Ten new lignans with anti-inflammatory activities from the leaves of Illicium dunnianum

Abstract

The anti-inflammatory phytochemical investigation of the leaves of Illicium dunnianum (I. dunnianum) resulted in the isolation of five pairs of new lignans (1-5), and 7 known analogs (6-12). The separation of enantiomer mixtures 1-5 to 1a/1b-5a/5b was achieved using a chiral column with acetonitrile−water mixtures as eluents. The planar structures of 1-2 were previously undescribed, and the chiral separation and absolute configurations of 3-5 were reported for the first time. Their structures were determined through comprehensive spectroscopic data analysis [nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass (HR-ESI-MS), infrared (IR), and ultraviolet (UV)] and quantum chemistry calculations (ECD). The new isolates were evaluated by measuring their inhibitory effect on NO in lipopolysaccharide (LPS)-stimulated BV-2 cells. Compounds 1a, 3a, 3b, and 5a demonstrated partial inhibition of NO production in a concentration-dependent manner. Western blot and real-time polymerase chain reaction (PCR) assays revealed that 1a down-regulated the messenger ribonucleic acid (mRNA) levels of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), COX-2, and iNOS and the protein expressions of COX-2 and iNOS. This research provides guidance and evidence for the further development and utilization of I. dunnianum.

Keywords

Illicium dunnianum / Lignan / Structural elucidation / Anti-inflammatory activity

References

[1] WFO. Illicium dunnianum Tutcher. 2003. http://www.worldfforaonline.org/taxon/wfo000121985.

[2] Wu Z. Flora of China. Beijing: Science Press. 1978:321-329.

[3] Lin Q. Medicinal plant resources of Illicium L. Chin Tradit Herb Drugs. 2002; 33(7):81-84.

[4] Deng HP, Sun L, Xi ZX, et al. Progress on chemical and pharmacological research of C6-C 3 compounds in genus Illicium. J Pharm Pract. 2012; 30(1):8-13. https://doi.org/10.3969/j.issn.006-0111.2012.01.003.

[5] Bai J, Chen H, Fang ZF, et al. Sesquiterpenes and neolignans from the roots of Illicium dunnianum. J Asian Nat Prod Res. 2012; 14(10):940-949. https://doi.org/10.1080/10286020.2012.729507.

[6] Li J, Geng D, Xu J, et al. Antidepressant-like effect of macranthol isolated from Illicium dunnianum tutch in mice. Eur J Pharmacol. 2013; 707(3):112-119. https://doi.org/10.1016/j.ejphar.2013.03.010.

[7] Geng D, Weng LJ, Han YY, et al. Chemical constituents from Illicium dunnianum. Adv Mater Res. 2012;550-553:1586-1589. https://doi.org/10.4028/www.scientific.net/AMR.550-553.1586.

[8] Geng D, Weng LJ, Han YY, et al. Flavonoids from Illicium dunnianum. Adv Mater Res. 2012;610-613:3375-3377. https://doi.org/10.4028/www.scientific.net/AMR.610-613.3375.

[9] Bai J, Chen H, Fang ZF, et al. Sesquiterpenes from the roots of Illicium dunnianum. Phytochemistry. 2012; 80:137-147. https://doi.org/10.1016/j.phytochem.2012.05.015.

[10] Zhang JW. Chemical constituents of the stems and leaves of Illicium dunnianum Tutch. Chin Tradit Herb Drugs. 1989; 14(1):36-37.

[11] Zhang LF, Lin KZ, Yang WD, et al. Identification of the original plant and miscible products of Illicium dunnianum. Chin J Tradit Chin Med. 1995; 20(12):717-718.

[12] Zeng WL, Song JL, Ceng YF, et al. Effect of alcohol extract of Illicium dunnianum on immune function in mice. J Guiyang Univ Tradit Chin Med. 1992; 14(2):60-62.

[13] Luo L, Liu XL, Li J, et al. Macranthol promotes hippocampal neuronal proliferation in mice via BDNF-TrkB-PI3K/Akt signaling pathway. Eur J Pharmacol. 2015; 762:357-363. https://doi.org/10.1016/j.ejphar.2015.05.036.

[14] Ma SJ, Li HB, Li T, et al. Illiciumlignans G-O from the leaves of Illicium dunnianum and their anti-inffammatory activities. RSC Adv. 2021; 11(49):30725-30733. https://doi.org/10.1039/D1RA03520G.

[15] Li HB, Ma SJ, Shan YX, et al. Eight new phenolic acids from the leaves of Illicium dunnianum and their osteoprotective activities. RSC Adv. 2022; 12(33):21655-21661. https://doi.org/10.1039/D2RA03589H.

[16] Shao JR, Ma SJ, Li T, et al. Two new chemical constituents from the leaves of Illicium dunnianum. Nat Prod Res. 2023; 37(8):1233-1240. https://doi.org/10.1080/14786419.2021.2004599.

[17] He XQ, Li HB, Li T, et al. One undescribed glycoside benzofuran derivative and a new p-hydroxybenzoate glycoside from the leaves of Illicium dunnianum Tutcher. Nat Prod Res. 2024; 38(18):3130-3139. https://doi.org/10.1080/14786419.2023.2216348.

[18] Su B, Takaishi Y, Kusumi T. Morinols A-L, twelve novel sesquineolignans and neolignans with a new carbon skeleton from Morina chinensis. Tetrahedron. 1999; 55(51):14571-14586. https://doi.org/10.1016/S0040-4020(99)00933-3.

[19] Mou L, Wei M, Wu H, et al. Structure elucidation of two new norlignans from Anemone vitifolia and their anti-inflammatory activities. Chem Biodivers. 2020; 17(7):e2000184. https://doi.org/10.1002/cbdv.202000184.

[20] Trung TN, Thi TL, Thi XD, et al. Amenyunnaosides A-C, three new neolignans isolated from Amentotaxus yunnanensis and their anti-inflammatory activities. Chem Biodivers. 2023; 20(6):e202300604. https://doi.org/10.1002/cbdv.202300604.

[21] Yen DTH, Hang DTT, Yen PH, et al. Four undescribed compounds isolated from the aerial parts of Phyllanthus cochinchinensis with antimicrobial activity and NO production inhibitory activity in LPS activated RAW 264.7 cells. Chem Biodivers. 2024; 21(3):e202302105. https://doi.org/10.1002/cbdv.202302105.

[22] Li W, Wu Z, Xia Y, et al. Antiviral and antioxidant components from the fruits of Illicium verum Hook. f. (Chinese Star Anise). J Agric Food Chem. 2022; 70(12):3697-3707. https://doi.org/10.1021/acs.jafc.1c08376.

[23] Sy L, Brown G. Novel phenylpropanoids and lignans from Illicium verum. J Nat Prod. 1998; 61(8):987-992. https://doi.org/10.1021/np9800553.

[24] Takara K, Matsui D, Wada K, et al. New phenolic compounds from Kokuto, noncentrifuged cane sugar. Biosci Biotech Bioch. 2003; 67(2):376-379. https://doi.org/10.1271/bbb.67.376.

[25] Kuang H, Xia Y, Yang B, et al. Lignan constituents from Chloranthus japonicus Sieb. Arch Pharm Res. 2009; 32:329-334. https://doi.org/10.1007/s12272-009-1303-1.

[26] Takeda Y, Mima C, Masuda T, et al. Glochidioboside, a glucoside of (7S,8R)-dihydrodehydrodiconiferyl alcohol from leaves of Glochidion obovatum. Phytochemistry. 1998; 49(7):2137-2139. https://doi.org/10.1016/S0031-9422(98)00362-8.

[27] Zhang Y, Liu Y, Li Y, et al. Phenolic constituents from the roots of Alangium chinense. Chin Chem Lett. 2017; 28(1):32-36. https://doi.org/10.1016/j.cclet.2016.05.012.

[28] Tang W, Liu Y, Yu S, et al. New sesquiterpene lactone and neolignan glycosides with antioxidant and anti-inflammatory activities from the fruits of Illicium oligandrum. Planta Med. 2007; 73(5):484-490. https://doi.org/10.1055/s-2007-967189.

[29] He Z, Ma C, Tan G, et al. Rourinoside and rouremin, antimalarial constituents from Rourea minor. Phytochemistry. 2006; 67(13):1378-1384. https://doi.org/10.1016/j.phytochem.2006.04.012.