Evidence-Based Complementary and Alternative Medicine

Review Article

Biological Significance of Urolithins, the Gut Microbial Ellagic Acid-Derived Metabolites: The Evidence So Far

Table 2

Biological effects of urolithins assayed on human cell lines.


Test compound	Activity	Test model	Dose/duration	Effect	Ref.

UA, UB, UC, UD	Antioxidant	PMA DCFH-DA HL-60 cells	0.04–137 M, 0.5 h	Inhibit cellular injury caused by ROS	[39]
UA, UB	Antioxidant	DMNQ SK-N-MC cells	0.1–20 M, 0.5 h	Increase cell survival	[40]
UA, UB	Estrogenic Anti-estrogenic	MCF-7 cells	0.1–40 M, 7 d	Induction of cell proliferation (estrogenic)/inhibition of cell proliferation in the presence of estradiol (anti-estrogenic)	[41]
UA, UB	Antimalarial	THP-1 stimulated with haemozoin or TNF-	25 M, 48 h	Inhibit the release and expression of MMP-9	[42]
UA, UB	Anti-inflammatory	CCD18-Co/THP-1 stimulated with TNF-	5–40 M, 48 h	Decrease fibroblasts migration and monocyte adhesion to fibroblasts	[43]
UA, UB	Anti-inflammatory	CCD18-Co stimulated with IL-1	0.1–40 M, 18 h	Inhibit PGE2 production and mPGES-1 and COX-2 expression	[44]
UA, UB, UAG, UBG	Anti-inflammatory	HAOEC/THP-1 stimulated with TNF-α	1–20 M, 4–24 h	Inhibit monocyte adhesion and endothelial cell migration	[45]
UA, UB, UC, UD	Anticancer	22Rv1 EROD assay	6.75–50 M, 0.5, 24 h	Inhibit CYP1B1 and CYP1A1 activity	[46]
UA, UB	Anticancer	Caco-2 cells	40 M, 24–96 h	Cell cycle arrest in S and G₂/M phases	[47]
UA	Anticancer	HEK T293 cells Wnt luciferase assay	0.2–200 g/mL 48 h	Wnt pathway inhibition	[48]
UA, UB, UC, UD	Anticancer	HT-29 cells	25–70 M	Apoptosis induction and CYP1 activity inhibition	[49]

Caco-2: human colon carcinoma cell line; CCD18-Co: human colon fibroblast cell line; CYP1A1: cytochrome P450, family 1, member A1; CYP1B1: cytochrome P450, family 1, member B1; DCFH-DA: 2′,7′-dichlorodihydrofluorescein diacetate; DMNQ: 2,3-dimethoxy-1,4-naphthoquinone; EROD: ethoxyresorufin-O-deethylase assay; HAOEC: human aortic endothelial cell line; HEK T293: human embryonic kidney cell line; HL-60: promyelocytic leukaemia cells; HT-29 human colon carcinoma cell line; MCF-7: human breast cancer cell line; PGE2: prostaglandin E2; PMA: phorbol 12-myristate-13-acetate; SK-N-MC: human neuroblastoma cells; THP-1: human acute monocytic leukaemia cell line; UA: urolithin A; UAG: urolithin A glucuronide; UB: urolithin B; UBG: urolithin B glucuronide; UC: urolithin C; UD: urolithin D; 22Rv1: human prostate carcinoma cell line.