{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T14:00:29Z","timestamp":1777039229985,"version":"3.51.4"},"reference-count":29,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T00:00:00Z","timestamp":1648598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["81873091"],"award-info":[{"award-number":["81873091"]}]},{"name":"National Natural Science Foundation of China","award":["81573566"],"award-info":[{"award-number":["81573566"]}]},{"name":"National Natural Science Foundation of China","award":["81673872"],"award-info":[{"award-number":["81673872"]}]},{"name":"National Natural Science Foundation of China","award":["82174266"],"award-info":[{"award-number":["82174266"]}]},{"name":"National Natural Science Foundation of China","award":["81974520"],"award-info":[{"award-number":["81974520"]}]},{"name":"Department of Education Guangdong of Province","award":["YQ2013043"],"award-info":[{"award-number":["YQ2013043"]}]},{"name":"Department of Science and Technology of Tibet autonomous region","award":["2016ZR-ZY-01"],"award-info":[{"award-number":["2016ZR-ZY-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>This research aimed to excavate compounds with activity reducing hepatocytes lipid accumulation from Delphinium brunonianum. Four novel diterpenoid alkaloids, brunodelphinine B\u2013E, were isolated from D. brunonianum together with eleven known diterpenoid alkaloids through a phytochemical investigation. Their structures were elucidated by comprehensive spectroscopy methods including HR-ESI-MS, NMR, IR, UV, CD, and single-crystal X-ray diffraction analysis. The inhibitory effects of a total of 15 diterpenoid alkaloids on hepatocytes lipid accumulation were evaluated using 0.5 mM FFA (oleate\/palmitate 2:1 ratio) to induce buffalo rat liver (BRL) cells by measuring the levels of triglyceride (TG), total cholesterol (TC), alanine transaminase (ALT), aspartate transaminase (AST), and the staining of oil red O. The results show that five diterpenoid alkaloids\u2014brunodelphinine E (4), delbruline (5), lycoctonine (7), delbrunine (8), and sharwuphinine A (12)\u2014exhibited significant inhibitory effects on lipid accumulation in a dose-dependent manner and without cytotoxicity. Among them, sharwuphinine A (12) displayed the strongest inhibition of hepatocytes lipid accumulation in vitro. Our research increased the understanding on the chemical composition of D. brunonianum and provided experimental and theoretical evidence for the active ingredients screened from this herbal medicine in the treatment of the diseases related to lipid accumulation, such as non-alcoholic fatty liver disease and hyperlipidemia.<\/jats:p>","DOI":"10.3390\/molecules27072257","type":"journal-article","created":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T21:28:39Z","timestamp":1648675719000},"page":"2257","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Diterpenoid Alkaloids Isolated from Delphinium brunonianum and Their Inhibitory Effects on Hepatocytes Lipid Accumulation"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6725-5030","authenticated-orcid":false,"given":"Huanhuan","family":"Ma","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0622-3996","authenticated-orcid":false,"given":"Yunxia","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5865-2085","authenticated-orcid":false,"given":"Zeren","family":"Dawa","sequence":"additional","affiliation":[{"name":"Institute of Tibetan Medicine, University of Tibetan Medicine, Lasa 850000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0747-2460","authenticated-orcid":false,"given":"Yufeng","family":"Yao","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2972-0832","authenticated-orcid":false,"given":"Meiqi","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5927-1794","authenticated-orcid":false,"given":"Kaihui","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4516-3885","authenticated-orcid":false,"given":"Chenchen","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2505-5414","authenticated-orcid":false,"given":"Fangle","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9340-4116","authenticated-orcid":false,"given":"Chaozhan","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1038\/s41591-018-0104-9","article-title":"Mechanisms of NAFLD development and therapeutic strategies","volume":"24","author":"Friedman","year":"2018","journal-title":"Nat. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.apsb.2019.11.017","article-title":"Herbal drug discovery for the treatment of nonalcoholic fatty liver disease","volume":"10","author":"Yan","year":"2020","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"6549","DOI":"10.3748\/wjg.v23.i36.6549","article-title":"Treatment options for alcoholic and non-alcoholic fatty liver disease: A review","volume":"23","author":"Singh","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_4","unstructured":"The Chinese Academy of Sciences, and Flora Reipublicae Popularis Sinicae Editorial Board (1979). Flora Reipublicae Popularis Sinicae, Science Press."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Thawabteh, A.M., Thawabteh, A., Lelario, F., Bufo, S.A., and Scrano, L. (2021). Classification, Toxicity and Bioactivity of Natural Diterpenoid Alkaloids. Molecules., 26.","DOI":"10.3390\/molecules26134103"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"826957","DOI":"10.3389\/fnut.2021.826957","article-title":"Two Alkaloids from Delphinium brunonianum Royle, Their Anti-inflammatory and Anti-oxidative Stress Activity via NF-\u03baB Signaling Pathway","volume":"20","author":"Tang","year":"2022","journal-title":"Front. Nutr."},{"key":"ref_7","first-page":"1833","article-title":"Phytochemical analysis and reappraisal of diuretic activity of Delphinium brunonianum Royle and its mode of action in experimental rats","volume":"33","author":"Asif","year":"2020","journal-title":"Pak. J. Pharm. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"112971","DOI":"10.1016\/j.phytochem.2021.112971","article-title":"Diterpenoid alkaloids from Delphinium forrestii var. viride and their anti-inflammation activity","volume":"192","author":"Song","year":"2021","journal-title":"Phytochemistry."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2982","DOI":"10.1080\/14786419.2019.1679134","article-title":"Phytochemical analysis of crude extract of Delphinium brunonianum and its effect on hypertension and metabolic perturbations in fructose fed rats","volume":"35","author":"Asif","year":"2021","journal-title":"Nat. Prod. Res."},{"key":"ref_10","first-page":"1897","article-title":"Delbruninol, a New Norditerpenoid Alkaloid from Delphinium brunonianum Royle","volume":"8","author":"Ulubelen","year":"1999","journal-title":"Heterocycles"},{"key":"ref_11","first-page":"4","article-title":"Three New C19-Diterpenoid Alkaloids, Delbrunine, Delbruline and Delbrusine from Delphinium brunonianum Royle","volume":"24","author":"Wei","year":"1986","journal-title":"Heterocycles"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"104186","DOI":"10.1016\/j.fitote.2019.104186","article-title":"New amide alkaloids from Delphinium brunonianum","volume":"136","author":"Zou","year":"2019","journal-title":"Fitoterapia"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.phytol.2015.02.010","article-title":"Six new norditerpenoid alkaloids from Delphinium elatum","volume":"12","author":"Wada","year":"2015","journal-title":"Phytochem. Lett."},{"key":"ref_14","first-page":"425","article-title":"Uraline, a new norditerpenoid alkaloid from aerial parts of Delphinium uralense nevski","volume":"31","author":"Gabbasov","year":"2005","journal-title":"Bioorg. Khim."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2098","DOI":"10.1021\/np50102a011","article-title":"New Norditerpenoid Alkaloids from the Leaves of Delphinium ajacis","volume":"56","author":"Lu","year":"1993","journal-title":"J. Nat. Prod."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"607","DOI":"10.3987\/COM-09-S(S)20","article-title":"A New Diterpenoid Alkaloid, Sharwuphinine A from Delphinium sharwurense","volume":"41","author":"Morita","year":"2010","journal-title":"Heterocycles"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1007\/s10600-007-0109-y","article-title":"Shawurensine, a new C19-diterpenoid alkaloid from Delphinium shawurense","volume":"43","author":"Gu","year":"2007","journal-title":"Chem. Nat. Compd."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1016\/j.jcmgh.2021.06.007","article-title":"6-Gingerol Ameliorates Hepatic Steatosis via HNF4\u03b1\/miR-467b-3p\/GPAT1 Cascade","volume":"12","author":"Ahn","year":"2021","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1007\/s43440-021-00241-3","article-title":"Effect of statins on lipid metabolism-related microRNA expression in HepG2 cells","volume":"73","author":"Cerda","year":"2021","journal-title":"Pharmacol. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.2217\/pgs.10.93","article-title":"Effects of lipid-lowering drugs on reverse cholesterol transport gene expressions in peripheral blood mononuclear and HepG2 cells","volume":"11","author":"Genvigir","year":"2010","journal-title":"Pharmacogenomics"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.freeradbiomed.2020.11.022","article-title":"The critical role of redox regulation of PTEN and peroxiredoxin III in alcoholic fatty liver","volume":"162","author":"Zhang","year":"2021","journal-title":"Free Radic. Biol. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.jep.2017.08.024","article-title":"Gangjihwan, a polyherbal composition, inhibits fat accumulation through the modulation of lipogenic transcription factors SREBP1C, PPAR\u03b3 and C\/EBP\u03b1","volume":"210","author":"Jang","year":"2018","journal-title":"J. Ethnopharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/s41419-020-2472-6","article-title":"Neddylation of sterol regulatory element-binding protein 1c is a potential therapeutic target for nonalcoholic fatty liver treatment","volume":"11","author":"Ju","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"119487","DOI":"10.1016\/j.lfs.2021.119487","article-title":"Naringin improves lipid metabolism in a tissue-engineered liver model of NAFLD and the underlying mechanisms","volume":"277","author":"Zhang","year":"2021","journal-title":"Life Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.3748\/wjg.v25.i12.1492","article-title":"Ursodeoxycholic acid ameliorates hepatic lipid metabolism in LO2 cells by regulating the AKT\/mTOR\/SREBP-1 signaling pathway","volume":"25","author":"Hu","year":"2019","journal-title":"World J. Gastroenterol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1038\/s41419-021-04090-z","article-title":"Circ_0057558 promotes nonalcoholic fatty liver disease by regulating ROCK1\/AMPK signaling through targeting miR-206","volume":"12","author":"Chen","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.phytochem.2018.10.013","article-title":"Flavone glycosides from Sicyos angulatus and their inhibitory effects on hepatic lipid accumulation","volume":"157","author":"An","year":"2019","journal-title":"Phytochemistry"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"16832","DOI":"10.1073\/pnas.1311528110","article-title":"Significance of endangered and threatened plant natural products in the control of human disease","volume":"110","author":"Ibrahim","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1016\/j.foodchem.2013.05.019","article-title":"Effects of flavonoids from Rosa laevigata Michx fruit against high-fat diet-induced non-alcoholic fatty liver disease in rats","volume":"141","author":"Zhang","year":"2013","journal-title":"Food Chem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/7\/2257\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:47:03Z","timestamp":1760136423000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/7\/2257"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,30]]},"references-count":29,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["molecules27072257"],"URL":"https:\/\/doi.org\/10.3390\/molecules27072257","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,30]]}}}