Integration of pharmacodynamics, network pharmacology and metabolomics to elucidate effect and mechanism of Artemisia capillaris Thunb. in the treatment of jaundice.

ETHNOPHARMACOLOGICAL RELEVANCE: As one of the most commonly used herbs, Artemisia capillaris Thunb. (ACT) display favorable effect in the treatment of jaundice. However, mechanism of ACT in the treatment of jaundice remains unclear at present, which limits its development and application. AIM OF THE STUDY: To investigate effect and mechanism of Artemisia capillaris Thunb. (ACT) in the treatment of jaundice using pharmacodynamics, network pharmacology and metabolomics. METHODS: Effect of ACT in treating jaundice was evaluated by biochemical assays and pathological observation using the α-naphthyl isothiocyanate (ANIT)-induced mice. Jaundice-relieving mechanism of ACT was investigated by integration of network pharmacology and metabolomics. RESULTS: After the mice with jaundice were administrated ACT extract for 9 days, compared to that of the model group, serum D-BIL, T-BIL and ALP levels of the mice in the low, medium, high dose of ACT group decreased by 39.81%, 15.30% and 16.92%; 48.06%, 42.54% and 36.91%; 26.90%, 12.34% and 16.90%, respectively. The pathologic study indicated that ACT improved the symptoms of liver injury of the mice with jaundice. The network of herb (i.e., ACT)-components-targets-disease (i.e., jaundice) was established, which consisted of 17 components classified in flavonoids, chromones, organic acids, terpenoids, and 234 targets related to treatment of jaundice. Metabolomics analysis showed that, compared to that in the model group, level of 8 differential metabolites were upregulated and level of 29 differential metabolites were downregulated in the mice liver in the ACT group, respectively. The main metabolic pathways involved in treatment of jaundice by ACT were pantothenate and CoA biosynthesis, glutathione metabolism, biosynthesis of unsaturated fatty acids, primary bile acid biosynthesis in the liver, respectively. The integrated analysis of network pharmacology and metabolomics showed that 3α,7α,12α a-Trihydroxy-5ß-cholanate, glycocholate, taurocholate, pantetheine 4'-phosphate, and d-4'-phosphopantothenate were the potential biomarkers for treatment of jaundice, and AKR1C4, ALDH2 and HSD11B were the potential drug targets in the treatment of jaundice by ACT. CONCLUSION: The study based on metabolomics and network pharmacology indicated that ACT can display favorable jaundice-relieving effect by its multiple components regulating multiple biomarkers, multiple targets and multiple pathways, and may be a rational therapy for the treatment of jaundice.

Antimicrobial activities and mechanisms of extract and components of herbs in East Asia.

Antibacterial drugs face increasing challenges due to drug resistance and adverse reactions, which has created a pressing need for the discovery and development of novel antibacterial drugs. Herbs have played an important role in the treatment of infectious diseases. This review aims to summarize, analyze and evaluate the antibacterial activities and mechanisms of components from popular herbs in East Asia. In this review, we have searched and summarized the scientific papers published during the past twenty-year period from electronic databases such as PubMed, ScienceDirect, and Web of Science. These herbs and their components, including alkaloids, flavonoids, essential oils, terpenes, organic acids, coumarins and lignans, display potential antimicrobial effects. Herbal medicine formulas (HMFs) usually show stronger antibacterial activity than single herbs. Herbs and HMFs bring forth antibacterial activities by damaging cell membranes and walls, inhibiting nucleic acid and protein synthesis, and increasing intracellular osmotic pressure. These herbs and their components can be developed as potential and promising novel antibacterial herbal products.

Inhibition of Human UDP-Glucuronosyltransferases1A1-Mediated Bilirubin Glucuronidation by the Popular Flavonoids Baicalein, Baicalin, and Hyperoside Is Responsible for Herb (Shuang-Huang-Lian)-Induced Jaundice.

Bilirubin-related adverse drug reactions (ADRs) or malady (e.g., jaundice) induced by some herbs rich in certain flavonoids have been widely reported. However, the causes and mechanisms of the ADRs are not well understood. The aim of this paper was to explore the mechanism of Shuang-huang-lian (SHL) injections and its major constituents-induced jaundice via inhibiting human UDP-glucuronosyltransferases1A1 (hUGT1A1)-mediated bilirubin glucuronidation. The inhibitory effects of SHL and its major constituents in the herbal medicine, including baicalein (BAI), baicalin (BA), and hyperoside (HYP), on bilirubin glucuroBBREVInidation were investigated. This study indicated that the average formation rates of bilirubin glucuronides [i.e., mono-glucuronide 1 (BMG1), BMG2, and bilirubin diglucuronide] displayed significant differences (P < 0.05). Specifically, the formation of BMGs was favored regardless of whether an inhibitor was absent or present. SHL, BAI, BA, and HYP dose-dependently inhibit bilirubin glucuronidation, showing the IC50 values against total bilirubin glucuronidation were in the range of (7.69 ± 0.94)-(37.09 ± 2.03) µg/ml, (4.51 ± 0.27)-(20.84 ± 1.99) µM, (22.36 ± 5.74)-(41.35 ± 2.40) µM, and (15.16 ± 1.12)-(42.80 ± 2.63) µM for SHL, BAI, BA, and HYP, respectively. Both inhibition kinetics assays and molecular docking simulations suggested that SHL, BAI, BA, and HYP significantly inhibited hUGT1A1-mediated bilirubin glucuronidation via a mixed-type inhibition. Collectively, some naturally occurring flavonoids (BAI, BA, and HYP) in SHL have been identified as the inhibitors against hUGT1A1-mediated bilirubin glucuronidation, which well explains the bilirubin-related ADRs or malady triggered by SHL in clinical settings. SIGNIFICANCE STATEMENT: Herbal products and their components (e.g., flavonoids), which been widely used across the entire world, may cause liver injury. As a commonly used herbal products rich in flavonoids, SHL injections easily lead to symptoms of liver injury (e.g., jaundice) owing to significant inhibition of hUGT1A1-mediated bilirubin glucuronidation by its flavonoid components (i.e., baicalein, baicalin, and hyperoside). Herb-induced bilirubin-related ADRs and the associated clinical significance should be seriously considered.

Effects of vitamin A supplementation in the diet of breeding geese on offspring intestinal tissue morphology and immune performance.

OBJECTIVE: The effects of maternal and offspring dietary vitamin A (VA) supplementation on early body weight, digestive tract function and immune function in goslings were studied. METHODS: Yangzhou geese (180 d old) were randomly divided into 5 experimental groups of 15 females and 3 males (the males were kept until slaughter). Eggs were collected for hatching during the peak laying period. A total of 96 goslings were selected from each treatment group (each fed a basic diet supplemented with 0, 4,000, 8,000, 12,000 or 16,000 IU/kg VA) and randomly divided into 2 groups, with 6 replicates in each group and 8 goslings in each replicate. The gosling diet was supplemented with 0 or 9,000 IU/kg VA. RESULTS: i) Villus length, villus width and the muscle thickness of the duodenum, jejunum and ileum were increased and the crypt depth was reduced after adding 12,000 IU/kg VA to the goslings' diet (p<0.05). Adding 9,000 IU/kg VA to the offspring diet increased the length of the duodenal villi and width of the ileum and decreased the crypt depth of the ileum (p<0.05). ii) Supplementing the maternal diet with 12,000 IU/kg VA increased immune organ weight, the immune organ index and immunoglobulin content in goslings (p<0.05). The bursa weight and immunoglobulin G content of offspring were higher in the 9,000 IU/kg VA supplementation group than in the group with no supplementation (p<0.05). CONCLUSION: Offspring growth and development were affected by the amount of VA added into maternal diet. The negative effect of maternal VA deficiency on offspring can be compensated by adding VA to the offspring diet. Continued VA supplementation in the offspring diet after excessive VA supplementation in the maternal diet is unfavorable for gosling growth and development.