Research progress of yeast microcapsules as oral drug delivery carrier / 中国药房

As a natural drug delivery carrier with rough and porous surface and hollow core， yeast microcapsules have good safety， high targeting and high stability， and have excellent application prospects in oral drug delivery systems. Yeast cells can be treated and washed with acid-base and organic solvents to obtain loose and porous yeast microcapsules. Yeast microcapsules can encapsulate drugs through electrostatic interactions， passive diffusion， hydrophobic interaction and other methods. The surface of yeast microcapsules is mainly composed of β-glucan， which can maintain stability in the gastrointestinal environment； it can be recognized by the surface-related receptors of immune cells， thus activating the immune response， and can be transported to the lesion site with the movement of lymphocytes after being ingested. Yeast microcapsules are safe and very suitable for delivering vaccines， anti-inflammatory drugs， and anti-tumor drugs. They can not only achieve oral delivery of the aforementioned drugs， but also enhance drug efficacy and improve drug targeting. In the future， more research on systemic transport mechanisms or the development of more efficient combination drug delivery systems can be carried out to fully exhibit the clinical value of yeast microcapsules.

β -Glucan Improves Protective Qi Status in Adults with Protective Qi Deficiency-A Randomized, Placebo-Controlled, and Double-Blinded Trial / 中国结合医学杂志

OBJECTIVE@#To test the hypothesis that β -glucan enhances protective qi (PQi), an important Chinese medicine (CM) concept which stipulates that a protective force circulates throughout the body surface and works as the first line of defense against "external pernicious influences".@*METHODS@#A total of 138 participants with PQi deficiency (PQD) were randomized to receive β -glucan (200 mg daily) or placebo for 12 weeks. Participants' PQi status was assessed every 2 weeks via conventional diagnosis and a standardized protocol from which a PQD severity and risk score was derived. Indices of participants' immune and general health status were also monitored, including upper respiratory tract infection (URTI), saliva secretory IgA (sIgA), and self-reported measures of physical and mental health (PROMIS).@*RESULTS@#PQi status was not significantly different between the β -glucan and placebo treatment groups at baseline but improved significantly in the β -glucan (vs. placebo) group in a time-dependent manner. The intergroup differences [95% confidence interval (CI)] in severity score (scale: 1-5), risk score (scale: 0-1), and proportion of PQD participants (%) at finish line was 0.49 (0.35-0.62), 0.48 (0.35-0.61), and 0.36 (0.25-0.47), respectively. Additionally, β -glucan improved URTI symptom (scale: 1-9) and PROMIS physical (scale: 16.2-67.7) and mental (scale: 21.2-67.6) scores by a magnitude (95% CI) of 1.0 (0.21-1.86), 5.7 (2.33-9.07), and 3.0 (20.37-6.37), respectively, over placebo.@*CONCLUSIONS@#β -glucan ameliorates PQi in PQD individuals. By using stringent evidence-based methodologies, our study demonstrated that Western medicine-derived remedies, such as β -glucan, can be employed to advance CM therapeutics. (ClinicalTrial.Gov registry: NCT03782974).

Micro-particulate Ganoderma lucidum spore β-glucanin enhances the antitumor activity of gemcitabin via remodeling immunosuppressive microenvironment in Lewis lung cancer / 药学学报

Gemcitabine (GEM) is a commonly used drug in the clinical treatment of non-small cell lung cancer. Due to the accumulation of cells mediating immune escape and T cell depletion after chemotherapy, tumor microenvironment (TME) tends to be immunosuppressive status, which ultimately leads to tumor metastasis. The experimental protocol was approved by the Medical Laboratory Animal Ethics Committee of Jiangsu Provincial Academy of Chinese Medicine. Therefore, we observed the immunomodulatory effects of micro-particulate Ganoderma lucidum spore β-glucan (PGSG) on macrophages in vitro experiments. Next, mice subcutaneous Lewis lung cancer models were established to observe the anti-tumor effects of PGSG through oral administration of PGSG combined with GEM. Flow cytometry analysis was used to analyze the ratio of anti-tumor T cells in tumors and spleen, as well as the proportion of myeloid-derived suppressor cells (MDSC), tumor-associated macrophages (TAM) and regulatory cells (Tregs). The results showed that PGSG can up-regulate the expression of major histocompatibility antigens (MHC-II), CD40, CD86 and CD80 on the surface of macrophages, enhance the ability to phagocytosis of neutral red and further mediate the release of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4) and interleukin-10 (IL-10). In vivo experiments, combined administration can significantly decrease the volume and weight of tumors, reduce the ratio of MDSC (CD11b+Gr-1+), M-MDSC (CD11b+Ly6G-Ly6Chigh) and Treg (CD4+Foxp3+). At the same time, PGSG promoted the conversion of M2 (F4/80+CD206+) to M1 (F4/80+MHC-II+) and enhanced the response of helper T cell-1 (Th1) (CD4+IFN-γ+) and cytotoxic T lymphocyte (CTL) (CD8+IFN-γ+), which is of great significance for killing tumors. These results suggest that PGSG can regulate innate and adaptive antitumor immune responses, reshape the immunosuppressive microenvironment and enhance the anti-lung cancer effect of GEM.

Proof-of-Concept and Feasibility Study to Evaluate the Effect of β-Glucan on Protective Qi Deficiency in Adults / 中国结合医学杂志

OBJECTIVE@#To preliminarily explore the potential effect of β-glucan on Chinese medicine (CM) concept protective qi deficiency (PQD), and the methodology for future definitive studies.@*METHODS@#To have a standardized assessment of PQD, a list of 13 potentially PQD-relevant parameters were firstly created, each with defined quantitative or categorial scales. Using the data from 37 participants with (21 cases) or without (16 cases) PQD, multivariate logistic modeling was conducted to create a preliminary diagnostic PQD risk score. Subsequently, 21 participants diagnosed with PQD were treated with β-glucan in a dose of 200 mg/day for 8 weeks. Data were collected for trial acceptability measures (rate of recruitment, withdrawal, and compliance), and the participants were assessed for PQD status at baseline and every 2 weeks thereafter.@*RESULTS@#The preliminary logistic model consisted of 3 parameters (low voice and apathy, aversion to wind and cold, and Cun pulse). The resulting risk score demonstrated a degree of PQD-predicting accuracy that, as evaluated by statistical (discrimination and classification) methods, was higher than those obtained from any of the individual candidate parameters. The 21 PQD participants treated with β-glucan demonstrated good receptibility and a time-dependent improvement in PQD status as evidenced by the decrease of PQD participant to 9.5% at the end of study.@*CONCLUSIONS@#This study demonstrated the effect of proof-of-concept of β-glucan on improving PQD and the proof-of-concept of a multivariate-model-derived diagnostic PQD risk score. It also indicated feasibility for future definitive studies. Studies like this embody an innovative approach that uses therapies derived from the mainstream biomedicine to enrich therapeutics guided by CM principle. (Trial registration No. NCT03829228).

Effect of berberine hydrochloride on cell wall integrity of Candida albicans hypha / 中国中药杂志

The aim of this paper was to investigate the effect of berberine hydrochloride on the cell wall integrity of Candida albicans hypha. The minimal inhibitory concentration(MIC) of berberine hydrochloride against clinical and standard C. albicans strains was detected by micro liquid-based dilution method; the effect of berberine hydrochloride on the colony formation of C. albicans SC5314 was investigated by spot assay; the effect of berberine hydrochloride on the metabolism of C. albicans SC5314 hypha was checked by XTT reduction assay, and the viability of C. albicans SC5314 hypha was tested by fluorescent staining assay. The effect of berberine hydrochloride on the morphology of C. albicans SC5314 hypha was examined by scanning electron microscope. The changes in the cell wall of C. albicans SC5314 hypha after berberine hydrochloride treatment were detected by transmission electron microscopy. The effect of berberine hydrochloride on β-glucan from C. albicans SC5314 was detected by flow cytometry. The effect of berberine hydrochloride on hypha-specific gene ECE1 and β-glucan synthase genes FKS1 and FKS2 in C. albicans was examined by qRT-PCR. The results showed that berberine hydrochloride showed a strong inhibitory effect on both clinical and standard strains of C. albicans, and the MIC was 64-128 μg·mL~(-1). Spot assay, XTT redunction assay and fluorescent staining assay showed that with the increase of berberine hydrochloride concentration, the viability of C. albicans SC5314 gradually decreased. The transmission electron microscopy scanning assay showed that this compound could cause cell wall damage of C. albicans. The flow cytometry analysis showed the exposure degree of C. albicans β-glucan. The qRT-PCR further showed that berberine hydrochloride could significantly down-regulate hypha-specific gene ECE1 and β-glucan synthase-related gene FKS1 and FKS2. In conclusion, this compound can down-regulate C. albicans and β-glucan synthase-related gene expressions, so as to destroy the cell wall structure of C. albicans, expose β-glucan and damage the integrity of the wall.

Alkali extraction of Ganoderma lucidum β-glucan and its anti-tumor immune regulation / 药学学报

In this study, an immunostimulating particulate β-glucan was isolated from a hot alkaline extract of the fruiting bodies of Ganoderma lucidum. The optimum conditions of 8 hours treatment time, 1∶20 solid - liquid ratio and 55 ℃ for the alkaline extract process were obtained after investigating by single-factor experiments and Box-Benhnken design in terms of the Ganoderma lucidum particulate β-glucan (GLG) increment, and these conditions resulted in a GLG yield of 8.57%. The experimental protocol was approved by the Medical Laboratory Animal Ethics Committee of Jiangsu Provincial Academy of Chinese Medicine. The result showed that resident macrophages were effectively activated by GLG, such as with the up-regulation of co-stimulatory molecules, the secretion of cytokines and phagocytic uptake. GLG could also promote the proliferation of spleen lymphocytes in mice. In addition, IFN-γ production of spleen CD4+ T cells and cytotoxic T lymphocyte (CTL) responses were significantly enhanced on GLG orally treatment, which ultimately resulted in significantly decreased tumor burden. Taken together, these data suggest that GLG might act as an immune stimulator to exert antitumor effects.

Effects of oat β-glucan on the expression of small intestine injury-related genes in septic rats / 中国比较医学杂志

Objective To explore the effect of oatβ-glucan on gene expression in small intestine injury in sepsis. Methods SD rats were randomly divided into normal control group ( NC group) , experimental control group ( TC group) and oat β-glucan group ( Oglu group) . TC group and Oglu group were used to establish sepsis model with CLP method ,and oglu group with different doses of oatβ-glucan. After 12 h the small intestine tissue were collected. Western blot was used to detect gene expression in the small intestine tissue injury. Results 1 ) Oat β-glucan reduced sepsis-induced small intestine injury,and reduced the TNF-α, IL-1βand IL-6 levels in small intestine of septic rats. (2) The expression of small intestinal injury-related proteins such as Bax, caspase-3, Toll-like, apoptotic genes FAS and FASL and NF-κB were significantly increased,and Bcl-2 expression was down-regulated in the TC group. (3) The expressions of Bax, caspase-3, Toll-like, apoptotic genes FAS and FASL and NF-κB in oat β-glucan-treated rats were lower than that in the septic rats, while Bcl-2 expression was higher than the TC group. Conclusions Oat β-glucan regulates the expression of small intestinal injury genes in septic rats and protects the small intestinal epithelium against sepsis-induced injury.

Noble strain of Sparassis latifolia produces high content of β-glucan

Objective: To classify four new Sparassis strains (CLM1, CKM1, CKM2, and KJM1) using the internal transcribed spacer sequence and to elucidate their β-glucan content and mycelial growth. Methods: Two different microbiological media were used to determine growth rate. The β-glucan contents were analyzed using the Megazyme Mushroom and Yeast Beta-Glucan kit. To determine the genetic relationships, phylogenetic trees were constructed using ClustalX. Multiple sequence alignments were printed and shaded with the BOXSHADE 3.21 program. Results: In this study, four new Sparassis strains were isolated from the southern region of the Korea Peninsula. They were all classified into the Sparassis latifolia clade as a monophyletic group based on the internal transcribed spacer sequence. Mycelial growth rate of the CLM1 strain was highest in potato dextrose agar and potato dextrose agar larch. The β-glucan content of the CLM1 strain was highest at 29.5% (w/w). A high degree of sequence divergence was detected in the RNA polymerase second largest subunit II gene (RPB2) within Sparassis spp. tested. The putative amino acid sequences of the RPB2 had a distinct sequence. The nucleotide sequences of the RPB2's intron were also divergent among Sparassis spp., even though their nucleotide length was well conserved within Sparassis latifolia. Conclusions: These results indicate that the nucleotide sequences and the amino acid sequences of RPB2 can be used to identify individual Sparassis sp. The Sparassis strain CLM1 may be best for developing a remedy to prevent or treat cancer and other chronic diseases.

Role of β-glucan receptor dectin-1 in anti-fungal infection of cornea / 中华实验眼科杂志

β-Glucan is a kind of highly conservative composition on fungal cell wall.As a recognition receptor of β-glucan,dendriticcell-associatedC-typelectin-1 (dectin-1)widely distributeinsingle-nuclea macrophages system,dendritic cells ( DC )and neutrophil cells.Through the identification of fungal cell wall composition and cells signal transduction,dectin-1 induces the production of cytokine and chemokine and then starts a nonspecific and specific immunity response.Dectin-1 plays a key role in antifungal immune response.Here,the molecular structure,tissue cells,signal transmission and the immune inflammation role of dectin-1 in corneal infection were reviewed.