New furofuran and tetrahydrofuran lignans from the flower buds of Magnolia biondii Pamp and their antiallergic effects

Abstract The dried flower buds of Magnolia biondii Pamp (herbal name, Xin-Yi) are a traditional Chinese medicine with a long history of clinical use in the treatment of allergic rhinitis and sinusitis. However, the constituents responsible for its antiallergic effects remain clearly unidentified. In the present study, totally 33 lignans were obtained from M. biondii. Among them, two novel furofuran lignans (1 and 2), two novel tetrahydrofuran lignans (3 and 4), and other 16 known lignans were isolated first time from M. biondii. The antiallergic effects of compounds 1-33 on mouse bone marrow-derived mast cells (BMMCs) degrunaliton were evaluated and results showed that compounds 7, 8, 13, 15 and 18 could significantly inhibited β-hex release on BMMCs. The results proved that furofuran and tetrahydrofuran lignans were the main constituents in M. biondii and their antiallergic effects were related with suppressing mast cell activation. Graphical Abstract


Introduction
Magnolia biondii Pamp is widely distributed in Korea, China, and Japan. The dried flower buds of Magnolia biondii Pamp (herbal name, Xin-Yi) have a long history of clinical use as Chinese Medicine for the treatment of allergic diseases, such as cutaneous pruritus, allergic rhinitis, sinusitis, and asthma ) . In vitro and in vivo experiments have confirmed that M. biondii exertsits antiallergic effects by inhibiting the degranulation of mast cells (Wei et al. 1997), inhibiting interleukin-2 (IL-2) expression in Jurkat T-cells (Nguyen et al. 2017), alleviating homologous passive skin anaphylaxis (Ji et al. 2010), and suppressing histamine-induced metatarsal swelling in rats (Deng et al. 2007). Phytochemical research has revealed that M. biondii contains abundant lignans, which exhibit a broad range of biological activities (Choi et al. 2014), such as anti-inflammatory, antioxidant, antimicrobial, anticancer, and antiplatelet activitiesas well as liver protection. Recent studies have revealed that various types of lignans, such as gomisin N (dibenzocylooctadiene lignan), meso-dihydroguaiaretic acid (dibenzylbutane lignan), and pinusthunbergiside A (benzodioxane lignan), exerted their antiallergic effects by suppressing mast cell activation (Sun et al. 2013;Wang et al. 2014). Our previous study found that some furofuran lignans from M. biondii exerted inhibitory effects on mouse bone marrow-derived mast cells (BMMCs) degranulation and tumour necrosis factor a (TNF-a) expression (Zhang et al. 2017). It suggests that lignans in M. biondii may exert their antiallergic effects by mainly suppressing mast cell activation.
The antiallergic effect of compounds 1-33 on BMMCs degrunaliton was evaluated. We incubated BMMCs with 0.5 lg/mL anti-DNP-IgE overnight. Then cells were treatment with 25 lM isolated compounds and subsequently were stimulated with 0.1 lg/mL DNP-BSA for 30 min. Results showed that compounds 7, 8, 13, 15 and 18 significantly inhibited b-hex release. In particular, compound 8 suppressed b-hex release up to 53.28% ( Figure S4).

Plant material
Xin-Yi was collected from Nanzhao, Henan, China, which is the main Xin-Yi-producing area in China. The authenticity of this medicinal material was verified by Professor Zhili Zhao at the School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China. A voucher specimen (20150101) has been deposited in the Department of Phytochemistry, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

ECD calculation of compounds 3 and 4
The conformers of compounds 3 and 4 were obtained using the MM2 force field with ChemBio3D software. Gaussian 09 software was utilized for the semiempirical PM3 quantum mechanical geometry optimizations and the time-dependent density functional theory (TDDFT). ECD was calculated at the b3lyp/6-31g(d) level. The ECD spectra conformers of 3 and 4 were obtained using Origin Pro 2015 64Bit and were compared with the experimental data.

Antiallergic assay
The antiallergic assay was performed as previously described (Zhang et al. 2017).