This study systematically investigated the therapeutic effects and the corresponding mechanisms of β-D-glucans from Ganoderma lucidum (G. lucidum) with different molecular weights (Mws) on ulcerative colitis (UC). Results showed that three β-d-glucans (GLPS, GLPN and GLPW) from G. lucidum with different Mws exhibited the significant activities on the reduction of typical symptoms of UC by regulating inflammatory cytokine levels, modulating intestinal immunity, improving intestinal microbiota and metabolism of short-chain fatty acids (SCFAs) in the dextran sulfate sodium (DSS)-induced mice model. Among them, the effects of the microwave assisted degraded fraction (GLPW) mainly containing two fractions with smaller Mw (1.33 × 104 and 3.51 × 103 g/mol) on the regulation of inflammatory factors and SCFAs metabolism were found to be comparable to those of GLPN with medium Mw (3.49 × 104 g/mol), and superior to those of GLPS with large Mw (2.42 × 106 g/mol). The effect of GLPW on regulation of intestinal microbiota was even better than that of GLPN. These findings suggested that lowering Mw by means of physical degradation could improve the anti-inflammatory activities of G. lucidum β-d-glucans. The analysis of anti-inflammatory mechanism also provided a feasible and theoretical basis for potential use of degraded β-d-glucans in the prevention and treatment of UC.

molecular weight, Ganoderma lucidum, anti-inflammatory activity, β-D-Glucans, SCFAs metabolism

There is only one chemically distinct structure:

SVGMWSMILES3D molIonize

 

[*]O[C@H]1[C@H](O)[C@@H](CO)O[C@@H](O[C@@H]2[C@@H](O)[C@H](O[C@@H]3[C@@H](O)[C@H]([*])O[C@H](CO)[C@H]3O)O[C@H](CO[C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)[C@H]2O)[C@@H]1O

648.564 g/mol (C₂₄H₄₀R₂O₂₀, R = next and previous repeats, not counted in mol weight)

The main characteristic of biofilm formation is extracellular matrix (ECM) production. The cells within the biofilm are surrounded by ECM which provides structural integrity and protection. During an infection, this protection is mainly against cells of the immune system and antifungal drugs. A. fumigatus forms biofilms during static growth on a solid substratum and in chronic aspergillosis infections. It is important to understand how, and which, A. fumigatus signal transduction pathways are important for the adhesion and biofilm formation in a host during infection. Here we investigated the role of MAP kinases and protein phosphatases in biofilm formation. The loss of the MAP kinases MpkA, MpkC and SakA had an impact on the cell surface and the ECM during biofilm formation and reduced the adherence of A. fumigatus to polystyrene and fibronectin-coated plates. The phosphatase null mutants ΔsitA and ΔptcB, involved in regulation of MpkA and SakA phosphorylation, influenced cell wall carbohydrate exposure. Moreover, we characterized the A. fumigatus protein phosphatase PphA. The ΔpphA strain was more sensitive to cell wall-damaging agents, had increased β-(1,3)-glucan and reduced chitin, decreased conidia phagocytosis by Dictyostelium discoideum and reduced adhesion and biofilm formation. Finally, ΔpphA strain was avirulent in a murine model of invasive pulmonary aspergillosis and increased the released of tumor necrosis factor alpha (TNF-α) from bone marrow derived macrophages (BMDMs). These results show that MAP kinases and phosphatases play an important role in signaling pathways that regulate the composition of the cell wall, extracellular matrix production as well as adhesion and biofilm formation in A. fumigatus.

polysaccharide, Biofilm, Extracellular matrix, Aspergillus fumigatus, mitogen activated kinases, phosphatases

There is only one chemically distinct structure:

SVGMWSMILES3D molIonize

 

*O[C@@H]1[C@@H](CO)O[C@@H](*)[C@H](NC(C)=O)[C@H]1O

203.194 g/mol (C₈H₁₃R₂NO₅, R = next and previous repeats, not counted in mol weight)

In this work we report the vasorelaxant activity of 7-β-O-glycosides obtained with biosynthesis of naringenin-7-β-O-glycoside (3) and quercetin-7-β-O-glycoside (4). These compounds were obtained from naringenin (1) and quercetin (2) glycosylation catalyzed by Beauveria bassiana ATCC 7159. Screening of the best strain as a catalyst for glycosylation was carried out and the reaction conditions established. Cultures were grown in PDSM medium for 7 days at 27 °C. After purification by reverse-phase preparative HPLC, naringenin-7-β-O-glycoside (3) and quercetin-7-β-O-glycoside (4) were identified by (1)H and (13)C NMR. The right position and β-configuration of the glucose was determined through HSQC and HMBC experiments. The vasorelaxation potential of naringenin, quercetin and its glycosylated derivatives was evaluated using isolated aorta in vitro models. Interestingly, results suggest that vasorelaxation properties of naringenin, rutin and its glycosides are due to different pathways.

glycosylation, quercetin, Beauveria bassiana, aorta relaxation, naringenin

13C NMR data:
Linkage	Residue	C1	C2	C3	C4	C5	C6	C7	C8	C9	C10	C11	C12	C13	C14	C15
7	bDGlcp	100.8	77.0	77.6	74.4	80.0	61.6
	Subst	80.4	43.7	198.3	164.3	96.7	166.6	97.7	129.1	104.6	130.5	128.9	116.7	158.9	116.1	128.9


1H NMR data:
Linkage	Residue	H1	H2	H3	H4	H5	H6	H7	H8	H9	H10	H11	H12	H13	H14	H15
7	bDGlcp	4.94-4.95	3.43	3.56	3.45	3.18-3.19	3.68-3.83
	Subst	5.37-5.38	2.74-3.17	-	-	-	6.19-6.20	-	6.17-6.18	-	-	7.31	6.28	-	6.28	7.31


1H/13C HSQC data:
Linkage	Residue	C1/H1	C2/H2	C3/H3	C4/H4	C5/H5	C6/H6	C7/H7	C8/H8	C9/H9	C10/H10	C11/H11	C12/H12	C13/H13	C14/H14	C15/H15
7	bDGlcp	100.8/4.94-4.95	77.0/3.43	77.6/3.56	74.4/3.45	80.0/3.18-3.19	61.6/3.68-3.83
	Subst	80.4/5.37-5.38	43.7/2.74-3.17				166.6/6.19-6.20		129.1/6.17-6.18			128.9/7.31	116.7/6.28		116.1/6.28	128.9/7.31

There is only one chemically distinct structure:

SVGMWSMILES3D molIonize

 

O=C1CC(c2ccc(O)cc2)Oc2cc(O[C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)cc(O)c21

434.397 g/mol (C₂₁H₂₂O₁₀)

In this work we report the vasorelaxant activity of 7-β-O-glycosides obtained with biosynthesis of naringenin-7-β-O-glycoside (3) and quercetin-7-β-O-glycoside (4). These compounds were obtained from naringenin (1) and quercetin (2) glycosylation catalyzed by Beauveria bassiana ATCC 7159. Screening of the best strain as a catalyst for glycosylation was carried out and the reaction conditions established. Cultures were grown in PDSM medium for 7 days at 27 °C. After purification by reverse-phase preparative HPLC, naringenin-7-β-O-glycoside (3) and quercetin-7-β-O-glycoside (4) were identified by (1)H and (13)C NMR. The right position and β-configuration of the glucose was determined through HSQC and HMBC experiments. The vasorelaxation potential of naringenin, quercetin and its glycosylated derivatives was evaluated using isolated aorta in vitro models. Interestingly, results suggest that vasorelaxation properties of naringenin, rutin and its glycosides are due to different pathways.

glycosylation, quercetin, Beauveria bassiana, aorta relaxation, naringenin

13C NMR data:
missing...

There is only one chemically distinct structure:

SVGMWSMILES3D molIonize

 

O=c1c(O)c(-c2ccc(O)c(O)c2)oc2cc(O[C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)cc(O)c12

464.379 g/mol (C₂₁H₂₀O₁₂)