The saponins in different parts of Gynostemma pentaphyllum were analyzed via UPLC-Q-TOF-MS~E. A total of 46 saponins were identified, and the underground part had 26 saponins more than the aboveground part, most of which were trisaccharide saponins. The rat model of hyperlipidemia was established with high-fat diet. This study explored the lipid-lowering activity of total saponins in the underground part of G. pentaphyllum, so as to provide a theoretical basis for the comprehensive utilization of the underground part of G. pentaphyllum. A total of 99 healthy SD rats were randomly assigned into a blank group, a model group, a positive drug group, an aboveground total saponins group, and low-, medium-, and high-dose underground total saponins groups. Except the blank group, the other groups were fed with high-fat diet for 6 weeks. Then, the blood was collected from the orbital cavity to determine whether the modeling was successful according to the serum levels of total cholesterol(TC) and triglyceride(TG). After intragastric administration of the corresponding agents for 30 continuous days, the physical state of the rats were observed, and the body weight and liver specific gravity were measured. Furthermore, the levels of TC, TG, low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), alanine transaminase(ALT), aspartate transaminase(AST), bilirubin, and total bile acids in serum, as well as the levels of superoxide dismutase(SOD), malondialdehyde(MDA), peroxidase proliferator-activated receptor(PPAR-γ) in the liver tissue, were determined. The pathological changes of liver was observed via HE staining. The results showed that the aboveground total saponins and medium-and high-dose underground total saponins can treat hepatocyte steatosis, lower TC, TG, LDL-C, ALT, AST, total bilirubin, MDA, and PPAR-γ levels, and increase HDL-C and SOD levels in the model rats. The effect tended to be more obvious with the increase in dosage. Therefore, the total saponins in the underground part of G. pentaphyllum have good pharmacological effect of reducing blood lipid, which provides a theoretical basis for the comprehensive utilization of the underground part of G. pentaphyllum.
Alanine Transaminase/analysis* ; Animals ; Aspartate Aminotransferases/analysis* ; Bile Acids and Salts/blood* ; Bilirubin/blood* ; Cholesterol, LDL/blood* ; Diet, High-Fat/adverse effects* ; Gynostemma/chemistry* ; Hypolipidemic Agents/therapeutic use* ; Lipoproteins, HDL/blood* ; Liver/metabolism* ; Malondialdehyde/analysis* ; Peroxisome Proliferator-Activated Receptors/analysis* ; Rats ; Rats, Sprague-Dawley ; Saponins/therapeutic use* ; Superoxide Dismutase ; Triglycerides/blood* ; Trisaccharides/therapeutic use*

This study systematically evaluated the efficacy and safety of Ganshuang Granules in the treatment of liver injury, so as to provide a new choice for patients with liver injury. CNKI, Wanfang, VIP, SinoMed, Cochrane Library, PubMed, EMbase, and Web of Science were systematically searched for the randomized controlled trial(RCT) of Ganshuang Granules in the treatment of liver injury. RevMan 5.4 was employed to perform the Meta-analysis of the included RCT according to the Cochrane Handbook 5.1. A total of 3 005 patients were included in 38 RCTs, including 1 536 patients in the observation group and 1 469 in the control group. The results of Meta-analysis showed that Ganshuang Granules combined with conventional therapy was superior to the therapy in the control group in reducing alanine aminotransferase(ALT)(MD=-24.12, 95%CI[-32.17,-16.07], P<0.000 01), aspartate aminotransferase(AST)(MD=-23.24, 95%CI[-29.70,-16.78], P<0.000 01), total bilirubin(TBiL)(MD=-12.42, 95%CI[-14.62,-10.22], P<0.000 01), and gamma-glutamyl transpeptidase(GGT)(MD=-21.32, 95%CI[-33.61,-9.03], P=0.000 7). Compared with the control group, the observation group had witnessed a significant increase in albumin(ALB)(MD=4.94, 95%CI[4.44, 5.45], P<0.000 01). No significant adverse reactions were observed. According to the available data, Ganshuang Granules combined with conventional therapy can effectively recover the levels of ALT, AST, TBiL, GGT, and ALB in patients with liver injury. Nevertheless, high-quality RCT is still needed to further verify the findings of this study.
Humans ; Liver ; Aspartate Aminotransferases ; Drugs, Chinese Herbal/adverse effects* ; Alanine Transaminase ; Bilirubin

OBJECTIVES: To investigate the incidence rate of adverse reactions of methimazole in children with hyperthyroidism. METHODS: A retrospective analysis was performed on the medical data of 304 children with hyperthyroidism who were hospitalized in Shengjing Hospital of China Medical University from January 2015 to May 2021. The incidence rate of methimazole-related adverse reactions was analyzed. The risk factors for common adverse reactions were evaluated. RESULTS: Among the 304 children, 87 (28.6%) experienced adverse reactions, among whom there were 20 boys (23%) and 67 girls (77%). Common adverse reactions included neutropenia (12.8%), rash (11.8%), elevated alanine aminotransferase (9.5%), and joint pain (3.0%), and some children experienced multiple adverse reactions simultaneously or intermittently. Neutropenia often occurred within 3 months after administration (25/39, 64%), elevated alanine aminotransferase often occurred within 1 month after administration (17/29, 59%), and rash often occurred within 3 months after administration (30/36, 83%). Most of the above adverse reactions returned to normal after symptomatic treatment. The multivariate logistic regression analysis showed that younger age and lower absolute neutrophil count before treatment were risk factors for neutropenia after methimazole treatment (P<0.05). CONCLUSIONS The adverse reactions of methimazole are common in children with hyperthyroidism, and most adverse reactions occur within 3 months after administration and can be relieved after symptomatic treatment. Children with a younger age or a lower baseline absolute neutrophil count may have a higher risk of neutropenia.
Male ; Child ; Female ; Humans ; Methimazole/adverse effects* ; Antithyroid Agents/adverse effects* ; Retrospective Studies ; Alanine Transaminase ; Hyperthyroidism/chemically induced* ; Neutropenia/chemically induced* ; Exanthema

OBJECTIVE: To elucidate the mechanism of Lizhong Decoction (LZD) in treating dextran sodium sulfate (DSS)-induced colitis in mice based on metabonomics. METHODS: Thirty-six mice were randomly divided into 6 groups, including normal, model, low- (1.365 g/kg), medium- (4.095 g/kg) and high dose (12.285 g/kg) LZD and salazosulfadimidine (SASP) groups, 6 mice in each group. Colitis model mice were induced by DSS admistration for 7 days, and treated with low, medium and high dose LZD extract and positive drug SASP. Metabolic comparison of DSS-induced colitis and normal mice was investigated by using ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass (UPLC-Q-TOF/MS) combined with Metabolynx™ software. RESULTS: The metabolic profiles of plasma and urine in colitis mice were distinctly ameliorated after LZD treatment (P<0.05). Potential biomarkers (9 in serum and 4 in urine) were screened and tentatively identified. The endogenous metabolites were mainly involved in primary bile acid, sphingolipid, linoleic acid, arachidonic acid, amino acids (alanine, aspartate, and glutamate), butanoate and glycerophospholipid metabolism in plasma, and terpenoid backbone biosynthesis, glycerophospholipid and tryptophan metabolism in urine. After LZD treatment, these markers notably restored to normal levels. CONCLUSIONS The study revealed the underlying mechanism of LZD on amelioration of ulcerative colitis based on metabonomics, which laid a foundation for further exploring the pathological and physiological mechanism, early diagnosis, and corresponding drug development of colitis.
Mice ; Animals ; Colitis, Ulcerative/drug therapy* ; Tryptophan/adverse effects* ; Aspartic Acid ; Dextrans/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Colitis/drug therapy* ; Biomarkers/metabolism* ; Amino Acids/adverse effects* ; Glycerophospholipids/therapeutic use* ; Sphingolipids/adverse effects* ; Bile Acids and Salts/adverse effects* ; Glutamates/adverse effects* ; Alanine/adverse effects* ; Arachidonic Acids/adverse effects* ; Linoleic Acids/adverse effects* ; Terpenes

This study aimed to explore the effects of Gynostemma pentaphyllum saponins(GPs) on non-alcoholic fatty liver disease(NAFLD) induced by high-fat diet in rats and reveal the underlying mechanism. The NAFLD model rats were prepared with high-fat diet. Forty male Sprague Dawley(SD) rats were randomly assigned into the control group, model group, and low-, moderate-, and high-dose GPs(50, 100, and 150 mg·kg~(-1), respectively) groups. After intragastric administration for 8 continuous weeks, we determined the body weight, liver weight, the levels of total cholesterol(TC), triglyceride(TG), low-density lipoprotein cholesterol(LDL-c), high-density lipoprotein cholesterol(HDL-c), alanine aminotransferase(ALT), and aspartate aminotransferase(AST) in serum, and the levels of TC, TG, malondialdehyde(MDA), superoxide dismutase(SOD), catalase(CAT), and interleukin 6(IL-6) in the liver. Furthermore, we observed the pathological changes of liver tissue by oil red O staining and hematoxylin-eosin(HE) staining, sequenced the 16 S rRNA of the intestinal flora in rat feces, and determined the content of short-chain fatty acids in rat feces. The results showed that GPs inhibited the excessive weight gain of high-fat diet-induced NAFLD in rats, reduced the liver weight, lowered the TC, TG, LDL-c, AST, and ALT levels in serum(P<0.05), and rose the HDL-c level in serum(P<0.01). GPs relieved the liver damage caused by high-fat diet, mainly manifested by the lowered levels of TC, TG, MDA, and IL-6 in the liver(P<0.01) and elevated levels of CAT and SOD in the liver. Furthermore, GPs reversed the intestinal flora disorder caused by high-fat diet, restored the diversity of intestinal flora, increased the relative abundance of Bacteroides, and reduced the relative abundance of Firmicutes and the ratio of Firmicutes to Bacteroides. Moreover, GPs promoted the proliferation of beneficial bacteria such as Akkermansia, Bacteroides, and Parabacteroides, and inhibited the growth of harmful bacteria such as Desulfovibrio, Escherichia-Shigella, and Helicobacter. GPs increased the content of short-chain fatty acids(acetic acid, propionic acid, and butyric acid)(P<0.01). These findings indicate that GPs can alleviate the high-fat diet-induced NAFLD in rats via regulating the intestinal flora and short-chain fatty acid metabolism.
Alanine Transaminase/metabolism* ; Animals ; Cholesterol, LDL/pharmacology* ; Diet, High-Fat/adverse effects* ; Gastrointestinal Microbiome ; Gynostemma ; Interleukin-6/metabolism* ; Liver ; Male ; Non-alcoholic Fatty Liver Disease/metabolism* ; Rats ; Rats, Sprague-Dawley ; Saponins/pharmacology* ; Superoxide Dismutase/metabolism*

BACKGROUND: Central nervous system (CNS) symptoms after efavirenz (EFV) treatment in people living with human immunodeficiency virus (HIV) could persist and impact their quality of life. We assessed the impact of EFV-based regimen replacement with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF), which is considered an alternative option for subjects who do not tolerate EFV. Most specifically, we assessed the safety and the efficacy of E/C/F/TAF and its effects on the participants' neuropsychiatric toxicity symptoms in a real-life setting. METHODS: A prospective cohort study was conducted among virologic suppressed HIV-positive participants receiving EFV-based regimens with ongoing CNS toxicity ≥ grade 2. The participants were switched to single-pill combination regimens E/C/F/TAF and followed up for 48 weeks. The neuropsychiatric toxicity symptoms were measured using a CNS side effects questionnaire, as well as the Hospital Anxiety and Depression Scale and the Pittsburgh Sleep Quality Index. The primary outcome measure was the proportion of participants experiencing grade 2 or higher CNS toxicity after EFV switch off at weeks 12, 24, and 48. Secondary endpoints included virologic and immunological responses and the effect on fasting lipids at week 48 after switch. RESULTS: One hundred ninety-six participants (96.9% men, median age: 37.5 years, median: 3.7 years on prior EFV-containing regimens) were included in the study. Significant improvements in anxiety and sleep disturbance symptoms were observed at 12, 24, and 48 weeks after switching to E/C/F/TAF (P < 0.05). No significant change in depression symptom scores was observed. At 48 weeks after switch, HIV viral load <50 copies/mL was maintained in all of the participants, median fasting lipid levels were moderately increased (total cholesterol [TC]: 8.2 mg/dL, low-density lipoprotein cholesterol [LDL-C]: 8.5 mg/dL, high-density lipoprotein cholesterol [HDL-C]: 2.9 mg/dL, and triglyceride (TG): 1.6 mg/dL, and the TC:HDL-C ratio remained stable. CONCLUSIONS The single-pill combination regimens E/C/F/TAF is safe and well tolerated. This study reveals that switching from EFV to E/C/F/TAF significantly reduces neuropsychiatric toxicity symptoms in people living with HIV with grade 2 or higher CNS complaints.
Adenine/therapeutic use* ; Adult ; Alanine ; Alkynes ; Anti-HIV Agents/adverse effects* ; Benzoxazines ; Central Nervous System ; Cobicistat/therapeutic use* ; Cyclopropanes ; Drug Combinations ; Emtricitabine/therapeutic use* ; Female ; HIV Infections/drug therapy* ; Humans ; Male ; Prospective Studies ; Quality of Life ; Quinolones ; Sleep Quality ; Tenofovir/analogs & derivatives*

PURPOSE: The incidence of drug-induced liver injury (DILI) has been increasing; however, few algorithms are available to identify DILI in electronic health records (EHRs). We aimed to identify and evaluate DILI with an appropriate screening algorithm.METHODS: We collected data from 3 university hospitals between June 2015 and May 2016 using our newly developed algorithm for identifying DILI. Among patients with alanine transferase (ALT) ≤ 120 IU/L and total bilirubin (TB) ≤ 2.4 mg/dL in blood test results within 48 hours of admission, those who either had 1) ALT > 120 IU/L and TB > 2.4 mg/dL or 2) ALT > 200 IU/L at least once during hospitalization were identified. After excluding patients with liver disease-related diagnosis at discharge, medical records were retrospectively reviewed to evaluate epidemiological characteristics of DILI.RESULTS: The total number of inpatients was 256,598, of whom 1,100 (0.43%) were selected by the algorithm as suspected DILI. Subsequently, 365 cases (0.14% of total inpatients, 95% confidence interval, 0.13–0.16) were identified as DILI, yielding a positive predictive value of 33.1%. Antibiotics (n = 214, 47.2%) were the major class of causative drug followed by chemotherapeutic agents (n = 87, 19.2%). The most common causative drug was piperacillin-tazobactam (n = 38, 8.4%); the incidence of DILI by individual agent was highest for methotrexate (19.4 cases/1,000 patients administered the drug). Common reasons for excluding suspected DILI cases were ischemic hepatitis and postoperative liver dysfunction.CONCLUSIONS: Using our EHR-based algorithm, we identified that approximately 0.14% of patients developed DILI during hospitalization. Further studies are needed to modify criteria for more accurate identification of DILI.
Alanine ; Anti-Bacterial Agents ; Bilirubin ; Diagnosis ; Drug-Induced Liver Injury ; Drug-Related Side Effects and Adverse Reactions ; Electronic Health Records ; Hematologic Tests ; Hepatitis ; Hospitalization ; Hospitals, University ; Humans ; Incidence ; Inpatients ; Liver ; Liver Diseases ; Mass Screening ; Medical Records ; Methotrexate ; Pharmacoepidemiology ; Retrospective Studies ; Transferases

PURPOSE: Since drug reaction with eosinophilia and systemic symptom (DRESS) syndrome is very rare and difficult to diagnose, its exact epidemiology is still unknown. If screening tools based on laboratory results or electronic medical records are available, the occurrence of DRESS syndrome can be monitored in real time. METHODS: To screen cases with DRESS syndrome, all the results of both eosinophil and alanine transaminase (ALT) level from July 2014 to June 2015 were analyzed by 36 searching conditions for the signal detection of 7 definite DRESS cases among 199,924 patients during the study period. Those searching conditions were diverse combinations of different cutoff levels of eosinophil and ALT with or without nursing records presenting skin symptoms. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value were calculated for individual searching conditions. RESULTS: As cutoff levels of eosinophil and ALT for screening DRESS increased from 3% to 5% and 40 U/L to 300 U/L, respectively, the sensitivity decreased from 100% to 42.9% and the PPV increased from 0.06% to 13.0%. A combination of eosinophil >10% and ALT >300 U/L which had the highest PPV among 36 search conditions could detect DRESS syndrome by sensitivity 42.9% and PPV 13.0%. When nursing records for skin symptoms were added, PPV was augmented to 21.4%. CONCLUSION: A combination of eosinophil and ALT levels is a useful search condition for the screening of DRESS syndrome. Nursing records can provide an additional increment in PPV.
Alanine Transaminase ; Drug Hypersensitivity Syndrome ; Drug-Related Side Effects and Adverse Reactions ; Electronic Health Records* ; Eosinophilia* ; Eosinophils ; Epidemiology ; Humans ; Mass Screening ; Methods* ; Nursing Records ; Sensitivity and Specificity ; Skin

The present study was designed to evaluate protective activity of an ethanol extract of the stems of Schisandra chinensis (SCE) and explore its possible molecular mechanisms on acetaminophen (APAP) induced hepatotoxicity in a mouse model. The results of HPLC analysis showed that the main components of SCE included schisandrol A, schisandrol B, deoxyschisandrin, schisandrin B, and schisandrin C and their contents were 5.83, 7.11, 2.13, 4.86, 0.42 mg·g, respectively. SCE extract was given for 7 consecutive days before a single hepatotoxic dose of APAP (250 mg·kg) was injected to mice. Our results showed that SCE pretreatment ameliorated liver dysfunction and oxidative stress, which was evidenced by significant decreases in aspartate transaminase (AST), alanine aminotransferase (ALT), malondialdehyde (MDA) contents and elevations in reduced glutathione (GSH) and superoxide dismutase (SOD) levels. These findings were associated with the result that the SCE pretreatment significantly decreased expression levels of 4-hydroxynonenal (4-HNE) and 3-nitrotyrosine (3-NT). SCE also significantly decreased the expression levels of Bax, mitogen- activated protein kinase (MAPK), and cleaved caspase-3 by APAP exposure. Furthermore, supplementation with SCE suppressed the expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), suggesting alleviation of inflammatory response. In summary, these findings from the present study clearly demonstrated that SCE exerted significant alleviation in APAP-induced oxidative stress, inflammation and apoptosis mainly via regulating MAPK and caspase-3 signaling pathways.
Acetaminophen ; adverse effects ; Alanine Transaminase ; metabolism ; Animals ; Apoptosis ; drug effects ; Aspartate Aminotransferases ; metabolism ; Caspase 3 ; genetics ; metabolism ; Chemical and Drug Induced Liver Injury ; genetics ; metabolism ; physiopathology ; prevention & control ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Glutathione ; metabolism ; Humans ; Liver ; drug effects ; metabolism ; Male ; Malondialdehyde ; metabolism ; Mice ; Mice, Inbred ICR ; Mitogen-Activated Protein Kinases ; chemistry ; genetics ; metabolism ; Oxidative Stress ; drug effects ; Schisandra ; chemistry ; Signal Transduction ; drug effects

Nonalcoholic fatty liver disease (NAFLD) and type 2 Diabetes Mellitus (T2DM) are highly prevalent diseases and are closely associated, with NAFLD being present in the majority of T2DM patients. In Asian traditional medicine, Mori Cortex is widely used for the treatment of diabetes and hyperlipidemia. However, whether it has a therapeutic effect on T2DM associated with NAFLD is still unknown. The present study showed that the oral treatment with Mori Cortex extract (MCE; 10 g·kg·d) lowered the blood lipid levels and reversed insulin resistance (IR) in high fat-diet/streptozotocin-induced type 2 diabetes in rats. The expression levels of sterol receptor element-binding protein-1c (SREBP-1c) and carbohydrate-responsive element binding protein (ChREBP), which are involved in steatosis in NAFLD rats, were measured in the liver samples. MCE decreased the protein and mRNA expression levels of SREBP-1c and ChREBP. In conclusion, down-regulation of SREBP-1c and ChREBP might contribute to the protective effect of MCE on hepatic injury and IR in the rats with T2DM associated with NAFLD.
Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; genetics ; Diabetes Mellitus, Type 2 ; blood ; chemically induced ; drug therapy ; metabolism ; Diet, High-Fat ; adverse effects ; Disease Models, Animal ; Down-Regulation ; drug effects ; Insulin ; blood ; Insulin Resistance ; physiology ; Lipid Metabolism ; drug effects ; genetics ; Liver ; drug effects ; physiopathology ; Male ; Morus ; Non-alcoholic Fatty Liver Disease ; blood ; chemically induced ; drug therapy ; metabolism ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Streptozocin