Rui-Jun Li

Calliviminones C–H: six new hetero- and carbon-Diels–Alder adducts with unusual skeletons from the fruits of Callistemon viminalis

Calliviminones C–H (1–6), six novel Diels–Alder adducts of a polymethylated phloroglucinol derivative and acyclic monoterpene (myrcene), were isolated from the fruits of Callistemon viminalis. Their structures were elucidated on the basis of extensive analysis of NMR spectroscopic data and calculated electronic circular dichroism spectra. Compounds 1 and 2 were the first examples of a polymethylated phloroglucinol derivative connected with myrcene in a hetero-Diels–Alder manner and 3–6 were carbon-Diels–Alder adducts featuring an unusual core of spiro-[5.5] undecene. Bioactivity scans indicated that 2–6 showed moderate inhibition on nitric oxide production in lipopolysaccharide-induced RAW264.7 macrophages.

The Anti-inflammatory Activities of Two Major Withanolides from Physalis minima Via Acting on NF-κB, STAT3, and HO-1 in LPS-Stimulated RAW264.7 Cells

Physalis minima has been traditionally used as a folk herbal medicine in China for the treatment of many inflammatory diseases. However, little is known about its anti-inflammatory constituents and associated molecular mechanisms. In our study, withaphysalin A (WA) and 2, 3-dihydro-withaphysalin C (WC), two major withanolide-type compounds, were obtained from the anti-inflammatory fraction of P. minima. Both WA and WC significantly inhibited the production of nitrite oxide (NO), prostaglandin E2 (PGE2), and several pro-inflammatory cytokines, such as interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) in lipopolysaccharide (LPS)-activated RAW264.7 macrophages. Further research indicated that they downregulated the LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the mRNA and protein levels. In addition, they also suppressed nuclear translocation of NF-κB p65, phosphorylation of STAT3, and upregulated HO-1 expression. Intriguingly, the activation of MAPKs was suppressed by WA but was not altered by WC. Taken together, these data provide scientific evidence for elucidating the major bioactive constituents and related molecular mechanisms for the traditional use of P. minima and suggest that WA and WC can be attractive therapeutic candidates for various inflammatory diseases.

Polyprenylated Tetraoxygenated Xanthones from the Roots of Hypericum monogynum and Their Neuroprotective Activities.

Ten new polyprenylated tetraoxygenated xanthones, monogxanthones A-J (1-10), together with eight known analogues (4b, 11-17) were identified from the roots of Hypericum monogynum. The structures of these new polyprenylated xanthones (1-10), a class of compounds rarely found in plants of the genus Hypericum, were elucidated by the interpretation of their HRESIMS, 1D and 2D NMR, and electronic circular dichroism data. Compounds 1 and 2 exhibited neuroprotective effects against corticosterone (Cort)-induced lesions of PC12 cells at concentrations of 6.25, 12.50, and 25.00 μM, with cell viability greater than 75%, as well as inhibitory effects on nitric oxide production in lipopolysaccharide-induced BV2 microglia cells, with IC50 values of 7.47 ± 0.65 and 9.60 ± 0.12 μM, respectively. Collectively, these results shed new light on the potential of polyprenylated xanthones from the genus Hypericum in the development of antidepression therapies.

Nitric Oxide Inhibitory Activity and Absolute Configurations of Arylalkenyl α,β-Unsaturated δ/γ-Lactones from Cryptocarya concinna.

During an ongoing exploration of potential anti-inflammatory agents from medicinal plants, eight new arylalkenyl α,β-unsaturated δ-lactones, cryptoconcatones A-H (1-8), and two unusual arylalkenyl α,β-unsaturated γ-lactones, cryptoconcatones I and J (9 and 10), were identified from the leaves and twigs of Cryptocarya concinna. The structures of these compounds were established based on spectroscopic data (MS, 1D/2D NMR), and their absolute configurations were determined with Rigueras method, the modified Moshers method, chemical derivatization, and the Snatzke chirality rule. Compounds 4-6 and 8-10 showed inhibitory activity toward nitric oxide (NO) production in lipopolysaccharide-induced RAW 264.7 macrophages, particularly compounds 4 and 8-10, with IC50 values of 3.2, 4.2, 3.4, and 7.5 μM, respectively.

Sarglaperoxides A and B, Sesquiterpene–Normonoterpene Conjugates with a Peroxide Bridge from the Seeds of Sarcandra glabra

Sarglaperoxides A (1) and B (2), a pair of unusual sesquiterpene-normonoterpene conjugates with a peroxide bridge, were isolated from the seeds of Sarcandra glabra. The structures and absolute configurations of 1 and 2 were determined on the basis of spectroscopic data analysis, including MS, NMR, CD, and XRD. The two compounds were screened in antimicrobial, anti-inflammatory, and cytotoxic bioassays and showed moderate bioactivities.

New Structurally Diverse Limonoids from the Seeds of Khaya senegalensis

Twelve new limonoids (khasenegasins O-Z; 1-12) with three different kinds of skeletons, including eight mexicanolides, two gedunins, and two andirobins, together with four known limonoids (13-16) were isolated from the seeds of Khaya senegalensis. Their structures were determined by extensive spectroscopic analyses (HR-ESI-MS, 1D/2D NMR), and the absolute configurations of 1 and 2 were established by the electronic circular dichroism exciton chirality method. Moreover, a new andirobin-type limonoid (12) showed significant neuroprotective activity against glutamate-induced injury in primary rat cerebellar granule neuronal cells with increased viability of 83.3 ± 6.0 % at 10 µM and 80.3 ± 3.2 % at 1 µM.

Anti-inflammatory activity of Khayandirobilide A from Khaya senegalensis via NF-κB, AP-1 and p38 MAPK/Nrf2/HO-1 signaling pathways in lipopolysaccharide-stimulated RAW 264.7 and BV-2 cells

BACKGROUND Immunocytes-involved inflammation is considered to modulate the damage in various diseases. Herein, novel therapeutics suppressing over-activation of immunocytes could prove an effective strategy to prevent inflammation-related diseases. PURPOSE The objective of this study is to evaluate the anti-inflammatory activity of Khayandirobilide A (KLA), a new andirobin-type limonoid with modified furan ring isolated from the Khaya senegalensis (Desr.) A. Juss., and to explore its potential underlying mechanisms in LPS-stimulated inflammatory models. METHODS The structure of KLA was elucidated on the basis of 1D- and 2D-NMR spectroscopic data as well as HR-ESI-MS. As for its anti-inflammatory effect, the production of pro-inflammatory mediators and cytokines in LPS-stimulated RAW 264.7 and BV-2 cells were measured by Griess reagent, ELISA and qRT-PCR. The relevant proteins including nuclear factor κB (NF-κB), p-AKT, p-p38 and Nrf2/HO-1 were investigated by western blot. Nuclear localisations of NF-κB, activator protein-1 (AP-1) and Nrf2 were also examined by western blot and immunofluorescence. RESULTS KLA could inhibit the production of LPS-induced NO with IC50 values of 5.04 ± 0.14 µM and 4.97 ± 0.5 µM in RAW 264.7 and BV-2 cells, respectively. KLA also attenuated interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the protein and mRNA levels. Further mechanistic studies demonstrated the activation of NF-κB and AP-1 were reduced by KLA. Moreover, KLA elevated expression of heme oxygenase-1(HO-1) via inducing Keap1 autophagic degradation and promoting Nrf2 nuclear translocation. Despite KLA induced the phosphorylation of mitogen-activated protein kinases (MAPKs) family, inhibiting the phosphorylation of p38 by its specific inhibitor SB203580 attenuated the degradation of KLA-induced Keap1, and then reduced KLA-induced Nrf2 nuclear translocation and HO-1 expression. Furthermore, SB203580, Brusatol (a Nrf2 specific inhibitor) and ZnPP (a HO-1 specific inhibitor) could partly reverse the suppressive effects of KLA on LPS-induced NO production and mRNA levels of pro-inflammatory genes. CONCLUSION These data displayed that KLA possessed anti-inflammatory activity, which was attributed to inhibit the release of LPS-stimulated inflammatory mediators via suppressing the activation of NF-κB, AP-1, and upregulating the induction of p38 MAPK/Nrf2-mediated HO-1.

Cytotoxic withanolides from Physalis angulata

Abstract A new withanolide (1), physagulide P, together with five known withanolides (2–6), was isolated from the aerial parts of Physalis angulata L. The structure of new compound was elucidated on the basis of extensive spectroscopic techniques, including 1D, 2D NMR and HRESIMS. The activity screening indicated that compound 1 showed significant cytotoxicities against the human osteosarcoma cell line MG-63, HepG-2 hepatoma cells and breast cancer cells MDA-MB-231 with the IC50 value of 3.50, 4.22 and 15.74 μM.

Phytosteroids and triterpenoids with potent cytotoxicities from the leaves of Chisocheton cumingianus

Six phytosteroids and three dammarane-type triterpenoids, namely chisopanoids A–F (1–6) and chisopanones G–I (7–9), together with nine known triterpenoids (10–18) were isolated from the leaves of Chisocheton cumingianus. Their structures were elucidated by extensive spectroscopic analysis, X-ray crystallographic analysis, Moshers method and Mo2(OAc)4-induced electronic circular dichroism (ECD) data. All compounds were evaluated for their cytotoxicities against HepG2, U2OS and MCF-7 human cancer cell lines, as well as inhibitory effects on nitric oxide (NO) production in LPS-activated RAW 264.7 macrophages. Compounds 5 and 6 showed potent cytotoxicities towards MCF-7 with IC50 values of 3.24 ± 1.39 and 8.85 ± 4.73 μM, and were further proved to inhibit the cell proliferation mainly by inducing apoptosis.

Sesquiterpenoids from the seeds of Sarcandra glabra and the potential anti-inflammatory effects

Five new sesquiterpenoids, including two linderanes (1-2) and three eudesmanes (3-5) were isolated from the seeds of Sarcandra glabra. Their structures and relative configurations were established by spectroscopic data analysis. 1 was a rare linderane derivative having an 18-membered triester ring which is a common characteristic in linderane dimers. Compounds 1-5 were investigated for their inhibitory effects on NO production in LPS-induced macrophages and 1 showed moderate bioactivity.