Oenothein B: Chemistry, Natural Occurrence, Pharmacology, Metabolism and Therapeutic Prospects of a Macrocyclic Ellagitannin

Oenothein B is a macrocyclic ellagitannin found in several medicinal plants, particularly Epilobium species traditionally used for prostate and urinary disorders. This review examines its chemistry, natural occurrence, pharmacological activities, molecular mechanisms, metabolism, and therapeutic potential. Preclinical studies suggest that oenothein B regulates several pathways involved in inflammation, oxidative stress, immune responses, and cell proliferation. It inhibits 5α-reductase and aromatase, increases neutral endopeptidase activity, and suppresses prostate-cell proliferation. Its antioxidant effects involve free radical scavenging, metal chelation, activation of Keap1–Nrf2 signaling, and restoration of antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase. It may also reduce inflammation by suppressing inducible nitric oxide synthase and nitric oxide production. Its effects on reactive oxygen species are cell-dependent, potentially supporting immune-cell activity while promoting oxidative stress in tumor cells. Experimental studies further suggest antimicrobial, antiviral, immunomodulatory, and antitumor activities, although the underlying pathways require further investigation. One randomized clinical trial reported improvements in nocturia and post-void residual volume following treatment with an oenothein B-rich Epilobium angustifolium extract. However, clinical efficacy of isolated oenothein B remains unproven. Its large molecular size and poor systemic absorption limit therapeutic translation. Gut microbial conversion into urolithin-related metabolites, followed by host conjugation and transport, may further influence biological activity and systemic exposure. Future research should focus on molecular targets, microbiota-dependent metabolism, standardized formulations, nanodelivery strategies, pharmacokinetics, safety, and controlled clinical trials.