration screening campaigns.
6. Packaging, Storage & Logistics Compliance
6.1 Storage Conditions
| Form | Temperature | Duration | Notes |
|---|---|---|---|
| Dry Powder | −20°C | 36 months | Protect from light and moisture; store in airtight container with desiccant |
| Dry Powder | 2–8°C | 24 months | Protected from light |
| DMSO Stock | −80°C | 12 months | Aliquot to avoid freeze-thaw cycles; amber vial |
| DMSO Stock | −20°C | 1 month | Single-use aliquots recommended |
| Ethanol Stock | −20°C | 1 month | Stability may vary; prepare fresh when possible |
6.2 Regulatory & Shipping Status
Non-Controlled Substance
Urolithin B is NOT listed on any controlled substance or scheduled chemical registry (DEA, CFDA, EMA, TGA). It is not a narcotic, psychotropic, or precursor chemical.
Ambient Shipping (Powder)
Dry powder is stable at ambient temperature during transit. Shipped in sealed, light-protective containers with desiccant. Cold-chain shipping is available upon request for temperature-sensitive destinations.
Customs Documentation
Full commercial invoice, packing list, COA, and MSDS (GHS-compliant) provided with international shipments. HS code: 2932.20 (lactones/heterocyclic compounds). Customs clearance support available.
6.3 GHS Hazard Classification
6.4 Packaging Options
| Pack Size | Container | Typical Use Case |
|---|---|---|
| 25 mg | Amber glass vial, PTFE-lined cap | Evaluation / pilot experiments |
| 100 mg | Amber glass vial, PTFE-lined cap | Standard research unit |
| 500 mg | Amber glass bottle, argon-flushed | Multi-assay laboratory supply |
| 1 g | Amber glass bottle, argon-flushed | In vivo study / formulation batch |
| 5 g+ (bulk) | Custom; contact for specifications | Institutional / multi-group studies |
7. Frequently Asked Questions
Q: What is Urolithin B and how does it differ from Urolithin A?
Urolithin B (UB) has 1 hydroxyl group (position 3) and primarily targets NF-κB, AMPK, and AR-mTORC1 signaling — driving anti-inflammatory effects and muscle hypertrophy. Urolithin A (UA) has 4 hydroxyl groups and primarily drives mitophagy via PINK1/Parkin and SIRT1 activation. UB crosses the BBB more efficiently; UA is better studied for mitochondrial quality control.
Q: Is Urolithin B a natural compound or synthetic?
Urolithin B is a naturally occurring gut microbiota metabolite produced from dietary ellagitannins. However, the 99% HPLC product offered here is synthetically manufactured under GMP-like conditions to ensure batch-to-batch consistency, high purity, and freedom from microbial contaminants — properties not achievable through fecal fermentation or botanical extraction.
Q: What is the purity level and how is it verified?
≥99% by HPLC (C18 reversed-phase, UV 305 nm). Identity is confirmed by 1H-NMR, 13C-NMR, and HR-LC-MS. Each batch ships with a full COA including residual solvents (ICH Q3C), heavy metals, and water content (Karl Fischer).
Q: Is Urolithin B a controlled or regulated substance?
No. Urolithin B is not listed on any DEA, CFDA, EMA, TGA, or FDA controlled substance schedule. It is not classified as a narcotic, psychotropic, precursor chemical, or hazardous cargo (non-DG). It is sold exclusively as a research chemical — not approved for human therapeutic use.
Q: Can Urolithin B be shipped internationally?
Yes. Urolithin B is non-DG and non-controlled — no import/export permits are required. We ship globally with full customs documentation (commercial invoice, COA, MSDS, packing list). Typical delivery: 5–10 business days (express) or 10–20 days (standard).
Q: What is the recommended solvent for in vitro studies?
DMSO is the primary solvent: prepare a 50–250 mM stock (sonicate with warming to 37°C), then dilute to working concentration in culture medium. Ethanol (to ~12 mg/mL) is a secondary option for ethanol-compatible assays. Urolithin B is nearly insoluble in water (~0.093 g/L) — aqueous formulations require co-solvents or cyclodextrin complexation.
Q: How does Urolithin B cross the blood-brain barrier?
Its single phenolic hydroxyl group gives Urolithin B moderate lipophilicity (LogP ~3.1) — within the optimal range for passive diffusion across the BBB. In silico predictions (2015, ACS Chem Neurosci) and in vivo tissue distribution studies (2021, Front Pharmacol) both confirm CNS penetration, a property not shared by parent ellagitannins or more hydroxylated urolithins.
Q: What in vivo doses have been used in published studies?
Muscle hypertrophy: 10 μg/day continuous infusion (28 days, mouse). Neuroprotection: 50–100 mg/kg i.p. or oral gavage (mouse). Hepatoprotection: 50–100 mg/kg oral (4 days, mouse). Intestinal immunity: 50 mg/kg (8 weeks, mouse). Researchers should conduct their own dose-ranging studies as these values are species-, route-, and endpoint-specific.
Q: Are there any human clinical trials of Urolithin B?
No. Unlike Urolithin A (which has completed multiple Phase I/II trials under the brand Mitopure/Timeline), Urolithin B has not yet entered human clinical investigation for any indication. All current evidence is preclinical (in vitro + rodent models).
Q: Does Urolithin B require special storage precautions?
Store dry powder at −20°C protected from light and moisture. Urolithin B is light-sensitive (phenolic compound); always use amber vials and avoid prolonged exposure to ambient light. DMSO stocks should be aliquoted and stored at −80°C to prevent freeze-thaw degradation. Do not store aqueous solutions — prepare fresh before use.
Q: Is bulk or custom packaging available?
Yes. We offer multi-gram to kilogram-scale bulk orders with dedicated batch reservation, custom aliquoting, and tailored packaging configurations. Contact our procurement team for volume pricing and delivery timelines.
Q: What documentation is provided with each order?
Every shipment includes: Certificate of Analysis (COA) with batch-specific HPLC chromatogram, NMR spectrum, and LC-MS trace; Material Safety Data Sheet (MSDS, GHS-compliant); commercial invoice and packing list. Additional documentation (stability data, residual solvent report, heavy metals analysis) is available upon request.
Source High-Purity Urolithin B for Your Research
≥99% HPLC purity, batch-specific COA with full spectroscopic characterization, flexible packaging from 25 mg to kilogram scale, and global shipping with customs support. Contact our team for pricing, technical documentation, or a custom quotation.