Main active components of Jiawei Gegen Qinlian decoction protects against ulcerative colitis under different dietary environments in a gut microbiota-dependent manner.

As an effective drug against acute enteritis diarrhea, Gegen Qinlian decoction (GQD) has a history of 2000 years. However, the potential molecular mechanism through which GQD could protect intestinal barrier from ulcerative colitis (UC) still remains undefined. As an important part of the homeostasis of the colon, gut microbiota is closely related to the dynamic evolution of the surrounding environment and the adjustment of dietary structure. At present, the effectiveness and mechanism of Jiawei Gegen Qinlian decoction against UC in different dietary environments are not clear. Here, the main active components of Jiawei Gegen Qinlian Decoction (PBM), were selected to construct a reasonable and effective compound scheme. We adopted "5% dextran sulfate sodium (DSS)" and "high temperature and humidity + high sugar and high fat + alcohol + 5%DSS" to induce UC rat models in general environment and UC rat models in Lingnan area, respectively. Then, we examined the therapeutic effects of PBM (89.96 mg/kg and 179.92 mg/kg) on two kinds of UC rats. The role of gut microbiota in the anti-UC effect of PBM was identified by intestinal flora consumption and fecal microbiota transplantation (FMT) experiments. Subsequently, we monitored the alterations of gut microbiota and fecal metabolism in the rat colon by 16Sr DNA technique and targeted metabonomics, respectively. The colon inflammation of the PBM-treated and the FMT-treated rats both showed significant relief, as evidenced by a reduction in body weight loss, bloody stool, diarrhea, disease activity index (DAI) score, shortening of colon length as well as decreased colon histology damage. Interestingly enough, the depletion of intestinal flora took away the protective effect of PBM, confirming the importance of intestinal flora in the anti-UC effect of PBM. Then our findings suggested that PBM could not only regulate the gut microbiota by increasing Akkermansia and Romboutsia but also decrease Escherichia-Shigella. More importantly, PBM could increase the production of propionate and total short-chain fatty acids (SCFAs) in colitis rats, regulate medium and long chain fatty acids (M-LCFAs), maintain bile acids (BAs) homeostasis, and regulate amino acids (AAs) metabolism. The transformation of intestinal environment might be related to the upregulation of anti-inflammation, anti-oxidation and tight junction protein expression in colonic mucosa. In summary, PBM showed potential for anti-UC activity through gut microbiota dependence and was expected to be a complementary and alternative medicine herb therapy.

Carboxymethylated Abrus cantoniensis polysaccharide prevents CTX-induced immunosuppression and intestinal damage by regulating intestinal flora and butyric acid content.

As a Chinese folk health product, Abrus cantoniensis exhibits good immunomodulatory activity because of its polysaccharide components (ACP), and carboxymethylation of polysaccharides can often further improve the biological activity of polysaccharides. In this study, we explored the impact of prophylactic administration of carboxymethylated Abrus cantoniensis polysaccharide (CM-ACP) on immunosuppression and intestinal damage induced by cyclophosphamide (CTX) in mice. Our findings demonstrated that CM-ACP exhibited a more potent immunomodulatory activity compared to ACP. Additionally, CM-ACP effectively enhanced the abundance of short-chain fatty acid (SCFA)-producing bacteria in immunosuppressed mice and regulated the gene expression of STAT6 and STAT3 mediated pathway signals. In order to further explore the relationship among polysaccharides, intestinal immunity and intestinal flora, we performed a pseudo-sterile mouse validation experiment and fecal microbiota transplantation (FMT) experiment. The findings suggest that CM-FMT and butyrate attenuate CTX-induced immunosuppression and intestinal injury. CM-FMT and butyrate show superior immunomodulatory ability, and may effectively regulate intestinal cell metabolism and repair the damaged intestine by activating STAT6 and STAT3-mediated pathways. These findings offer new insights into the mechanisms by which CM-ACP functions as functional food or drug, facilitating immune response regulation and maintaining intestinal health.

The Protective Effects of Three Polysaccharides From Abrus cantoniensis Against Cyclophosphamide-Induced Immunosuppression and Oxidative Damage.

This study was designed to systematically elucidate the immunomodulatory and antioxidant effects of three polysaccharide fractions (ACP60, ACP80, and ACPt2) from Abrus cantoniensis on cyclophosphamide (CTX)-induced immunosuppressive mice. The experimental mice were divided into 12 groups, then modeled and administrated with different doses of three polysaccharides (50, 150, 300 mg/kg/day) by gavage. The results showed that ACP could markedly recover the CTX-induced decline in immune organ and hemocytes indexes and promote proliferation of splenocytes, earlap swelling rate, secretion of cytokines (TNF-α, IFN-γ, IL-1ß, IL-6), and immunoglobulin (Ig-M and Ig-G). Additionally, ACP improved the enzymatic activities of T-SOD and GSH-PX greatly, while the level of MDA was significantly decreased in the liver. In particular, ACPt2 had higher immunomodulatory and antioxidant activities than ACP60 and ACP80. Based on the present findings, ACP could be utilized as an efficacious candidate for immunomodulators and antioxidants, which provide a new application prospect in the food and pharmaceutical industries.

Characterization and macrophages immunomodulatory activity of two water-soluble polysaccharides from Abrus cantoniensis.

The study aims to elucidate the physicochemical properties and immunomodulatory activity of two polysaccharides (ACP t0 and ACP t2) from Abrus cantoniensis. Results revealed that ACP t0 with a molecular weight of 26.0 kDa, was mainly composed of glucose (83.1%) and galactose (6.1%), and that ACP t2 with a molecular weight of 145.6/8.9 kDa, consisted of galactose (25.6%), galacturonic acid (22.2%), arabinos (16.6%) and galactose (11.0%) respectively. AFM and Congo red experiments suggested that ACP t0 and ACP t2 might be spherical particles with triple-helix conformation in aqueous solution. ACP t0 and ACP t2 exhibited immunomodulatory activity by promoting the proliferation, augmenting pinocytic and phagocytic capacities, releasing immunoactive molecules such as ROS, NO, iNOS, TNF-α, IL-6 and IL-1ß, upregulation of the mRNA levels of corresponding cytokines in macrophages. Moreover, ACP t0 and ACP t2 were recognized by toll-like receptor 4 (TLR4) and exerted immunomodulatory effects via activating Myeloid differentiation factor 88 (MyD88), mitogen-activated protein kinases (MAPKs) and serine/threonine kinase (Akt) signaling pathways in macrophages. Notably, ACP t2 had higher immunomodulatory activity than ACP t0. Based on the present findings, ACP t0 and ACP t2 could be explored as an active component of immunomodulators in the food and pharmaceutical fields.

Effects of Different Sources of Calcium in the Diet on Growth Performance, Blood Metabolic Parameters, and Intestinal Bacterial Community and Function of Weaned Piglets.

Despite a well-documented effect of calcium on the piglet's intestinal microbiota composition, it is less known about changes in microbial function or the effect of different sources of calcium. The experiment was designed to study the effects of dietary calcium from different sources on production, immune indexes, antioxidant capacity, serum biochemical indexes, and intestinal microflora of weaning piglets. A total of 1,000 piglets were randomly assigned to five groups (10 replicate pens per treatment with 20 pigs per pen) and fed diets supplemented with calcium carbonate, calcium citrate, multiple calcium, organic trace minerals, and different concentrations of acidifier. The results showed that the replacement of calcium carbonate with calcium citrate and multiple calcium had almost no significant difference in the growth performance of pigs compared with the control group, and only the diet of multiple calcium dramatically decreased the average daily feed intake (ADFI) compared to the calcium citrate diet on days 15-28 (p < 0.05). The five groups did not change the content of MDA, SOD, and GSH-Px (p > 0.10). A similar situation occurs in the immune function of the blood. There was no significant effect in immune indexes (IgA, IgG, and IgM) among different treatments after weaning at 6 weeks for piglets (p > 0.10). The 16S rRNA sequencing of ileal and cecal microbiota revealed that only the relative abundance of Actinobacteriota at the phyla level was significantly greater in the ileum of the A group compared to the other treatments (p < 0.05). There was a clear effect on seven bacteria in the top 30 genera of ileum and cecum for five groups (p < 0.05). The result of PICRUSt predicted that the intestinal microbe was mainly involved in carbohydrate and amino acid metabolism, membrane transport, and metabolism of cofactors and vitamins. Besides, adding calcium citrate to a weaned piglet diet is better than other choices from the third week to the fourth week. In conclusion, diets with different calcium sources changed ADFI and some intestinal microbial composition of weaned piglets but had little effect on intestinal microbial function.