Urolithin A
(Synonyms: 尿石素A) 目录号 : GC15168
Urolithin A是由鞣花酸和鞣花单宁代谢产生的一种活性成分，可作为酪氨酸酶（IC50值为71.44±10.07µmol/L）和单胺氧化酶A（IC50值为29.41±9.01µmol/L）的强效抑制剂。
Cas No.:1143-70-0
Sample solution is provided at 25 µL, 10mM.
Urolithin A is a metabolite generated from ellagic acid and ellagitannins, acting as a potent inhibitor of tyrosinase(IC50 value of 71.44±10.07µmol/L) and Monoamine Oxidase A(IC50 value of 29.41±9.01µmol/L)[1]. Urolithin A can enhance mitophagy and mitochondrial function, and reduce excessive inflammatory response, which is used in anti-cancer and anti-inflammatory research[2].
In vitro, Urolithin A can inhibit the cell growth of HCT116 colon cancer cells by >50% with an IC50 value of 39.2µmol/L after 48h and 19.6µmol/L after 72h[3]. Urolithin A (30μmol/L, 24h) significantly inhibited new adipocyte formation and attenuated triglyceride accumulation by reducing triglyceride (TG) accumulation and lipogenic protein and gene expression, while increasing fatty acid (FA) oxidation in adipocytes and Huh7 hepatoma cells[4]. Pretreatment with Urolithin A (40µmol/L) for 2 hours inhibited lipopolysaccharide-induced activation of PI3-K/Akt and MAPK signal pathways in RAW 264 macrophages[5].
In vivo, Urolithin A treatment (20mg/kg/day, p.o.) for 42 days inhibited tumor growth, reduced AKT and p70S6K phosphorylation, decreased proliferation, and increased apoptosis in both PANC1 and MiaPaCa2 xenograft mouse models[6]. Oral administration of Urolithin A (20mg/kg/day) for 8 weeks significantly ameliorated the development of osteoarthritis and reduced the degree of cartilage surface calcification in the mouse model of destabilization of the medial meniscus (DMM)[7]. Intraperitoneal injection of Urolithin A (2.5mg/kg/day) for 7 consecutive days successfully upregulated Nrf2 expression and ameliorated myocardial injury and fibrosis in a rat model of myocardial infarction[8].
References:
[1] Cásedas G, Les F, Choya-Foces C, et al. The metabolite urolithin-A ameliorates oxidative stress in neuro-2a cells, becoming a potential neuroprotective agent[J]. Antioxidants, 2020, 9(2): 177.
[2] D’Amico D, Andreux P A, Valdés P, et al. Impact of the natural compound urolithin A on health, disease, and aging[J]. Trends in molecular medicine, 2021, 27(7): 687-699.
[3] Norden E, Heiss E H. Urolithin A gains in antiproliferative capacity by reducing the glycolytic potential via the p53/TIGAR axis in colon cancer cells[J]. Carcinogenesis, 2019, 40(1): 93-101.
[4] Kang I, Kim Y E, Tomás‐Barberán F A, et al. Urolithin A, C, and D, but not iso‐urolithin A and urolithin B, attenuate triglyceride accumulation in human cultures of adipocytes and hepatocytes[J]. Molecular nutrition & food research, 2016, 60(5): 1129-1138.
[5] Komatsu W, Kishi H, Yagasaki K, et al. Urolithin A attenuates pro-inflammatory mediator production by suppressing PI3-K/Akt/NF-κB and JNK/AP-1 signaling pathways in lipopolysaccharide-stimulated RAW264 macrophages: Possible involvement of NADPH oxidase-derived reactive oxygen species[J]. European journal of pharmacology, 2018, 833: 411-424.
[6] Totiger T M, Srinivasan S, Jala V R, et al. Urolithin A, a novel natural compound to target PI3K/AKT/mTOR pathway in pancreatic cancer[J]. Molecular cancer therapeutics, 2019, 18(2): 301-311.
[7] Fu X, Gong L F, Wu Y F, et al. Urolithin A targets the PI3K/Akt/NF-κB pathways and prevents IL-1β-induced inflammatory response in human osteoarthritis: in vitro and in vivo studies[J]. Food & Function, 2019, 10(9): 6135-6146.
[8] Chen P, Pei J, Wang X, et al. Gut bacterial metabolite Urolithin A inhibits myocardial fibrosis through activation of Nrf2 pathway in vitro and in vivo[J]. Molecular Medicine, 2022, 28(1): 19.
Urolithin A是由鞣花酸和鞣花单宁代谢产生的一种活性成分，可作为酪氨酸酶（IC50值为71.44±10.07µmol/L）和单胺氧化酶A（IC50值为29.41±9.01µmol/L）的强效抑制剂[1]。Urolithin A能够增强线粒体自噬、改善线粒体功能，并减轻过度炎症反应，用于抗癌和抗炎研究 [3]。
在体外，Urolithin A对HCT116结肠癌细胞的生长抑制率>50%的IC50值在48小时处理后为39.2µmol/L，在72小时处理后的IC50值为19.6µmol/L[3]。当以30μmol/L浓度处理24小时后，Urolithin A能显著抑制新脂肪细胞形成，并减轻甘油三酯(TG)沉积，降低脂肪生成相关蛋白及基因表达，增强脂肪细胞和Huh7肝癌细胞中的脂肪酸(FA)氧化[4]。用40µmol/L浓度的Urolithin A预处理2小时，可抑制脂多糖诱导的RAW264巨噬细胞中PI3-K/Akt和MAPK信号通路的活化[5]。
在体内，Urolithin A处理（20mg/kg/天，口服给药）42天可抑制PANC1和MiaPaCa2移植瘤小鼠模型的肿瘤生长，降低AKT和p70S6K磷酸化水平、减少细胞增殖并促进细胞凋亡[6]。在膝关节内侧半月板不稳定（DMM）小鼠模型中，口服Urolithin A（20mg/kg/天）8周能显著缓解骨关节炎进展，并减轻软骨表面钙化程度[7]。在大鼠心肌梗死模型中，连续7天腹腔注射Urolithin A（2.5mg/kg/天）可有效上调Nrf2表达，改善心肌损伤和纤维化程度[8]。
| Cell experiment [1]: | |
Cell lines | K562 cells |
Preparation Method | K562 cells were cultured in RPMI medium which included 10% fetal bovine serum (FBS), penicillin at 50U/mL concentration, and streptomycin at 50mg/mL concentration, at a temperature of 37°C with 5% CO2 for 48 hours. Plant 1 × 104 cells into 96-well plates and expose cells to various Urolithin A concentrations ranging from 5 to 25µmol/L. After 48 hours of treatment, MTT with a concentration of 5mg/mL was added to the cells in a 1:10 ratio to the culture medium and mixed. Slowly shake the plate for 5 minutes. The plate underwent a 4-hour incubation at 37°C inside a CO2 incubator. Remove the media, then add 100µL DMSO before incubating for 10 minutes to dissolve all crystals, and measure the OD at 540nm. Detection of apoptotic cells through the application of Annexin V-FITC together with propidium iodide (PI). K562 cells received Urolithin A treatment at concentrations of 5, 10, 15, 20, and 25µmol/L. Following treatment, the cells underwent three washes with PBS and then were resuspended in 100μL 1X binding buffer with 10μL Annexin V-FITC and 5μL PI. K562 cells underwent incubation in the dark for 20min at room temperature. Flow cytometry analysis of K562 cells led to the calculation of apoptosis percentage. |
Reaction Conditions | 5, 10, 15, 20, 25µmol/L; 48h |
Applications | Urolithin A significantly inhibited the proliferation of the leukemic cell line K562 and promoted apoptosis of the K562 cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | Male Wistar rats |
Preparation Method | Research employed 39 male Wistar rats aged 12–14 weeks and weighing 376.4 ± 4.9g, which lived in unisexual groups of four from weaning at 4 weeks of age until experiment initiation in a room with controlled temperatures between 22–24°C and light from 0700 to 1900h. Wood shavings made up the cage bedding while food and water remained accessible at all times for the animals. A single intra-peritoneal injection induced type 1 diabetes in 29 animals belonging to Group D. The remaining 10 control rats (CTRL group) received only vehicle injections of 0.9% NaCl. The research team took glucose measurements and body weights from animals that had fasted for 4 hours before receiving streptozotocin (STZ, 60mg/kg) injections and vehicle treatments, then conducted follow-up measurements after 2 days and continued weekly until the animals were sacrificed at the three-week mark post-hyperglycaemia induction. Rats in group D received no treatment (D3 group, n=9) or daily intraperitoneal injections (D3-UA, n=10). The subjects received daily i.p. injections of either Urolithin A (D3-UA) or Urolithin B (D3-UB) at 2.5mg/kg/day dosage. Hemodynamic measurements occurred under anaesthesia for every CTRL rat as well as each D group animal following three weeks of hyperglycaemia (including D3, D3-UA and D3-UB subjects). |
Dosage form | 2.5mg/kg/day for 3 weeks; i.p. |
Applications | Urolithin A treatment prevented the initial inflammatory response of myocardial tissue to hyperglycemia and the negative effects of the altered diabetic environment on cardiac function in male Wistar rats. |
References: | |
| Cas No. | 1143-70-0 | SDF | |
| 别名 | 尿石素A | ||
| 化学名 | 3,8-dihydroxy-6H-benzo[c]chromen-6-one | ||
| Canonical SMILES | OC1=CC(C2=O)=C(C3=C(O2)C=C(O)C=C3)C=C1 | ||
| 分子式 | C13H8O4 | 分子量 | 228.20 |
| 溶解度 | ≥ 22.8mg/mL in DMSO | 储存条件 | Store at -20°C |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 4.3821 mL | 21.9106 mL | 43.8212 mL |
| 5 mM | 0.8764 mL | 4.3821 mL | 8.7642 mL |
| 10 mM | 0.4382 mL | 2.1911 mL | 4.3821 mL |
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动物平均体重 | g | |
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动物数量 | 只 |
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