{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T01:22:51Z","timestamp":1791076971343,"version":"4.1.0"},"reference-count":113,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,10,28]],"date-time":"2022-10-28T00:00:00Z","timestamp":1666915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["22K06688"],"award-info":[{"award-number":["22K06688"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The seed oil of Carapa guianensis Aublet (Andiroba) has been used in folk medicine for its insect-repelling, anti-inflammatory, and anti-malarial activities. This study aimed to examine the triglyceride (TG) reducing effects of C. guianensis-derived limonoids or other commercially available limonoids in human hepatoblastoma HepG2 cells and evaluate the expression of lipid metabolism or autophagy-related proteins by treatment with 7-deacetoxy-7-oxogedunin (DAOG; 1), a principal limonoid of C. guianensis. The gedunin-type limonoids, such as DAOG (% of control at 20 \u03bcM: 70.9 \u00b1 0.9%), gedunin (2, 74.0 \u00b1 1.1%), epoxyazadiradione (4, 73.4 \u00b1 2.0%), 17\u03b2-hydroxyazadiradione (5, 79.9 \u00b1 0.6%), 7-deacetoxy-7\u03b1-hydroxygedunin (6, 61.0 \u00b1 1.2%), andirolide H (7, 87.4 \u00b1 2.2%), and 6\u03b1-hydroxygedunin (8, 84.5 \u00b1 1.1%), were observed to reduce the TG content at lower concentrations than berberine chloride (BBR, a positive control, 84.1 \u00b1 0.3% at 30 \u03bcM) in HepG2 cells pretreated with high glucose and oleic acid. Andirobin-, obacunol-, nimbin-, and salannin-type limonoids showed no effect on the intracellular TG content in HepG2 cells. The TG-reducing effect of DAOG was attenuated by the concomitant use of compound C (dorsomorphin), an AMPK inhibitor. Further investigation on the detailed mechanism of action of DAOG at non-cytotoxic concentrations revealed that the expressions of autophagy-related proteins, LC3 and p62, were upregulated by treatment with DAOG. These findings suggested that gedunin-type limonoids from Andiroba could ameliorate fatty liver, and that the action of DAOG in particular is mediated by autophagy.<\/jats:p>","DOI":"10.3390\/ijms232113141","type":"journal-article","created":{"date-parts":[[2022,10,30]],"date-time":"2022-10-30T07:26:50Z","timestamp":1667114810000},"page":"13141","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["A Gedunin-Type Limonoid, 7-Deacetoxy-7-Oxogedunin, from Andiroba (Carapa guianensis Aublet) Reduced Intracellular Triglyceride Content and Enhanced Autophagy in HepG2 Cells"],"prefix":"10.3390","volume":"23","author":[{"given":"Akifumi","family":"Nagatomo","sequence":"first","affiliation":[{"name":"Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashiosaka 577-8502, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyofumi","family":"Ninomiya","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashiosaka 577-8502, Osaka, Japan"},{"name":"School of Pharmacy, Shujitsu University, 1-6-1 Nishigawara, Naka-ku, Okayama 703-8516, Okayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinsuke","family":"Marumoto","sequence":"additional","affiliation":[{"name":"Joint Research Center, Kindai University, 3-4-1 Kowakae, Higashiosaka 577-8502, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chie","family":"Sakai","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashiosaka 577-8502, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuta","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashiosaka 577-8502, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wakana","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashiosaka 577-8502, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiaki","family":"Manse","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashiosaka 577-8502, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Kikuchi","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki 569-1094, Osaka, Japan"},{"name":"Faculty of Pharmacy, Toho University, 2-2-1 Miyama, Funabashi 274-8510, Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Yamada","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki 569-1094, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reiko","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki 569-1094, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Muraoka","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashiosaka 577-8502, Osaka, Japan"},{"name":"Antiaging Center, Kindai University, 3-4-1 Kowakae, Higashiosaka 577-8502, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2794-5365","authenticated-orcid":false,"given":"Toshio","family":"Morikawa","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashiosaka 577-8502, Osaka, Japan"},{"name":"Antiaging Center, Kindai University, 3-4-1 Kowakae, Higashiosaka 577-8502, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Gualdani, R., Cavalluzzi, M.M., Lentini, G., and Habtemariam, S. 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