Rhodiola rosea polysaccharides-based nanoparticles loaded with DOX boosts chemo-immunotherapy for triple-negative breast cancer by re-educating tumor-associated macrophages.

The activity of polysaccharides is usually related to molecular weight. The molecular weight of polysaccharides is critical to their immunological effect in cancer therapy. Herein, the Codonopsis polysaccharides of different molecular weights were isolated using ultrafiltration membranes of 60- and 100-wDa molecular weight cut-off to determine the relationship between molecular weight and antitumor activities. First, three water-soluble polysaccharides CPPS-I (<60 wDa), CPPS-II (60–100 wDa), and CPPS-III (>100 wDa) from Codonopsis were isolated and purified using a combination of macroporous adsorption resin chromatography and ultrafiltration. Their structural characteristics were determined through chemical derivatization, GPC, HPLC, FT–IR, and NMR techniques. In vitro experiments indicated that all Codonopsis polysaccharides exhibited significant antitumor activities, with the tumor inhibition rate in the following order: CPPS-II > CPPS-I > CPPS-III. The treatment of CPPS-II exhibited the highest inhibition rate at a high concentration among all groups, which was almost as efficient as that of the DOX·HCL (10 μg/mL) group at 125 μg/mL concentration. Notably, CPPS-II demonstrated the ability to enhance NO secretion and the antitumor ability of macrophages relative to the other two groups of polysaccharides. Finally, in vivo experiments revealed that CPPS-II increased the M1/M2 ratio in immune system regulation and that the tumor inhibition effect of CPPS-II + DOX was superior to that of DOX monotherapy, implying that CPPS-II + DOX played a synergistic role in regulating the immune system function and the direct tumor-killing ability of DOX. Therefore, CPPS-II is expected to be applied as an effective cancer treatment or adjuvant therapy.

/pdf/isolation-purification-and-structural-characterization-of-3oqrxwct.pdf

Isolation, Purification, and Structural Characterization of Polysaccharides from Codonopsis pilosula and Their Anti-Tumor Bioactivity by Immunomodulation

Damage to the intestinal mucosal barrier play an important role in the pathogenesis of ulcerative colitis (UC). Discovering the key regulators and repairing the disturbed barrier are crucial for preventing and treating UC. Traditional Chinese medicine (TCM) has been proved to be effective on treating UC and has exhibited its role in repairing the intestinal mucosal barrier. We summarized the evidence of TCM against UC by protecting and repairing the physical barrier, chemical barrier, immune barrier, and biological barrier. Mechanisms of increasing intestinal epithelial cells, tight junction proteins, and mucins, promoting intestinal stem cell proliferation, restoring the abundance of the intestinal microbiota, and modulating the innate and adaptive immunity in gut, were all involved in. Some upstream proteins and signaling pathways have been elucidated. Based on the existing problems, we suggested future studies paying attention to patients’ samples and animal models of UC and TCM syndromes, conducting rescue experiments, exploring more upstream regulators, and adopting new technical methods. We hope this review can provide a theoretical basis and novel ideas for clarifying the mechanisms of TCM against UC via repairing the intestinal mucosal barrier.

Repairing the intestinal mucosal barrier of traditional Chinese medicine for ulcerative colitis: a review

Introduction: Inflammatory bowel disease (IBD) affects about 7 million people globally, which is a chronic inflammatory condition of the gastrointestinal tract caused by gut microbiota alterations, immune dysregulation, genetic and environmental factors. Nanoparticles (NPs) deliver an active natural compound to a site harbored by disordered microbiota, they are used to interact, target and act intentionally on microbiota. Although there is accumulating evidence indicating that berberine and polysaccharide play an important role in IBD via regulating microbiota, there is limited research that presents a complete picture of exactly how their carrier-free co-assembled nanodrug affects IBD. Methods: The study establishes the carrier-free NPs formed by berberine and rhubarb polysaccharide based on the combination theory of Rheum palmatum L. and Coptis chinensis Franch., and characterizes the NPs. The IBD treatment efficacy of NPs are evaluated via IBD efficacy index, and explore the mechanism of NPs via 16S rRNA test and immunohistochemistry including occludin and zonula occludens-1. Results: The results showed that DHP and BBR were co-assembled to nanoparticles, and the BD can effectively relieve the symptoms of UC mouse induced by DSS via regulating gut microbiota and repair the gut barrier integrity, because BD have a longer retention on the colon tissue and react with the microbiota and mucus thoroughly. Interestingly, BD can enrich more probiotic than free BBR and DHP. Discussion: This design provides a better strategy and encourages future studies on IBD treatment via regulating gut microbiota and the design of novel plant polysaccharide based carrier-free co-assembly therapies.

/pdf/rhubarb-polysaccharide-and-berberine-co-assembled-btoeute2.pdf

Rhubarb polysaccharide and berberine co-assembled nanoparticles ameliorate ulcerative colitis by regulating the intestinal flora

Inflammatory bowel disease (IBD) comprises a group of highly prevalent and chronic inflammatory intestinal tract diseases caused by multiple factors. Despite extensive research into the causes of the disease, IBD's pathogenic mechanisms remain unclear. Moreover, side effects of current IBD therapies restrict their long-term clinical use. In contrast, natural polysaccharides exert beneficial anti-IBD effects and offer advantages over current anti-IBD drugs, including enhanced safety and straightforward isolation from abundant and reliable sources, and thus may serve as components of functional foods and health products for use in IBD prevention and treatment. However, few reviews have explored natural polysaccharides with anti-IBD activities or the relationship between polysaccharide conformation and anti-IBD biological activity. Therefore, this review aims to summarize anti-IBD activities and potential clinical applications of polysaccharides isolated from plant, animal, microorganismal, and algal sources, while also exploring the relationship between polysaccharide conformation and anti-IBD bioactivity for the first time. Furthermore, potential mechanisms underlying polysaccharide anti-IBD effects are summarized, including intestinal microbiota modulation, intestinal inflammation alleviation, and intestinal barrier protection from IBD-induced damage. Ultimately, this review provides a theoretical foundation and valuable insights to guide the development of natural polysaccharide-containing functional foods and nutraceuticals for use as dietary IBD therapies.

Research progress in the treatment of inflammatory bowel disease with natural polysaccharides and related structure-activity relationships.

Background: Various potential effect of drugs on alleviating diseases by regulating intestinal microbiome as well as the pharmaceutical excipients on gut microbiota has been revealed. However, the interaction between them is rarely investigated. Methods: Histological analysis, immunohistochemistry analysis, enzyme-linked immunosorbent assay (ELISA) analysis, RT-qPCR, and 16S rRNA analysis were utilized to explore the effect mechanism of the five excipients including hydroxypropyl methylcellulose (HPMC) F4M, Eudragit (EU) S100, chitosan (CT), pectin (PT), and rheum officinale polysaccharide (DHP) on berberine (BBR) to cure UC. Results: The combined BBR with PT and DHP group exhibited better therapeutic efficacy of UC with significantly increased colon length, and decreased hematoxylin-eosin (H&E) scores than other groups. Furthermore, the expression of tight junction ZO-1 and occludin in colon tissue were upregulated, and claudin-2 was downregulated. Ultimately, the serum content of tumor necrosis (TNF)-α, interleukin (IL)-1β, and IL-6 was decreased. Moreover, the combined BBR with PT significantly promoted the restoration of gut microbiota. The relative abundance of Firmicutes and Lactobacillus was significantly increased by the supplement of PT and DHP, and the relative abundance of Proteobacteria was downregulated. Conclusions: Our study may provide a new perspective that the selection of pharmaceutical excipients could be a crucial factor affecting the drugs’ therapeutic efficiency outcome.

/pdf/effect-and-mechanism-of-pharmaceutical-excipients-on-1hmzu26a.pdf

Effect and Mechanism of Pharmaceutical Excipients on Berberine to Alleviate Ulcerative Colitis via Regulating Gut Microbiota

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Effect and Mechanism of Pharmaceutical Excipients on Berberine to Alleviate Ulcerative Colitis via Regulating Gut Microbiota