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1.
Journal of Preventive Medicine ; (12): 253-257, 2022.
Article in Chinese | WPRIM | ID: wpr-920762

ABSTRACT

Abstract@#As the largest human microecosystem, intestinal microorganisms participate in human material and energy metabolisms and pose a significant impact on human health. Diabetes mellitus is likely to cause imbalance of abundance and component alterations in intestinal microorganisms, and reduce the diversity and balance, leading to intestinal microflora dysregulation. It has been shown that intestinal microflora dysregulation may promote diabetes development and progression through the reduction of intestinal microbial metabolites, inflammatory reaction and insulin resistance. This review summarizes the involvement of intestinal microorganisms in the pathogenesis of diabetes through metabolites including short-chain fatty acid, bile acid and lipopolysaccharide, and describes the current status of intestinal microorganisms-mediated treatments for diabetes, so as to provide the theoretical basis for the researches on diabetes and intestinal microorganisms.

2.
Acta Pharmaceutica Sinica ; (12): 392-398, 2022.
Article in Chinese | WPRIM | ID: wpr-922919

ABSTRACT

Numerous in vitro studies have shown that most pyrrolizidine alkaloids (PAs) are hepatotoxic after being metabolically activated by cytochrome P450 (CYP) 3A4. However, the key role of CYP3A4 has not been confirmed in vivo. Therefore, the CYP3A4 chemical inhibitor ritonavir was employed in this work and the effect of ritonavir on Gynura japonica-induced liver injury in rats was investigated. All experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine. Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Shanghai University of Traditional Chinese Medicine. Acute liver injury was induced by a single gavage of Gynura japonica extracts (GJE, 8 g·kg-1); rats in the protection group were gavaged with ritonavir (RIT, 30 mg·kg-1) 1 h before GJE treatment. The results show that RIT could significantly attenuate GJE-induced liver injury in rats. Rats in the protection group showed decreased serum activities for alanine aminotransferase and aspartate aminotransferase, as well as lower total bile acids. In addition, the infiltration of inflammatory cells, sinusoidal hemorrhage, and hepatic necrosis in GJE-treated rats were markedly attenuated in the protection group. The content of pyrrole-protein adducts (PPAs), a recommended biomarker for PA-induced hepatotoxicity in clinics, was determined at 10 min to 24 h after GJE treatment. The content of 13 bile acids was also quantified. RIT treatment reduced the content of PPAs in serum dramatically and restored the impaired bile acid homeostasis caused by GJE. These studies indicate that RIT attenuated Gynura japonica-induced liver injury in rats, which was closely related to the inhibition of the metabolic activation of PAs and the regulation of bile acid metabolism. These results provide a better understanding of the relationship between CYP3A4 and PA-induced toxicity. This work will also be helpful in developing effective treatments for PA-induced liver injury and making a reasonable evaluation of the safety of drugs containing PAs in clinic.

3.
Article in Chinese | WPRIM | ID: wpr-921685

ABSTRACT

To investigate the changes of bile acid(BA) levels in mice with sleep deprivation and the regulatory effect of Jiaotai Pills(JTP) on bile acid metabolism, this study established an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method for simultaneous determination of 23 BAs in mice. A total of 24 ICR mice were randomized into normal group, model group, and JTP group. Mice in the model group and JTP group were deprived of sleep at 20 h·d~(-1) by sleep deprivation apparatus for 8 consecutive days. Mice in the JTP group were given(ig, qd) JTP 3.3 g·kg~(-1) and those in the normal group and model group received(ig) the same volume of purified water. UPLC conditions are as follows: Waters ACQUITY UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 μm), gradient elution with the mobile phase of 0.1% formic acid in water-methanol. MS conditions are as below: negative-ion electrospray ionization, multiple reaction monitoring(MRM). Thereby, the content of 23 BAs in serum, liver, and ileum was determined and methodological investigation of the method was performed. The results showed that 23 BAs could be accurately determined within 15 min and the correlation coefficients were all higher than 0.99. The precision, accuracy, specificity, reproducibility, matrix effect, and recovery of BAs all met the requirement. The levels of BAs were significantly increased in the serum, liver, and ileum of sleep-deprived mice, but JTP can significantly reduce the levels. The UPLC-MS/MS method is simple, rapid, and accurate, which can be used for the determination of 23 BAs in biological samples, and JTP can adjust the elevated BA levels of sleep-deprived mice.


Subject(s)
Animals , Bile Acids and Salts , Chromatography, High Pressure Liquid , Chromatography, Liquid , Drugs, Chinese Herbal , Mice , Mice, Inbred ICR , Reproducibility of Results , Sleep , Tandem Mass Spectrometry
4.
Article in Chinese | WPRIM | ID: wpr-921626

ABSTRACT

Bile of animal(mainly chicken, pig, snake, cow, and bear) has long been used as medicine. As the major active components of bile, bile acids mainly include cholic acid, deoxycholic acid, chenodeoxycholic acid, ursodeoxycholic acid, and taurochenodeoxycholic acid. They interact with intestinal microorganisms in enterohepatic circulation, thereby playing an important part in nutrient absorption and allocation, metabolism regulation, and dynamic balance. Bile acids have pharmacological effects such as protecting liver, kidney, heart, brain, and nerves, promoting bile secretion, dissolving gallstones, anti-cancer, relieving cough and dyspnea, dispelling phlegm, treating eye diseases, and regulating intestinal function and blood glucose, which are widely used in clinical practice. This study summarized and analyzed the research on the chemical constituents and pharmacological effects of bile acids from medicinal animals, in a bid to provide scientific basis and reference for the further development and utilization of bile acids.


Subject(s)
Animals , Bile Acids and Salts , Cattle , Chenodeoxycholic Acid , Cholic Acids , Deoxycholic Acid , Female , Swine , Ursodeoxycholic Acid
5.
Chinese Journal of Biotechnology ; (12): 3734-3744, 2021.
Article in Chinese | WPRIM | ID: wpr-921461

ABSTRACT

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.


Subject(s)
Animals , Cattle , Cholesterol , Gammaproteobacteria , Humans , Proteus mirabilis , Providencia
6.
Article in Chinese | WPRIM | ID: wpr-910315

ABSTRACT

Objective:To study the effect of emulsifier Tween-80 on radiation-induced bile acid enterohepatic circulation disturbance and the treatment strategy.Methods:Male C57BL/6 J mice were randomly divided into healthy control group, radiation-only group, radiation + Tween-80 group and radiation + Tween-80 + butyric acid group. The mice were exposed to total abdominal irradiation (TAI) using a specific steel lead chamber and γ-ray irradiator was used throughout the experiments. Mice in radiation+ Tween-80 group and radiation+ Tween-80+ butyric acid group were intragastrically administrated with Tween-80 for 7 d before irradiation, while healthy control group and radiation-only group were treated with sterile water. After irradiation, butyric acid was administrated to mice in radiation+ Tween-80+ butyric acid group until euthanasia, while healthy control group, radiation-only group and radiation+ Tween-80 group were treated with sterile water until euthanasia. Small intestine and fecal particles were collected 21 d after irradiation. The concentrations of bile acid in small intestinal and fecal samples were measured using enzyme linked immunosorbent assay (ELISA), the expression of TGR5 and JAM-A, as well as the ratio of IL-10/IL-12 in intestine were detected by quantitative real-time PCR (qRT-PCR). The expression levels of GPR43 in the colon were compared using immunohistochemistry (IHC).Results:Tween-80 pretreated mice exhibited lower concentration of bile acid in small intestine and higher level of bile acid in fecal sample after irradiation (7.92%, 7.99%, t=3.93, 2.94, P<0.05), the expression of TGR5, which mediating the biological function of bile acid, and it′s downstream JAM-A gene were down-regulated (20.93%, 9.91%, t=4.85, 5.14, P<0.05), the ratio of IL-10/IL-12 (indicator related to inhibition of inflammation) (4.59%, t=3.39, P<0.05) as well as the expression of GPR43 protein, a G-protein-coupled receptor for butyric acid, decreased in the colon of Tween-80-pretreated mice compared with the radiation-only group. ELISA assay revealed that butyric acid administration elevated bile acid level in small intestines (8.06%, t=9.25, P<0.05), but reduced that in feces (14.41%, t=4.71, P<0.05). In addition, TGR5 and JAM-A showed higher expression in the intestine of butyric acid-treated mice (19.35%, 32.71%, t=7.69, 19.23, P<0.05), as well as the ratio of IL-10/IL-12 (2.39%, 4.05%, t=3.38, 5.92, P<0.05) and the content of GPR43 protein in colon. Conclusions:Tween-80 deteriorates the disturbance of bile acid enterohepatic circulation induced by ionizing radiation in mice. Butyric acid administration erases the adverse effects of Tween-80.

7.
Article in Chinese | WPRIM | ID: wpr-878922

ABSTRACT

Polygonum multiflorum is a traditional Chinese herbal medicine and has many biological activities such as hair-blacking, anti-atherosclerosis, anti-inflammatory and anti-aging. However, the liver injury induced by P. multiflorum has aroused wide attention in recent years. 2,3,5,4'-tetrahydroxystibane-2-O-β-D-glucoside(TSG) is a main component of P. multiflorum, but the role of TSG in inducing liver injury is unclear. The aim of present study was to evaluate TSG's potential liver injury and effects on bile acid homeostasis and phospholipids efflux. C57 BL/6 J mice received intraperitoneal administration of 400 mg·kg~(-1) of TSG daily for 15 days, and then biochemical indexes of liver injury and changes of phospholipid content were detected. The changes of bile acid compositions were detected by LC-MS/MS. The results showed TSG 400 mg·kg~(-1) significantly increased the content of serum total bile acid(TBA) and alkaline phosphatase(ALP). Elevated free bile acid levels were observed in TSG-treated groups, including β-muricholic acid(β-MCA), ursodeoxycholic acid(UDCA), hyodeoxycholic acid(HDCA), chenodeoxycholic acid(CDCA), deoxcholic acid(DCA) in serum and β-MCA, CDCA in liver. TSG inhibited the protein expression of farnesoid X receptor(FXR) and down stream bile salt export pump(BSEP), which may result in the accumulation of bile acid. TSG also inhibited the expression of 25-hydroxycholesterol-7 alpha-hydroxylase(CYP7 B1), which may disturb the alternative pathway for bile acid synthesis. In addition, intraperitoneal injection of TSG 400 mg·kg~(-1) significantly decreased the content of phospholipids in bile. The research showed that TSG significantly inhibited the expression of multidrug resistance protein 2(MDR2) and destroyed the regular distribution of MDR2 on the bile duct membrane of liver. In vitro results showed that the IC_(50) of TSG on HepG2 cells was about 1 500 μmol·L~(-1) and TSG at 500 μmol·L~(-1)(for 24 h) could destroy the distribution of MDR2 on the bile duct membrane of liver. In conclusion, TSG induced liver injury by disrupting bile acid homeostasis and phospholipids efflux.


Subject(s)
Animals , Bile Acids and Salts , Chromatography, Liquid , Glucosides , Homeostasis , Liver , Mice , Phospholipids , Tandem Mass Spectrometry
8.
Article in Chinese | WPRIM | ID: wpr-878921

ABSTRACT

As a precious traditional Chinese medicine(TCM), snake bile has been widely used in numerous Chinese medicine prescriptions. Bile acid(BA) derivatives have been demonstrated as the primary chemical family in snake bile. In-depth chemical characterization of BAs is of great importance towards the establishment of quality standards and clarification of the effective material basis for snake bile. This study firstly employed ~1H-NMR to preliminarily analyze the chemical profiles of snake bile, an automated fraction collector was subsequently implemented to obtain the fractions-of-interest. The fraction was then concentrated and re-analyzed by LC-MS. Based on ~1H-NMR, BAs were found to be the main components of snake bile, and six BAs including CDCA, CA, TCDCA, TCA, TDCA and GCA were tentatively identified from the representative spectrum with the assistance of literature and reference compounds. Whereas the content of TCA in snake bile was too great, resulting in a great obstacle for the detection of trace components, the automated fraction collector was subsequently implemented to obtain the fractions-of-interest for LC-MS analysis. According to matching MS/MS information and retention time with reference compounds as well as database retrieval, a total of 57 BAs were detected and annotated. Because of the combination of ~1H-NMR and LC-MS platforms, the findings are beneficial for the in-depth characterization of BAs in snake bile, which provides references for the establishment of quality control and evaluation methods of snake bile.


Subject(s)
Animals , Bile , Bile Acids and Salts , Chromatography, Liquid , Snakes , Tandem Mass Spectrometry
9.
Acta Pharmaceutica Sinica ; (12): 823-830, 2021.
Article in Chinese | WPRIM | ID: wpr-876531

ABSTRACT

Drug-induced liver injury and herbal preparations containing pyrrolizidine alkaloid (PA) have gained global attention. The purpose of this research was to investigate the effects and mechanisms of Alismatis Rhizoma, a traditional Chinese medicine, to protect against acute liver injury in mice induced by senecionine (SEN), a representative toxic PA compound. All experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine. Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Shanghai University of Traditional Chinese Medicine. Acute liver injury was induced by a single intragastric administration of SEN (50 mg·kg-1). Mice in the protection groups received intragastric administration of Alismatis Rhizoma water extract (WE, 18 g·kg-1 per day) or ethanol extract (EE, 18 g·kg-1 per day) 5 days before SEN treatment. The results show that Alismatis Rhizoma extracts can significantly attenuate acute liver injury in mice. Mice in the protection groups showed decreased serum activities of alanine aminotransferase and aspartate aminotransferase, as well as decreased total bile acids. In addition, the infiltration of inflammatory cells, sinusoidal hemorrhage, and hepatic necrosis in SEN-treatment mice was clearly attenuated in the protection groups. Interestingly, EE showed a better effect than WE. The content of principal bile acids in serum and the mRNA and protein expression of key factors related to bile acid metabolism were also measured. Alismatis Rhizoma up-regulated the bile acid transporters and drug metabolism enzymes, consistent with the observed bile acid homeostasis and alleviation of SEN-induced injury to hepatocytes. The present study points to the possibility of utilizing Alismatis Rhizoma for protection against liver injury caused by drugs and preparations containing PA.

10.
Journal of Clinical Hepatology ; (12): 480-484, 2021.
Article in Chinese | WPRIM | ID: wpr-873426

ABSTRACT

Liver failure is a common critical medical disease, and extensive liver cell necrosis within a short period of time exceeds the regeneration capacity of liver cells and thus results in an extremely high fatality rate. Promotion of effective liver regeneration is the key to antagonizing liver failure. Recent studies have shown that bile acid, farnesoid X receptor (FXR), and intestinal microecology play an important role in liver failure and liver regeneration. This article reviews the association between bile acid, FXR, and intestinal microecology and their role in liver failure and liver regeneration, so as to provide new ideas for the treatment of liver failure in clinical practice.

11.
Acta Pharmaceutica Sinica ; (12): 2260-2265, 2021.
Article in Chinese | WPRIM | ID: wpr-887042

ABSTRACT

In order to clarify the influence of acute hypobaric hypoxia on the bile acids of the rat small intestine, we used ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) to identify bile acids in the contents of the small intestine from untreated and acute hypobaric hypoxia-treated rats. Thirty-nine bile acids were detected; PCA and OPLS-DA analysis revealed marked differences in the composition of bile acids between the untreated and the acute hypobaric hypoxia groups. Bile acids were screened with VIP > 1, |log2FC| ≥ 1, P < 0.05, and a total of 7 bile acids with significant differences in content between the two groups were obtained, including 5 conjugated bile acids, 2 unconjugated bile acids; in addition, the content of conjugated bile acids has risen in the treated group. This study demonstrated the influence of high-altitude hypoxic environment on bile acid composition and metabolism in rats. All the animal experiments in this study were approved by the 940th Hospital Ethics Committee (approval No: 2020KYLL012).

12.
Acta Pharmaceutica Sinica B ; (6): 727-737, 2021.
Article in English | WPRIM | ID: wpr-881165

ABSTRACT

The constitutive androstane receptor (CAR, NR3I1) belongs to nuclear receptor superfamily. It was reported that CAR agonist TCPOBOP induces hepatomegaly but the underlying mechanism remains largely unknown. Yes-associated protein (YAP) is a potent regulator of organ size. The aim of this study is to explore the role of YAP in CAR activation-induced hepatomegaly and liver regeneration. TCPOBOP-induced CAR activation on hepatomegaly and liver regeneration was evaluated in wild-type (WT) mice, liver-specific YAP-deficient mice, and partial hepatectomy (PHx) mice. The results demonstrate that TCPOBOP can increase the liver-to-body weight ratio in wild-type mice and PHx mice. Hepatocytes enlargement around central vein (CV) area was observed, meanwhile hepatocytes proliferation was promoted as evidenced by the increased number of KI67

13.
Article in English | WPRIM | ID: wpr-880723

ABSTRACT

Gestational diabetes mellitus (GDM) is characterized by glycemia and insulin disorders. Bile acids (BAs) have emerged as vital signaling molecules in glucose metabolic regulation. BA change in GDM is still unclear, which exerts great significance to illustrate the change of BAs in GDM. GDM patients and normal pregnant women were enrolled during the oral glucose tolerance test (OGTT) screening period. Fasting serums were sampled for the measurement of BAs. BA metabolism profiles were analyzed in both pregnant women with GDM and those with normal glucose tolerance (NGT). Delivery characteristics, delivery gestational age, and infant birthweight were extracted from medical records. GDM patients presented distinctive features compared with NGT patients, including higher body mass index (BMI), elevated serum glucose concentration, raised insulin (both fasting and OGTT), and increased hemoglobin A1c (HbA1c) levels. Higher homeostasis model assessment of insulin resistance (HOMA-IR) and decreased β-cell compensation (i.e., oral disposition index (DI

14.
Acta Pharmaceutica Sinica B ; (6): 3847-3856, 2021.
Article in English | WPRIM | ID: wpr-922445

ABSTRACT

Bile acids (BAs) are amphipathic molecules important for metabolism of cholesterol, absorption of lipids and lipid soluble vitamins, bile flow, and regulation of gut microbiome. There are over 30 different BA species known to exist in humans and mice, which are endogenous modulators of at least 6 different membrane or nuclear receptors. This diversity of ligands and receptors play important roles in health and disease; however, the full functions of each individual BA

15.
Article in Chinese | WPRIM | ID: wpr-906424

ABSTRACT

Objective:To investigate the hepatotoxicity of different doses of geniposide on the liver of rats and the effects on bile acid profile in serum, liver tissue and feces. Method:The 60 Sprague Dawley rats, half male and half female, were randomly divided into 5 groups according to body weight: blank group and four different doses (50, 100, 200, 400 mg·kg<sup>-1</sup>) geniposide groups, 12 rats in each group. The rats were treated by gavage once a day for 7 consecutive days, and the serum, liver and cecal contents were collected on the 8<sup>th</sup> day of treatment. The activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), the contents of albumin (ALB), total bilirubin (TBIL), total bile acid (TBA), creatinine (Crea) and carbamide (Urea) were detected in each group. The sections of liver tissue were stained with hematoxylin-eosin(HE), and the protein expressions of cytokeratin 7(CK7) and cytokeratin 19(CK19) were detected by immunohistochemistry. The protein expressions of CK7 and CK19 in the liver tissue were detected by Western blot. And the mRNA expressions of cholesterol 7<italic>α</italic>-hydroxylase (CYP7A1), cholesterol 27<italic>α</italic>-hydroxylase ( CYP27A1) and cholesterol 12<italic>α</italic>-hydroxylase (CYP8B1) were detected by real-time PCR. The contents of 18 kinds of bile acids in serum, liver and cecal contents were determined by ultra-performance liquid chromatography-mass spectrometry(UPLC-MS). Result:Compared with the control group, TBIL level in each dose of geniposide group was increasesd significantly (<italic>P</italic><0.01). ALT, AST activity and TBA content in 400 mg·kg<sup>-1</sup> geniposide group were increased significantly (<italic>P</italic><0.05, <italic>P</italic><0.01). HE staining showed that, compared with control group, there was bile duct reaction in the portal area and inflammatory cells infiltrate around bile duct in 200 mg·kg<sup>-1</sup> and 400 mg·kg<sup>-1</sup> geniposide groups, especially 400 mg·kg<sup>-1</sup>. The expressions of CK7 and CK19 in liver tissue of 400 mg·kg<sup>-1</sup> geniposide group were significantly higher than those in the control group (<italic>P</italic><0.05, <italic>P</italic><0.01). Compared with the control group, the contents of glycoursodeoxycholic acid (GUDCA) and glycohyodeoxycholic acid (GHDCA) in liver tissue of 400 mg·kg<sup>-1</sup> geniposide group decreased significantly (<italic>P</italic><0.05, <italic>P</italic><0.01), the contents of sodium taurochenodeoxycholate (TCDCA), hyodeoxycholic acid (HDCA), cholic acid (CA) and chenodeoxycholic acid (CDCA) in liver tissue increased significantly (<italic>P</italic><0.01), the contents of glycocholic acid hydrate (GCA), glycochenodeoxycholic acid (GCDCA), glycodeoxycholic acid hydrate (GDCA), glycocholic acid (GLCA), tauroursodeoxycholic acid (TUDCA), GUDCA, GHDCA, ursodeoxycholic (UDCA) and taurolithocholic acid (TLCA) decreased, the proportions of TCDCA, HDCA, CA, CDCA and deoxycholic acid (DCA) in liver tissue increased, the contents of GHDCA and lithocholic acid (LCA) in serum decreased significantly (<italic>P</italic><0.01), while sodium taurohyodeoxycholate hydrate (THDCA), taurocholic acid (TCA), GCA, TCDCA, UDCA, CA, CDCA, DCA in serum decreased significantly (<italic>P</italic><0.05, <italic>P</italic><0.01). The contents of CA, UDCA, CA, CDCA and DCA increased significantly (<italic>P</italic><0.05), the ratio of CA/DCA increased significantly (<italic>P</italic><0.05), and the ratio of CA and CDCA increased by 19.60% and 4.63%, respectively; Compared with the control group, the contents of all bile acids in cecal contents of 400 mg·kg<sup>-1</sup> were decreased, and the contents of GCA, UDCA, HDCA, GCDCA, GDCA, TLCA, GLCA, CDCA, DCA and LCA were decreased significantly (<italic>P</italic><0.05, <italic>P</italic><0.01). In addition, real-time PCR results showed that the mRNA expressions of CYP7A1, CYP27A1 in the 400 mg·kg<sup>-1</sup> geniposide group were significantly higher than those in the control group (<italic>P</italic><0.05, <italic>P</italic><0.01). Conclusion:The 400 mg·kg<sup>-1 </sup>geniposide can cause obvious hepatotoxicity in rats, and the bile acid profile in liver, serum and excrement changes significantly, and the changes of the each bile acid in liver, serum and feces are different. However, the causal relationship between the gardenoside-induced liver injury and the changes in bile acid profile are<italic> </italic>not clear. It needs to be further studied.

16.
Article in Chinese | WPRIM | ID: wpr-906154

ABSTRACT

Objective:To explore active components and mechanism of Dipsaci Radix in treating rheumatoid arthritis (RA) based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS) and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP). Method:UPLC-QTOF-MS/MS with electrospray ionization (ESI) was used to qualitatively analyze the chemical components in methanol extract of Dipsaci Radix under positive and negative ion scanning modes. The mobile phase consisted of 0.1% formic acid aqueous solution (A)-acetonitrile (B) for gradient elution (0-10 min, 0.2%-20%B; 10-20 min, 20%-40%B; 20-25 min, 40%-50%B; 25-33 min, 50%-98%B; 33-35 min, 98%-0.2%B), and the scanning range was <italic>m</italic>/<italic>z</italic> 50-2 000. Based on TCMIP, candidate target groups of Dipsaci Radix, RA and syndrome with Yin deficiency of liver and kidney were obtained, and correlation analysis on "disease-syndrome-prescription" was used to enrich the main active components and key targets. Cytoscape 3.8.0 and STRING 11.0 database were used to construct protein-protein interaction (PPI) network diagram. Metascape platform was used to analysis gene ontology biological progress and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways. Result:A total of 81 ingredients were identified by UPLC-QTOF-MS/MS. Based on TCMIP, 283 candidate targets corresponding to 81 ingredients, 7 RA related targets and 215 genes corresponding to syndrome with Yin deficiency of liver and kidney were collected. With further correlation analysis on "disease-syndrome-prescription", 17 key active ingredients were predicted, mainly including saponins and fatty acids of Dipsaci Radix. It mainly involved 7 hub targets, namely tumor necrosis factor (TNF), nuclear factor-<italic>κ</italic>B subunit 1 (NF-<italic>κ</italic>B<sub>1</sub>), hepatocyte nuclear factor 4 alpha (HNF4A), nuclear receptor subfamily 3 group C member 1 (NR3C1), peroxisome proliferator activated receptor gamma (PPARG), nuclear receptor subfamily 1 group H member 4 (NR1H4) and nuclear receptor coactivator 1 (NCOA1). All of them were related to inflammation, and two of them were related to bile acid pathway. The 7 hub targets and 7 pathways played an important role in RA were screen out, including 4 bile acid related pathways and 3 inflammatory related pathways. Conclusion:UPLC-QTOF-MS/MS combined with TCMIP preliminarily elucidates the regulatory effect of multi-components in Dipsaci Radix on several pathways related to the inflammatory response and bile acid synthesis and metabolism, which lays a foundation for further study on the mechanism of Dipsaci Radix against RA.

17.
Acta Pharmaceutica Sinica B ; (6): 2449-2468, 2021.
Article in English | WPRIM | ID: wpr-888869

ABSTRACT

Orally administered drug entities have to survive the harsh gastrointestinal environment, penetrate the enteric epithelia and circumvent hepatic metabolism before reaching the systemic circulation. Whereas the gastrointestinal stability can be well maintained by taking proper measures, hepatic metabolism presents as a formidable barrier to drugs suffering from first-pass metabolism. The pharmaceutical academia and industries are seeking alternative pathways for drug transport to circumvent problems associated with the portal pathway. Intestinal lymphatic transport is emerging as a promising pathway to this end. In this review, we intend to provide an updated overview on the rationale, strategies, factors and applications involved in intestinal lymphatic transport. There are mainly two pathways for peroral lymphatic transport-the chylomicron and the microfold cell pathways. The underlying mechanisms are being unraveled gradually and nowadays witness increasing research input and applications.

18.
Acta Pharmaceutica Sinica B ; (6): 2416-2448, 2021.
Article in English | WPRIM | ID: wpr-888868

ABSTRACT

Proteins and peptides (PPs) have gradually become more attractive therapeutic molecules than small molecular drugs due to their high selectivity and efficacy, but fewer side effects. Owing to the poor stability and limited permeability through gastrointestinal (GI) tract and epithelia, the therapeutic PPs are usually administered by parenteral route. Given the big demand for oral administration in clinical use, a variety of researches focused on developing new technologies to overcome GI barriers of PPs, such as enteric coating, enzyme inhibitors, permeation enhancers, nanoparticles, as well as intestinal microdevices. Some new technologies have been developed under clinical trials and even on the market. This review summarizes the history, the physiological barriers and the overcoming approaches, current clinical and preclinical technologies, and future prospects of oral delivery of PPs.

19.
Article | IMSEAR | ID: sea-208030

ABSTRACT

Background: Intrahepatic cholestasis of pregnancy (IHCP) is the most common cholestatic liver disease, which may impact the foeto-maternal health. The present study is conducted to determine various factors including maternal and neonatal outcome in IHCP comparing with the controls.Methods: In this prospective case control study, pregnancy with IHCP is compared with asymptomatic non-IHCP controls. Classical pruritus, icterus, elevated liver enzymes were considered in diagnostic criteria of IHCP. Dermatological lesion, acute or chronic liver disease, and other causes of pruritus were excluded from study.Results: Out of 100 patients, 50 cases and 50 controls were included in this study. Incidence of IHCP was seen 3.914% of which 66% were primi presented maximum at 31-33 weeks. 86% of IHCP responded to medication. Mean value of ALT, AST and ALP was found significantly raised (p value-<0.001) in IHCP patients. 66% in IHCP and 64% in non-IHCP group had normal delivery and remaining 34% and 36 % had caesarean delivery respectively. There was no significant increase in foetal distress or low Apgar (<7 at 5 min) at birth or adverse neonatal or maternal outcome in IHCP group. However, there was a statistically high meconium stained liquor (MSL), neonatal jaundice, IUGR and NICU admission were noted in the IHCP group in comparison to non-IHCP group.Conclusions: There is a significant incidence of IHCP in the obstetrical population. The biochemical changes, meconium stained liquor, neonatal jaundice, IUGR and NICU admission were significantly high in IHCP in pregnancy.

20.
Article in Chinese | WPRIM | ID: wpr-846332

ABSTRACT

Objective: The effect of triptolide (TP) on endogenous metabolites in mice with ulcerative colitis (UC) was analyzed by means of metabolomics, and the metabolic pathway and possible mechanism of TP in UC were discussed. Methods: C57BL/6 mice were randomly divided into blank control group, model group, and triptolide group. Dextran sulfate (DSS) was used to induce UC mice model. The serum samples of mice were detected by high performance liquid chromatography-mass spectrometry and characterized by principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) to identify the potential biomarkers and possible metabolic pathways. Results: Compared with the blank control group, a total of 15 potential biomarkers, such as cholic acid, bezoar cholic acid, goose-deoxycholic acid, citrulline, guanidine butyric acid, aminoacetic acid, and cis-aconitic acid, were found and identified in serum. Compared with the model group, the potential biomarkers showed a tendency of callback to normal level after TP intervention. Conclusion: Metabolomics analysis reveals that TP had certain therapeutic effects on UC mice, and its mechanism may be related to regulating primary bile acid biosynthesis, arginine, and proline metabolism.

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