Zingiberis Rhizoma Research Articles

Mechanism Study of Xiaoyao San against Nonalcoholic Steatohepatitis-Related Liver Fibrosis Based on a Combined Strategy of Transcriptome Analysis and Network Pharmacology.

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disease worldwide. Nonalcoholic steatohepatitis (NASH) is an advanced form of NAFLD. The livers of patients with NASH are more likely to develop fibrosis. Xiaoyao San (XYS) is a classic traditional Chinese medicine (TCM) formula that has been widely used in treating liver diseases. In this study, we elucidated the effects and mechanism of XYS in treating NASH-related liver fibrosis by combining high-throughput sequencing-based high-throughput screening with network pharmacology analysis. Our work revealed that XYS may play a role in preventing NASH-related liver fibrosis by regulating biological functions related to the extracellular matrix (ECM), inflammation, and metabolism. Additionally, Bupleuri Radix, Poria, Zingiberis Rhizoma Recens, and Paeoniae Radix Alba are the key herbs of XYS that could partially represent the functions of XYS. These regulatory effects are mediated by targeting signal transducer and activator of transcription 3 (STAT3), nuclear factor kappa B (NFκB), and peroxisome proliferator-activated receptor gamma (PPARγ) signaling. Narcissin, casuarictin, and γ-sitosterol were identified as representative active compounds in XYS targeting STAT3, NFκB, and PPARγ, respectively. Taken together, our findings provide a novel strategy for investigating the pharmacological effects and biological mechanisms of a TCM formula.

Effects of Extraction Methods on Volatile Oil Profiles of Cinnamomi ramulus–Zingiberis rhizoma recens Couplet Medicines

Cinnamomi ramulus (CR, Guizhi in Chinese) and Zingiberis rhizoma recens (ZRR, Shengjiang in Chinese) are couplet medicines (drug pairs or drug combinations) in traditional Chinese medicine prescriptions. They contain a high amount of volatile oils which endow them with unique flavors and pharmacological activities. Extraction methods have a great influence on the extraction efficiency and composition of volatile oils. Firstly, the volatile oils of CR and ZRR were extracted by steam distillation (SD) and analyzed by GC-MS to obtain their chemical profiles. In total, 35 and 55 compounds were identified in the volatile oils of CR and ZRR, respectively. In order to find a suitable extraction method for the couplet medicine CR-ZRR, subsequently, steam distillation (SD), azeotropic distillation (AD) and supercritical fluid extraction (SFE) were applied to extract the volatile oils from CR-ZRR. The average extraction yields by SD, AD and SFE were 0.573%, 0.62% and 2.135%, respectively. The chemical composition of the volatile oils was then analyzed by GC-MS. In total, 73, 59 and 71 compounds were identified from the extracts obtained by SD, AD and SFE, respectively. Principal component analysis (PCA) and OPLS-DA showed that citral, (E)-cinnamaldehyde dimethyl acetal, zingiberene, cinnamaldehyde and β-sesquiphellandrene were the main contributors to distinguish the volatile oils that were obtained by different processes. Considering the chemical diversity and the total content of the main bioactive components of the volatiles oils, SD was more suitable for CR-ZRR volatile oil extraction. This study provides a basis for elucidating the chemical composition and suitable extraction method for the volatile oils of CR-ZRR.

Comparative pharmacokinetics of multi-components in normal and stomach cold syndrome rats after oral administration of Zingiberis Rhizoma − Jujubae Fructus herb pair and its single herb extracts by UHPLC-MS/MS

The Zingiberis Rhizoma − Jujubae Fructus herb pair (ZJHP) is a classic herb pair in traditional Chinese medicine. The herb pair shows the effect of dispelling cold, harmonizing the middle and improving gastrointestinal function, and is widely used for patients with stomach cold syndrome (SCS), stomachache and anemofrigid cold. The gingerols, shogaols, flavonoids and triterpenic acids are the important bioactive ingredients of ZJHP. However, few pharmacokinetic studies have been investigated in vivo for the above compounds. To comprehend the kinetics of active components and promote their curative application, a fast and sensitive ultra-high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS/MS) method was established for simultaneous determination of 12 analytes in normal and SCS rats in this study. The results showed that the pharmacokinetic parameters (Cmax, Tmax, t1/2z, MRT0-t, AUC0-t and AUC0-∞) in SCS model were significantly different from those in normal rats. In addition, the pharmacokinetics of rats given ZJHP were also varied from single herb oral administration, especially in model condition. These results indicated that the in vivo processes of the above analytes changed under pathological conditions and the compatibility of the herb pair could significantly influence the absorption of active components, which might provide an insight and further supports for the clinical application of ZJHP.

Untargeted serum and gastric metabolomics and network pharmacology analysis reveal the superior efficacy of zingiberis rhizoma recens-/euodiae fructus-processed Coptidis Rhizoma on gastric ulcer rats

Ethnopharmacological relevanceZingiberis rhizoma recens-/wine-/euodiae fructus-processed Coptidis Rhizoma (CR, zCR/wCR/eCR) are the commonly used processed products of CR in clinic. After being processed with different excipients, the efficacy of CR will change accordingly. I.e., wCR could resolve excessive heat of the upper energizer, zCR could eliminate gastric heat and harmonize the stomach, eCR could smooth the liver and harmonize the stomach. However, the underlying mechanisms were still unclear. Aim of the studyTo further verify the differential efficacy of the three processed CR products and compare the mechanisms on gastric ulcer. Material and methodsFirst, a GU model, whose onset is closely related to the heat in stomach and the disharmony between liver and stomach, was established, and the therapeutic effects of zCR/wCR/eCR/CR were evaluated by pathologic observation and measurement of cytokine levels. Second, metabolomics analysis and network pharmacology were conducted to reveal the differential intervening mechanism of zCR/eCR on GU. Third, the predicted mechanisms from metabolomics analysis and network pharmacology were validated using western blotting, flow cytometry and immunofluorescence. ResultszCR/wCR/eCR/CR could alleviate the pathologic damage to varying degrees. In metabolomics research, fewer metabolic pathways were enriched in serum samples, and most of them were also present in the results of gastric tissue samples. The gastroprotective, anti-inflammatory, antioxidant, and anti-apoptotic effects of zCR/wCR/eCR/CR might be due to their interference on histidine, arachidonic acid, and glycerophospholipids metabolism. Quantitative results indicated that zCR/eCR had a better therapeutic effect than wCR/CR in treating GU. A comprehensive analysis of metabolomics and network pharmacology revealed that zCR and eCR exerted anti-GU effects via intervening in five core targets, including AKT, TNF, IL6, IL1B and PPARG. In the validation experiment, zCR/eCR could significantly reverse the abnormal expression of proteins related to apoptosis, inflammation, oxidative stress, gastric function, as well as the PI3K/AKT signaling pathways. ConclusionzCR and eCR could offer gastroprotective benefits by resisting inflammation and apoptosis, inhibiting gastric-acid secretion, as well as strengthening gastric mucosal defense and antioxidant capacity. Integrating network pharmacology and metabolomics analysis could reveal the acting mechanism of drugs and promote the development of medications to counteract GU.

Study of Banxia Xiexin Prescription Combined with Diet Nursing on Improving the Clinical Symptoms, Inflammatory Factor Levels and Prognosis of Hospitalized Patients with Peptic Ulcer

Western medicine is the first choice for the clinical treatment of peptic ulcer (PU), which can quickly improve the symptoms of patients. However, the efficacy of western medicine can be influenced by PU patients’ unhealthy lifestyle and other factors, leading to various adverse reactions during and after treatment. Therefore, it is necessary to actively find ways to increase the efficacy of PU patients without increasing adverse reactions. Traditional Chinese Medicine (TCM) treatment for PU focuses on warming and tonifying deficiencies and alleviating urgency. The medicinal composition of Banxia Xiexin Decoction is Pinellia, Scutellaria baicalensis, Zingiberis rhizoma, fried licorice, Rhizoma coptidis and jujube, etc. β-sitosterol, 6-gingerol and berberine, the active components of Pinellia, Zingiberis rhizoma and Rhizoma coptidis, have been proved to have anti-ulcer effects. In this study, a rat model of PU was established in the animal experiment, and it was found that Banxia Xiexin prescription could effectively reduce the levels of ET-1 and NO in PU rats (P < 0.05). In the clinical trial, the Western Medicine convention (W-Con) group consisted of 61 PU patients who were hospitalized in our facility from 2020.01 to 2022.12 and received conventional western medicine treatment, while the Banxia combination (B-Com) group included PU patients who received Banxia xiexin decoction along with dietary care during the same period. The analysis of treatment outcomes between the two groups revealed that patients treated with Banxia Xiexin decoction combined with dietary care exhibited more significant improvements in clinical symptoms and inflammatory state compared to those relying solely on traditional western medicine (P < 0.05). In addition, we found that combined diet care helped to improve the prognosis of patients (P < 0.05). Therefore, this study suggests that Banxia Xiexin decoction combined with diet nursing can be used as an optimal treatment for PU patients. Banxia Xiexin decoction can effectively treat PU, which may be the main active ingredients in Banxia Xiexin decoction, such as β-sitosterol, 6-gingerol and berberine, which have anti-ulcer effects.

Effectiveness analysis of herbal medicine for gastroesophageal reflux disease: A retrospective study.

This study aimed to identify the clinical features of gastroesophageal reflux disease (GERD) in primary clinics and the effectiveness and safety of herbal medicine (HM). Thirty-five patients with gastroesophageal-reflux symptom who visited the 16 Korean medicine (KM) primary clinics from June 2022 to October 2022 were included in the study. We retrospectively analyzed the charts of 35 patients and collected clinical characteristics, HM, and outcome variables such as the numerical rating scale, gastroesophageal reflux disease questionnaire, frequency scale for symptoms of gastroesophageal reflux disease, Euro-Quality Of Life-5 Dimension, and adverse events. Of the 35 patients, 12 (34.3%) were men, and the average age of all patients was 47.0 ± 14.3 years. HM was prescribed for all 35 patients; Pinelliae Tuber (n = 31, 88.57%), Zingiberis Rhizoma Recens (n = 30, 85.71%), and Poria Sclerotium (n = 28, 80%) were the most prescribed herbs. All scores including numerical rating scale, frequency scale for symptoms of gastroesophageal reflux disease, gastroesophageal reflux disease questionnaire, and Euro-Quality Of Life-5 Dimension after 30 and 60 days from baselines showed significant improvement, and there were only a few adverse events. This study supports the effectiveness and safety of HM in reducing GERD symptoms in primary Korean medicine clinics. The most frequently used herbs may play significant roles in GERD symptom management.

Unifying Theory and Experiments: Multi-Target Pharmacology of Dajihan Pill Against Hyperlipidemia

Background: The increasing incidence of hyperlipidemia (HLP) is attributed to the imbalance in redox homeostasis, aberrant lipid metabolism, and the excessive intake of empty calories. Dajihan Pill (DJHP) is a Traditional Chinese Medicine (TCM) formula composed of Zingiberis Rhizoma (ZR), Piperis Longi Fructus (PLF), Alpiniae Officinarum Rhizome (AOR), and Cinnamomi Cortex (CC) in a ratio of 3:2:3:2. It exhibits a significant preventive effect on HLP. Certainly, the active components and the precise mechanism of action are not fully understood. Therefore, this study aims to elucidate the preventive and ameliorative mechanisms of DJHP against HLP by integrating network pharmacology, molecular docking, and experimental validation. Method: Based on the pharmacological method, active ingredients in DJHP and targets were extracted from Traditional Chinese Medicine System Pharmacology (TCMSP) and UniProt. Then core compounds and targets were obtained by constructing “compounds-targets-disease” and proteinprotein interaction (PPI) network. Gene Ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed to elucidate further the associated action mechanism. The molecular binding mechanisms between the core ingredients and targets were elucidated through molecular docking. Additionally, the antioxidant capacities of DJHP extracts were investigated by assessing their DPPH, hydroxyl, and ABTS radical scavenging activities. Results: A total of 45 active compounds and 258 targets were identified in DJHP. Network analysis indicated that quercetin, beta-sitosterol, kaempferol, and oleic acid might serve as core bioactive compounds. Seven core targets, including AKT1, INS, and TNF, were identified as potential preventive targets. GO analysis suggested the improvement of HLP by DJHP may be related to the lipid metabolic process, high-density lipoprotein particle, triglyceride binding, and inflammatory response. The KEGG analysis indicated TNF, HIF-1, and AMPK signaling pathways were involved. The observations of active compounds binding with core targets indicated an excellent combination. Additionally, antioxidant results showed that DJHP exhibited significant DPPH, hydroxyl, and ABTS radical scavenging activities. Conclusion: Theoretical and experimental investigations indicate that DJHP can effectively modulate various signaling pathways and enhance the redox system, thus mitigating HLP. Our work provided a basis for the pharmacological study of DJHP in preventing HLP and further research.

Hexahydrocurcumin from Zingiberis rhizoma attenuates lipopolysaccharide-induced acute pneumonia through JAK1/STAT3 signaling pathway.

Pneumonia is one of the major causes of death after pathogens infection. Zingiberis rhizoma (GAN JIANG) is a herb that used in combination with other Chinese medicines to treat pathogen such as virus induced pneumonia. However, the affect of hexahydrocurcumin (HHC), a component from Zingiberis rhizoma, on pneumonia remains unknown. This study aims to explore the effects of HHC on lipopolysaccharide (LPS)-induced acute pneumonia, and to clarify the underlying mechanism. The pneumonia model of C57BL/6 mice was established by intratracheal injection of LPS to evaluate the therapeutic effect of HHC on lung injury and inflammation in vivo. RAW264.7 macrophages were utilized to illustrate the cellular mechanism of HHC in vitro. HHC alleviated lung injury, ROS and inflammatory cytokine IL-6 production in pneumonia mice in vivo. Molecular docking results disclosed the binding of HHC to JAK1 protein. The study further showed that HHC suppressed the inflammatory cytokines such as IL-6, TNF-α, IL-1β gene expression, inhibited the phosphorylation of JAK1 but not JAK3, and the subsequent STAT3 phosphorylation in LPS-activated macrophages. HHC exhibited no effects on the protein levels of JAK1 and STAT3 in vitro. Consistently, HHC also attenuated the JAK1, STAT3 phosphorylation in pneumonia mice in vivo. The results reveal that HHC attenuates pneumonia by targeted inhibition of JAK1/STAT3 signaling pathway. It indicates the novel role of HHC to treat pneumonia, and its potential applications for JAK inhibitor-treated diseases.

DNA metabarcoding uncovers fungal communities in Zingiberis Rhizoma

ObjectiveZingiberis Rhizoma (ZR, Ganjiang in Chinese), also known as dried ginger, is a popular spice and medicinal herb that has been used for several thousand years. However, ZR is easily contaminated by fungi and mycotoxin under suitable conditions, and might be hazardous to the health and safety of consumers, thus concerns about the herb’s safety have been raised. In this study, we aim to investigate the fungal community and the effects of collection areas and processing methods on the fungal community in ZR. MethodsA total of 18 ZR samples were collected from four provinces of China, and the samples were divided into four groups based on collecting sites. Meanwhile, the samples collected in Sichuan Province were divided into three groups based on the processing methods. We employed the Illumina MiSeq PE300 platform and targeted the internal transcribed spacer 2 (ITS2) sequences to investigate fungal contamination in ZR samples, and the difference in fungal community among the groups of different collection sites and processing methods. ResultsAll 18 samples were contaminated with fungi. Ascomycota was the dominant phyla, accounting for 34.46 %−100 % of the fungal reads. At the genus level, Candida, Diutina, and Aspergillus were the most dominant genera, with relative abundances of 0–98.37 %, 0–99.82 %, and 0–79.08 %, respectively. Meanwhile, four potential toxigenic fungi and seven human pathogens were found. Furthermore, differences in the community composition of ZR samples from four collecting sites and three processing methods were observed. ConclusionDNA metabarcoding provides a novel insight into fungal community diversity in ZR samples, providing references to ensure the sustainable utilization and quality research of ZR.

Zingiberis rhizoma-based carbon dots alter serum oestradiol and follicle-stimulating hormone levels in female mice

Chinese herbs contain substances that regulate female hormones. Our study confirmed that Zingiberis rhizoma carbonisata contains Zingiberis rhizoma-based carbon dots (ZR-CDs), which exert regulatory effects on serum oestradiol and FSH in mice and show impacts on endometrial growth and follicular development that potentially affect the ability of female fertility. ZR-CDs were characterized to clarify the microstructure, optical features, and functional group characteristics. It shows that ZR-CDs are spherical carbon nanostructures ranging from 0.97 to 2.3 nm in diameter, with fluorescent properties and a surface rich in functional groups. We further investigated the impact of ZR-CDs on oestradiol and FSH in serum, growth, and the development of ovarian and uterine using normal female mice and exogenous oestradiol intervention model. It was observed that ZR-CDs accelerated oestrogen metabolism and attenuated oestradiol-induced endometrial hyperplasia. Simultaneously, ZR-CDs triggered an increase in FSH, even in the presence of high-serum oestradiol that inhibits FSH secretion. Our findings suggest that ZR-CDs could be a potential therapeutic treatment for anovulatory menstruation.

Using ultra-performance liquid chromatography with linear ion trap-electrostatic field orbitrap mass spectrometry, network pharmacology, and molecular docking to explore the constituent targets and action mechanisms of decoction of Angelica sinensis, Zingiberis Rhizoma Recens, and Mutton in the treatment of diarrhea-predominant irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a chronic intestinal disorder characterized by abdominal discomfort, stool characteristics, and changes in bowel habits. Among them, diarrhea-type (diarrhea-predominant irritable bowel syndrome, abbreviated as IBS-D) is the most common. Because its pathogenesis is not understood, symptomatic treatment is currently used in clinical practice, and its long-term effect is still unclear. Decoction of Angelica sinensis, Zingiberis Rhizoma Recens, and Mutton (DAZM) is a famous traditional Chinese medicine recipe created by Zhang Zhongjing, a famous doctor in the Eastern Han Dynasty 2000 years ago, and is still in use today. Our research team has previously investigated the clinical study of DAZM in the treatment of IBS-D and conducted animal experiment research, indicating that DAZM has a significant effect on improving IBS-D. Yet, there are few reports on the specific mechanism of action of DAZM in improving the treatment of IBS and related types. Most studies discuss and verify its efficacy and protection from a clinical perspective. For this reason, this research will explore the constituent targets and mechanisms of DAZM to improve the treatment of IBS-D, provide relevant scientific evidence, and also provide reference evidence for the efficacy of food therapy decoction in improving the treatment of diseases and mechanism to open up new experimental research ideas. Identification of drug ingredients and collection of targets for DAZM using ultra-performance liquid chromatography with linear ion trap-electrostatic field orbitrap mass spectrometry and the Bioinformatics Analysis Tool for Molecular Mechanisms of Traditional Chinese Medicine database, active ingredients were selected based on their oral bioavailability and drug-like properties. Obtained IBS-D targets using the GeneCards database, took the intersection of IBS-D targets and DAZM targets and obtained potential targets of DAZM for the treatment of IBS-D. Using Cytoscape software to draw a network diagram of "Food therapy decoction-ingredient-target-disease" and selected the ingredients with larger parameter values by topological analysis. Correlation analysis of the selected active and parametric ingredients with prominent symptoms of IBS-D using SymMap database, and selection of potential core ingredients. The construction of protein interaction networks from the String database and the selection of potential core targets. Gene Ontology functional and Kyoto Encyclopedia of Genes and Genomes signaling pathway enrichment analyses using the Metascape database, establishing the bioinformatic processes and signaling pathways involved. Molecular docking of core ingredients and potential core targets was performed using AutoDock Vina, and the results were visualized using Python molecule (PyMOL) and LigPlus+. Finally, based on the results of this research combined with previous literature reports, the discussion section of this paper summarizes in detail the key core ingredients, targets, and signaling pathways of DAZM in improving IBS-D. DAZM may act on eight potential core targets (threonine kinase 1, insulin, tumour necrosis factor, tumour protein p53, interleukin 6, epidermal growth factor receptor, connexin β1, and interleukin 1β) through eight core ingredients (Zingiberone, Shyobunone, Palmitic acid, Sebiferic acid, β-Bisabolene, β-Sitosterol, Stigmasterol, and Oleic acid). inhibit pro-inflammatory factors through Advanced Glycation End Products-Receptor (AGE-RAGE) signaling pathway, Cyclic Adenosine Monophosphate (cAMP) signaling pathway, MAPK signaling pathway, IL-17 signaling pathway, Calmodulin (CaM) signaling pathway, and other pathways. It can alleviate the inflammatory response, enhance the intestinal mucosal barrier and regulate intestinal motility, and play a role in the treatment and improvement of IBS-D. This research mainly found the mechanism of DAZM on IBS-D, which may involve multiple ingredients, multiple targets, and multiple pathways. DAZM with medicinal and edible functions can effectively improve the treatment of IBS-D. This kind of dietary therapy is suitable for long-term treatment and is worthy of promotion.

UPLC-Q-Exactive/MS based analysis explore the correlation between components variations and anti-influenza virus effect of four quantified extracts of Chaihu Guizhi decoction

Ethnopharmacological relevanceChaihu Guizhi decoction (CGD) is a classic Traditional Chinese Medicine (TCM) prescription for the treatment of influenza and fever, composes of Bupleuri Radix (Chaihu), Cinnamomi Ramulus (Guizhi), Scutellariae Radix (Huangqin), Codonopsis Radix (Dangshen), Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle (Zhigancao), Pinelliae Rhizoma Praeparatum (Fabanxia), Zingiberis Rhizoma Recens (Shengjiang), Paeoniae Radix Alba (Baishao) and Jujubae Fructus (Dazao) in the ratio of 12:4.5:4.5:4.5:3:6:4.5:4.5:4. The efficacy of TCM, if there are differences, depends on the different extraction methods and extracted components. Aim of the studyThis study was to evaluate the anti-influenza virus effect of CGD extracts with different extraction methods, analyze the components and explore their correlation. Materials and methodsCGD were prepared with four extraction methods respectively, the traditional decoction (TD), two steps alcohol-water extraction (AWE), alcohol reflux extraction (AE) and water reflux extraction (WE). Based on the influenza mouse model, the efficacy of anti-influenza virus in vivo of the four CGD extracts were evaluated with the therapeutic index of body weight, rectal temperature, lung index, thymus index and lung viral load of mice. The chemical components in four CGD extracts, and compounds absorbed in rats blood with prototypes or metabolites were identified by UPLC-Q-Exactive/MS. The partial least squares (PLS) method was used to explore the correlation between the components variation in CGD extracts and the comprehensive efficacy index. The potential effective components were further accessed by molecular docking. ResultsComparing with the other three extracts, AWE has the best anti-influenza effect. It could ameliorate the symptoms caused by influenza virus infection in mice, increase body weight and rectal temperature, reduce the lung index and virus load in lung tissue. 129, 144, 140 and 129 components were identified from TD, AWE, AE, and WE respectively. The identified components were mainly including flavonoids, terpenoids, organic acids, phenylpropanoids, amino acids, nucleosides, phenols, alkaloids, etc. 43 prototypes and 49 metabolites of CGD were detected in rat plasma after oral administration. Seven components, cinnamaldehyde, wogonoside, baicalin, baicalein, gallic acid, oroxylinA-7-O-glucuronide and coumarin, showed significant correlation with anti-influenza effects, all of which had good binding activity with NA, IL-6, STAT3, AKT1, EGFR and TNF. ConclusionTwo steps alcohol-water extraction was optimal for CGD preparation. Cinnamaldehyde, wogonoside, oroxylinA-7-O-glucuronide, coumarin, gallic acid, baicalein and baicalin play a certain essential role in anti-influenza effects and may be taken as a potential maker compounds for quality evaluation of CGD.

Characterization of chemical constituents in Huangqi Guizhi Wuwu decoction using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

Huangqi Guizhi Wuwu decoction (HGWWD) is a classic traditional Chinese medicine prescription for the treatment of ischemic stroke, etc. However, the material basis of its efficacy remains unclear, seriously affecting drug development and clinical applications. In the present study, an ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry method was developed to separate and identify the chemical components of HGWWD. A total of 81 compounds were identified and tentatively characterized. Eight compounds were accurately identified by comparing the retention time and mass spectrometry data with those of reference substances, the remaining compounds were characterized by comparing the mass spectrometry data and reference information. Based on the results of compound attribution, 35 compounds were from Astragali Radix, six compounds were from Cinnamomi Ramulus, 23 compounds were from Paeoniae Radix Alba, eight compounds were from Zingiberis Rhizoma Recens and nine compounds were from Jujubae Fructus. The results showed that monoterpenoids, flavonoids, organic acids, triterpenes, amino acids, gingerols, alkaloids, and glycosides were the main chemical components of HGWWD. This analytical method is suitable for characterizing the chemical constituents of HGWWD, and the results provide important information for elucidating its pharmacodynamic material basis and mechanism of action.

GC-MS/MS Method for Determination of Polycyclic Aromatic Hydrocarbons in Herbal Medicines.

Polycyclic aromatic hydrocarbons (PAHs) are hydrophobic organic contaminants that have a highly carcinogenic and mutagenic nature. This study aimed to develop and validate a sensitive analytical method to determine 8 PAHs in 51 herbal medicines (HMs) using gas chromatography (GC)-tandem mass spectrometry (MS/MS). Liquid--liquid extraction and florisil SPE cartridge purification were basically adopted for pretreatment. For the samples containing essential oil, starch grain, etc., N,N-dimethyl formamide/water mixture (9:1, v/v) was added in the extraction step. The multiple reaction monitoring (MRM) conditions were newly obtained by the infusion of reference solutions of the targeted compounds at a concentration of 100 ng/mL into the GC-MS/MS system used in this study. The 51 items were classified according to whether or not they contained essential oil. Eight PAHs were not detected in 39 (8.3%) of the 459 samples monitored. The total content of 8 PAHs ranged from 0.45 μg/kg in Anemarrhenae Rhizoma to 270.94 μg/kg in Zingiberis Rhizoma. The average content of those ranged from 0.9 μg/kg in Araliae Continentalis Radix to 110.8 μg/kg in Coptidis Rhizoma Preparata cum Vinum. The results of this study prove that the proposed method is useful for determining 8 PAHs in HMs.

Banxia Xiexin decoction alleviates AS co-depression disease by regulating the gut microbiome-lipid metabolic axis

Ethnopharmacological relevanceBanxia Xiexin decoction (BXD) is a classic Chinese herbal formulation consisting of 7 herbs including Pinelliae Rhizoma, Scutellariae Radix, Zingiberis Rhizoma, Ginseng Radix, Glycyrrhizae Radix, Coptidis Rhizoma, and Jujubae Fructus, which can exert effects on lowering lipids and alleviating depressive mood disorders via affecting gastrointestinal tract. Aim of the studyThe pathogenesis of atherosclerosis (AS) co-depression disease has not been well studied, and the current clinical treatment strategies are not satisfactory. As a result, it is critical to find novel methods of treatment. Based on the hypothesis that the gut microbiome may promote the development of AS co-depression disease by regulating host lipid metabolism, this study sought to evaluate the effectiveness and action mechanism of BXD in regulation of the gut microbiome via an intervention in AS co-depression mice. Materials and methodsTo determine the primary constituents of BXD, UPLC-Q/TOF-MS analysis was carried out. Sixteen C56BL/6 mice were fed normal chow as a control group; 64 ApoE−/− mice were randomized into four groups (model group and three treatment groups) and fed high-fat chow combined with daily bind stimulation for sixteen weeks to develop the AS co-depression mouse model and were administered saline or low, medium or high concentrations of BXD during the experimental modeling period. The antidepressant efficacy of BXD was examined by weighing, a sucrose preference test, an open field test, and a tail suspension experiment. The effectiveness of BXD as an anti-AS treatment was evaluated by means of biochemical indices, the HE staining method, and the Oil red O staining method. The impacts of BXD on the gut microbiome structure and brain (hippocampus and prefrontal cortex tissue) lipids in mice with the AS co-depression model were examined by 16S rDNA sequencing combined with lipidomics analysis. ResultsThe main components of BXD include baicalin, berberine, ginsenoside Rb1, and 18 other substances. BXD could improve depression-like behavioral characteristics and AS-related indices in AS co-depression mice; BXD could regulate the abundance of some flora (phylum level: reduced abundance of Proteobacteria and Deferribacteres; genus level: reduced abundance of Clostridium_IV, Helicobacter, and Pseudoflavonifractor, Acetatifactor, Oscillibacter, which were significantly different). The lipidomics analysis showed that the differential lipids between the model and gavaged high-dose BXD (BXH) groups were enriched in glycerophospholipid metabolism, and lysophosphatidylcholine (LPC(20:3)(rep)(rep)) in the hippocampus and LPC(20:4)(rep) in the prefrontal cortex both showed downregulation in BXH. The correlation analysis illustrated that the screened differential lipids were mainly linked to Deferribacteres and Actinobacteria. ConclusionBXD may exert an anti-AS co-depression therapeutic effect by modulating the abundance of some flora and thus intervening in peripheral lipid and brain lipid metabolism (via downregulation of LPC levels).

Characterizing the specific mechanism of series processed Coptidis Rhizoma by multi-organ metabolomics combined with network pharmacology and molecular docking

BackgroundAfter being processed with different excipients, the clinical application of Coptidis Rhizoma (CR) is differentially investigated. However, the underlying mechanism and material basis are not clear, and there is a lack of attention to the collaborative working mode of herbal medicine during exploration. PurposeTo characterize the specific mechanism of wine/zingiberis rhizoma recens/euodiae fructus processed CR (wCR/zCR/eCR) and to investigate the role of excipients during processing. MethodsThe multi-organ metabolomics approach was employed to explore the target organs of wCR/zCR/eCR and multiple pathways being triggered in each organ. The tissue distribution of CR and wCR/zCR/eCR components was compared to indicate the material basis of efficacy change after processing. Further, the network pharmacology study coupled with experimental validation was conducted to support metabolomic research and predicted active ingredients and core targets, and the molecular docking coupled with binding test was performed to identify the binding between active ingredient and core target. ResultsThe multi-organ metabolomics and network pharmacology study elucidated the intervening effect of wCR on heart/lung, zCR on stomach/colon, and eCR on liver/colon/stomach. Combined with molecular docking, binding test and tissue distribution studies, the specific mechanism was as follows: the wine made iso-quinoline alkaloids in CR more likely to accumulate in heart/lung, thus triggering the core targets of PTGS2, NOS2, ESR1 and SLC6A4 in heart/lung, and thereby highlighting the detoxifying and cardiopulmonary protective effect of wCR. The zingiberis rhizoma recens and euodiae fructus made organic acids in CR more likely to accumulate in stomach/colon and liver/colon/stomach respectively, thus triggering the core targets of ACTB, TNF and PRKCA in stomach/colon, the core targets of ACTB, TNF, PRKCA and GPT in stomach/colon/liver, and thereby highlighting the improving effect of zCR/eCR on digestive function. ConclusionIso-quinoline alkaloids were the material basis of CR for anti-inflammation, and organic acids were mainly responsible for regulating gastrointestinal function. Due to the influence of excipients on the accumulation tendency of CR components, the differentially highlighted application of wCR/zCR/eCR was achieved. These findings propose a novel strategy for processing mechanism research.

Inhibitory Effects and Related Molecular Mechanisms of Huanglian-Ganjiang Combination Against H1N1 Influenza Virus.

The online version contains supplementary material available at 10.1007/s43450-023-00372-z.

Simultaneous determination of twenty-nine active compounds in fuzhengjiedu granules by HPLC-QQQ-MS/MS

As an empirical medicine of traditional Chinese medicine, Fuzhengjiedu Granules have shown an effect against COVID-19 in clinical and inflammatory animal models. It is formulated with eight herbs, including Aconiti Lateralis Radix Praeparata, Zingiberis Rhizoma, Glycyrrhizae Radix Et Rhizoma, Lonicerae Japonicae Flos, Gleditsiae Spina, Fici Radix, Pogostemonis Herba, and Citri Reticulatae Pericarpium. This study established a high-performance liquid chromatography-triple quadrupole mass spectrometry (HPLC-QQQ-MS/MS) method by simultaneously determining 29 active compounds in the granules with significant content differences. Separation by gradient elution using acetonitrile and water (0.1% formic acid) as mobile phases was performed on a Waters Acquilty UPLC T3 column (2.1 mm × 100 mm, 1.7 μm). A triple quadrupole mass spectrometer, operating in positive and negative ionization modes, was used for multiple reaction monitoring to detect the 29 compounds. All calibration curves showed good linear regression (r2 > 0.998). RSDs of precision, reproducibility, and stability of active compounds were all lower than 5.0%. The recovery rates were 95.4–104.9%, with RSDs< 5.0%. This method was successfully used to analyze the samples, and the results showed that 26 representative active components from 8 herbs were detected in the granules. While aconitine, mesaconitine, and hypaconitine were not detected, indicating that the existing samples were safe. The granules had the maximum and minimum content of hesperidin (27.3 ± 0.375 mg/g) and benzoylaconine (38.2 ± 0.759 ng/g). To conclude, a fast, accurate, sensitive, and reliable HPLC-QQQ-MS/MS method was established, which can simultaneously detect 29 active compounds that have a considerable difference in the content of Fuzhengjiedu Granules. This study can be used to control the quality and safety of Fuzhengjiedu Granules and provide a basis and guarantee for further experimental research and clinical application.

Determination of oxalic acid in herbal medicines by semi-micro hydrophilic interaction liquid chromatography coupled with electrochemical detection.

In this study, the determination of oxalic acid in herbal medicines was performed by using a hydrophilic interaction liquid chromatography coupled with electrochemical detection (HILIC-ECD) method. A semi-micro column packed with amide-silica particles and an acetonitrile-30mM phosphate buffer (pH 6.8) mixture (65:35, v/v) were used as the stationary and mobile phases, respectively, in the HILIC-ECD. A potential of + 1.1V vs. Ag/AgCl was applied to a glassy carbon working electrode. The ratio of the peak height of oxalic acid to that of the internal standard (synephrine) was proportional to the concentration of 0.45μg L-1 to 1.8mg L-1 with a correlation coefficient of 0.999. The detection limit (signal-to-noise ratio, S/N = 3) of oxalic acid was 0.17μg L-1. By the HILIC-ECD, the oxalic acid content in crude drugs and Kampo medicine extract granules (Zingiberis Rhizoma Processum, Pinelliae Tuber, Sho-seiryu-to, Hange-shashin-to, etc.) were determined with less than 2.9% relative standard deviation (RSD, n = 6), and their recoveries were more than 88.7% with less than 3.3% RSD (n = 6). In conclusion, we demonstrated that the HILIC-ECD performed measurements that were quite selective, accurate, and precise for the determination of oxalic acid in herbal medicines.

A Prospective, Randomized, Placebo-Controlled Study Assessing the Efficacy of Chinese Herbal Medicine (Huangqi Guizhi Wuwu Decoction) in the Treatment of Albumin-Bound Paclitaxel-Induced Peripheral Neuropathy.

Objective: This study aimed to evaluate the efficacy and safety of Huangqi Guizhi Wuwu decoction (HGWD), which is composed of five crude drugs (Astragali Radix, Cinnamomi Ramulus, Paeoniae Radix Alba, Zingiberis Rhizoma Recens, and Jujubae Fructus), in the treatment of albumin-bound paclitaxel (nab-PTX)-induced peripheral neuropathy (PN) in Chinese patients with breast cancer (BC). Methods: This trial was conducted at the National Cancer Center in China from January 2020 to June 2022. The eligible participants were assigned randomly in a 1:1 ratio to an HGWD group or a control group. The outcome measure was EORTC QLQ-CIPN20 questionnaire. Results: 92 patients diagnosed with BC were enrolled and randomized to either HGWD group (n = 46) or control group (n = 46). There were no significant differences in baseline characteristics between the two groups (p > 0.05). A statistical analysis of the sensory and motor functions of the EORTC QLQ-CIPN20 scores showed that patients in the HGWD group reported a larger decrease in CIPN sensory scores than those in the control group (p < 0.001). The EORTC QLQ-CIPN20 autonomic scores showed no statistical significance between the two groups (p > 0.05). Conclusions: HGWD packs could significantly improve patients’ nab-PTX-induced PN, increase the tolerance for nab-PTX-containing chemotherapy, and further improve the quality of life of patients with BC.