Coptis chinensis and Berberine Ameliorate Chronic Ulcerative Colitis: An Integrated Microbiome-Metabolomics Study.

Coptis chinensis Franch (RC), has historically been used for the treatment of "Xiao Ke" and "Xia Li" symptoms in China. "Xia Li" is characterized by abdominal pain and diarrhea, which are similar to the clinical symptoms of ulcerative colitis (UC). For the first time, this study aims to compare the anti-colitis effects of berberine (BBR) and total RC alkaloids (TRCA) and investigate the underlying metabolites and gut microbiota biomarkers. Metabolomics results showed that several colitis-related biomarkers, including lysophosphatidyl ethanolamine, lysophosphatidylcholine, scopolamine-methyl-bromide, N1-methyl-2-pyridone-5-carboxamide, 4-hydroxyretinoic acid, and malic acid, were significantly improved in model mice after BBR and TRCA treatments. High-dose BBR and TRCA treatments reversed the mouse colon shortening caused by dextran sodium sulfate (DSS), alleviated bowel wall swelling, and reduced inflammatory cell infiltration. BBR and TRCA restored the damaged mucosa integrity in colitis mice by upregulating claudin 1 and occludin, preventing colon epithelium apoptosis by inhibiting the cleavage of caspase 3. Additionally, BBR and TRCA significantly decreased the richness of the pathogenic bacteria Bacteroides acidifaciens but increased the abundance of the probiotic Lactobacillus spp. Notably, TRCA exhibited superior anti-colitis effects to those of BBR. Thus, this agent warrants further study and application in the treatment of inflammatory bowel disease in the clinic.

Study of the Antimicrobial Activity of the Chinese Dong Ethnic Minority Medicine, Madeng'ai.

The overuse of antibiotics has contributed to the emergence of multidrug-resistant bacteria, which poses a challenging task for clinical therapy. Thus, new agents with antibiotic efficacy against multidrug-resistant infections are needed. The traditional Dong ethnic minority medicines have emerged as a new source for prodrug selection. Among them, Madeng'ai (PotentillafreynianaBornm) is widely used by the folk for anti-infection and wound healing, although the mechanisms remain unclear. In this study, the antimicrobial activities of Dong medicine Madeng'ai were evaluated both in vitro and in vivo. S. aureus, E. coli, E. faecalis, P. aeruginosa, K. pneumoniae, and A. baumannii were cultured in LB media, different concentrations of Madeng'ai powder solution were added to the LB agar plates to evaluate minimal inhibitory concentration. An animal study was performed on a mouse excisional wound model combined with bacterial solution injection in the wound area. After Madeng'ai or PBS treatment, hematoxylin and eosin analysis were used for pathological analysis of skin tissues from the infected area. Madeng'ai powder solution over 2 mg/mL concentration completely inhibited E. coli growth. At 4.0 mg/mL, Madeng'ai significantly inhibited the growth of E. faecalis, Pseudomonas aeruginosa (PAE), Klebsiella pneumoniae, and Acinetobacter baumannii. The mouse model revealed that Madeng'ai could suppress the growth of MRSA and PAE and accelerate healing of cutaneous wounds. Madeng'ai, a newly discovered Dong ethnic minority medicine possesses considerable antimicrobial activity against both human normal pathogenic bacteria and multiresistance bacteria such as Pseudomonas aeruginosa, S. aureus, and Acinetobacter baumannii. Therefore, Madeng'ai has great potential for further study and clinical application.

[Research progress on chemical constituents and pharmacological activities of Potentilla].

There are 200-500 species of Potentilla(Rosaceae) worldwide, among which 90 species are widely distributed in China and have a long history of ethnic medicinal use. According to our statistics, a total of 367 compounds have been isolated and identified from plants of this genus, including terpenoids, flavonoids, phenolic acids, tannins, and phenylpropanoids. The medicinal materials made from these plants mainly have antioxidative, blood sugar-lowering, anti-inflammatory, anti-tumor, cardiovascular system-protecting, neuroprotective, and hepatoprotective activities. This study systematically reviews the research progress on chemical constituents and pharmacological activities of Potentilla plants to provide a basis for further research and clinical application.

Water extract of Cayratia albifolia C.L.Li root relieves zymosan A-induced inflammation by restraining M1 macrophage polarization.

BACKGROUND: Cayratia albifolia C.L.Li (CAC) is a traditional Chinese herbal medicine used to treat inflammatory diseases. Our laboratory has firstly reported that the water extract from CAC relieved lipopolysaccharide (LPS)-induced inflammation, however stronger evidence is still needed to prove its anti-inflammatory effects and the mechanisms involved are also ambiguous. PURPOSE: This study sought to provide more evidence for the application of CAC in alleviating infectious inflammation and disclose novel pharmacological mechanisms. METHODS: Mice were injected with zymA into their paws or peritoneal cavities, and then treated with CAC. ELISA, immunofluorescence and flow cytometry were performed to detect the cytokines (IL-1ß, IL-6, TNF-α and IL-10) generation, the cell infiltration, and the CD86 or CD206 expression of macrophages. Then in vitro assays were performed on bone marrow-derived macrophages (BMDMs) and peritoneal macrophages (PMs) to detect their expression of iNOS, arg-1 and the cytokines above. On mechanisms, western blotting (WB), electrophoretic mobility shift assay (EMSA) and flow cytometry were carried out to measure NF-κB transcriptional activity, mitochondrial bioactivity and the mTORC1 activation when BMDMs were stimulated by zymA and treated with CAC. Finally, the chemical components consisted in the extract were analyzed by LC-MS. RESULTS: 200 mg/kg CAC clearly inhibited zymA induced mouse paw edema and reduced the contents of IL-1ß, IL-6 and TNF-α rather than IL-10 in local tissues. CAC also reduced CD86 but not CD206 in macrophages in situ. Through in vitro experiments, it was discovered that CAC reduced the protein and mRNA levels of IL-1ß, IL-6 and TNF-α, and also inhibited iNOS expression, but showed no influence on IL-10 and arg-1 in macrophages. We found CAC reduced NF-κB transcriptional activity, down-regulated mitochondrial membrane potential and ROS levels, and inhibited mTORC1 activity. Finally, we identified 15 major compounds in the extract, among which 4-guanidinobutyric acid and kynurenic acid were the most abundant. CONCLUSION: This study provides further evidence that CAC significantly reduces zymA induced infectious inflammation. In addition, this novel data revealed that CAC restrained M1 rather than promoting M2 macrophages polarization via multi-target inhibitory effects, based on its potentially active components.

Rapid Identification and Systematic Mechanism of Flavonoids from Potentilla freyniana Bornm. Based on UHPLC-Q-Exactive Orbitrap Mass Spectrometry and Network Pharmacology.

Potentilla freyniana Bornm. (P. freyniana), belonging to the family Rosaceae, has been used as a folk medicine in China. However, as we know, the constituents and the systematic elucidation of the mechanism were not fully investigated. Therefore, it is necessary to develop a rapid method using LC-MS and network pharmacology for the detection and identification of constituents and the systematic mechanism of P. freyniana. Firstly, the flavonoids were detected and identified based on ultra-high-performance liquid chromatography coupled with Quadrupole-Exactive Focus Orbitrap MS (UHPLC-Q-Exactive Orbitrap MS). After that, the potential targets of those constituents were obtained by database mining. Then, the core targets were predicted by protein-protein interaction network and network analysis. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out via DAVID. This finding revealed that P. freyniana possessed 43 flavonoids (40 of them were first reported) with 23 core target genes, which are associated with PI3K-Akt, MAPK, TNF signaling pathway, and pathway in cancer. This study demonstrated the multicompound, multitarget, and multimechanism of P. freyniana, which are very beneficial to develop the further study and utilization of this plant including the material basis and quality control research.

The water extract of "Jiao Mei Gu" attenuates the lipopolysaccharide-induced inflammatory response via inhibiting NF-κB activity in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiao Mei Gu (JMG), Cayratia albifolia C.L.Li, is a type of Dong plant widely growing in Dong autonomous counties, Hunan province, China. As a type of traditional herbal medicine, the root of JMG plant has been used to treat inflammatory-related diseases such as arthritis because of its prominent anti-inflammatory effects in Dong medicine. AIM OF THE STUDY: This work investigated the anti-inflammatory effects and mechanisms of the water extract from the root of JMG on lipopolysaccharide (LPS)-induced inflammatory models. METHODS: Endotoxemia was induced in C57BL/6 mice by intraperitoneal injection of LPS (20 mg/kg), meanwhile intraperitoneal administration of safe doses of JMG. The survival curve of mice was determined. Serum inflammatory cytokines were detected by the Bio-Plex Mouse Cytokine 23-Plex Panel Kit and enzyme-linked immunosorbent assay (ELISA) at 6 h after drug treatment. Hematoxylin-eosin (HE) staining of important organs was completed at 24 h after treatment. The mechanism of inflammatory action was investigated in vitro on LPS-stimulated macrophages. Macrophage inflammation was then induced using 10 µg/mL LPS. The anti-inflammatory effect of JMG was investigated by the quantitative polymerase chain reaction (qPCR) and ELISA. The anti-inflammatory mechanism was determined using western blotting, the electrophoretic mobility shift assay, and immunocytochemistry. Finally, the antimicrobial activity of JMG was verified by survival experiments in vivo and by bacterial culture experiments in vitro. RESULTS: A 200 mg/kg water extract of JMG was safe for mice and had a significant protective effect on LPS-induced sepsis. Organ damage of heart, liver, lung and kidney was also significantly reduced at 24 h in the JMG group, when compared with the LPS group. The serum MIP-1α (CCL-3), MIP-1ß (CCL-4), IL-1ß, and TNFα cytokines were significantly decreased at 6 h in the JMG group, when compared with the LPS group. In a similar manner, 0.2µg/ml JMG significantly reduced mRNA and protein levels of MIP-1α (CCL-3), MIP-1ß (CCL-4), IL-1ß, and TNFα in LPS-stimulated macrophage. JMG treatment inhibited the phosphorylation of NF-κB p65 and reduced nuclear transduction, thus reducing transcriptional activity. At the same time, we showed that JMG had no protective effect on Escherichia coli-induced sepsis, as well as no antimicrobial activity. CONCLUSIONS: Our results showed that a water-soluble extract of JMG inhibited LPS-induced inflammation via attenuating the NF-κB signaling pathway, which provides an important rationale for the treatment of inflammation-related diseases.

Hypolipidemic effects of Myrica rubra extracts and main compounds in C57BL/6j mice.

The present study evaluated the antihyperlipidemic activity of myricetin, myricetrin, the alcohol fraction (AF) and the ethyl acetate fraction (EF) obtained from the bark of Myrica rubra (MR) in high-fat and high-cholesterol (HFHC) induced hyperlipidemic C57BL/6j mice. Mice were treated with myricetin, myricetrin, AF and EF with a dose of 130 mg per kg per day for 35 days. After treatment, serum parameters including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), total bile acids (TBA), etc., were examined. The results revealed that EF showed the highest weight lowering activity (P < 0.01). All tested samples decreased the levels of the TC, TG, LDL-C, TBA and LPS (lipopolysaccharide) content in the serum of mice to different extents. Liver fat deposition was significantly reduced after myricetin, myricetrin, AF and EF therapy (P < 0.01). Additionally, the cell size of epididymal adipose tissue was also decreased in myricetin, AF and EF groups (P < 0.05). The antihyperlipidemic activity of these samples may be attributed to the inhibition of lipid synthesis via suppressing the expression of HMGCR (3-hydroxy-3-methylglutaryl coenzyme A reductase) and ACC1 (acetyl-CoA carboxylase), promoting the metabolism and excretion of lipids via up-regulating the expression of SREBP2 (sterol regulatory element binding proteins), LDLR (low density lipoprotein receptor), UCP2 (uncoupling protein 2) and CYP7A1 (cholesterol 7α-hydroxylase). These results may provide a powerful foundation for seeking and utilizing Myrica rubra bio-active compounds for the treatment of hyperlipidemia and cardiovascular diseases.

Synergy effects of herb extracts: pharmacokinetics and pharmacodynamic basis.

Herbal medicine, especially traditional Chinese medicine and Ayurvedic medicine have played and still play an important role in fighting against various diseases. Emerging clinical studies regarding traditional Chinese medicine have provided convincing evidence for the first time to gain credibility and reputation outside China. Although synergistic therapeutic actions of herbal ingredients have been frequently reported, few reports have offered clear underlying mechanisms. This might be the main reason for the conflicting views with respect to the therapeutic efficacy of medicinal herbs. Therefore, this paper reviews the herb synergisms reported in the recent literature and discusses thoroughly the mechanisms underlying synergistic actions of herbal ingredients. The authors conducted an electronic literature search to detect articles published mainly in the last five years. Articles were included if they pertained to synergy research of ethnomedicines or the active compounds derived from them, included verification of synergy effects using modern analytical tools and molecular-biological methods. Results have revealed that the multi-component nature of medicinal herbs makes them particularly suitable for treating complex diseases and offers great potential for exhibiting synergistic actions. The mechanisms underlying synergistic therapeutic actions of herb medicines are (1): different agents may regulate either the same or different target in various pathways, and therefore cooperate in an agonistic, synergistic way; (2): regulate the enzymes and transporters that are involved in hepatic and intestinal metabolism to improve oral drug bioavailability; (3): overcome the drug resistance mechanisms of microbial and cancer cells; and (4): eliminate the adverse effects and enhance pharmacological potency of agents by "processing" or by drug-drug interaction. The exploration of synergistic mechanisms of herbal ingredients will not only help researchers to discover new phytomedicines or drug combinations but also help to avoid the possible negative synergy. Further clinical research is required for verifying these reported drug combinations and discovered synergistic mechanisms.

[A randomized controlled trial study of pulmonary rehabilitation with respiratory physiology as the guide on prognosis in patients with chronic obstructive pulmonary disease].

OBJECTIVE: To observe the effect of pulmonary rehabilitation with respiratory physiology as guide in patients with chronic obstructive pulmonary disease (COPD). METHODS: Sixty patients of severe and very severe COPD as categorized by global proposed diagnostic criteria for COPD (GOLD, 2006) were enrolled for study. They were randomly divided into three groups, and with 20 patients in each group. The patients in group A were given pulmonary rehabilitation guided by respiratory physiology thrice a day, 15 minutes each time for 8 weeks. The patients in group B were given pulmonary rehabilitation with pursed lip respiration thrice a day, 15 minutes per time for 8 weeks. The patients in group C were given no pulmonary rehabilitation. Six minute-walk-distance (6MWD), medical research council (MRC) dyspnea scale, activities of daily living (ADL), maximal expiratory pressure (MEP), maximal inspiratory pressure (MIP), and quality of life (QOL) were determined before and after respective pulmonary rehabilitation course. RESULTS: (1) There were 3, 5, 5 patients in group A, group B, group C dropped off in the course of rehabilitation respectively. (2) The patients' MRC grade after pulmonary rehabilitation in group A and group B decreased compared with that before pulmonary rehabilitation (both P<0.01), but the difference was not significant between two groups (P>0.05). (3) 6MWD, ADL, MEP, MIP of patients in group A and group B increased after pulmonary rehabilitation compared with that before pulmonary rehabilitation, and 6MWD, ADL, MEP, MIP of patients in group A were increased after pulmonary rehabilitation more than those in group B (P<0.05 or P<0.01). (4)The patients' body status, shortness of breath, social activity, home chores in group A and group B, and uneasiness in group A after pulmonary rehabilitation were improved more than those before pulmonary rehabilitation (P<0.05 or P<0.01), but the difference in state of mind, headache, appetite was not markedly different before and after pulmonary rehabilitation in two groups (all P>0.05). The difference in QOL was not marked between group A and group B after pulmonary rehabilitation (all P>0.05). CONCLUSION: (1) The pulmonary rehabilitation with pursed lip respiration and the pulmonary rehabilitation with the guide of respiratory physiology ameliorates dyspnea, improves ADL, QOL, exercise tolerance, function of respiratory muscle in the severe and very severe COPD patients remarkably. (2) The effect of the pulmonary rehabilitation with the guide of respiratory physiology is better than that of the pulmonary rehabilitation with pursed lip respiration, and it can be considered as a more effective pulmonary rehabilitation method for the patients with severe and very severe COPD.