Table 1. Summary of pertinent findings.
HCL, human cell line; UA, urolithin A; MMP, matrix metalloproteinase; ATP, adenosine triphosphate; ROS, reactive oxygen species; SIRT1, sirtuin 1; RCT, randomized controlled trial; PO, per os; CRP, C-reactive protein; RANKL, receptor activator of nuclear factor 𝜅B ligand; mRNA, messenger ribonucleic acid; PARK2, Parkinson’s disease-associated gene 2; SQSTM1, sequestosome 1; MMP-1, matrix metalloproteinase 1; DNA, deoxyribonucleic acid; UVA, ultraviolet A; Akt, Ak strain transforming kinase; MMP-9, matrix metalloproteinase 9; CCA, cholangiocarcinoma
| - | Author | Study type | Intervention | Sample size | Pertinent results |
| 1 | Esselun et al. (2021) [14] | HCL | 1 or 10 μM UA in vitro | N/A | 10 μM doses of UA decreased MMP and ATP levels; 1 uM dose of UA increased mitochondrial gene expression for biogenesis and oxidative phosphorylation |
| 2 | Kim et al. (2020) [15] | HCL | 1.25, 2.5, or 5 μM UA in vitro | N/A | Pretreatment with UA significantly increased neuronal cell viability in a H2O2-induced oxidative damage model; pretreatment with UA decreased ROS in neuronal cells in a H2O2-induced oxidative damage model; pretreatment with UA decreased concentrations of pro-apoptotic proteins in a H2O2-induced oxidative damage model |
| 3 | Lee et al. (2021) [16] | HCL | 100 nM UA in vitro | N/A | UA treatment decreased high glucose-induced ROS; UA treatment inhibits high glucose-stimulated mitochondrial calcium accumulation |
| 4 | Velagapudi et al. (2019) [17] | HCL | 2.5-10 μM in vitro | N/A | UA treatment reversed the effects of autophagy inhibitors in human neural cells; UA treatment increased SIRT-1 and autophagic activity in human neural cells |
| 5 | Andreux et al. (2019) [18] | RCT | 250, 500, 1,000, or 2,000 mg UA PO | n = 60 | Oral doses up to 1,000 mg of UA are both safe and tolerable; UA is bioavailable at doses ranging from 250 to 1,000 mg in elderly adults; 500-1,000 mg doses for 28 days showed improved mitochondrial biomarkers |
| 6 | Liu et al. (2022) [19] | RCT | 1,000 mg UA PO | n = 66 | Oral doses of 1,000 mg resulted in significant improvement in muscle endurance; plasma levels of acylcarnitines, ceramides, and CRP decreased with UA supplementation |
| 7 | Singh et al. (2022) [20] | RCT | 500 or 1,000 mg UA PO | n = 88 | UA supplementation showed significant improvement in muscle strength, aerobic endurance, and physical performance; decreased plasma acylcarnitines and CRP; and increased expression of proteins associated with mitophagy |
| 8 | Tao et al. (2022) [21] | HCL | 5 or 10 μM UA in vitro | N/A | UA treatment inhibited RANKL-induced osteoclastogenesis in bone marrow macrophages; UA treatment significantly reduced bone resorption and osteoclastic gene expression; UA treatment significantly improved autophagic abilities of bone marrow macrophages |
| 9 | D’Amico et al. (2022) [22] | HCL | 6.25 or 12 μM UA in vitro | N/A | UA treatment significantly improved cellular respiration in primary human chondrocytes; 24-hour UA treatment did not increase mRNA expression of mitochondrial biogenesis or oxidative phosphorylation genes; UA treatment significantly upregulated expression of PARK2 and SQSTM1 |
| 10 | Liu et al. (2019) [12] | HCL | 50 μM in vitro | N/A | UA treatment significantly increased type I collagen expression and reduced MMP-1 expression; UA treatment inhibited cell proliferation due to cell cycle arrest |
| 11 | Liu et al. (2022) [23] | HCL | 0.1 or 1 μM in vitro | N/A | Treatment with UA resulted in the prevention of senescence, DNA damage, and morphologic changes caused by UVA radiation in human dermal fibroblasts; treatment with UA reduced mitochondrial damage in photoaging models |
| 12 | Dirimanov and Högger (2019) [10] | HCL | 10 μM in vitro | N/A | UA caused statistically significant inhibition of Akt phosphorylation; of the ellagic acid metabolites, UA is the only one that inhibited Akt phosphorylation |
| 13 | Zhao et al. (2018) [8] | HCL | 1.5, 15, or 30 μM in vitro | N/A | UA treatment dose-dependently decreased cancer cell proliferation, delayed cell migration, and decreased MMP-9 activity; UA treatment induced autophagy and apoptosis in cancer cells; UA treatment promotes cell cycle arrest and inhibited DNA synthesis in cancer cells |
| 14 | Giménez-Bastida et al. (2020) [9] | HCL | 0.5, 1, or 10 μM in vitro | N/A | Treatment with UA led to a dose-dependent decrease in cancer cell proliferation |
| 15 | Sahashi et al. (2022) [24] | HCL | 10 or 40 μM UA in vitro | N/A | UA treatment of 40 μM for 48 hours significantly reduced cell proliferation, resulting in cell cycle arrest in the G2/M phase in HuCCT-1 and SSP-25 cells; UA treatment of 40 μM significantly reduced CCA tumor cell migration and invasion; UA treatment of 10 or 40 μM for 24 hours did not increase apoptosis when compared to controls; 24-hour UA treatment increased autophagy within HuCCT-1 and SSP-25 cells |