Le, Tam Thi Tran, Son Hung Lee, Sohyun Ko, Hyejin Cha, Jin Wook Park, Jin-Soo Nguyen, Hai Yen Kim, Won Kyu Kang, Kyungsu Jung, Sang Hoon 2026-01-13T07:00:20Z 2026-01-13T07:00:20Z 2026-01-12 2026-01 0021-8561 https://pubs.kist.re.kr/handle/201004/153980 Boletopsis leucomelasis a widely consumed edible mushroom with a dark-gray fruiting body. Four new p-terphenyls (1–4, boletamins A–D), one previously reported compound without detailed characterization (5, boletamin E), and seven known compounds (6–12) were isolated from its fruiting body and structurally elucidated via NMR and HRESIMS. Among them, compounds 2 and 3 (boletamins B and C) exhibited significant anti-neuroinflammatory, neuroprotective, and antioxidant activities in BV2 microglial and HT22 neuronal cells. Mechanistically, these dual effects were associated with the modulation of the NF-κB/COX-2 and Keap1/Nrf2 signaling pathways, as demonstrated through network pharmacology analysis, molecular docking studies, and experimental verification. Compounds 2 and 3 also effectively restored neuronal dysfunction and suppressed the intracellular ROS production in the in vivo Caenorhabditis elegans model induced by Pseudomonas aeruginosa PAO1, without causing toxicity. These findings position boletamins B and C as promising leads for the development of neuroprotective functional foods or nutraceuticals. English American Chemical Society p-Terphenyls from the Fruiting Bodies of Boletopsis leucomelas with Neuroprotective, Anti-Neuroinflammatory, and Antioxidant Activities Article 10.1021/acs.jafc.5c14063 1 Journal of Agricultural and Food Chemistry, v.74, no.1, pp.952 - 967 Journal of Agricultural and Food Chemistry 74 1 952 967 N scie scopus 001649790000001 Agriculture, Multidisciplinary Chemistry, Applied Food Science & Technology Agriculture Chemistry Food Science & Technology Article MECHANISMS MICROGLIA KYNAPCIN-12 DERIVATIVES ACTIVATION NRF2 neuroinflammation network pharmacology NF-kappa B/COX-2 Keap1/Nrf2 edible mushroom <italic>p</italic>-terphenyls