2026-10-13T10:02:05Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33703114 2026-09-13T14:07:23Z category_4 category_7 category_13 category_14 category_21 category_873 category_46 category_734 category_931 portal_63 item_type_3 month_year_09_2026

Exploring Hippuric Acid’s Putative Protective Role in Aging through In Silico and In Vitro Screening Domenico Gadaleta (1562416) Sofia Ghironi (24857290) Federica Maggi (7361360) Melissa Tiddia (24857293) Flavia Funari (24857296) Aurora Paffetti (24857299) Elisa Caiola (6050852) Alessandra Roncaglioni (2459236) Emilio Benfenati (2423125) Laura Brunelli (6050861) Biochemistry Medicine Genetics Molecular Biology Biotechnology Chemical Sciences not elsewhere classified Immunology Biological Sciences not elsewhere classified Information Systems not elsewhere classified soluble epoxide hydrolase potential molecular interactions organic anion transporters multifingerprint similarity approach histone deacetylases ), guide future functional findings remain exploratory associated protein tau additional evidence pointed offering candidate targets investigate mechanisms underlying screening hippuric acid putative protective role candidate ha targets silico </ italic vitro </ italic protective role reported targets mediated mechanisms silico </ vitro </ protective associations vivo </ vitro ,</ yet whether vascular homeostasis validation experiments specific proteins solute carriers scavenging activity reported potencies proteins involved passive biomarker nonspecific pathways neprilysin ). multidrug resistance mostly inconclusive inflammatory activity ha ’ ha analogues generating strategy enzymes linked energy metabolism direct antioxidant database screenings carbonic anhydrases Hippuric acid (HA) is a diet- and microbiome-derived metabolite consistently associated with healthy aging, yet whether it is a passive biomarker or an active effector remains unresolved. To investigate mechanisms underlying its protective role, in silico screening of large bioactivity data sets was performed and integrated with results from in vitro assays. A multifingerprint similarity approach was employed to identify close HA analogues and their reported targets. HA analogues were identified with reported potencies in the low-micromolar or nanomolar range toward transporters (solute carriers, organic anion transporters, multidrug resistance-associated proteins), epigenetic regulators (histone deacetylases), and enzymes linked to inflammation, proteostasis, or vascular homeostasis (carbonic anhydrases, cyclooxygenase-2, soluble epoxide hydrolase, neprilysin). Additional evidence pointed to proteins involved in detoxification, energy metabolism, and neurodegeneration (kynureninase, microtubule-associated protein tau, 2-amino-3-carboxymuconate-6-semialdehyde decarboxylase), supporting their plausibility as candidate HA targets. By contrast, database screenings for direct antioxidant or anti-inflammatory activity were mostly inconclusive, whereas in vitro assays suggested limited radical-scavenging activity and no modulation of nitric oxide production pathways. Results suggest that HA’s protective associations with aging might involve modulation of specific proteins or transporter-mediated mechanisms, rather than acting solely through target-nonspecific pathways. While these findings remain exploratory and require further confirmation, this integrated in silico and in vitro analysis provides an initial, hypothesis-generating strategy to narrow the spectrum of potential molecular interactions, offering candidate targets to guide future functional in silico, in vitro, and in vivo validation experiments. 2026-09-13T00:00:00Z Dataset Dataset 10.1021/acsomega.6c03636.s001 https://figshare.com/articles/dataset/Exploring_Hippuric_Acid_s_Putative_Protective_Role_in_Aging_through_In_Silico_and_In_Vitro_Screening/33703114 CC BY-NC 4.0