Evodiae Fructus Research Articles

Structural characteristics of a purified Evodiae fructus polysaccharide and its gastroprotection and relevant mechanism against alcohol-induced gastric lesions in rats

Evodiae fructus polysaccharide (EFP) has been previously shown to protect against alcohol-induced gastric lesions. However, which and how active fractions in EFP exert gastroprotection remains unclear. This study aimed to characterize the structure of the purified fraction (EFP-2-1) of EFP, and investigate its gastroprotection and underlying mechanisms. EFP-2-1 was obtained through column chromatography, and was characterized using instrumental analytical techniques. Gastroprotective effect of EFP-2-1 was evaluated using alcohol-induced gastric lesions in rats, and its mechanism was explored through proteomics, metabolomics and diversity sequencing. Results showed that EFP-2-1 had a molecular weight of 7.3 kDa, and consisted mainly of rhamnose, galacturonic acid, galactose and arabinose. Its backbone contained HG and RG-I domains, and branched with →5)-α-l-Araf-(1→, α-l-Araf-(1→ and →4)-β-d-Galp-(1→ residues. EFP-2-1 reduced gastric lesions and the levels of MDA, TNF-α and IL-6, activated PPARγ, primarily altered protein digestion and absorption and bile secretion metabolic pathways, regulated gut microbiota like Faecalibaculum and Lachnoclostridium, and increased short-chain fatty acids production. Correlations were observed among the gut microbiota, metabolites and biochemical indexes influenced by EFP-2-1. These findings suggest that EFP-2-1 is an active fraction of EFP for protecting against alcohol-induced gastric lesions, which may be linked to PPARγ activation, gut microbiota and serum metabolism.

The Extracts of Evodiae Fructus and Stephaniae Tetrandrae Radix Show Synergy in Blocking the Entry of SARS-CoV-2

Given the fact that herbal extracts have been effectively used in clinical applications and have well-established safety records, our current findings suggest that these drug combinations might be considered as potential anti-COVID-19 treatments.

Toxicity evaluation of processing Evodiae fructus based on intestinal microbiota.

With the development of healthcare services, drug efficacy, and safety have become the focus of drug use, and processing alters drug toxicity and efficacy, exploring the effects of processing on Evodiae fructus (EF) can guide the clinical use of drugs. Fifty male Kunming mice were randomly divided into the control group (CCN), raw small-flowered EF group (CRSEF), raw medium-flowered EF group (CRMEF), processing small-flowered EF group (CPSEF), and processing medium-flowered EF group (CPMEF). The CRSEF, CRMEF, CPSEF, and CPMEF groups were gavaged with aqueous extracts of raw small-flowered EF dry paste (RSEF), medium-flowered EF dry paste (RMEF), processing small-flowered EF dry paste (PSEF) and processing medium-flowered EF dry paste (PMEF), respectively, for 21 days at 5 times the pharmacopeial dosage. Upon concluding the experiment, histopathological sections of liver and kidney tissues were examined. Additionally, levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum creatinine (SCr), and blood urea nitrogen (BUN) were determined. DNA from the intestinal contents of the mice was extracted, and 16S rRNA full-length high-throughput sequencing was performed. After fed EF 21 days, mice exhibited a decreasing trend in body weight. Comparative analysis with the CCN group revealed an upward trend in SCr, BUN, AST, and ALT levels in both CRSEF and CRMEF groups. The CRMEF group displayed notably elevated BUN and AST levels, with an observed increasing trend in Scr and ALT. Kidney sections unveiled cellular edema and considerable inflammatory cell infiltrates, whereas significant liver damage was not evident. Compared with CRSEF, Bun levels were significantly lower while AST levels were significantly higher in the CPMEF group. Additionally, the intestinal microbiota diversity and the relative abundance of Psychrobacter decreased significantly, and the relative abundance of Staphylococcus, Jeotgalicoccus, and Salinicoccus increased significantly in the CPMEF group. AST, ALT, and SCr were positively correlated with Staphylococcus, Jeotgalicoccus, and Salinicoccus. In conclusion, PMEF significantly increased harmful bacteria (Staphylococcus, Jeotgalicoccus, and Salinicoccu) and decreased beneficial bacteria. SEF with 5 times the clinical dose showed nephrotoxicity and SEF nephrotoxicity decreased after processing, but EF hepatotoxicity was not significant, which may be due to insufficient dose concentration and time.

Evodiae Fructus extract suppresses inflammatory response in HaCaT cells and improves house dust mite-induced atopic dermatitis in NC/Nga mice

This study was conducted to assess the effect of Evodiae Fructus 70% ethanol extract (EFE) on the pathology of atopic dermatitis using in vitro and in vivo models. The major compounds in EFE were identified by ultra-performance liquid chromatography with tandem mass spectrometry as rutaecarpine, evodiamine, evodol, dehydroevodiamine, limonin, synephrine, evocarpine, dihydroevocarpine, and hydroxyevodiamine. EFE significantly decreased chemokine levels in tumor necrosis factor-α/interferon-γ-stimulated HaCaT cells. In house dust mite-treated NC/Nga mice, topical application of EFE significantly decreased the dermatitis score, epidermal hyperplasia and thickening, mast cell infiltration, and plasma levels of histamine and corticosterone. Thymic stromal lymphopoietin, CD4+ T cells, interleukin-4, and intercellular adhesion molecule-1 expression in the lesioned skin was reduced in the treated mice. The mechanism of EFE was elucidated using transcriptome analysis, followed by experimental validation using Western blotting in HaCaT cells. EFE down-regulated the activation of Janus kinase (JAK)-signal transducers and activators of transcription (STAT) and mitogen-activated protein kinases (MAPK) signaling pathways in HaCaT cells. EFE improves atopic dermatitis-like symptoms by suppressing inflammatory mediators, cytokines, and chemokines by regulating the JAK-STAT and MAPK signaling pathways, suggesting its use as a potential agent for the treatment of atopic dermatitis.

Licorice processing involving functions of Evodiae Fructus on liver inflammation and oxidative stress are associated with intestinal mucosal microbiota.

This study aimed to investigate the effects of licorice processing of different Evodiae Fructus (EF) specifications on liver inflammation and oxidative stress associated with the intestinal mucosal microbiota. The 25 Kunming mice were divided into control (MCN), raw small-flowered Evodiae Fructus (MRSEF), raw medium-flowered EF (MRMEF), licorice-processed small-flowered EF (MLSEF), and licorice-processed medium-flowered EF (MLSEF) groups. The EF intervention groups were given different specifications of EF extract solutions by gavage. After 21 days, indices of liver inflammation and oxidative stress and intestinal mucosal microbiota were measured in mice. Compared with the MCN, malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels were significantly increased in the MRMEF. Although the trends of oxidative stress and inflammatory indexes in the MLSEF and MLMEF were consistent with those in the raw EF groups, the changes were smaller than those in the raw EF groups. Compared to the raw EF groups, the MLSEF and MLMEF showed closer approximations of metabolic function to the MCN. The abundance of Corynebacterium in MRMEF was significantly lower than that in the MCN, and it was not significantly different from the MCN after licorice processing. The probiotic Candidatus Arthromitus was enriched in the MLSEF. The probiotic Lactobacillus was enriched in the MLMEF. Correlation analysis revealed significant negative correlations between IL-1β, some metabolic functions and Corynebacterium. The effects of medium-flowered EF on oxidative stress and inflammatory factors in the liver of mice were stronger than those of small-flowered EF. The licorice processing can reduce this difference by modulating the abundance of Corynebacterium and intestinal mucosal metabolic function.

Protective effect of Evodiae Fructus extract in HCl/ethanol-induced gastritis mice

Protective effect of Evodiae Fructus extract in HCl/ethanol-induced gastritis mice

Interpreting the chemical changes and therapeutic effect of Coptidis Rhizoma against ulcerative colitis before and after processing based on mathematical statistics and network pharmacology.

Coptidis Rhizoma (CR) is one of the most frequently used herbs to treat ulcerative colitis (UC) and is often processed before usage. However, the composition changes and therapeutic effects of CR before and after processing in the treatment of UC are still unclear. The purpose of the study is to explore the chemical components and therapeutic effects of crude and processed CR. CR was processed according to the 2020 version of the Chinese Pharmacopoeia. The liquid chromatography-mass spectrometry (LC-MS) and multivariate statistical analysis were used to screen the different compounds before and after processing. The network pharmacological prediction was carried out. The mechanism and therapeutic effects between crude and processed CR were verified by using dextran sulphate sodium-induced UC mice assay. Ten compounds distinguish crude and processed CR based on multivariate statistical analysis. Network pharmacology predicts that the 10 compounds mainly play a role through TNF-α and IL-6 targets and PI3K/Akt and HIF-1 signalling pathways, and these results are verified by molecular biology experiments. For IL-6, IL-10 and TNF-α inflammatory factors, CR is not effective, while CR stir-fried with Evodiae Fructus (CRFE) and ginger juice (CRGJ) are. For PI3K/p-Akt, Cleaved caspase3, NF- κBp65 and HIF-1α signalling pathways, CR has therapeutic effects, while CRFE and CRGJ are significant. Overall, CRFE and CRGJ show better effects in treating UC. The chemical changes of processing and the efficacy of processed CR are correlated, which provides a scientific basis for the clinical use of crude and processed CR.

Zhuyu Pill Alleviates Nonalcoholic Fatty Liver Disease by Regulating Bile Acid Metabolism through the Gut-Liver Axis.

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide, but there are currently limited treatment options available. Therefore, it is necessary to research new treatment strategies. Zhuyu Pill (ZYP) is a well-known herbal recipe consisting of Huanglian (Coptidis rhizoma) and Wuzhuyu (Evodiae Fructus) that has been clinically used to treat NAFLD. This study aimed to investigate the impact of ZYP on NAFLD induced by a high-fat diet (HFD) and to identify its potential mechanism. In this investigation, we used ZYP to treat a mouse model of NAFLD induced by an HFD. We conducted various analyses including assessment of serum biochemical indices, histological evaluation, fecal metabonomics analysis, western blot, and quantitative real-time polymerase chain reaction. ZYP effectively improved blood lipid levels and reduced inflammatory response in HFD mice, while also alleviating liver cell damage and lipid accumulation. Additionally, ZYP influenced the fecal bile acid (BA) metabolism profiles of HFD mice by inhibiting the signal transduction of ileal farnesoid X receptor (FXR) fibroblast growth factor 15 (FGF15), enhancing the expression of cytochrome P450 family 7 subfamily A member 1(CYP7A1), promoting BA synthesis and increasing the metabolic elimination of cholesterol. ZYP shows promise as a potential treatment for alleviating NAFLD by modulating BA metabolism through the FXR-FGF15-CYP7A1 pathway.

Study on the molecular mechanism of anti-liver cancer effect of Evodiae fructus by network pharmacology and QSAR model.

Introduction: Evodiae Fructus (EF) is the dried, near ripe fruit of Euodia rutaecarpa (Juss.) Benth in Rutaceae. Numerous studies have demonstrated its anti-liver cancer properties. However, the molecular mechanism of Evodiae fructus against liver cancer and its structure-activity connection still require clarification. Methods: We utilized network pharmacology and a QSAR (2- and 3-dimensional) model to study the anti-liver cancer effect of Evodiae fructus. First, by using network pharmacology to screen the active substances and targets of Evodiae fructus, we investigated the signaling pathways involved in the anti-liver cancer actions of Evodiae fructus. The 2D-QSAR pharmacophore model was then used to predict the pIC50 values of compounds. The hiphop method was used to create an ideal 3D-QSAR pharmacophore model for the prediction of Evodiae fructus compounds. Finally, molecular docking was used to validate the rationality of the pharmacophore, and molecular dynamics was used to disclose the stability of the compounds by assessing the trajectories in 10ns using RMSD, RMSF, Rg, and hydrogen bonding metrics. Results: In total, 27 compounds were acquired from the TCMSP and TCM-ID databases, and 45 intersection targets were compiled using Venn diagrams. Network integration analysis was used in this study to identify SRC as a primary target. Key pathways were discovered by KEGG pathway analysis, including PD-L1 expression and PD-1 checkpoint pathway, EGFR tyrosine kinase inhibitor resistance, and ErbB signaling pathway. Using a 2D-QSAR pharmacophore model and the MLR approach to predict chemical activity, ten highly active compounds were found. Two hydrophobic features and one hydrogen bond acceptor feature in the 3D-QSAR pharmacophore model were validated by training set chemicals. The results of molecular docking revealed that 10 active compounds had better docking scores with SRC and were linked to residues via hydrogen and hydrophobic bonds. Molecular dynamics was used to show the structural stability of obacunone, beta-sitosterol, and sitosterol. Conclusion:Pharmacophore 01 has high selectivity and the ability to distinguish active and inactive compounds, which is the optimal model for this study. Obacunone has the optimal binding ability with SRC. The pharmacophore model proposed in this study provides theoretical support for further screening effective anti-cancer Chinese herbal compounds and optimizing the compound structure.

The Ethanol Extract of Evodiae Fructus and Its Ingredient, Rutaecarpine, Inhibit Infection of SARS-CoV-2 and Inflammatory Responses

COVID-19, derived from SARS-CoV-2, has resulted in millions of deaths and caused unprecedented socioeconomic damage since its outbreak in 2019. Although the vaccines developed against SARS-CoV-2 provide some protection, they have unexpected side effects in some people. Furthermore, new viral mutations reduce the effectiveness of the current vaccines. Thus, there is still an urgent need to develop potent non-vaccine therapeutics against this infectious disease. We recently established a series of detecting platforms to screen a large library of Chinese medicinal herbs and phytochemicals. Here, we reveal that the ethanolic extract of Evodiae Fructus and one of its components, rutaecarpine, showed promising potency in inhibiting the activity of 3C-like (3CL) protease, blocking the entry of the pseudo-typed SARS-CoV-2 (including wild-type and omicron) into cultured cells. In addition, inflammatory responses induced by pseudo-typed SARS-CoV-2 were markedly reduced by Evodiae Fructus extract and rutaecarpine. Together our data indicate that the herbal extract of Evodiae Fructus and rutaecarpine are potent anti-SARS-CoV-2 agents, which might be considered as a treatment against COVID-19 in clinical applications.

Chromatographic and mass spectrometric technologies for chemical analysis of Euodiae fructus: A review.

Euodiae fructus, also known as Evodiae fructus, is a popular Chinese herbal medicine derived from the dried, nearly ripe fruits of Tetradium ruticarpum (A. Juss.) T. G. Hartley. The main bioactive constituents of Euodiae fructus are alkaloids, limonoids, flavonoids, and anthraquinones. The contents of these compounds vary greatly between different plant species, geographic locations, and harvest times, which thus affect the therapeutic effects. We aimed to summarize the chromatographic and mass spectrometric technologies applied for chemical analysis and quality evaluation of Euodiae fructus. Moreover, we aimed to emphasize the diverse soft ionization techniques and mass analyzers of LC-MS methods for assessment of Euodiae fructus. A literature study was carried out by retrieving articles published between January 1988 and December 2021 from well-known databases, including PubMed, ASC, Elsevier, ScienceDirect, J·STAGE, Thieme, Taylor & Francis, Springer Link, Wiley Online Library, and CNKI. The chemical analysis methods were described in several categories in accordance with the used analytical techniques, including thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), high-performance liquid chromatography-mass spectrometry (HPLC-MS), gas chromatography-mass spectrometry (GC-MS), capillary electrophoresis (CE), and counter-current chromatography (CCC). This review systematically summarizes the achievements in chemical analysis and quality evaluation of Euodiae fructus published in over three decades, covering the various chromatographic and mass spectrometric technologies applied for identification and quantification of phytochemical constituents. The summary serves as an important basis for future phytochemical research and implementation of quality control methods in order to ensure the efficacy and safety of Euodiae fructus.

The pharmacokinetics profiles, pharmacological properties, and toxicological risks of dehydroevodiamine: A review.

Dehydroevodiamine (DHE) is a quinazoline alkaloid isolated from Evodiae Fructus (EF, Wuzhuyu in Chinese, Rutaceae family), a well-known traditional Chinese medicine (TCM) which is clinically applied to treat headache, abdominal pain, menstrual pain, abdominal distension, vomiting, acid regurgitation, etc. Modern research demonstrates that DHE is one of the main components of EF. In recent years, DHE has received extensive attention due to its various pharmacological activities. This review is the first to comprehensively summarize the current studies on pharmacokinetics profiles, pharmacological properties, and toxicological risks of DHE in diverse diseases. Pharmacokinetic studies have shown that DHE has a relatively good oral absorption effect in the mean concentration curves in rat plasma and high absorption in the gastrointestinal tract. In addition, distribution re-absorption and enterohepatic circulation may lead to multiple blood concentration peaks of DHE in rat plasma. DHE possesses a wide spectrum of pharmacological properties in the central nervous system, cardiovascular system, and digestive system. Moreover, DHE has anti-inflammatory effects via downregulating pro-inflammatory cytokines and inflammatory mediators. Given the favorable pharmacological activity, DHE is expected to be a potential drug candidate for the treatment of Alzheimer's disease, chronic stress, amnesia, chronic atrophic gastritis, gastric ulcers, and rheumatoid arthritis. In addition, toxicity studies have suggested that DHE has proarrhythmic effects and can impair bile acid homeostasis without causing hepatotoxicity. However, further rigorous and well-designed studies are needed to elucidate the pharmacokinetics, pharmacological effects, potential biological mechanisms, and toxicity of DHE.

Mechanisms of Chinese Medicine in Gastroesophageal Reflux Disease Treatment: Data Mining and Systematic Pharmacology Study.

To identify specific Chinese medicines (CMs) that may benefit patients with gastroesophageal reflux disease (GERD), and explore the action mechanism. Domestic and foreign literature on the treatment of GERD with CMs was searched and selected from China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, and PubMed from October 1, 2011 to October 1, 2021. Data from all eligible articles were extracted to establish the database of CMs for GERD. Apriori algorithm of data mining techniques was used to analyze the rules of herbs selection and core Chinese medicine formulas were identified. A system pharmacology approach was used to explore the action mechanism of these medicines. A total of 278 prescriptions for GERD were analyzed, including 192 CMs. Results of Apriori algorithm indicated that Evodiae Fructus and Coptidis Rhizoma were the highest confidence combination. A total of 32 active ingredients and 66 targets were screened for the treatment of GERD. Enrichment analysis showed that the mechanisms of action mainly involved pathways in cancer, fluid shear stress and atherosclerosis, advanced glycation end product (AGE), the receptor for AGE signaling pathway in diabetic complications, bladder cancer, and rheumatoid arthritis. Evodiae Fructus and Coptidis Rhizoma are the core drugs in the treatment of GERD and the potential mechanism of action of these medicines includes potential target and pathways.

Evodiamine as the Active Compound of Evodiae fructus to Inhibit Proliferation and Migration of Prostate Cancer through PI3K/AKT/NF-κB Signaling Pathway.

Evodiae fructus (EF) is a traditional Chinese medicine which is widely used for the treatment of obesity, inflammation, cardiovascular disease, and diseases of the central nervous system. Recent studies have demonstrated the anticancer property of EF, but the active compounds of EF against prostate cancer and its underlying mechanism remain unknown. In this study, a network pharmacology-based approach was used to explore the multiple ingredients and targets of EF. Through protein-protein interaction (PPI), Gene Ontology (GO) enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, the potential targets and corresponding ingredients of EF against prostate cancer cells were obtained. CCK8 and colony formation assays were performed to evaluate the antiproliferative effect of the active compounds on DU145 cells. Cell cycle analysis, Annexin V-FITC/PI staining assay, and Hoechst 33258 staining assay were used to explore the way of evodiamine-induced cell death. The capacities of cell migration after evodiamine treatment were evaluated by wound-healing assay. PharmMapper database was used to predict the potential targets of evodiamine against cancer cell migration. Western blot assay was performed to investigate the signaling pathway through which evodiamine inhibits cell proliferation and migration. The binding of evodiamine to PI3K and AKT was verified by molecular docking. As a consequence, 24 active compounds and 141 corresponding targets were obtained through a network pharmacology-based approach. The results of PPI analysis, GO enrichment, and KEGG pathway enrichment indicated that molecules in the PI3K/AKT/NF-κB signaling pathway were the potential targets of EF against prostate cancer, and evodiamine was the potential active compound. In vitro study demonstrated that evodiamine displays antiproliferative effect on DU145 cells obviously. Evodiamine induces G2/M cell cycle arrest by Cdc25c/CDK1/cyclin B1 signaling. Additionally, evodiamine also promotes mitochondrial apoptosis and inhibits cell migration through PI3K/AKT/NF-κB signaling in DU145 cells. In conclusion, evodiamine is the active compound of EF to inhibit proliferation and migration of prostate cancer through PI3K/AKT/NF-κB signaling pathway, indicating that evodiamine may serve as a potential lead drug for prostate cancer treatment.

Protective effects of Evodiae Fructus extract against ultraviolet-induced MMP-1 and MMP-3 expression in human dermal fibroblasts

Evodiae Fructus (EF) has been used as a traditional medicine for abdominal pain, headache, bleeding, and menorrhea in Asian countries. However, the effect of EF extract (EFE) on ultraviolet (UV)B-induced photoaging remains unknown. This study aimed to investigate the effects and molecular mechanisms of UVB-induced matrix metalloproteinase (MMP)−1 and MMP-3 expression in primary human dermal fibroblasts (HDFs). In HDFs, the expression of MMP-1, MMP-3 and pro-collagenA2 were analyzed using western blotting and real-time polymerase chain reaction. The phosphorylation levels of mitogen-activated protein kinase (MAPK) and activation of nuclear factor (NF)-κB and activator protein (AP)−1 were assessed using western blotting. Results showed that EFE reduced UVB-induced MMP-1 and MMP-3 expression, and this effect was mediated by the inhibition of MAPK/NF-κB and AP-1 activation. Moreover, EFE prevented UVB-induced inhibition of collagen synthesis. Taken together, these results suggest that EFE may have a preventive potential against photoaging.

Chemical Investigation of Tetradium ruticarpum Fruits and Their Antibacterial Activity against Helicobacter pylori.

The fruit of Tetradium ruticarpum, known as Evodiae Fructus, is a traditional herbal medicine used to treat gastric and duodenal ulcers, vomiting, and diarrhea. The traditional usage can be potentially associated with the antibacterial activity of T. ruticarpum fruits against Helicobacter pylori. However, so far, the antibacterial activity of T. ruticarpum fruits and antibacterial components against H. pylori has not been investigated despite the traditional folk use. The current study was conducted to investigate the bioactive chemical components of T. ruticarpum fruits and evaluate their antibacterial activity against H. pylori. Phytochemical investigation of the EtOH extract of T. ruticarpum fruits led to the isolation and identification of nine compounds (1–9), including phellolactone (1), the absolute configuration of which has not yet been determined. The chemical structures of the isolated compounds were elucidated by analyzing the spectroscopic data from one-dimensional (1D) and two-dimensional (2D) NMR and high-resolution electrospray ionization mass spectrometry (HR-ESIMS) experiments. Specifically, the absolute configuration of compound 1 was established by the application of computational methods, including electronic circular dichroism (ECD) calculation and the NOE/ROE-based interproton distance measurement technique via peak amplitude normalization for the improved cross-relaxation (PANIC) method. In the anti-H. pylori activity test, compound 3 showed the most potent antibacterial activity against H. pylori strain 51, with 94.4% inhibition (MIC50 and MIC90 values of 22 and 50 μM, respectively), comparable to that of metronidazole (97.0% inhibition, and MIC50 and MIC90 values of 17 and 46 μM, respectively). Moreover, compound 5 exhibited moderate antibacterial activity against H. pylori strain 51, with 58.6% inhibition (MIC50 value of 99 μM), which was higher than that of quercetin (34.4% inhibition) as a positive control. Based on the bioactivity results, we also analyzed the structure–activity relationship of the anti-H. pylori activity. Conclusion: These findings demonstrated that T. ruticarpum fruits had antibacterial activity against H. pylori and could be used in the treatment of gastric and duodenal ulcers. Meanwhile, the active compound, 1-methyl-2-(8E)-8-tridecenyl-4(1H)-quinolinone (3), identified herein also indicated the potential application in the development of novel antibiotics against H. pylori.

An Open-Label Exploratory Clinical Trial Evaluating the Effects of GLS (Coptidis Rhizoma-Evodiae Fructus 2 : 1) on Fibroblast Growth Factor 21 in Patients with Nonalcoholic Fatty Liver Disease.

Methods In a 12-week, open-label, exploratory clinical trial, 126 NAFLD patients were randomly divided into the GLS group (lifestyle intervention plus GLS) or the polyene phosphatidylcholine (PPC) group (lifestyle intervention plus PPC). Random numbers generated by DPS software were used in combination with opaque, sealed envelopes for allocation concealment. At baseline as well as at the end of the study, anthropometric parameters, glucose, lipids, hepatic enzymes, and FGF 21 were measured, with hepatic fat accumulation assessed by ultrasound (US) and US-based controlled attenuation parameter (CAP). Results 119 patients completed the study. Baseline parameters did not significantly differ between the two groups (P > 0.05). Compared with PPC, GLS decreased more significantly in hepatic fat accumulation, body weight index, waist circumference, waist-to-hip ratio, serum glucose, total cholesterol, triglyceride, low-density lipoprotein cholesterol, alanine transaminase, aspartate transaminase, gamma-glutamyl transferase, and FGF 21 (P < 0.05). The effects of GLS on waist circumference, waist-to-hip ratio, CAP, and gamma-glutamyl transferase (GGT) were positively correlated with serum FGF 21 (r = 0.343, 0.342, 0.315, and 0.374, respectively, P < 0.05). The GGT and FGF-21 changes were also confirmed by multiple linear regression analysis (B, 0.777; 95% CI: 0.307–1.247, P < 0.05). Conclusion GLS has a significant hepatoprotective effect on NAFLD patients, causing a decrease in FGF-21 secretion in response to the damage itself.

HERG Channel-Related Cardiotoxicity Assessment of 13 Herbal Medicines

Objectives: As the use of herbal medicinal products (HMPs) increases worldwide, systematic verification of the safety of HMPs is required. The induction of cardiotoxicity is one of the major factors in post-approval withdrawal of medicinal products, and drug-induced cardiotoxicity assessment is emerging as an important step in drug development. In the present study, we evaluated human ether-à-go-go-related gene (hERG) potassium channel-related cardiotoxicity to predict the risk of cardiac arrhythmia in thirteen herbal medicines known to have cardiac toxicity. Methods: We measured the inhibition rate of hERG potassium channel activity of 13 medicinal herbal extracts in hERG-expressing HEK 293 cells using an automated patch-clamping system. Quinidine was used as a positive control for inhibition of hERG activity. Results: Extracts of Evodiae Fructus, Strychni Semen, and Corydalis Tuber potently inhibited the activity of hERG, and IC&lt;sub&gt;50&lt;/sub&gt; values were 3.158, 19.87, and 41.26 &lt;i&gt;μ&lt;/i&gt;g/mL, respectively. Cnidi Fructus, Ephedra Herba, Lithospermi Radix, Polygoni Multiflori Radix, Visci Ramulus et Folium, Asiasari Radix et Rhizoma, and Scolopendra weakly inhibited hERG activity, and the IC&lt;sub&gt;50&lt;/sub&gt; value for each herbal medicine was more than 400 &lt;i&gt;μ&lt;/i&gt;g/mL. Aconiti Kusnezoffii Tuber and two types of Aconiti Lateralis Radix Preparata (Po and Yeom) had weak inhibitory activity against hERG, and the IC&lt;sub&gt;50&lt;/sub&gt; values were more than 700 &lt;i&gt;μ&lt;/i&gt;g/mL. The IC&lt;sub&gt;50&lt;/sub&gt; value of quinidine against hERG was 1.021 &lt;i&gt;μ&lt;/i&gt;M. Conclusion: Evodiae Fructus, Strychni Semen, and Corydalis Tuber acted as potent inhibitors against hERG. These herbal medicines may cause cardiac arrhythmia through QT prolongation, so care should be taken when taking them.

In-depth investigation of the effective substances of traditional Chinese medicine formula based on the novel concept of co-decoction reaction-using Zuojin decoction as a model sample

Zuojin decoction (ZJD) is a classic pair composed of Coptidis Rhizoma and Evodiae Fructus, which is suitable for treating gastrointestinal diseases and tumours, etc. In recent years, scientists have been widely focused on research into the treatment of liver cancer using ZJD; however, the effective substances have not yet been comprehensively elucidated. The difference between the co-decoction and the single decoction of ZJD is revealed in this paper based on the UPLC-QE-Orbitrap-MS, and the chemical components absorbed into the blood and liver of mice have been analyzed simultaneously. In addition, the combination of prototype components absorbed into the liver with liver cancer-related targets has been performed via molecular docking to explore the mechanism of ZJD in treating liver cancer. By comparing the co-decoction and single decoction of ZJD, 44 new components appeared during co-decoction and 76 known chemical compounds have been identified at the same time. It has been confirmed that 35 known components and 11 new components were absorbed into the blood. Furthermore, 20 known components were discovered from the sample of liver tissue. Molecular docking results showed that 3-O-feruloylquinic acid has good conjugation with Bcl-2, Stat3, mTOR, and mmp9. Catechin has the lowest binding energy with CDK6 and β-catenin. The study provides data for the further confirmation of the material basis and mechanism of ZJD in treating liver cancer, and provides a new idea for the researches on the compatibility mechanism of prescriptions of traditional Chinese medicine.

Effect of Evodiae Fructus and Arecae Semen Mixture on Esophageal Mucosa in Chronic Acid Reflux Esophagitis

Effect of Evodiae Fructus and Arecae Semen Mixture on Esophageal Mucosa in Chronic Acid Reflux Esophagitis