A pectic polysaccharide isolated from Achyranthes bidentata is metabolized by human gut Bacteroides spp.

Achyranthes bidentata (A. bidentata) is a famous traditional Chinese medicine (TGM) for treatment osteoporosis. Polysaccharides, a major factor for shaping the gut microbiota, are the primary ingredients of A. bidentata. However, bioactivity of A. bidentata polysaccharide on human gut microbiota (HGM) remains unknown. Here, a homogeneous pectic polysaccharide A23-1 with average molecular weight of 93.085 kDa was extracted and purified from A. bidentata. And A23-1 was compsed of rhamnose, glucuronic acid, galacturonic acid, glucose, galactose and arabinose in a molar ratio of 7.26: 0.76: 5.12: 2.54: 23.51: 60.81. GC-MS, partial acid hydrolysis and NMR results indicated the backbone of A23-1 was composed of 1, 2, 4-Rhap and 1, 4-GlapA, while the branches were composed of galactose, arabinose, glucose and glucuronic acid. Further, A23-1 was found to be degraded into monosaccharides and fragments. Taking Bacteroides thetaiotaomicron (BT) as a model, we suggested three polysaccharide utilization loci (PULs) might be involved in the A23-1 degradation. Degraded products generated by BO might not support the growth of probiotics. Besides, acetate and propionate as the main end products were generated by Bacteroides spp. and probiotics utilizing A23-1. These findings suggested A23-1 was possible one of food sources of human gut Bacteroides spp.

A novel branched galacturonan from Gardenia jasminoides alleviates liver fibrosis linked to TLR4/NF-κB signaling.

Gardenia jasminoides (GJ) is a classic edible medicine in China of which the fruit has been proved to alleviate liver damage. We hypothesized whether polysaccharide in the fruit could have comparable bioactivity. To address this, a novel polysaccharide GJE0.2-2, is purified from the fruit of Gardenia jasminoides. Indeed, GJE0.2-2 may attenuate CCl4-induced liver fibrosis in mice and impede the expression of critical fibrogenesis associated molecules such as α-SMA, FN1, and Collagen I induced by TGF-ß in human hepatic stellate LX-2 cells. Mechanism studies suggest that this bioactivity may be implicated in TLR4/NF-κB signaling pathway via directly binding to TLR4. The structure characterization shows that the backbone of this polysaccharide is mainly composed of galacturonic acid with minor rhamnose, branched with galactose and arabinose, galacturonic acid, and esterified hexenuronic acid (HexpA). These findings provide evidence for a novel pectin-linked polysaccharide-based new drug candidate development for liver fibrosis therapy.

A novel peptidoglycan isolated from Semiaquilegia adoxoides inhibits Aß42 production via activating autophagy.

The accumulation of amyloid ß (Aß) containing senile plaques is one of the key histopathological hallmarks of Alzheimer's disease (AD). Increasing evidences demonstrated the important role of autophagy in Aß clearance. Recent studies implied that extracts from Semiaquilegia adoxoides (DC.) Makino could ameliorate the memory of D-galactose induced aging mice. However, the bioactive substance and underlying mechanism remains unknown. Thus, the present study sought to explore the effects of a novel homogenous peptidoglycan on Aß42 secretion and the underlying mechanism. Briefly, we extracted a novel peptidoglycan named SA02C using hot water extraction and alcohol precipitation with the Mw of 13.72 kDa. SA02C contains 73.33% carbohydrate and 27.83% protein. The structure characterization revealed that its glycan part might mainly composed of galacturonic acid with minor rhamnose in backbone, and branched with glucose, galactose, arabinose, xylose and galacturonic acid. The protein or peptide moiety in SA02C was bonded to the polysaccharide via threonine. Bioactivities test showed that SA02C could reduce Aß42 production in a dose dependent manner with no obvious cytotoxicity. Mechanism study demonstrated that SA02C could modulate APP processing by upregulating the expression of ADAM10, sAPPα and downregulating BACE1, sAPPß. Furthermore, SA02C also could stimulate autophagy by promoting the expression of the markers of autophagy such as LC3B and ATG5, resulting in the promotion of Aß42 phagocytosis.

A structure defined pectin SA02B from Semiaquilegia adoxoides is metabolized by human gut microbes.

Polysaccharide is one of the major factors for shaping the gut microbiota. However, bioactivity of polysaccharide isolated from Semiaquilegia adoxoides on human gut microbiota remains unclear. Thus, we hypothesize gut microbes may act on it. Herein, pectin SA02B from the roots of Semiaquilegia adoxoides with molecular weight 69.26 kDa was elucidated. The backbone of SA02B was composed of alternate 1, 2-linked α-Rhap and 1, 4-linked α-GalpA, with branches of terminal (T) -, 1, 4-, 1, 3- and 1, 3, 6-linked ß-Galp, T-, 1, 5- and 1, 3, 5-linked α-Araf and T-, 1, 4-linked-ß-Xylp substituted at C-4 of 1, 2, 4-linked α-Rhap. Bioactivity screening showed SA02B promoted the growth of Bacteroides spp. which deconstructed it into monosaccharide. Simultaneously, we observed competition might exist between Bacteroides spp. and probiotics. Besides, we found that both Bacteroides spp. and probiotics could generate SCFAs grown on SA02B. Our findings highlight SA02B may deserve as a prebiotic to be explored to benefit the health gut microbiota.

Heparin mimetics as potential intervention for COVID-19 and their bio-manufacturing.

The COVID-19 pandemic has caused severe health problems worldwide and unprecedented decimation of the global economy. Moreover, after more than 2 years, many populations are still under pressure of infection. Thus, a broader perspective in developing antiviral strategies is still of great importance. Inspired by the observed multiple benefits of heparin in the treatment of thrombosis, the potential of low molecular weight heparin (LMWH) for the treatment of COVID-19 have been explored. Clinical applications found that LMWH decreased the level of inflammatory cytokines in COVID-19 patients, accordingly reducing lethality. Furthermore, several in vitro studies have demonstrated the important roles of heparan sulfate in SARS-CoV-2 infection and the inhibitory effects of heparin and heparin mimetics in viral infection. These clinical observations and designed studies argue for the potential to develop heparin mimetics as anti-SARS-CoV-2 drug candidates. In this review, we summarize the properties of heparin as an anticoagulant and the pharmaceutical possibilities for the treatment of virus infection, focusing on the perspectives of developing heparin mimetics via chemical synthesis, chemoenzymatic synthesis, and bioengineered production by microbial cell factories. The ultimate goal is to pave the eminent need for exploring novel compounds to treat coronavirus infection-caused diseases.

A Novel Pectin-Like Glycopeptide Isolated from the Fruit of Fructus Mori Impedes Aggregation and Production of Aß42.

The fruit of Fructus Mori is food and medicine, which has been demonstrated to have a significant neuroprotective effect. However, the effective constituent remains unknown. We speculate that the glycopeptide in the extract of the fruit has similar activity. To address this hypothesis, we isolated a novel pectin-like glycopeptide (FMP-6-S4) with a molecular weight of 11.23 kDa from the fruit. It contains about 20% of peptide comprising 17 amino acids and 80% glycan consisting of L-rhamnose (L-Rha), D-galactose (D-Gal), D-galacturonic acid (D-GalA), L-arabinose (L-Ara) and d-glucose (D-Glc) in molar ratios of 7.25:4.62:77.66:5.62:4.85. The backbone of the glycan part consisted of 1,4-linked α-D-GalpA and 1, 2-linked α-L-Rhap, while the branches were composed of hexenuronic acid (HexA) substituted at the C-3 position of partial galacturonic acid, and traces of galactose, glucose, and arabinose were substituted at the C-4 position of rhamnose. The in vitro experiments revealed that FMP-6-S4 might inhibit Aß42 (ß-amyloid peptides 42) aggregation and decrease Aß42 production by modulating APP (amyloid precursor protein) processing.

Discrete genetic loci in human gut Bacteroides thetaiotaomicron confer pectin metabolism.

Although the polysaccharide utilization loci (PULs) activated by pectin have been defined, due to the complex of side-chain structure, the degradative mechanisms still remain vague. Thus, we hypothesize that there may have other specific PULs to target pectin. Here, we characterize loci-encoded proteins expressed by Bacteroides thetaiotaomicron (BT) that are involved in the pectin capturing, importation, de-branching and degradation into monosaccharides. Totally, four PULs contain ten enzymes and four glycan binding proteins which including a novel surface enzyme and a surface glycan binding protein are identified. Notably, PUL2 and PUL3 have not been reported so far. Further, we show that the degradation products support the growth of other Bacteroides spp. and probiotics. In addition, genes involved in this process are conservative in other Bacteroides spp. Our results further highlight the contribution of Bacteroides spp. to metabolism the pectic network.

An arabinogalactan from fruits of Lycium barbarum L. inhibits production and aggregation of Aß42.

The ß amyloid (Aß) induced neurodegeneration is believed to be one of pathological mechanisms of Alzheimer's disease (AD). The inhibition of Aß production or aggregation is one of the promising therapeutic strategies for anti-AD drug discovery. Here, a homogeneous neutral polysaccharide designated LBP1A1-1 with an average molecular weight of 45.0 kDa was purified from fruits of Lycium barbarum L. Its structure was characterized to possess a backbone of 1, 3-linked ß-Galp, 1, 6-linked ß-Galp, 1, 4-linked α-Glcp with branches substituted at C-3 position of 1, 6-linked ß-Galp or C-6 position of 1, 3-linked ß-Galp. The branches contained terminal (T)-linked ß-Galp, T-linked α-Araf, T-linked ß-Araf, 1, 5-linked α-Araf and T-linked ß-Rhap. The in vitro experiments revealed that LBP1A1-1 could inhibit Aß42 production and impede Aß42 aggregation in a dose-dependent-manner without cytotoxicity. These results suggested that LBP1A1-1 might have the multiple potential for the treatment of AD.

Structural elucidation of a pectic polysaccharide from Fructus Mori and its bioactivity on intestinal bacteria strains.

Many studies suggested that polysaccharides could impact on the gut microbiota. To discover new polysaccharides which influence intestinal beneficial bacteria, a pectin polysaccharide FMP-6-S2 with an average molecular weight of 86.83 kDa was purified from Fructus Mori. The monosaccharide residue analysis indicated that FMP-6-S2 was composed of rhamnose, galacturonic acid, galactose and arabinose in a molar ratio of 30.86: 24.78: 28.70: 15.61. The backbone of FMP-6-S2 contained 1, 4-linked α-GalpA and 1, 2-linked α-Rhap with branches substituted at C-4 position of rhamnose. The branches were composed of 1, 4-linked ß-Galp, terminal (T) - and 1, 3, 6-linked ß-Galp, T- and 1, 5-linked α-Araf. Bioactivity test results suggested that FMP-6-S2 and its degraded product could promote growth of intestinal bacteria, B. thetaiotaomicron, which is a dominate strain in the gut of human to benefit intestinal mucosa. These results suggested that FMP-6-S2 and its degraded product might improve human wellness by modulating B. thetaiotaomicron.

Structural Characterization of Mannoglucan from Dendrobium nobile Lindl and the Neuritogenesis-Induced Effect of Its Acetylated Derivative on PC-12 Cells.

A water-soluble polysaccharide (JCS1) was isolated from the stems of Dendrobium nobile Lindl. JCS1 was structurally characterized using a combination of chemical and spectral analysis, including methylation analysis, partial acid hydrolysis, Fourier-transform infrared (FTIR) spectroscopy, gas chromatography (GC), GC-mass spectrometry (MS), and nuclear magnetic resonance (NMR) spectroscopy. The molecular weight was estimated to be 2.3 × 104 Da using high-performance gel permeation chromatography (HPGPC). The sugar composition analysis indicated it was composed of glucose, mannose, xylose, and arabinose in a 40.2:2.3:1.7:1.0 molar ratio. The structure analysis showed that JCS1 was a mannoglucan with a backbone consisting of (1→4)-linked ß-Manp and (1→4)-linked α-Glcp with branches at C-6 of (1→4)-linked α-Glcp residues. The branches were composed of T-α-Glcp, 1,4-α-Xylp, and T-α-Araf. In vitro bioactivity tests revealed that the acetylated derivative of JCS1, YJCS1, induced neuritogenesis of PC-12 cells. These results demonstrate that YJCS1 might be a promising bioactive polysaccharide for development as a drug candidate for the possible prevention and treatment of neurodegeneration diseases.