Discovery and bioinspired total syntheses of unprecedented sesquiterpenoid dimers unveiled bifurcating [4 + 2] cycloaddition and target differentiation of enantiomers.

[4 + 2] cycloaddition has led to diverse polycyclic chiral architectures, serving as novel sources for organic synthesis and biological exploration. Here, an unprecedented class of cadinane sesquiterpene [4 + 2] dimers, henryinins A-E (1-5), with a unique 6/6/6/6/6-fused pentacyclic system, were isolated from Schisandra henryi. The divergent total syntheses of compounds 1-5 and their enantiomers (6-10) were concisely accomplished in eight linear steps using a protection-free approach. Mechanistic studies illustrated the origin of selectivity in the key [4 + 2] cycloaddition as well as the inhibition of reaction pathway bifurcation via desymmetrization. The chemical proteomics results showed that a pair of enantiomers shared common targets (PRDX5 C100 and BLMH C73) and had unique targets (USP45 C588 for 4 and COG7 C419 for 9). This work provides experimental evidence for the discovery of unprecedented cadinane dimers from selective Diels-Alder reaction and a powerful strategy to explore the biological properties of natural products.

Structural characterization and biological evaluation of a new O-acetyl-1,4-linked-ß-d-mannan possessed potential application in hydrophilic polymer materials from Dendrobium devonianum.

To explore the active polysaccharides from Dendrobium devonianum, a novel O-acetylmannan (DDP-1) with molecular weight of 117 kDa was isolated from D. devonianum. The chemical and instrumental analysis indicated that the DDP-1 was a homopolysaccharide containing a backbone chain composed of →4)-ß-d-Manp-(1 â†’ (71.4%) residue with internal →4)-2-O-acetyl-ß-d-Manp-(1 â†’ (14.2%), →4)-3-O-acetyl-ß-d-Manp-(1 â†’ (7.1%), and non-reducing end ß-d-Manp-(1 â†’ (7.3%) residues. Anticancer assay in vitro revealed that DDP-1 had anticancer activity against the growth of HepG2 and MCF-7 cancer cells. Moreover, cytokine secretion assays also presented that DDP-1 can promote cytokine production of TNF-α and IL-6 in THP-1 macrophage stimulated by PMA. Finally, the effects of isolation and purification on the microstructure of DDP-1 was studied by scanning electron microscope. The morphological features of DDP-1 indicated that DDP-1 hold high potential application in hydrophilic polymer materials.

Schipropins A-J, structurally diverse triterpenoids from Schisandra propinqua.

Schipropins A-J, a series of undescribed lanostane and cycloartane-type triterpenoids, were isolated from the stems and leaves of Schisandra propinqua. Their structures, most of which were characterized by C-3/C-4 cleavage, were elucidated by extensive spectroscopic analyses. Noteworthily, the absolute configurations of schipropins A, D-G, and I were determined by single-crystal X-ray diffraction. Furthermore, schipropins E and G were found to possess moderate NO production inhibitory activity.

Neuroprotective schinortriterpenoids with diverse scaffolds from Schisandra henryi.

Eleven undescribed schinortriterpenoids (SNTs) and one known analogue (12) were isolated from the stems and leaves of Schisandra henryi. Their diverse structures included preschisanartane (1), 18-norschiartane (2-5, 12), schiartane (6 and 7), and schisanartane (8-11) skeletons, which were elucidated by comprehensive NMR, MS, electronic circular dichroism analyses, single crystal X-ray diffraction and biogenetic considerations. 1 was the first case of preschisanartane-type SNT with six-membered lactone ring, and 2 was one of the most highly oxygenated 18-norschiartane SNTs. Three types of the highly oxygenated SNTs, 1, 4, 10 and 11, effectively prevent apoptosis induced by corticosterone in PC12 cells. In addition, 11 showed neurite outgrowth-promoting activity.

1,4-ß-d-Glucomannan from Dendrobium officinale Activates NF-кB via TLR4 to Regulate the Immune Response.

2,3-O-acetylated-1,4-ß-d-glucomannan (DOP-1-1) is a polysaccharide isolated from the stem of Dendrobium officinale. DOP-1-1 has been demonstrated to have remarkable immunomodulatory properties, but little is known about the influence of its structural diversity on bioactivity (and even less about the exact mechanism underlying its immune responses). First, DOP-1-1 was stabilized at different temperatures and pH conditions based on differential scanning calorimetry and size exclusion-chromatography⁻high-performance liquid chromatography. Then, a detailed study on the effects of DOP-1-1 on a human leukemia monocytic cell line (THP-1) under normal conditions was undertaken. DOP-1-1 promoted the translocation of nuclear factor-kappa B (NF-κB) and degradation of IκB proteins. The expression of genes and proteins closely associated with the immune, survival and apoptotic functions of NF-κB were analyzed by quantitative real-time RT-PCR. Furthermore, CCL4 and IP10 were confirmed to be the novel targets of the immune response stimulated by DOP-1-1. The phosphorylation of NF-кB was inhibited by treatment with a toll-like receptor 4 (TLR4) antagonist (TAK-242) and myeloid differentiation factor 88 (MyD88) inhibitor (ST2825). These data suggested: (i) the O-acetylated glucomannan DOP-1-1 is present in the steady state in low-pH solutions; (ii) DOP-1-1 can induce an immune response through NF-кB mediated by a TLR4 signaling pathway; and (iii) CCL4 and IP10 could be the novel targets of the immune response stimulated by O-acetylated glucomannan.

Structural elucidation and antioxidant activity of an arabinogalactan from the leaves of Moringa oleifera.

A novel arabinogalactan (MOP-1) was isolated from leaves of Moringa oleifera and was purified by macro-porous resin, DEAE-52 Cellulose and Sepharose 6B gel filtration chromatography. High performance gel permeation chromatography (HPGPC) analysis showed that the molecular weight of MOP-1 was 7.65 × 107 Da. Monosaccharide composition analysis indicated that sugar composition is Rha: Ara: Gal in a molar ratio of 1:7.32:12.12. Structural analysis indicated that MOP-1 has a backbone of →1)-ß-d-Galp-(3,4→ with highly branched chains at O-4 position. The branches were composed of →1)-ß-d-Galp-(4→, →1)-α-d-Galp-(2→, Araf-(1→, Galp-(1→. Its antioxidant activities were evaluated by DPPH radical scavenging capacity, 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) radical cation scavenging capacity, and ferric-reducing antioxidant power (FRAP). The results indicated MOP-1 exhibited significant antioxidant activities.

Structural characterization and immunomodulating activity of polysaccharide from Dendrobium officinale.

A neutral heteropolysaccharide (DOP-1-1) consisted by mannose and glucose (5.9:1) with an average molecular weight at about 1.78×10(5) Da was purified from Dendrobium officinale. Based on Fourier transform infrared spectrum (FT-IR) and nuclear magnetic resonance (NMR) spectra, it suggested that partial structure of DOP-1-1 is an O-acetylated glucomannan with ß-d configuration in pyranose sugar forms. The immunomodulatory activity of DOP-1-1 was evaluated by secretion level of cytokine (interleukin (IL)-1ß and IL-10) and tumor necrosis factor (TNF)-α in vitro. Our results suggested that DOP-1-1 could stimulate cytokine production (TNF-α, IL-1ß) in cells. These findings demonstrated that the purified polysaccharide from D. officinale presented significant immune-modulating activities. Furthermore, by Western-blot we can found that the signaling pathways of DOP-1-1 induced immune activities involving ERK1/2 and NF-кB. As to antioxidant activity, DOP-1-1 hadn't showed remarkable scavenging capacity of 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) in contrast with other studies of polysaccharides from D. officinale.