Five new meroterpenoids from Rhododendron anthopogonoides and their anti-inflammatory activity

Abstract

Five meroterpenoids, rhodonoids K-M (1-2), daurichromene E (3), and grifolins A-B (4-5), together with seven known compounds (6-12), were isolated from Rhododendron anthopogonoides. The chemical structures of these compounds were elucidated through comprehensive analysis of high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), ultraviolet (UV), infrared spectroscopy (IR), and nuclear magnetic resonance (NMR) data. Their absolute configurations were determined by comparing experimental electronic circular dichroism (ECD) spectra with computed values. Notably, compounds 1 and 3 demonstrated significant inhibitory effects on lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells. These compounds markedly suppressed the mRNA expressions of inflammatory factors, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) while also down-regulating the protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2).

Keywords

Anti-inflammatory / Tibetan medicine / Natural products / Isolation and identification / Rhododendron athopogonosides Maxim

References

[1] Committee of Flora of China. Flora of China. Beijing: Science Press. 1990:180.

[2] Yang K, Zhou YX, Cheng FW, et al. Toxicity of Rhododendron anthopogonoides essential oil and its constituent compounds towards Sitophilus zeamais. Molecules. 2011; 16(9):7320-7330. https://doi.org/10.3390/molecules16097320.

[3] Demar DP. JinDru Bencao. Shanghai Scientific & Technical Publishers. 2012:68.

[4] Jing LL, Ma HP, Fan PC, et al. Antioxidant potential, total phenolic and total flavonoid contents of Rhododendron anthopogonoides and its protective effect on hypoxia-induced injury in PC12 cells. BMC Complem Altern Med. 2015; 15:1-12. https://doi.org/10.1186/s12906-015-0520-z.

[5] Liang JY, Yang Q, Ma XM, et al. The content and antibacterial activity of volatile oil from three species of Rhododendron in Gansu Province. Chin Wild Plant Resour. 2014; 33(4):9-10. https://doi.org/10.3969/j.issn.1006-9690.2014.04.003. doi: 10.3969/j.issn.1006-9690.2014.04.003

[6] Shi Q, Li TT, Wu YM, et al. Meroterpenoids with diverse structures and anti-inflammatory activities from Rhododendron anthopogonoides. Phytochemistry. 2020;180:112524. https://doi.org/10.1016/j.phytochem.2020.112524.

[7] Zhao L, Ge J, Qiao CD, et al. Separation and quantification of flavonoid compounds in Rhododendron anthopogonoides Maxim by high-performance liquid chromatography. Acta Chromatogr. 2008; 20(1):135-146. https://doi.org/10.1556/AChrom.20.2008.1.11.

[8] Guleria S, Jaitak V, Saini R, et al. Comparative studies of volatile oil composition of Rhododendron anthopogon by hydrodistillation, supercritical carbon dioxide extraction and head space analysis. Nat Prod Res. 2011; 25(13):1271-1277. https://doi.org/10.1080/14786419.2011.576395.

[9] Dai SJ, Yu DQ. Triterpenoids of Rhododendron anthopogonoides. Chin J Nat Med. 2005; 3(6):347-349.

[10] Li XF, Jin HZ, Chen G, et al. Study advances on chemical constituents and pharmacological activities of the Tibetan medicine Dali. Nat Prod Res Dev. 2008; 20:1125-1128. https://doi.org/10.16333/j.1001-6880.2008.06.019.

[11] Nazir M, Saleem M, Tousif MI, et al. Meroterpenoids: a comprehensive update insight on structural diversity and biology. Biomolecules. 2021; 11(7):957. https://doi.org/10.3390/biom11070957.

[12] Huang GH, Zhu LC, Wang PP, et al. Enantiomeric pairs of meroterpenoids with diverse heterocyclic systems from Rhododendron nyingchiense. J Nat Prod. 2018; 81(8):1810-1818. https://doi.org/10.1021/acs.jnatprod.8b00273.

[13] Liu XJ, Su HG, Peng XR, et al. An updated review of the genus Rhododendron since 2010: traditional uses, phytochemistry, and pharmacology. Phytochemistry. 2024;217:113899. https://doi.org/10.1016/j.phytochem.2023.113899.

[14] Fuloria NK, Raheja RK, Shah KH, et al. Biological activities of meroterpenoids isolated from different sources. Front Pharmacol. 2022;13:830103. https://doi.org/10.3389/fphar.2022.830103.

[15] Iwata N, Kitanaka S. New cannabinoid-like chromane and chromene derivatives from Rhododendron anthopogonoides. Chem Pharm Bull. 2011; 59(11):1409-1412. https://doi.org/10.1248/cpb.59.1409.

[16] Shang ZC, Yang MH, Jian KL, et al. ¹H NMR-guided isolation of formyl-phloroglucinol meroterpenoids from the leaves of Eucalyptus robusta. Chem Eur J. 2016; 22(33):11778-11784. https://doi.org/10.1002/chem.201601732.

[17] Shang ZC, Han C, Xu JL, et al. Twelve formyl phloroglucinol meroterpenoids from the leaves of Eucalyptus robusta. Phytochemistry. 2019; 163:111-117. https://doi.org/10.1016/j.phytochem.2019.04.008.

[18] Liao HB, Huang GH, Yu MH, et al. Five pairs of meroterpenoid enantiomers from Rhododendron capitatum. J Org Chem. 2017; 82(3):1632-1637. https://doi.org/10.1021/acs.joc.6b02800.

[19] Iwata N, Wang N, Yao X, et al. Structures and histamine release inhibitory effects of prenylated orcinol derivatives from Rhododendron dauricum. J Nat Prod. 2004; 67(7):1106. https://doi.org/10.1021/np0303916.

[20] Mahiou V, Roblot F, Hocquemiller R, et al. Piperogalin, a new prenylated diphenol from Peperomia galioides. J Nat Prod. 1995; 58(2):324-328. https://doi.org/10.1021/np50116a031.

[21] Willuhn G, Westhaus RG. Loliolide (calendin) from Calendula officinalis. Planta Med. 1987; 53(3):304. https://doi.org/10.1055/s-2006-962718.

[22] Jouogo DCN, Eckhardt P, Tamokou J, et al. A new phenolic glycoside from the leaves of Flacourtia flavescens Willd. Nat Prod Res. 2024; 3816:2737-2747. https://doi.org/10.1080/14786419.2023.2232078.

[23] Yang SP, Chen HD, Yue JM. Sesquiterpenoids from Chloranthus spicatus. Chin J Chem. 2012;30:6. https://doi.org/10.1002/cjoc.201200455.

[24] Buděínsky M, Holub M, Saman D, et al. Structure of istanbulin A and istanbulin B, two sesquiterpenic lactones from Smyrnium olusatrum L. Collect Czechoslov Chem Commun. 1984; 49(5):1311-1317. https://doi.org/10.1135/cccc19841311.

[25] Xiao Z, Wang X, Zhang G, et al. Terpenoids from roots of Chloranthus spicatus. Helv Chim Acta. 2010; 93(4):803-810. https://doi.org/10.1002/hlca.200900299.

[26] Ohshiro M, Kuroyanagi M, Ueno A. Structures of sesquiterpenes from Curcuma longa. Phytochemistry. 1990; 29(7):2201-2205. https://doi.org/10.1016/0031-9422(90)83038-3.