Intestinal flora and osteoporosis and exercise intervention / 中国组织工程研究

BACKGROUND:Intestinal flora and its metabolites can participate in the pathological process of osteoporosis and play an important role in the diagnosis and treatment of osteoporosis.In addition,exercise can regulate the intestinal flora and thus affect the occurrence and development of osteoporosis. OBJECTIVE:To summarize the effects and mechanism of intestinal flora on osteoblasts,osteoclasts,and bone marrow mesenchymal stem cells,and the potential role of exercise-mediated intestinal flora in regulating osteoporosis. METHODS:"Intestinal flora,intestinal bacteria,metabolites of intestinal flora,bone metabolism,osteoporosis,exercise"were selected as keywords.Literatures from 1990 to 2023 were retrieved from PubMed and CNKI databases. RESULTS AND CONCLUSION:Changes in the abundance and diversity of intestinal flora and changes in the levels of intestinal flora metabolites such as trimethylamine oxide and bile acid can be used as biomarkers for the diagnosis of osteoporosis.The imbalance of intestinal flora can lead to intestinal barrier dysfunction and excessive production of lipopolysaccharides and trimethylamine oxide,induce the secretion of tumor necrosis factor-α and other inflammatory cytokines,activate the nuclear factor κB signaling pathway and aggravate oxidative stress,thus promoting osteoclast differentiation,inducing osteoblast apoptosis and affecting bone marrow mesenchymal cell migration.Remodeling intestinal flora homeostasis can inhibit inflammatory response,downregulate oxidative stress,inhibit osteoclast differentiation,promote osteoblast differentiation,and regulate the osteogenic migration of bone marrow mesenchymal cells to prevent and treat osteoporosis.Exercise can regulate intestinal flora homeostasis,improve intestinal barrier function,promote the secretion of short-chain fatty acids and bile acids,down-regulate serum lipopolysaccharide level,reduce oxidative stress,and then inhibit osteocyte apoptosis,inhibit osteoclast differentiation,promote osteoblast differentiation,and regulate osteocyte nutrient metabolism to exert the potential of preventing and treating osteoporosis.

Content assay and metabolic study of flavonoids from Citrus reticulata 'Chachi' / 药学学报

In this study, a high-performance liquid chromatography method was established to simultaneously determine three flavonoids including hesperidin (HES), nobiletin (NOB) and tangeretin (TAN) in 10 batches of Citrus reticulata 'Chachi' planted and collected in Xinhui District, Jiangmen City, Guangdong Province. Moreover, we studied the metabolism and transformation of three flavonoids in liver and intestinal flora in vitro, and sequenced 16S rRNA of bacteria flora samples after incubation. The RP-HPLC system consisted of Alltima C18 column (250 mm × 4.6 mm, 5 μm) and a mobile phase of water (A) - methanol (B). The column temperature was 25 ℃ and the detection wavelength was both 283 nm and 330 nm while the flow rate was 1.0 mL·min-1. The results showed that the retention time of HES, NOB and TAN ranged from 12.313 min to 34.271 min. The content of HES, NOB and TAN in 10 batches of Citrus reticulata 'Chachi' was 26.81-39.80 mg·g-1, 4.06-7.90 mg·g-1 and 1.81-3.93 mg·g-1, respectively. There were differences in the content of flavonoids in different batches and growing areas. The three flavonoids were metabolized in various degrees after incubation of rat and human liver S9, cytosol, microsomes or intestinal flora in vitro, especially HES. The results of 16S rRNA showed that the main flavonoids of Citrus reticulata 'Chachi' could regulate lipid metabolism by regulating intestinal flora related to energy metabolism. This study established a rapid, simple, reproducible and stable quantitative analysis method for detecting the main flavonoids in Citrus reticulata 'Chachi' which evaluated the content of flavonoids from Citrus reticulata 'Chachi' in different growing areas and different storage periods. The intestinal bacteria can metabolize and transform the flavonoids of Citrus reticulata 'Chachi' to varying degrees, which provides a valuable scientific basis for the subsequent study on the material basis of the efficacy of Citrus reticulata 'Chachi' from the perspective of metabolism. Animal experiments were approved by the Medical Ethics Committee of Guangdong Jiangmen Chinese Medicine College (No. 20190419).

Recent advances in intestinal flora characteristics and sexual dimorphism during puberty / 中国学校卫生

Abstract@#Gut flora undergoes a dynamic colonization and development process at different stages of human life. Sex specific gut flora development begins during puberty, which is influenced by sex hormone levels. The potential relationship between sex hormone levels, which suggests that there may be a two way interaction between intestinal flora and sex hormones. In addition, evidence is emerging for bidirectional effects of the microbiome in human health. Therefore, the review presents the dimorphism of intestinal flora, the characteristics of intestinal flora during puberty and the latest research progress, explores the close relationship between intestinal flora and precocious puberty and reproductive system diseases, and further explains the influence mechanism and treatment measures of considering gender factors in intestinal microflora, precocious puberty and reproductive system related diseases.

Isolation and identification of cholesterol-degrading intestinal bacteria by culturomics and evaluation of their functions / 生物工程学报

High cholesterol is one of the important factors inducing cardiovascular and cerebrovascular diseases. Drug therapy is the main method for reducing cholesterol, but has the disadvantages such as high cost and side effects. Studies have shown that intestinal bacteria play important roles in cholesterol metabolism. However, there are few reports on the screening and functional evaluation of cholesterol-lowering intestinal bacteria. In this study, 36 bile-tolerant bacteria were screened from healthy people stool through culturomics using bovine bile acid or artificial mixed bile acids as substrates. Taking Lactobacillus rhamnosus GG (LGG) as a positive control, three bile acid concentration groups (0 g/L, 0.3 g/L, 3 g/L) were set up to evaluate the cholesterol-lowering ability of bile-tolerant bacteria in vitro. Ten bacteria (including Proteus mirabilis, Providencia stuartii, Proteus vulgaris et al) were identified as the dominant cholesterol-lowering bacteria. Six of the above bacteria, Proteus mirabilis, Providencia stuartii, Proteus vulgaris, Proteus penneri, Wohlfahrtiimonas chitiniclastica, Providencia rettger, were evaluated for their ability to reduce triglycerides in vitro and tolerance to artificial gastric juice. Comparing with strain LGG, the six bacteria showed better triglyceride-lowering ability in vitro. With the decrease of pH value of artificial gastric juice and the increase of treatment time, the survival rate of six bacteria decreased. The above screening experiments and functional evaluation provide a basis for further development of potential cholesterol-lowering bacterial products.

Clinical analysis of fecal microbiota transplantation for the treatment of radiation intestinal injury / 国际外科学杂志

Objective To evaluate the efficacy and safety of fecal microbiota transplantation for radiation intestinal injury.Methods Retrospective analysis of the clinical data of 32 radiation intestinal injury patients including 6 males and 26 females,aged (59.4 ± 9.5) years,with an age range of 51-86 years who underwent fecal microbiota transplantation from August 2017 to August 2018 in the Intestinal Microenvironment Treatment Centre,Tenth People's Hospital of Tongji University was performed.The efficacy (cure rate,improvement rate),nutritional indicators (body weight,albumin,hemoglobin),inflammation index (C-reactive protein),gastrointestinal quality of life index score and adverse events were compared after 1 year of fecal microbiota transplantation.The patients were followed up for 1 year by telephone,outpatient and network.The follow-up was carried out in combination with the above-mentioned effectiveness and safety indicators.The time was until August 2019.The measurement data were expressed as mean ± standard deviation (Mean ± SD),the count data were expressed as percentage.The paired t test was used for comparison between groups.Results The clinical cure rate and clinical improvement rate of patients who received fecal microbiota transplantation for 1 year were 56.3％ and 15.6％,respectively.Body weight increased from pre-treatment (53.7 ± 9.6) kg to (60.8 ± 2.1) kg after 1 year of fecal microbiota transplantation,albumin increased from pre-treatment (30.7 ± 4.6) g/L to (37.5 ± 3.8) g/L after 1 year of fecal microbiota transplantation,and hemoglobin increased from pre-treatment (108.5 ± 13.1) g/L to (123.3 ± 13.4) g/L after 1 year of fecal microbiota transplantation.C-reactive protein decreased from pre-treatment (24.1 ±4.5) mg/L to (3.2 ±4.5) mg/L after 1 year of fecal microbiota transplantation.Gastrointestinal quality of life index scores were significantly increased after fecal microbiota transplantation,from (88.4 ± 7.1) scores to (112.2 ± 3.2) scores after 1 year of fecal microbiota transplantation.No serious adverse events occurred during the whole follow-up.The difference was statistically significant (P ＜ 0.05).Conclusions Fecal microbiota transplantation techndogy is effective and safe for radiation intestinal injury patients,which is worthy of clinical research.

Diagnosis and treatment value of detecting fecal primary and secondary bile acid in infants with infantile cholestatic hepatopathy / 中国实用儿科杂志

OBJECTIVE: To detect the level of fecal primary and secondary bile acids in infants with infantile cholestatic hepatopathy(ICH)and analyze its clinical value. METHODS: Thirty infants with ICH were enrolled in this study,who were diagnosed with infantile cholestatic hepatopathy. Thirty infants with good health condition were enrolled as the healthy control group. The fecal samples were collected respectively in the preparatory treatment phase and treatment phase from infants with ICH and from the healthy infants. Bile acids were extracted from infants' feces and were quantitatively analyzed by liquid chromatography-mass spectroscopy. RESULTS: Among the fecal primary bile acids,the level of cholic acid,chenodeoxycholic and glycochenodeoxycholic acid both in the ICH preparatory treatment group and ICH treatment group was significantly lower than that in the healthy control group(P<0.016).The level of fecal cholic acid and chenodeoxycholic acid of ICH treatment group was higher than in the ICH preparatory treatment group(P<0.016).Among the fecal secondary bile acids,the level of lithocholic acid both in the ICH preparatory treatment group and ICH treatment group was significantly lower than that in the healthy control group(P<0.016),and the level of ursodeoxycholic acid in the ICH preparatory treatment group was lower than that in the ICH treatment group and healthy control group(P<0.016). CONCLUSION: In infants with ICH, the changes of fecal primary bile acids and fecal secondary bile acids have their own characteristics at the early stage of treatment, which may be caused by the short-term treatment,the prognosis of the disease itself and the changes of intestinal function, including intestinal bacteria. Clinical attention should be paid to these changes.

Clinical analysis of fecal microbiota transplantation for the treatment of radiation intestinal injury / 国际外科学杂志

Objective@#To evaluate the efficacy and safety of fecal microbiota transplantation for radiation intestinal injury.@*Methods@#Retrospective analysis of the clinical data of 32 radiation intestinal injury patients including 6 males and 26 females, aged (59.4±9.5) years, with an age range of 51-86 years who underwent fecal microbiota transplantation from August 2017 to August 2018 in the Intestinal Microenvironment Treatment Centre, Tenth People′s Hospital of Tongji University was performed. The efficacy (cure rate, improvement rate), nutritional indicators (body weight, albumin, hemoglobin), inflammation index (C-reactive protein), gastrointestinal quality of life index score and adverse events were compared after 1 year of fecal microbiota transplantation. The patients were followed up for 1 year by telephone, outpatient and network. The follow-up was carried out in combination with the above-mentioned effectiveness and safety indicators. The time was until August 2019. The measurement data were expressed as mean±standard deviation (Mean±SD), the count data were expressed as percentage. The paired t test was used for comparison between groups.@*Results@#The clinical cure rate and clinical improvement rate of patients who received fecal microbiota transplantation for 1 year were 56.3% and 15.6%, respectively. Body weight increased from pre-treatment (53.7 ± 9.6) kg to (60.8 ± 2.1) kg after 1 year of fecal microbiota transplantation, albumin increased from pre-treatment (30.7±4.6) g/L to (37.5±3.8) g/L after 1 year of fecal microbiota transplantation, and hemoglobin increased from pre-treatment (108.5±13.1) g/L to (123.3±13.4) g/L after 1 year of fecal microbiota transplantation. C-reactive protein decreased from pre-treatment (24.1±4.5) mg/L to (3.2±4.5) mg/L after 1 year of fecal microbiota transplantation. Gastrointestinal quality of life index scores were significantly increased after fecal microbiota transplantation, from (88.4±7.1) scores to (112.2±3.2) scores after 1 year of fecal microbiota transplantation. No serious adverse events occurred during the whole follow-up. The difference was statistically significant (P<0.05).@*Conclusions@#Fecal microbiota transplantation techndogy is effective and safe for radiation intestinal injury patients, which is worthy of clinical research.

Relationship between akkermansia muciniphila and obesity / 第二军医大学学报

Akkermansia muciniphila (A. muciniphila) is a normal flora of human gastrointestinal tract. The A. muciniphila abundance of intestinal flora in obese patients is significantly decreased. Many evidences suggest that A. muciniphila is negatively related to obesity, diabetes, cardiovascular diseases and low-grade inflammation. A. muciniphila not only plays a metabolic protective role by protecting the integrity of intestinal epithelial cells and mucus layer, but also plays an anti-inflammatory role by regulatory T cells, endogenous cannabinoid system and non-classical Toll-like receptor in the process of inflammatory reaction. This article reviews the relationship between A. muciniphila and obesity, and the molecular mechanism and application of A. muciniphila in obesity.

Effect of intestinal bacteria on motor function and its mechanism in amyotrophic lateral sclerosis mice / 中华神经医学杂志

Objective To study the effect of intestinal bacteria on motor ability of amyotrophic lateral sclerosis (ALS) mice models and its mechanism. Methods Twenty wild type C57BL/6J mice (WT group) and 20 SOD1-G93A transgenic ALS mice (ALS group) were selected as the research subjects. (1) Ten mice in both WT group and ALS group were selected, respectively; 5 mice in each group were fed in SPF environment, and the remaining 5 mice were fed in aseptic environment; they were defined as WT+SPF group, WT+aseptic group, ALS+SPF group and ALS+aseptic group. (2) Ten mice in WT group and ALS group were fed in sterile environment; 5 mice in each group were transplanted with fecal bacteria, and the remaining 5 mice were not interfered; they were defined as WT+transplantation group, WT+non-transplantation group, ALS+transplantation group and ALS+non transplantation group. The grip strength of mice was measured by grip force meter, the motor coordination ability of mice was tested by roller treadmill and rotating rod test, the number of motor neurons in the anterior horn of spinal cord was measured by Nissl staining, the expression of microglia activation marker ionic calcium junction protein (IBA-1) in spinal cord tissues was detected by immunohistochemical staining, and the expressions of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in spinal cord tissues were detected by Western blotting; the β-N-methylamino-L-alanine (BMAA) expression was detected by high performance liquid chromatography-tandem mass spectrometry. Results (1) The grip strength, drop latency and drop time of ALS+aseptic mice were significantly higher than those of ALS+SPF mice, the number of Nissl-stained positive cells was significantly larger than that of ALS+SPF mice, the number of IBA-1 positive cells was significantly smaller than that of ALS+SPF mice, the levels of TNF-α and IL-6 protein expressions and BMAA concentration were statistically lower than those of ALS+SPF mice (P<0.05). (2) The grip strength, drop latency and drop time of ALS+transplantion mice were significantly lower than those of ALS+non-transplantation mice, the number of Nissl-stained positive cells was significantly smaller than that of ALS+non-transplantation mice, the number of IBA-1 positive cells was significantly larger than that of ALS+non-transplantation mice, the TNF-α and IL-6 protein expressions and BMAA concentration were significantly higher than those of ALS+non-transplantation mice (P<0.05). Conclusion Imbalance of intestinal bacteria homeostasis can decrease the motor ability of ALS mice, which is related to the activation of microglia.

UPLC-Q-TOF-MS-based metabolomics study of celastrol / 中国中药杂志

The mass spectrometry-based metabolomics method was used to systematically investigate the formation of celastrol metabolites,and the effect of celastrol on endogenous metabolites. The mice plasma,urine and feces samples were collected after oral administration of celastrol. Ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry( UPLC-QTOF-MS) was applied to analyze the exogenous metabolites of celastrol and its altered endogenous metabolites. Mass defect filtering was adopted to screen for the exogenous metabolites of celastrol. Multivariate statistical analysis was used to identify the endogenous metabolites affected by celastrol. Celastrol and its eight metabolites were detected in urine and feces of mice,and 5 metabolites of them were reported for the first time. The hydroxylated metabolites were observed in the metabolism of both human liver microsomes and mouse liver microsomes. Further recombinant enzyme experiments revealed CYP3 A4 was the major metabolic enzyme involved in the formation of hydroxylated metabolites. Urinary metabolomics revealed that celastrol can affect the excretion of intestinal bacteria-related endogenous metabolites,including hippuric acid,phenylacetylglycine,5-hydroxyindoleacetic acid,urocanic acid,cinnamoylglycine,phenylproplonylglycine and xanthurenic acid. These results are helpful to elucidate the metabolism and disposition of celastrol in vivo,and its mechanism of action.

Detoxification mechanism of Jujubae Fructus and Crotonis Semen Pulveratum based on the toxicity of gastrointestinal system and diuretic effect in mice / 药学学报

The aim of this study was to investigate the effect of Jujubae Fructus (JF) on the gastrointestinal toxicity and diuretic effect of Crotonis Semen Pulveratum (CT). Forty-eight mice were randomly divided into the control group, low dose of CT group (0.039 g·kg-1·d-1, CTL), high dose of CT group (0.078 g·kg-1·d-1, CTH), JF group (9.75 g·kg-1·d-1), low dose of CT combined with JF group (CT 0.039 g·kg-1·d-1 and JF 9.75 g·kg-1·d-1, JFCTL), high dose of CT combined with JF group (CT 0.078 g·kg-1·d-1 and JF 9.75 g·kg-1·d-1, JFCTH). On the 9th day of oral administration, the urine output of all mice was measured. After oral administration for ten days, fresh fecal samples were collected, and the 16S rDNA sequencing method was used to study the changes of intestinal bacteria when CT used alone and combined with JF. All experimental protocols were approved by the Animal Ethics Committee of Nanjing University of Chinese Medicine. The results showed that JF slowed down the rapid diuretic effect of CT, and significantly increased serum interleukin-2 (IL-2), interleukin-6 (IL-6), gastrin (GAS), somatostatin (SS). JF also reduced small intestine injury and improved the disorder of intestinal flora caused by CT. Low dose CT combined with JF significantly decreased the relative abundance of Sphingomonas and Oscillospira. The level of Bilophila was decreased after the combined application of high dose CT and JF. The results suggest that JF exhibited a tendency to reduce the toxicity of CT in the aspects of serum immune index, intestinal movement, intestinal damage, and intestinal microflora structure. In addition, the JF could also slow down the rapid diuretic effect of CT, behaving a tendency to reduce the clinical effect of CT.

Applications of engineered intestinal bacteria in disease diagnosis and treatment / 生物工程学报

Intestinal bacteria interact closely with human health and diseases. With the development of high-throughput sequencing technologies, researchers have discovered the potential of intestinal bacteria in the diagnosis and treatment of diseases. Meanwhile, synthetic biology strategies are applied to engineer these bacteria for clinical applications. These engineered intestinal microbial are constructed by designing editing tools and feedback loops to gain functions of diagnose or targeted therapy. Consequently, these engineered bacteria are capable of sensing, calculating and responding to the environment. In this review, we summarize the recent advances in engineered intestinal bacteria in disease diagnosis and treatment. Furthermore, we also discuss the current status and future prospect of the engineered intestinal bacteria regarding their clinical applications, market, and safety issues.

The community structure of intestinal bacteria from cirrhosis patients and its influence factors / 中华消化内镜杂志

Objective To investigate the community structure of intestinal bacteria from patients with cirrhosis and its influencing factors. Methods From 2016 to 2017, 24 patients with liver cirrhosis ( the LC group) and 23 healthy family members of patients ( the HC group) were enrolled at the First Hospital of Lanzhou University. A comparative analysis of the community structure of intestinal bacteria was performed using 16S rRNA gene sequencing in LC and HC groups. Combined with LEfSe analysis and NMDS analysis, the differential markers were screened and the factors affecting the intestinal community structure of subjects were studied. Results The dominant six phylum of bacteria in intestines in LC and HC groups included Firmicutes, Bacteroides, Proteobacteria, Actinobacteria, Fusobacteria and Tenericumes. However, in the LC sample, Firmicutes was significantly reduced, while Bacteroides was significantly increased. The diversity of intestinal bacteria was significantly reduced, and the Firmicutes/Bacteroides ratio was significantly decreased, suggesting a variation of the community structure in intestinal bacteria of cirrhosis patients. The LEfSe result indicated that the abundance of Enterococcus, Lactobacillales, Bacilli, and Bacteroidetes showed a significant difference in the LC sample, which may be used as potential marked bacterial groups for cirrhosis. The NMDS analysis revealed a positive relationship between the concentration of Cd and Pb and the abundance of intestinal bacteria in the LC sample. Conclusion The community structure of intestinal bacteria from patients with cirrhosis has changed. Enterococcus, Lactobacillales, Bacilli, and Bacteroidetes are potential marked bacterial groups. The concentration of Cd and Pb in the intestinal tract of cirrhosis patients may interact with the abundance and structure of bacteria, and further affect the occurrence and development of cirrhosis.

Identification of active compound combination contributing to anti-inflammatory activity of Xiao-Cheng-Qi Decoction via human intestinal bacterial metabolism / 中国天然药物

Human intestinal bacteria play an important role in the metabolism of herbal medicines, leading to the variations in their pharmacological profile. The present study aimed to investigate the metabolism of Xiao-Cheng-Qi decoction (XCQD) by human intestinal bacteria and to discover active component combination (ACC) contributing to the anti-inflammatory activity of XCQD. The water extract of XCQD was anaerobically incubated with human intestinal bacteria suspensions for 48 h at 37 °C. A liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry (LC-Q-TOF/MS) method was performed for identification of the metabolites. In addition, the anti-inflammatory effects of XCQD and biotransformed XCQD (XCQD-BT) were evaluated in vitro with cytokines in RAW264.7 cells induced by lipopolysaccharide (LPS). A total of 51 compounds were identified in XCQD and XCQD-BT. Among them, 20 metabolites were proven to be transformed by human intestinal bacteria. Significantly, a combination of 14 compounds was identified as ACC from XCQD-BT, which was as effective as XCQD in cell models of inflammation. In conclusion, this study provided an applicable method, based on intestinal bacterial metabolism, for identifying combinatory compounds responsible for a certain pharmacological activity of herbal medicines.

Bacterial signatures for diagnosis of colorectal cancer by fecal metagenomics analysis / 上海交通大学学报（医学版）

Objective • To construct bacterial signatures by analyzing fecal metagenomics for the screening and diagnosis of colorectal cancer (CRC). Methods • A total of 285 samples were included in the study. Diagnostic models for CRC according to six different machine learning algorithms were developed using the featured bacteria selected by random forest algorithm, and validated in validation sets. Results • Nine bacteria that differentiated CRC and the control were identified, with which 6 models were established. The best model was random forest model, with an accuracy of 0.847 7 in the training set. Its accuracy in two test sets was 0.815 8 and 0.734 4, respectively. The area under curve (AUC) of receiver operating characteristic of the random forest model in the set including all samples was 0.894. Conclusion • Bacterial signatures based on random forest algorithm for the diagnosis of CRC can differentiate patients with CRC and the control effectively, which suggests the potential clinical value of the bacterial signatures.

Identification of poliumoside metabolites in rat plasma, urine, bile, and intestinal bacteria with UPLC/Q-TOF-MS / 中国天然药物

Poliumoside is representative of phenylethanoid glycosides, which are widely found in many plants. Poliumoside is also regarded as the main active component of Callicarpa kwangtungensis Chun (CK), though its oral bioavailability in rat is extremely low (0.69%) and its in vivo and in vitro metabolism has not yet been systematically investigated. In the present study, an ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) method was employed to identify the metabolites and investigate the metabolic pathways of poliumoside in rat after oral administration 1.5 g·kg of poliumoside. As a result, a total of 34 metabolites (30 from urine, 17 from plasma, and 4 from bile) and 9 possible metabolic pathways (rearrangment, reduction, hydration, hydrolyzation, dehydration, methylation, hydroxylation, acetylation, and sulfation) were proposed in vivo. The main metabolite, acteoside, was quantified after incubated with rat intestinal bacteria in vitro. In conclusion, the present study systematically explored the metabolites of poliumoside in vivo and in vitro, proposing metabolic pathways that may be significant for further metabolic studies of poliumoside.

Identification of active compound combination contributing to anti-inflammatory activity of Xiao-Cheng-Qi Decoction via human intestinal bacterial metabolism / 中国天然药物

Human intestinal bacteria play an important role in the metabolism of herbal medicines, leading to the variations in their pharmacological profile. The present study aimed to investigate the metabolism of Xiao-Cheng-Qi decoction (XCQD) by human intestinal bacteria and to discover active component combination (ACC) contributing to the anti-inflammatory activity of XCQD. The water extract of XCQD was anaerobically incubated with human intestinal bacteria suspensions for 48 h at 37 °C. A liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry (LC-Q-TOF/MS) method was performed for identification of the metabolites. In addition, the anti-inflammatory effects of XCQD and biotransformed XCQD (XCQD-BT) were evaluated in vitro with cytokines in RAW264.7 cells induced by lipopolysaccharide (LPS). A total of 51 compounds were identified in XCQD and XCQD-BT. Among them, 20 metabolites were proven to be transformed by human intestinal bacteria. Significantly, a combination of 14 compounds was identified as ACC from XCQD-BT, which was as effective as XCQD in cell models of inflammation. In conclusion, this study provided an applicable method, based on intestinal bacterial metabolism, for identifying combinatory compounds responsible for a certain pharmacological activity of herbal medicines.

Incompatible mechanism of compatibility of Chinese medicines based on Qianjinzi and Gancao effect on intestinal flora/barrier system / 中国中药杂志

The study was based on the toxic characteristics of the compatibility between "Zaojisuiyuan" and Gancao, with intestinal tract and intestinal bacteria as subject. From the angle of intestinal barrier function, motor function, steady state of intestinal flora and metabolism genes, the toxic and side effects of the compatibility between Qianjinzi and Gancao with similar properties, bases and chemical composition and types were further explored. The results showed that the combined application of Qianjinzi and Gancao enhanced intestinal mucosa damage, and led to abnormal changes in intestinal bacteria structure and metabolic function. It improved the degradation functions of mucus and aromatic amino acids on intestinal bacteria, which may increase the risk of disease and derived from intestinal urotoxin and other toxic substances. This study considered intestinal bacteria as an important target to study the interactions of traditional Chinese medicine. The "drug-intestinal bacteria-metabolism-toxicity" was applied in the experiment. Meanwhile, it provides ideas for exploring incompatible mechanism of traditional Chinese medicines.

Identification of poliumoside metabolites in rat plasma, urine, bile, and intestinal bacteria with UPLC/Q-TOF-MS / 中国天然药物

Poliumoside is representative of phenylethanoid glycosides, which are widely found in many plants. Poliumoside is also regarded as the main active component of Callicarpa kwangtungensis Chun (CK), though its oral bioavailability in rat is extremely low (0.69%) and its in vivo and in vitro metabolism has not yet been systematically investigated. In the present study, an ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) method was employed to identify the metabolites and investigate the metabolic pathways of poliumoside in rat after oral administration 1.5 g·kg of poliumoside. As a result, a total of 34 metabolites (30 from urine, 17 from plasma, and 4 from bile) and 9 possible metabolic pathways (rearrangment, reduction, hydration, hydrolyzation, dehydration, methylation, hydroxylation, acetylation, and sulfation) were proposed in vivo. The main metabolite, acteoside, was quantified after incubated with rat intestinal bacteria in vitro. In conclusion, the present study systematically explored the metabolites of poliumoside in vivo and in vitro, proposing metabolic pathways that may be significant for further metabolic studies of poliumoside.

Metabolism of Inula cappa extract by rat intestinal bacteria in vitro / 中国中药杂志

To investigate the metabolism of major components in Inula cappa by rat intestinal bacteria in vitro. I. cappa extract was incubated for 24 h with rat intestinal bacteria under anaerobic environment. After the samples were precipitated by n-butanol, UPLC-Q-TOF-MS/MS was applied for the qualitative analysis of the metabolites, combined with data software such as Metabolite Tools, Data Analysis and so on. The potential metabolites in rat intestinal bacteria were analyzed by comparing the total ion current of the test samples and blank samples and analyzing the quasi-molecular ion and fragment ion of all chromatograms. The results injected that fourteen metabolites were detected in rat intestinal flora. Various types of metabolic reactions happen to caffeoylquinic acid in intestinal flora, including isomerization, hydrolyzation, there were also methylation, hydrogenation and acetylation of caffeic acid. At the same time, a methylate of dicaffeoylquinic acid was also detected. Presumably, caffeoylquinic acids were gradually transformed into more hydrophobic metabolites with smaller molecular mass, which were better absorbed by the intestinal tract.