[Screening of bioactive components endowing hawthorn with turbidity-eliminating and lipid-lowering functions and development of quality control method of hawthorn].

Hawthorn has the efficacy of eliminating turbidity and lowering the blood lipid level, and it is used for treating hyperlipidemia in clinic. However, the bioactive components of hawthorn are still unclear. In this study, the spectrum-effect relationship was employed to screen the bioactive components of hawthorn in the treatment of hyperlipidemia, and then the bioactive components screened out were verified in vivo. Furthermore, the quality control method for hawthorn was developed based on liquid chromatography-mass spectrometry(LC-MS). The hyperlipidemia model of rats was built, and different polar fractions of hawthorn extracts and their combinations were administrated by gavage. The effects of different hawthorn extract fractions on the total cholesterol(TC), triglycerides(TG), and low-density lipoprotein-cholesterol(LDL-C) in the serum of model rats were studied. The orthogonal projections to latent structures(OPLS) algorithm was used to establish the spectrum-effect relationship model between the 24 chemical components of hawthorn and the pharmacodynamic indexes, and the bioactive components were screened out and verified in vivo. Finally, 10 chemical components of hawthorn, including citric acid and quinic acid, were selected to establish the method for evaluating hawthorn quality based on LC-MS. The results showed that different polar fractions of hawthorn extracts and their combinations regulated the TG, TC, and LDL-C levels in the serum of the model rats. The bioactive components of hawthorn screened by the OPLS model were vitexin-4″-O-glucoside, vitexin-2″-O-rhamnoside, rutin, citric acid, malic acid, and quinic acid. The 10 chemical components of hawthorn, i.e., citric acid, quinic acid, rutin, gallic acid, vitexin-4″-O-glucoside, vitexin-2″-O-rhamnoside, malic acid, vanillic acid, neochlorogenic acid, and fumaric acid were determined, with the average content of 38, 11, 0.018, 0.009 5, 0.037, 0.017, 8.1, 0.009 5, 0.073, and 0.98 mg·g~(-1), respectively. This study provided a scientific basis for elucidating the material basis of hawthorn in treating hyperlipidemia and developed a content determination method for evaluating the quality of hawthorn.

Optimized dual therapy for treatment-naive patients of Helicobacter pylori infection: A large-scale prospective, multicenter, open-label, randomized controlled study.

BACKGROUND: The efficacy and safety of high-dose amoxicillin (AMX) and proton pump inhibitors (PPI) dual therapy raises much more attention in recent years. Comparative studies among the dual therapies are required to explore more suitable regimens. This study compared the efficacy, adverse events, and patient compliance of three different high-dose dual regimens in treatment-naive patients of Helicobacter pylori (H. pylori) infection. MATERIALS AND METHODS: The study was a prospective, multicenter, open-label, randomized controlled trial, including H. pylori-infected treatment-naive patients at 12 tertiary hospitals in China. The eligible subjects received high-dose AMX and esomeprazole (ESO) dual therapy of different regimens. They were randomly assigned to group A (ESO 20 mg plus AMX 750 mg, Qid for 14 days), group B (ESO 40 mg Bid plus AMX 1 g Tid for 14 days), or group C (ESO 20 mg plus AMX 1 g, Tid for 14 days). The eradication rates, adverse events, and patient compliance of the three groups were compared. RESULTS: Between April 2021 and January 2022, a total of 1080 subjects were screened and 945 were randomized. The eradication rates in groups A, B, and C were 88.6% (95% CI 84.5%-91.9%), 84.4% (95% CI 80.0%-88.3%), and 86.7% (95% CI 82.4%-90.2%; p = .315), respectively, based on intention-to-treat analysis; 90.3% (95% CI 86.4%-93.3%), 85.5% (95% CI 81.1%-89.2%), and 87.8% (95% CI 83.6%-91.2%; p = .197), respectively, according to modified intention-to-treat analysis; and 90.4% (95% CI 86.5%-93.5%), 85.8% (95% CI 81.4%-89.5%), and 88.3% (95% CI 84.1%-91.7%; p = .202) in per-protocol analysis. History of antibiotics use in 2 years reduced eradication effect in group B (ESO 40 mg Bid, AMX 1 g Tid). The modified intention-to-treat eradication rates were 81.4% vs 90.0% among those with or without a history of antibiotics use in group B (p = .031). The adverse event rates were 13.7%, 12.7%, and 12.1% in groups A, B, and C, respectively (p = .834). Patient compliance of the three groups was similar. CONCLUSIONS: Two optimized AMX and PPI dual regimens (ESO 40 mg Bid or 20 mg Tid plus AMX 1 g Tid for 14 days) had similar efficacy, safety and compliance as compared with classical dual regimen (ESO 20 mg plus AMX 750 mg Qid for 14 days) in H. pylori-infected treatment-naive patients.

Comparison of high-dose dual therapy with bismuth-containing quadruple therapy in Helicobacter pylori-infected treatment-naive patients: An open-label, multicenter, randomized controlled trial.

OBJECTIVE: Bismuth-containing quadruple therapy for Helicobacter pylori (H. pylori) eradication has a relatively high rate of side effects and high cost, thus the option of a high-dose dual therapy with a high eradication rate and fewer adverse events is a consideration. However, studies of dual therapy are still scarce and are mostly single-center studies with limited generalizability. Large-scale, multicenter studies are required. Our study investigated and compared the effectiveness, adverse events, patient compliance, and costs of high-dose dual therapy with those of bismuth-containing quadruple therapy in H. pylori-infected treatment-naive patients in a prospective, multicenter, open-label, randomized controlled trial. METHOD: Treatment-naive patients infected with H. pylori were randomly assigned to receive high-dose dual therapy (esomeprazole 20 mg 4 times daily and amoxicillin 1000 mg 3 times daily, for 14 days) or bismuth-containing quadruple therapy (esomeprazole 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and bismuth potassium citrate 220 mg, all twice daily for 14 days). The effectiveness, adverse events, patient compliance, and costs of both groups were compared. RESULTS: A total of 700 patients were enrolled. The high-dose dual therapy group (N = 350) achieved eradication rates of 89.4% (intention-to-treat), 90.4% (modified intention-to-treat), and 90.6% (per-protocol), which were similar to rates in the bismuth-containing quadruple therapy group (N = 350), 84.6%, 88.0%, and 88.2%, respectively (p > 0.05). The high-dose dual therapy group had a lower rate of adverse events (12.9% vs. 28.1%, p < 0.001) and lower costs (¥590.2 vs. ¥723.22) compared with the quadruple therapy group, respectively. The compliance of both groups was satisfactory (97.7% high-dose dual vs. 96.8% quadruple, p > 0.05). CONCLUSION: High-dose dual therapy for H. pylori eradication had similar efficacy and compliance, fewer adverse events, and lower costs than bismuth-containing quadruple therapy for treatment-naive patients.

Natural Herbal Remedy Wumei Decoction Ameliorates Intestinal Mucosal Inflammation by Inhibiting Th1/Th17 Cell Differentiation and Maintaining Microbial Homeostasis.

BACKGROUND: Evidence has shown that the traditional Chinese herbal medicine Wumei decoction (WMD) has a protective effect on ulcerative colitis. Here, we studied the anti-inflammatory effects and potential mechanisms of WMD on chronic colitis in mice. METHODS: A dextran sulfate sodium (DSS)-induced chronic colitis model and CD45RBhighCD4+ T cell transfer model were established in mice. Body weight, Disease Activity Index, and colon length were assessed, and histopathology was confirmed by hematoxylin and eosin staining. Colon tissue samples were collected to detect the frequencies of various immune cells, expression of cytokines, and tight junction-related proteins using flow cytometry, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay, respectively. 16S ribosomal DNA sequencing was performed to distinguish differential microbiota of fecal samples. RESULTS: Severe chronic colitis was observed in mice after DSS exposure and in Rag1-/- mice reconstituted with CD45RBhighCD4+ T cells, as manifested by weight loss, hematochezia, and shortening and thickening of the colon, which were reversed by WMD treatment. WMD markedly suppressed intestinal mucosal CD4+ T cell differentiation and the secretion of proinflammatory cytokines (eg, tumor necrosis factor α, interleukin-1ß, interferon γ, and IL-17A) by flow cytometry, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay, respectively. Moreover, WMD promoted the expression of occludin, zonula occludens-1, and E-cadherin, thereby maintaining the epithelial barrier function. Additionally, 16S ribosomal DNA sequencing revealed that WMD regulated the dysbiosis of gut microbiota in CD45RBhighCD4+ T cell-reconstituted Rag1-/- mice, evidenced by an increase of Allobaculum and Bacteroides and a decrease of Ileibacterium. CONCLUSIONS: WMD ameliorates chronic colitis in mice induced by DSS or reconstituted with CD45RBhighCD4+ T cells through suppressing Th1/Th17 cell differentiation and the secretion of proinflammatory cytokines, maintaining epithelial barrier function, and improving the dysbiosis.

LC-MS-based plasma metabolomics study of the intervention effect of different polar parts of hawthorn on gastrointestinal motility disorder rats.

Dyspepsia, one of the most prevalent diseases of the digestive tract that impacts the quality of patient life, is mainly caused by gastrointestinal motility disorder. Hawthorn is a commonly used traditional Chinese medicine for treating dyspepsia, and has been proven to improve gastrointestinal motility. Herein, a rat model of gastrointestinal motility disorder was established by subcutaneous injection with atropine. The modeled rats were treated with four polar parts (T1-4 in descending polarity, corresponding to water, n-butanol, ethyl acetate and petroleum ether extracts, respectively) of hawthorn. Through metabolomics analysis, a total of 20 significantly metabolites were identified with significant changes in their abundance levels and these metabolites were related to many metabolic pathways such as amino acid metabolism and primary bile acid biosynthesis. The results showed that T3 had the best therapeutic effect of promoting gastrointestinal motility. Other parts showed no obvious therapeutic effect, demonstrating that the effective components of hawthorn may be compounds of medium polarity. T3 might achieve good therapeutic effects owing to the gastrointestinal motility promotion activity, and by rectifying the disturbed metabolic pathways in the gastrointestinal motility disorder model.

LC-MS based plasma metabolomics study of the intervention effect of different polar parts of Hawthorn on hyperlipidemia rats.

Hawthorn, a well-known traditional Chinese medicine is used for the treatment of dyspepsia syndrome, cardiovascular disease, and hyperlipidemia. Hawthorn has complex composition. However, the effective fraction and mechanisms of action in alleviating hyperlipidemia are unknown. Therefore, the aim of this study was to evaluate the effects of four different polar components of hawthorn on hyperlipidemia rats, and to explore underlying mechanisms of action through liquid chromatography-mass spectrometry based plasma metabolomics. Hyperlipidemia rat model was established by feeding rats using a high-fat diet. High-fat model rats were then treated with four polar components of hawthorn for 14 consecutive days. Plasma samples were collected and subjected to biochemical and metabolomics analysis. Biochemical analysis showed that hawthorn n-butanol and ethyl acetate extracts had the highest efficacy on hyperlipidemia rats. Water fraction showed a partial effect, whereas petroleum ether extract was not effective against hyperlipidemia rats. Furthermore, liquid chromatography-mass spectrometry metabolomics analysis showed that the most effective fraction of hawthorn reversed the metabolic disorder in plasma of hyperlipidemia rats. Metabolomics analysis showed that hawthorn exerts its activity by modulating lipid metabolism, energy metabolism, oxidative stress, and amino acid metabolism.

The Associations between the Duration of Folic Acid Supplementation, Gestational Diabetes Mellitus, and Adverse Birth Outcomes based on a Birth Cohort.

This study aimed to examine the associations between the duration of folic acid (FA) supplementation, gestational diabetes mellitus (GDM), and adverse birth outcomes. A total of 950 mother-offspring pairs participated in the cohort study during 2015 in Changsha, China. The data were collected through home visits and perfected by maternal and child healthcare handbooks. Generalized linear models and stratified analyses were used for statistical analyses. The incidence of GDM in our cohort was 10.2%. FA supplementation for ≥3 months before pregnancy was associated with an increased risk of GDM (adjusted relative risk (aRR): 1.72; 95% CI: 1.17-2.53) and decreased risk of small-for-gestational-age (SGA) birth (aRR: 0.40; 95% CI: 0.18-0.88). In the group of FA supplementation for ≥3 months during pregnancy, GDM was associated with an increased risk of cesarean delivery (aRR: 1.36; 95% CI: 1.06-1.75) and macrosomia (aRR: 2.11; 95% CI: 1.06, 4.20), but the aRRs were lower than the RRMH 1.53 (95% CI: 1.01-2.34) and 2.43 (95% CI: 1.27-4.66). Our study suggested that the longer duration of FA supplementation before pregnancy might increase the risk of GDM, but decrease the risk of SGA birth. Longer duration of FA supplementation during pregnancy had beneficial effects on birth outcomes in women with GDM. Further studies should consider a larger sample size to confirm these findings.

A NMR-Based Metabonomics Approach to Determine Protective Effect of a Combination of Multiple Components Derived from Naodesheng on Ischemic Stroke Rats.

Naodesheng (NDS) is a widely used traditional Chinese medicine (TCM) prescription for the treatment of ischemic stroke. A combination of 10 components is derived from NDS. They are: Notoginsenoside R1, ginsenoside Rg1, ginsenoside b1, ginsenoside Rd, hydroxysafflor yellow A, senkyunolide I, puerarin, daidzein, vitexin, and ferulic acid. This study aimed to investigate the protective effect of the ten-component combination derived from NDS (TCNDS) on ischemic stroke rats with a middle cerebral artery occlusion (MCAO) model by integrating an NMR-based metabonomics approach with biochemical assessment. Our results showed that TCNDS could improve neurobehavioral function, decrease the cerebral infarct area, and ameliorate pathological features in MCAO model rats. In addition, TCNDS was found to decrease plasma lactate dehydrogenase (LDH) and malondialdehyde (MDA) production and increase plasma superoxide dismutase (SOD) production. Furthermore, 1H-NMR metabonomic analysis indicated that TCNDS could regulate the disturbed metabolites in the plasma, urine, and brain tissue of MCAO rats, and the possible mechanisms were involved oxidative stress, energy metabolism, lipid metabolism, amino acid metabolism, and inflammation. Correlation analysis were then performed to further confirm the metabolites involved in oxidative stress. Correlation analysis showed that six plasma metabolites had high correlations with plasma LDH, MDA, and SOD. This study provides evidence that an NMR-based metabonomics approach integrated with biochemical assessment can help to better understand the underlying mechanisms as well as the holistic effect of multiple compounds from TCM.

Effects of rumen-protected pantothenate supplementation on lactation performance, ruminal fermentation, nutrient digestion and blood metabolites in dairy cows.

BACKGROUND: Lactation performance of dairy cow has considerably increased with animal breeding and management improvement in recent years. Ruminal net synthesised pantothenic acid is insufficient to meet the requirement of high producing dairy cows. The objective was to investigate the effects of rumen-protected pantothenate (RPP) on lactation performance, ruminal fermentation, nutrient digestion and blood metabolites in dairy cows. RESULTS: Dry matter (DM) intake tended to increase, whereas milk yields, milk fat percentage and yield, body condition score (BCS) changes and net energy output except for maintenance increased linearly with increasing RPP supplementation. Ruminal pH and ammonia N concentration tended to decrease, total VFA tended to increase, while acetate-to-propionate ratio increased linearly with increasing RPP supplementation. Digestibilities of DM, organic matter and crude protein increased linearly, but neutral detergent fibre and acid detergent fibre digestibility tended to increase. Blood glucose, total protein, non-esterified fatty acids, pantothenic acid, pantothenate kinase, succinyl CoA, acyl carrier protein and acetyl CoA also increased linearly with increasing RPP supplementation. CONCLUSION: The results indicated that supplementary RPP improved lactation performance, nutrient digestion and blood parameters in a dose-dependent manner, and the optimal dose was 12 g RPP per cow per day in the current study. © 2017 Society of Chemical Industry.

[Influential factors of iron deficient anemia among infants aged 8 months based on a case-control study].

OBJECTIVE: To study the status and influential factors of iron deficient anemia (IDA) among infants aged 8 months in Changsha City.
 Methods: A case-control study was performed in this research. The case group including 105 8-month-old infants definitely diagnosed as IDA based on standardized blood test. Four-times numbers of age- and genger-matched infants without IDA were selected as a control group. Chi-square test and conditional logistic regression was used to analyze the influential factors for IDA.
 Results: The incidence rate of IDA among infants aged 8 months in Changsha City was 14.7%. The risk factors were as follows: mother with anemia in late pregnancy (OR=3.540, 95% CI 1.898 to 6.601), mixed feeding within 6 months old (OR=1.682, 95% CI 1.099 to 2.574), artificial feeding within 6 months old (OR=4.162, 95% CI 1.343 to 12.896), complementary feeding before 6 months old (OR=1.423, 95% CI 1.022 to 1.982), complementary feeding at or after 7 months old (OR=4.415, 95% CI 2.150 to 9.064), recurrent respiratory tract infections within 8 months old (OR=2.878, 95% CI 1.224 to 6.764), and repeated diarrhea within 8 months old (OR=3.710, 95% CI 1.533 to 8.980).
 Conclusion: There is certain incidence rate of IDA among infants aged 8 months in Changsha City. To prevent the IDA among infants, we should treat mothers' anemia during pregnancy, advocate scientific feeding, encourage complete breastfeeding until 6 months old, add complementary food timely and reasonably, treat infants suffering from respiratory or digestive diseases actively.

[Influential factors for anemia in pregnancy based on a nested case-control study in Changsha].

OBJECTIVE: To explore the prevalence of anemia during pregnancy and the influential factors in changsha city, and to provide scientific evidence for prevention and intervention of anemia during pregnancy. 
 METHODS: A cluster sampling of 713 mothers, who delivered baby between January 1, 2013 and December 31, 2013 in the three streets of kaifu district of Changsha, was selected to establish a retrospective cohort. The maternal health information during pregnancy was collected within 15 days after the delivery. The influential factors of anemia during pregnancy were analyzed by the method of retrospective nested case-control study and conditional logistic regression.
 RESULTS: The prevalence of anemia during pregnancy in Changsha was 9.96%. The multiple conditional logistic regression results show that high family income (OR=0.632, P=0.020), high education level (OR=0.276, P=0.033), folic acid supplement (OR =0.248, P=0.050), iron supplement (OR=0.272, P<0.001) and eating blood products (OR=0.588, P=0.044) were the beneficial factors for anemia during pregnancy, while multipara (OR=2.917, P=0.003), long duration of menstrual period before pregnancy (OR=1.335, P=0.041), living in new decoration housing (OR=3.690, P=0.045) and tea-drinking (OR=1.365, P=0.094) were the risk factors for anemia during pregnancy. 
 CONCLUSION: The prevalence of anemia during pregnancy in Changsha is below the average levels. The occurrence of anemia during pregnancy is closely related to the women's economic level and nutritional status. Women should strengthen maternal nutrition during pregnancy and bedroom environment monitor, drink little strong tea and improve the nutritional status of iron during pregnancy.

Acute hepatitis induced by a Chinese herbal product Qibao Meiran Wan: a case study.

Qibao Meiran Wan is a Chinese herbal product sold as a therapy for tonifying the liver and kidney, dizziness, premature graying of hair, backache, constipation, and night sweats. It is widely available in Chinese pharmacies and drugstores and is sold without prescription. We describe a case of acute liver injury in a 26-year-old Chinese man who developed symptomatic hepatitis 1 month after starting Qibao Meiran Wan. There was no evidence of viral hepatitis, Epstein-Barr virus, cytomegalovirus, autoimmune hepatitis, or Budd-Chiari syndrome. The liver injury slowly resolved over 20 days after discontinuing the herbal product. Herbal toxicity was later confirmed by a liver biopsy. Qibao Meiran Wan contains a mixture of several plants including Polygonum multiflorum, which was previously associated with hepatotoxicity. To our knowledge, this is the first report of hepatotoxicity by Qibao Meiran Wan. Clinicians treating patients with acute hepatitis of unclear etiology should pay attention to the consumption of Qibao Meiran Wan.

Antitumor activity of caffeic acid 3,4-dihydroxyphenethyl ester and its pharmacokinetic and metabolic properties.

Caffeic acid 3,4-dihydroxyphenethyl ester (CADPE), a natural polyphenol from Sarcandra glabra, has potent in vitro anticancer activity through multiple targets. This study investigated its in vivo anticancer efficacy and its pharmacokinetic and metabolic characteristics. CADPE at any of the dosage regimes (ip 2.5 mg/kg at an interval of 7 h, 12 h, or 24 h for eight days) significantly decreased tumor growth in hepatoma H22 and sarcoma S180 tumor-bearing mice. CADPE also significantly inhibited H22-induced acute ascites development. The in vivo anticancer efficacies of CADPE in these tumor models were equivalent to those of 5-fluorouracil (10 mg/kg, ip) and cyclophosphamide (10 mg/kg, ip), and CADPE did not show any toxicity. A high performance liquid chromatography method with the aid of liquid chromatography/mass spectrometry was established and validated for the pharmacokinetic and metabolic studies of CADPE. CADPE was detected in blood and the organs including liver, kidney, heart, spleen, and brain 1 min after tail intravenous administration, indicating that CADPE was able to quickly distribute to these organs. CADPE was quickly hydrolyzed both in mice and in vitro mice plasma, but was much stable in vitro human plasma, suggesting a better bioavailability of CADPE in human than in mice. The major metabolites of CADPE in mice were caffeic acid, hydroxytyrosol, and a CADPE glucuronide. This was the first time to reveal the pharmacokinetic and metabolic characteristics of CADPE. Taken together, CADPE had potent in vivo antitumor activity and was able to rapidly reach the body organs and to be hydrolyzed in blood to anticancer agents of caffeic acid and hydroxytyrosol. This study suggested that CADPE has the potential for the treatment of cancers and is worthy of further study.

Effects of replenishing qi, promoting blood circulation and resolving phlegm on vascular endothelial function and blood coagulation system in senile patients with hyperlipemia.

OBJECTIVE: To observe the curative effect of the method of replenishing qi, promoting blood circulation and resolving phlegm on senile hyperlipemia and its effects on vascular endothelial function and blood coagulation system. METHOD: 96 patients with senile hyperlipemia were randomly divided into a treatment group and a control group. 56 patients in the treatment group orally took danshen jueming granules while 40 patients in the control group orally took xuezhikang capsules. Observed were indexes of blood lipid, vascular endothelial function, blood coagulation system and safety. RESULTS: After treatment, the treatment group was obviously superior to the control group (P < 0.05) in reducing plasma total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) as well as in the ratio of thromboxane B2 (TXB2) to 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha), D-dimer (D-D) and fibrinogen (FIB). CONCLUSION: Danshen Jueming Granules have the effect of regulating metabolism of blood lipid, and improving vascular endothelial function and blood coagulation system in senile patients with hyperlipemia.