Cangumycins A-F, six new angucyclinone analogues with immunosuppressive activity from Streptomyces

Cangumycins A-F(1–6), six new angucyclinone analogues, together with two known ones(7 and 8), were isolated from the fermentation broth of a soil-derived Streptomyces sp. KIB-M10. Structures of these compounds were elucidated via a joint use of spectroscopic analyses and single-crystal X-ray diffractions. Among them, cangumycins E(5) and F(6) share a C-ring cleaved backbone, and cangumycins B(2) and E(5) exhibit potent immunosuppressive activity(IC50 8.1 and 2.7 μmol·L^-1, respectively) against human T cell proliferation at a non-cytotoxic concentration.

Meroterpenoids with Potent Immunosuppressive Activity from Fungus Bipolaris zeicola

Six new meroterpe no ids,bipolarinoids A-F(1-6),and two known congen ers(7-8)were isolated from a soil-derived fungus Bipolaris zeicola.Their structures were elucidated based on extensive spectroscopic techniques(ineluding HRESIMS and ID and 2D NMR data),and the absolute configurations of 1-4 were further confirmed viasingle-crystal X-ray diffraction an alysis and comparis on of experimental electronic circular dichroism(ECD)data.Structurally,compound 1 represents the first case of cochlioquinone derivatives featuring a formaldehyde group at C-11, and compou nd 3 features a rareamino group at C-11.In the immunosuppressive activity assay,compounds 5-8 showed potent inhibitory activity against concanavalin A(ConA)-induced T lymphocyte proliferation with IC50 values of 78.3,81.1,48.3,and 48.0 nmol/L,respectively,which provided promising leads for designing and developing new im-muno suppressive agents to treat auto-immunological diseases.

Immunosuppressive terpenoids from Tripterygium wilfordii

Two new terpenes,triptobenzene P（1）and wilforone（2）were isolated from Tripterygium wilfordii,as well as 10 known terpenes.Their structures were elucidated by spectroscopic methods.Compounds 2-4,8,10,and 11 showed significant immunosuppressive activities.

Two new terpenes from Tripterygium wilfordii

Two new terpenes,wilfornine H(1) and triptobenzene Q(2) were isolated from Tripterygium wilfordii,as well as 11 terpenes. Their structures were elucidated by spectroscopic methods.Compounds 5,9-13 showed significant immunosuppressive activities.

Three new pyrrole alkaloids from the endophytic fungus Albifimbria viridis

Three new pyrrole alkaloids albifipyrrols A-C(1-3),were isolated from the endophytic fungus Albifimbria viridis col-lected from the Chinese medicinal plant.Their structures were elucidated by extensive NMR and HRESIMS spectro-metric analyses.All compounds were evaluated for immunosuppressive activity.Fortunately,compound 2 exhibits certain inhibition specifically against the LPS-induced proliferation of B lymphocyte cells with IC50 value 16.16μM.

Role of aryl hydrocarbon receptor in mesenchymal stromal cell activation:A minireview

Mesenchymal stromal cells(MSCs) possess great therapeutic advantages due to their ability to produce a diverse array of trophic/growth factors related to cytoprotection and immunoregulation.MSC activation via specific receptors is a crucial event for these cells to exert their immunosuppressive response.The aryl-hydrocarbon receptor(Ah R) is a sensitive molecule for external signals and it is expressed in MSCs and,upon positive activation,may potentially regulate the MSC-associated immunomodulatory function.Consequently,signalling pathways linked to Ah R activation can elucidate some of the molecular cascades involved in MSC-mediated immunosuppression.In this minireview,we have noted some important findings concerning MSC regulation via Ah R,highlighting that its activation is associated with improvement in migration and immunoregulation,as well as an increase in pro-regenerative potential.Thus,Ah R-mediated MSC activation can contribute to new perspectives on MSC-based therapies,particularly those directed at immune-associated disorders.

Hyparillums A and B: polycyclic polyprenylated acylphloroglucinols from Hypericum patulum

Hyparillums A(1)and B(2),two previously unidentified polycyclic polyprenylated acylphloroglucinols(PPAPs)with intricate architectures,were isolated from Hypericum patulum Thunb.Hyparillum A was the first PPAP with eight-carbon rings based on an unprecedented 6/6/5/6/6/5/6/4 octocyclic system featuring a rare heptacyclo[10.8.1.11,10.03,8.08,21.012,19.014,17]docosane core.In contrast,hyparillum B featured a novel heptacyclic architecture(6/6/5/6/6/5/5)based on a hexacyclo[9.6.1.11,9.03,7.07,18.011,16]nonadecane motif.Furthermore,hyparillums A and B demonstrated promising inhibitory effects on the proliferation of murine splenocytes stimulated by anti-CD3/anti-CD28 monoclonal antibodies and lipopolysaccharide,exhibiting half-maximal inhibitory concentration(IC50)values ranging from 6.13±0.86 to 12.69±1.31μmol·L−1.

FOXP3 ＋ regulatory T cells and their functional regulation

FOXP3＋ regulatory T （Treg） cells are critical in maintaining immune tolerance and homeostasis of the immune system. The molecular mechanisms underlying the stability, plasticity and functional activity of Treg cells have been much studied in recent years. Here, we summarize these intriguing findings, and provide insight into their potential use or manipulation during Treg cell therapy for the treatment of autoimmune diseases, graft-versus-host disease （GVHD） and cancer.