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Introduction: Drug dosages and combinations are the main factors that affect the efficacy of pleiotropic traditional Chinese medicine (TCM). Coptis chinensis Franch. (CF) is a representative TCM with multiple effects and is often combined with Tetradium ruticarpum (A. Jussieu) T. G. Hartley (TR) to treat cholestasis. The present study assessed the influence of CF dose and its combination with TR on the efficacy of CF in cholestasis treatment, including their effects on fecal metabolism and fecal microorganisms. Methods: Rats with a-naphthylisothiocyanate (ANIT, 50 mg/kg)-induced cholestasis were administered low (0.3 g/kg) and high (0.6 g/kg) doses of CF, as well as CF combined with TR at doses of 0.6 g/kg and 0.9 g/kg, respectively. The anti-cholestatic effects of these treatments were assessed by determining their anti-inflammatory, hypolipidemic, and anti-oxidative stress properties. Additionally, fecal metabolomics and fecal microorganisms were analyzed. Results: Low dose CF had a more potent hypolipidemic effect than high dose CF, whereas high dose CF had more potent anti-inflammatory and anti-oxidative stress effects. Combination with TR enhanced the hypolipidemic effect, but antagonized the anti-inflammatory effect, of CF. Analyses of fecal metabolomics and fecal microorganisms showed differences in the regulation of lipid- and amino acid metabolism-related pathways, including pathways of linoleic acid, tyrosine, and arachidonic acid metabolism, and amino acid biosynthesis between different doses of CF as well as between different doses of CF in combination with TR. These differences may contribute to differences in the anti-cholestatic effects of these preparations. Conclusion: CF dose influences its anti-cholestatic efficacy. The combination with TR had synergistic or antagonistic effects on the properties of CF, perhaps by altering fecal metabolism and fecal microbial homeostasis. [ABSTRACT FROM AUTHOR]

Pengqi Zhang,1 Tianye Wang,1 Xiaoting Zhu,2 Lina Feng,1 Jiale Wang,1 Yunqiang Li,1 Xinyue Zhang,1 Tingting Cui,1 Mingquan Li2 1College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin Province, People’s Republic of China; 2Neurology Department, Third Affiliated Clinical Hospital of Changchun University of Traditional Chinese Medicine, Changchun, Jilin Province, People’s Republic of ChinaCorrespondence: Mingquan Li, Neurology Department, Third Affiliated Clinical Hospital of Changchun University of Traditional Chinese Medicine, Changchun, 130033, People’s Republic of China, Tel +86-15543120222, Email liminhquan0001@126.comObjective: The objective of this study was to explore the neuroprotective mechanism of JDYZF in treating AD from the perspective of inflammation and intestinal microflora.Methods: A total of 24 APP/PS1 mice were randomly divided into four groups: model (n = 6), JDYZF low-dose (n = 6), JDYZF high-dose (n = 6), and positive drug (n = 6), six C57 mice were used as the control group. The body weights and diets of all mice were examined daily. After 8 weeks of administration, the learning and memory of mice were evaluated by the Morris water maze test. The histopathological changes of hippocampus, liver and kidney in mice were observed by HE staining after being euthanized. The expression of p-tau in hippocampus tissue was detected by immunohistochemistry. After that, 16S rDNA sequencing was used to investigate the relationship between JDYZF and intestinal microbiota. Finally, a comparison of TLR4, p65, p-p65, iκB, p-iκB, and IL-1β protein expression in the hippocampus tissue of mice in each group was measured by Western blot.Results: The results showed that APP/PS1 mice taking JDYZF orally were generally in good condition. Compared with the control group, JDYZF significantly improved learning and memory ability in ethology. Histology showed that JDYZF improved the hippocampal structure of mice and inhibited the deposition of p-tau. JDYZF treatment could regulate the gut microbiota of APP/PS1 mice by increasing the richness of Lachnospiraceae, Ruminococcaceae, and Actinobacteria and reducing that of Alistipes and Muribaculaceae. It also significantly inhibited the activation of the TLR4/NF-κB signaling pathway in the brain. In addition, no obvious toxic reactions were found in the liver and kidney of APP/PS1 mice after taking JDYZF for 8 weeks.Conclusion: The findings revealed that JDYZF improved cognitive ability and alleviated the TLR4/NF-κB signaling pathway in APP/PS1 mice, and the modulating the gut microbiota presented here may help illuminate its activation mechanism.Keywords: Jiedu Yizhi Formula, Alzheimer’s disease, fecal microbial diversity, NF-κB, APP/PS1 mice

Zhuyu pill (ZYP) is a traditional Chinese medicine prescription composed of two drugs, Coptis chinensis Franch. and Tetradium ruticarpum (A. Jussieu) T. G. Hartley, and is commonly used in the clinical treatment of diseases of the digestive system. However, the mechanism underlying the effect of ZYP on colitis remains unclear. In this study, a colitis rat model was induced with 2,4,6-trinitro-benzenesulfonic acid (TNBS, 100 mg/kg) and treated with ZYP (low dose: 0.6 g/kg, high dose: 1.2 g/kg). Disease activity index, colonic weight index, and weight change ratio were used to evaluate the model and efficacy. LC-MS and 16S rRNA gene sequencing were used to measure differences in fecal metabolism and microorganism population among the control, model, lowdose ZYP, and high-dose ZYP groups. To elucidate the mechanism of interventional effect of ZYP, Spearman correlation analysis was used to analyze the correlation between fecal metabolism and fecal microbial number. High-dose and low-dose ZYP both exhibited significant interventional effects on colitis rat models, and high-dose ZYP produced a better interventional effect compared with low-dose ZYP. Based on a metabolomics test of fecal samples, significantly altered metabolites in the model and high-dose ZYP treatment groups were identified. In total, 492 metabolites were differentially expressed. Additionally, sequencing of the 16S rRNA gene in fecal samples revealed that the high-dose ZYP could improve TNBS-induced fecal microbiota dysbiosis. Ultimately, changes in tryptophan metabolism and Firmicutes and Gammaproteobacteria populations were detected after ZYP treatment in both colitis and cholestasis. Therefore, we conclude that tryptophan metabolism and Firmicutes and Gammaproteobacteria populations are the core targets of the anti-inflammatory effect of ZYP. These findings provide a scientific basis for further investigation of the anti-inflammatory mechanism of ZYP in the future. [ABSTRACT FROM AUTHOR]

In this study, the laxative effect of Bacillus coagulans BC01 (BC01) in mice was investigated using a functional constipation mouse model. Six-week-old male specific pathogen-free (SPF) Kunming mice were randomly divided into five groups: normal control group (saline), model group (loperamide hydrochloride), drug control group (bisacodyl), BC01 low-dose group (4.0 × 108 CFU/mL) and BC01 high-dose group (4.0 × 109 CFU/mL). Except for the normal group, the functional constipation model was established by administering 0.25 mL of a loperamide hydrochloride suspension (1 mg/mL) twice daily for four consecutive days by oral gavage. After modeling, the BC01 groups were administered 0.25 mL of BC01. The bisacodyl served as a control and was administered orally at a dose of 100 mg/kg, while the other groups were administered 0.25 mL of sterile saline. After 7 days of continuous administration, the experimental mice were again induced by loperamide hydrochloride. During this period, the mechanism of BC01 to improve constipation symptoms in mice was analyzed by measuring the changes in body weight, fecal water content, small intestine propulsion rate, histology of small intestinal tissue sections, fecal microbial diversity, serum indices, as well as mRNA and protein expression levels in the small intestinal tissue. BC01 was found to significantly promote the intestinal propulsion rate and increase the fecal water content in the mice. BC01 could also alleviates constipation by regulating gastrointestinal motility (substance P, motilin, endothelin-1, somatostatin, and vasoactive intestinal peptide), gene expression (c-Kit, SCF, COX-2, NF-κB, iNOS, and eNOS), intestinal inflammation (eNOS, iNOS, NF-κB), and the intestinal microbiota composition in the constipated mice. In addition, the high-dose BC01 treatment had the best preventive effect on constipation. BC01 is a probiotic strain to effectively relieve the adverse effects of constipation.

Objective To evaluate the effect of feeding acidified milk on the growth and fecal microbial diversity of dairy calves. Methods Twenty healthy 3-day-old female Holstein calves with similar body weights were selected and randomly divided into two groups. One group was fed pasteurized milk (PM, Control), while the other was fed acidified milk (AM) ad libitum until weaned (day 60). The experiment lasted until day 180. Results There was no difference in the nutritional components between PM and AM. The numbers of Escherichia coli and total bacteria in AM were lower than in PM. At 31 to 40 and 41 to 50 days of age, the milk intake of calves fed AM was higher than that of calves fed PM (p

Cholestasis is a clinical condition resulting from impaired bile flow. Currently, patients with cholestasis face several barriers in seeking diagnosis and treatment. Zhuyu Pill (ZYP) is an ancient classic formula of the Coptis-Evodia herb couples (CEHC), and has been used for cholestasis treatment in the clinic, however, its underlying biological activity in cholestasis remain to be clarified. In this study, an α-naphthyl-isothiocyanate (ANIT, 50 mg/kg)-induced rat model of cholestasis was treated with ZYP. Serum biochemical indices and histopathological evaluation was performed, together with the metabolomics analyses of feces and 16S rDNA sequencing of the fecal microbiota. We evaluated the anti-cholestatic activity of ZYP and investigated the mechanisms underlying its correlation with fecal microbiota and fecal metabolite regulation. The relationships between biochemical indices and changes in gene expression associated with liver injury, levels fecal metabolites, and composition of fecal microbiota were analyzed. The results showed that both high (1.2 g/kg) and low (0.6 g/kg) doses of ZYP could effectively improve biochemical parameters in the blood of cholestasis-induced rat models; the intervention effect of high dose ZYP was superior to that that of lower dose ZYP. Based on a metabolomics test of fecal samples, significantly altered metabolites in the ANIT and ZYP treatment group were identified. In total, 734 metabolites were differentially expressed, and whose biological functions were mainly associated with amino acid metabolism, steroid hormone biosynthesis, and bile secretion. In addition, sequencing of the 16S rDNA unit in fecal samples revealed that the ZYP could improve the fecal microbiota dysbiosis that ANIT had induced. Therefore, we conclude that ANIT altering of blood biochemical and metabolic profiles and of fecal microbiota could effectively be alleviated with ZYP treatment. This study contributes to the “TCM wisdom” applied in clinical diagnosis and treatment of cholestasis.

Cholestasis is a clinical condition resulting from impaired bile flow. Currently, patients with cholestasis face several barriers in seeking diagnosis and treatment. Zhuyu Pill (ZYP) is an ancient classic formula of the Coptis-Evodia herb couples (CEHC), and has been used for cholestasis treatment in the clinic, however, its underlying biological activity in cholestasis remain to be clarified. In this study, an α-naphthyl-isothiocyanate (ANIT, 50 mg/kg)-induced rat model of cholestasis was treated with ZYP. Serum biochemical indices and histopathological evaluation was performed, together with the metabolomics analyses of feces and 16S rDNA sequencing of the fecal microbiota. We evaluated the anti-cholestatic activity of ZYP and investigated the mechanisms underlying its correlation with fecal microbiota and fecal metabolite regulation. The relationships between biochemical indices and changes in gene expression associated with liver injury, levels fecal metabolites, and composition of fecal microbiota were analyzed. The results showed that both high (1.2 g/kg) and low (0.6 g/kg) doses of ZYP could effectively improve biochemical parameters in the blood of cholestasis-induced rat models; the intervention effect of high dose ZYP was superior to that that of lower dose ZYP. Based on a metabolomics test of fecal samples, significantly altered metabolites in the ANIT and ZYP treatment group were identified. In total, 734 metabolites were differentially expressed, and whose biological functions were mainly associated with amino acid metabolism, steroid hormone biosynthesis, and bile secretion. In addition, sequencing of the 16S rDNA unit in fecal samples revealed that the ZYP could improve the fecal microbiota dysbiosis that ANIT had induced. Therefore, we conclude that ANIT altering of blood biochemical and metabolic profiles and of fecal microbiota could effectively be alleviated with ZYP treatment. This study contributes to the "TCM wisdom" applied in clinical diagnosis and treatment of cholestasis. [ABSTRACT FROM AUTHOR]