Top

09-05-2024 | Original Paper

Hinokione: an abietene diterpene with pancreatic β cells regeneration and hypoglycemic activity, and other derivatives with novel structures from the woods of Agathis dammara

Authors: Zheng Wang, Zhe-Wei Yu, Yi Zhang, Wen-Hui Wang, Xin-Yi Wu, Shun-Zhi Liu, Yan-Lin Bin, Bang-Ping Cai, Shi-Yan Huang, Mei-Juan Fang, Rong Qi, Ming-Yu Li, Ying-Kun Qiu

Published in: Journal of Natural Medicines

Abstract

In this study, 14 abietene and pimarene diterpenoids were isolated from the woods of Agathis dammara. Among them, 4 new compounds, dammarone A-C and dammaric acid A (1–4), were firstly reported, respectively. The structure of the new compounds was determined by HR ESI–MS and 1D/2D NMR spectroscopy, and their absolute configuration was determined by electronic circular dichroism (ECD) exciton chirality method. The hypoglycemic effect of all compounds was evaluated by transgenic zebrafish model, and the structure–activity relationship was discussed. Hinokione (7, HO) has low toxicity and significant hypoglycemic effects on zebrafish, the mechanism is mainly by promoting the differentiation of zebrafish pancreatic endocrine precursor cells (PEP cells) into β cells, thereby promoting the regeneration of pancreatic β cells.

Graphical abstract

Available only for authorised users

Ahda M, Jaswir I, Khatib A, Ahmed QU, Mahfudh N, Ardini YD (2023) A review on selected herbal plants as alternative anti-diabetes drugs: chemical compositions, mechanisms of action, and clinical study. Int J Food Prop 26:1414–1425. https://doi.org/10.1080/10942912.2023.2215475CrossRef

Rippe JM, Angelopoulos TJ (2015) Fructose-containing sugars and cardiovascular disease. Adv Nutr 6:430–439. https://doi.org/10.3945/an.114.008177CrossRefPubMedPubMedCentral

Ma X, Nan F, Liang H, Shu PY, Fan XZ, Song XS, Hou YF, Zhang DF (2022) Excessive intake of sugar: an accomplice of inflammation. Front Immunol 13:988481. https://doi.org/10.3389/fimmu.2022.988481CrossRefPubMedPubMedCentral

Xue HK, Hao ZT, Gao YC, Cai X, Tang JT, Liao XJ, Tan JQ (2023) Research progress on the hypoglycemic activity and mechanisms of natural polysaccharides. Int J Biol Macromol 252:126199. https://doi.org/10.1016/j.ijbiomac.2023.126199CrossRefPubMed

Zhang XW (2002) Research on the introduction and cultivation of Agathis dammara and seedling breeding technology. Straits Science, 41–42+44.

Wang AY, Yue SS, Peng AK, Qi R (2021) A review of research progress on agathis dammara and its application prospects for cardiovascular diseases and fatty liver disease. Mini-Rev Med Chem 21:670–676. https://doi.org/10.2174/1389557520666201117110834CrossRefPubMed

Di X (2013) Damar minyak of agathis. Furniture & Interior Design, 90–93. DOI https://doi.org/10.16771/j.cnki.cn43-1247/ts.2013.12.024.

Zhang QY, Cai ZY, Yu ZW, Di C, Qiu YK, Qi R (2023) Agathis dammara extract and its monomer araucarone attenuate abdominal aortic aneurysm in mice. Cardiovasc Drugs Ther. https://doi.org/10.1007/s10557-023-07518-0CrossRefPubMed

Guo K, Liu YC, Liu Y, Luo SH, Li WY, Li XN, Li SH (2019) Diversified abietane family diterpenoids from the leaves of Leucosceptrum canum and their cytotoxic activity. Phytochemistry 157:43–52. https://doi.org/10.1016/j.phytochem.2018.10.010CrossRefPubMed

10.

Zhou XQ, Rao KE, Chen XG (2021) Diterpenoids from the Tripterygium wilfordii stems and their biological activities. Natural Product Research and Development 33:1137–1146. https://doi.org/10.16333/j.1001-6880.2021.7.008CrossRef

11.

Zhang X, Wwang JI, Zhao CX, Jiang CY, Jing QX, Yuan YZ, Li DH, U ZI, Hua HM, Bai J, (2021) Diterpenoids from stems and leaves of Cephalotaxus fortunei. Chinese Traditional and Herbal Drugs 52:3174–3179

12.

Bustos BC, Nieto CA, Hernandez OS, Rivera CJ, Quijano L, Esquivel B (2020) Structural elucidation of malonylcommunol and 6β-Hydroxy-trans-communic Acid, two undescribed diterpenes from Salvia cinnabarina. First examples of labdane diterpenoids from a Mexican Salvia Species. Molecules 25:1808. https://doi.org/10.3390/molecules25081808CrossRef

13.

Polonsky J, Baskevitch Z, Cagnoli-Bellavita N, Ceccherelli P, Buckwalter BL, Wenkert E (1972) Carbon-13 nuclear magnetic resonance spectroscopy of naturally occurring substances. XI. Biosynthesis of the virescenosides. J Am Chem Soc 94:4369–4370. https://doi.org/10.1021/ja00767a071CrossRef

14.

Tian RY, Lu Y, Chen DF (2016) Four New Diterpenoids from the Roots of Euphorbia pekinensis. Chem Biodivers 13:1404–1409. https://doi.org/10.1002/cbdv.201600091CrossRefPubMed

15.

Cagnoli N, Ceccherelli P, Curini M, Spagnoli N, Ribaldi M (1980) 19-Norisopimara-7,15-dien-3-one: a new norditerpenoid from Acremonium luzulae (Fuckel) Gams. Journal of Chemical Research Synopsis, 276.

16.

Cho JG, Cha BJ, Lee SM, Shrestha S, Jeong RH, Lee DS, Kim YC, Lee DG, Kang HC, Kim JY, Baek NI (2015) Diterpenes from the roots of oryza sativa L. and their Inhibition activity on NO production in LPS-stimulated RAW264.7 MACROPHAGES. Chem Biodivers 12:1356–1364. https://doi.org/10.1002/cbdv.201400239CrossRefPubMed

17.

Heckler K (2017) Kroll J (2017) Zebrafish as a model for the study of microvascular complications of diabetes and their mechanisms. Int J Mol Sci 18:2002. https://doi.org/10.3390/ijms18092002CrossRefPubMedPubMedCentral

18.

Jia JX, Kang Q, Liu SZ, Song YB, Wong FS, Qiu YK, Li MY (2022) Artemether and aspterric acid induce pancreatic alpha cells to transdifferentiate into beta cells in zebrafish. Br J Pharmacol 179:1962–1977. https://doi.org/10.1111/bph.15769CrossRefPubMed

19.

Li M, Maddison LA, Page-McCaw P, Chen W (2014) Overnutrition induces β-cell differentiation through prolonged activation of β-cells in zebrafish larvae. Am J Physiol Endocrinol Metab 306:E799-807. https://doi.org/10.1152/ajpendo.00686.2013CrossRefPubMedPubMedCentral

20.

Lee J, Jung DW, Kim WH, Um JI, Yim SH, Oh WK, Williams DR (2013) Development of a highly visual, simple, and rapid test for the discovery of novel insulin mimetics in living vertebrates. ACS Chem Biol 8:1803–1814. https://doi.org/10.1021/cb4000162CrossRefPubMed

21.

Dalgin G, Ward AB, Hao LT, Beattie CE, Nechiporuk A, Prince VE (2011) Zebrafish mnx1 controls cell fate choice in the developing endocrine pancreas. Dev Biol 356:189–189. https://doi.org/10.1016/j.ydbio.2011.05.238CrossRef

22.

Bouldin CM, Kimelman D (2014) Dual fucci: a new transgenic line for studying the cell cycle from embryos to adults. Zebrafish 11:182–183. https://doi.org/10.1089/zeb.2014.0986CrossRefPubMedPubMedCentral

23.

Sato Y, Hatta M, Karim MF, Sawa T, Wei FY, Sato S, Magnuson MA, Gonzalez FJ, Tomizawa K, Akaike T, Yoshizawa T, Yamagata K (2012) Anks4b, a novel target of HNF4α protein, interacts with GRP78 protein and regulates endoplasmic reticulum stress-induced apoptosis in pancreatic β-cells. J Biol Chem 287:23236–23245. https://doi.org/10.1074/jbc.M112.368779CrossRefPubMedPubMedCentral

24.

Cui F, He X (2022) IGF-1 ameliorates streptozotocin-induced pancreatic β cell dysfunction and apoptosis via activating IRS1/PI3K/Akt/FOXO1 pathway. Inflamm Res 71:669–680. https://doi.org/10.1007/s00011-022-01557-3CrossRefPubMed

25.

Becerra J, Flores C, Mena J, Aqueveque P, Alarcón J, Bittner M, Hernández V, Hoeneisen M, Ruiz E, Silva M (2002) Antifungal and antibacterial activity of diterpenes isolated from wood extractables of Chilean Podocarpaceae. Bol Soc Chil Quim 47:151–157. https://doi.org/10.4067/S0366-16442002000200011CrossRef

26.

Borras-Linares I, Perez-Sanchez A, Lozano-Sanchez J, Barrajon-Catalan E, Arraez-Roman D, Cifuentes A, Micol V, Segura Carretero A (2015) A bioguided identification of the active compounds that contribute to the antiproliferative/cytotoxic effects of rosemary extract on colon cancer cells. Food Chem Toxicol 80:215–222. https://doi.org/10.1016/j.fct.2015.03.013CrossRefPubMed

27.

Yan HY, Feng RH, Chen LB, Chen AL, Li GZ, Zhang X (2007) Isolation, identification and insecticidal activities of six terpenoids in sabina vulgaris. Acta Botanica Boreali-Occidentalla Sinica 27:163–167

28.

Ulubelen A, Topcu G, Johansson CB (1997) Norditerpenoids and diterpenoids from Salvia multicaulis with antituberculous activity. J Nat Prod 60:1275–1280. https://doi.org/10.1021/np9700681CrossRefPubMed

29.

Zhang M, Lin Q, Qi T, Wang T, Chen CC, Riggs AD, Zeng D (2016) Growth factors and medium hyperglycemia induce Sox9+ ductal cell differentiation into β cells in mice with reversal of diabetes. Proc Natl Acad Sci USA 113:650–655. https://doi.org/10.1073/pnas.1524200113CrossRefPubMedPubMedCentral

30.

Meulen T, Huising MO (2015) Role of transcription factors in the transdifferentiation of pancreatic islet cells. J Mol Endocrinol 54:R103–R117. https://doi.org/10.1530/jme-14-0290CrossRefPubMedPubMedCentral

31.

Ghaye AP, Bergemann D, Tarifeño-Saldivia E, Flasse LC, Von Berg V, Peers B, Voz ML, Manfroid I (2015) Progenitor potential of nkx6.1-expressing cells throughout zebrafish life and during beta cell regeneration. BMC Biol 13:70. https://doi.org/10.1186/s12915-015-0179-4CrossRefPubMedPubMedCentral

32.

Mi J, Liu KC, Andersson O (2023) Decoding pancreatic endocrine cell differentiation and β cell regeneration in zebrafish. Sci Adv 9:eadf5142. https://doi.org/10.1126/sciadv.adf5142CrossRefPubMedPubMedCentral

Title: Hinokione: an abietene diterpene with pancreatic β cells regeneration and hypoglycemic activity, and other derivatives with novel structures from the woods of Agathis dammara
Authors: Zheng Wang
Zhe-Wei Yu
Yi Zhang
Wen-Hui Wang
Xin-Yi Wu
Shun-Zhi Liu
Yan-Lin Bin
Bang-Ping Cai
Shi-Yan Huang
Mei-Juan Fang
Rong Qi
Ming-Yu Li
Ying-Kun Qiu
Publication date: 09-05-2024
Publisher: Springer Nature Singapore
Published in: Journal of Natural Medicines
Print ISSN: 1340-3443
Electronic ISSN: 1861-0293
DOI: https://doi.org/10.1007/s11418-024-01816-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Hinokione: an abietene diterpene with pancreatic β cells regeneration and hypoglycemic activity, and other derivatives with novel structures from the woods of Agathis dammara

Abstract

Graphical abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Graphical abstract

Please log in to get access to this content