Ephedrae Herba Research Articles

Preventive and therapeutic effects of ephedrine alkaloids-free Ephedra Herb extract on paclitaxel-induced neuropathic pain.

Currently, there are no effective prophylactic or therapeutic drugs for the treatment of paclitaxel (PTX)-induced peripheral neuropathic pain (PTX-PNP), highlighting the urgent need for the development of effective prophylactic and therapeutic drugs. In this study, we initially compared the efficacy of Ephedra Herb extract (EHE) with that of ephedrine alkaloids-free Ephedra Herb extract (EFE), which lacked ephedrine alkaloids (EAs)-associated side effects, against the onset of PTX-induced mechanical allodynia, thermal hyperalgesia, and cold allodynia in mice. EHE and EFE demonstrated comparable preventive effects on the PTX-PNP in a dose-dependent manner. These results indicated that the preventive properties of EHE were independent of the EAs. Since elderly people are overwhelmingly more susceptible to developing cancer, we considered that EFE has greater benefits than EHE, so we conducted a study focused on the effects of EFE. EFE showed dose-dependent preventive effects on the onset of PTX-PNP. As a result of detailed investigation, coadministration of PTX and EFE (Co-EFE) was more effective than preadministration of EFE alone (Pre-EFE). And the effects of Co-EFE was same with the effect of preadministrationof EFE and then coadministration of PTX and EFE (P&C-EFE). Additionally, Co-EFE after the onset of PTX-PNP improved PTX-induced mechanical allodynia, thermal hyperalgesia, and cold allodynia, confirming the therapeutic efficacy of EFE on PTX-PNP. In contrast, goshajinkigan, a Kampo medicine, and diclofenac, a non-steroidal anti-inflammatory drug, showed minimal therapeutic effects on PTX-PNP. These findings demonstrate the significant potential of EFE as a novel, safe prophylactic and therapeutic agent against PTX-PNP.

Exploring medication rules and mechanism of Chinese medicine for children with cough variant asthma based on data mining, network pharmacology, and molecular docking.

Cough variant asthma (CVA) is a common disease with high incidence among children. Cough is the main clinical symptom and Chinese medicine (CM) has an exact effect on CVA. However, the rules of herb formulation, the pharmacodynamic substances, and the mechanism remained unclear. Therefore, we conducted this article to explore medication rules and molecular mechanism of CM against CVA in children using data mining, network pharmacology, molecular docking, and molecular dynamics simulation. Relevant literatures were collected from China National Knowledge Infrastructure, Chinese Scientific and Technical Journals database, Wanfang database, Pubmed, and Web of science. Excel 2016 was used to extract related data and establish the database for Chinese medical frequency, properties, tastes, and meridian analysis. Association rules were analyzed based on Apriori algorithm using IBM SPSS Modeler 18.0 software and core herb combination was identified. The active ingredients and targets of the core herb combination were acquired form the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database. The main targets of CVA were obtained from the GeneCards and Online Mendelian Inheritance in Man database. Core targets were selected by using STRING platform and Cytoscape 3.7.2 software. Metascape platform was utilized to perform gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. The results were verified by molecular docking. SwissADME and pkCSM website were used to analyze the pharmacokinetic profiles and toxicity of key components of the core herb combination. Molecular dynamics simulation was utilized to evaluate the stable of protein-ligand complex. Two hundred seventy-five literatures containing 202 herbs were finally collected. Statistics indicated that these herbs possessed bitter, pungent taste, and warm properties, and belonged to lung meridian. Glycyrrhizae radix et rhizome, Ephedrae herba, and Armeniacae semen amarum were the most frequently used herbs. "Glycyrrhizae radix et rhizoma-ephedrae herba-Armeniacae semen amarum" was the core herb combination with highest support and confidence. Network pharmacology predicted that the main active ingredients, like quercetin, kaempferol, luteolin, etc, might target on RAC-alpha serine/threonine-protein kinase, tumor necrosis factor, interleukin-6, vascular endothelial growth factor A, transcription factor AP-1, interleukin-1 beta, matrix metalloproteinase-9, etc. They played a pivotal role in regulating multiple signaling pathways, such as tumor necrosis factor signaling pathway, IL-17 signaling pathway, and PI3K-Akt signaling pathway. Molecular docking revealed that the key active ingredients were well docked with core targets. The absorption, distribution, metabolism, excretion, and toxicity analysis showed that formononetin, luteolin, naringenin, and quercetin have high gastrointestinal absorption, no AMES toxicity, hepatotoxicity, and skin sensitization. Molecular dynamics simulation revealed that the formononetin-matrix metalloproteinase-9 complex was relatively stable. This article revealed that CM against CVA in children focused on dispelling wind and reducing phlegm, warming lung, and relieving cough. The mechanism of the core herb combination of CM for CVA through muti-components, muti-targets, and muti-pathways.

Research on the quality evaluation of crude drugs.

As crude drugs are natural products, their quality may vary. However, the degradation of the active ingredients in the compositional changes that occur during processing and preparation also affects the medicinal properties of the Kampo formula, which uses herbal medicines; therefore, a detailed investigation of the effects of compositional changes during preparation is required. Plant constituents vary in content depending on the year of cultivation and the plant part; however, detailed studies have rarely been reported for some crude drugs. Liquid chromatography-nuclear magnetic resonance/mass spectrometry revealed the degradation process of saponins, which are unstable components of the crude drug "Achyranthes root." The presence of diterpenes unstable with respect to drying temperature in the leaves of the crude drug "Leonurus herb" was revealed and their structures were elucidated. At the examination stage of the degradation process of perillaldehyde, the characteristic aromatic component of Perilla herb, it was elucidated that some specimens contained a small amount of perillaldehyde and that they contained more α-asarone. A trend toward lower ephedrine content was observed toward the tip of the above-ground branching of the Ephedra herb. Multivariate analysis was also introduced into the quality assessment of crude drugs and was established as a tool to identify bioactive compounds using the component diversity of crude drugs and to elucidate component differences due to the cultivation environment.

Discovery and characterization of naturally occurring covalent inhibitors of SARS-CoV-2 Mpro from the antiviral herb Ephedra

The Chinese herb Ephedra (also known as Mahuang) has been extensively utilized for the prevention and treatment of coronavirus-induced diseases, including coronavirus disease 2019 (COVID-19). However, the specific anti-SARS-CoV-2 compounds and mechanisms have not been fully elucidated. The main protease (Mpro) of SARS-CoV-2 is a highly conserved enzyme responsible for proteolytic processing during the viral life cycle, making it a critical target for the development of antiviral therapies. This study aimed to identify naturally occurring covalent inhibitors of SARS-CoV-2 Mpro from Ephedra and to investigate their covalent binding sites. The results demonstrated that the non-alkaloid fraction of Ephedra (ENA) exhibited a potent inhibitory effect against the SARS-CoV-2 Mpro effect, whereas the alkaloid fraction did not. Subsequently, the chemical constituents in ENA were identified, and the major constituents’ anti-SARS-CoV-2 Mpro effects were evaluated. Among the tested constituents, herbacetin (HE) and gallic acid (GA) were found to inhibit SARS-CoV-2 Mpro in a time- and dose-dependent manner. Their combination displayed a significant synergistic effect on this key enzyme. Additionally, various techniques, including inhibition kinetic assays, chemoproteomic methods, and molecular dynamics simulations, were employed to further elucidate the synergistic anti-Mpro mechanisms of the combination of HE and GA. Overall, this study deciphers the naturally occurring covalent inhibitors of SARS-CoV-2 Mpro from Ephedra and characterizes their synergistic anti-Mpro synergistic effect, providing robust evidence to support the anti-coronavirus efficacy of Ephedra.

A Study on the Effects and Mechanisms of the Combination Extract of Ephedrae Herba and Coicis Semen on Lipid Accumulation and Glucose Absorption in Non-Alcoholic Fatty Liver Disease

A Study on the Effects and Mechanisms of the Combination Extract of Ephedrae Herba and Coicis Semen on Lipid Accumulation and Glucose Absorption in Non-Alcoholic Fatty Liver Disease

Exploration of chemical components and metabolite synthesis pathways in eight Ephedra species based on HS-GC-MS and UPLC-Q-TOF-MS.

Ephedra, widely used in clinical practice as a medicinal herb, belongs to the genus Ephedra in the family Ephedraceae. However, the presence of numerous Ephedra varieties and variants requires differentiation for accurate identification. In this study, we employed headspace gas chromatography mass spectrometry (HS-GC-MS), ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS), and global natural products social molecular networking (GNPS) for chemical component identification. Chemometric analysis was used to analyze the differential components. Metabolic analysis and Kyoto encyclopedia of genes and genomes (KEGG) enrichment were utilized to explore the synthesis pathways of different components. A total of 83 volatile and 79 non-volatile components were identified in Ephedra species. Differential analysis revealed that among the eight Ephedra stems, 18 volatile and 19 non-volatile differential compounds were discovered, whereas Ephedra roots exhibited 21 volatile and 17 non-volatile markers. Volatile compounds were enriched in four synthetic pathways, while non-volatile components were enriched in five pathways among the differentiated components. This study is the first to conduct a comparative analysis of chemical components in different Ephedra species and parts. It provides a foundational reference for authenticating Ephedra herbs, evaluating medicinal resources, and comparing quality in future studies.

비만 치료에서 마황 및 에페드린의 안전성 고찰: 간을 중심으로

Objectives The purpose of this study is to examine whether the use of Ephedrae herba and Ephedrine in obesity treatment is safe for the liver. Methods Toxicology studies and randomized controlled trials (RCTs) from systematic review (SR), meta-analysis related to Ephedrae herba or Ephedrine, which refer to liver function were collected through Pubmed and RISS databases. Results There were no findings that hepatotoxicity was induced by Ephedrae herba in the 2-week acute, 4-week subacute, and 13-week repeated administration toxicology studies. In the RCT studies of Ephedrae herba, Ephedrine, or herbal medicine including Ephedrae herba, there were no significant changes in liver function levels. Conclusions This study suggests that it is difficult to find clear evidence that Ephedrae herba and Ephedrine cause liver injury.

A ternary correlation multi-symptom network strategy based on in vivo chemical profile identification and metabolomics to explore the molecular basis of Ephedra herb against viral pneumonia.

Ephedra herb (EH), an important medicine prescribed in herbal formulas by Traditional Chinese Medicine practitioners, has been widely used in the treatment of viral pneumonia in China. However, the molecular basis of EH in viral pneumonia remains unclear. In this study, a ternary correlation multi-symptom network strategy was established based on in vivo chemical profile identification and metabolomics to explore the molecular basis of EH against viral pneumonia. Results showed that 143 compounds of EH and 70 prototype components were identified in vivo. EH could reduce alveolar-capillary barrier disruption in rats with viral pneumonia and significantly downregulate the expression of inflammatory factors and bronchoalveolar lavage fluid. Plasma metabolomics revealed that EH may be involved in the regulation of arachidonic acid, tryptophan, tyrosine, nicotinate, and nicotinamide metabolism. The multi-symptom network showed that 12 compounds have an integral function in the treatment of viral pneumonia by intervening in many pathways related to viruses, immunity and inflammation, and lung injury. Further verification demonstrated that sinapic acid and frambinone can regulate the expression of related genes. It has been shown to be a promising representative of the pharmacological constituents of ephedra.

Biomarker Identification for Gender Specificity of Alzheimer's Disease Based on the Glial Transcriptome Profiles.

Many sex-specific biomarkers have been recently revealed in Alzheimer's disease (AD); however, cerebral glial cells were rarely reported. This study analyzed 220,095 single-nuclei transcriptomes from the frontal cortex of thirty-three AD individuals in the GEO database. Sex-specific Differentially Expressed Genes (DEGs) were identified in glial cells, including 243 in astrocytes, 1,154 in microglia, and 572 in oligodendrocytes. Gene Ontology (GO) functional annotation analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed functional concentration in synaptic, neural, and hormone-related pathways. Protein-protein interaction network (PPI) identified MT3, CALM2, DLG2, KCND2, PAKACB, CAMK2D, and NLGN4Y in astrocytes, TREM2, FOS, APOE, APP, and NLGN4Y in microglia, and GRIN2A, ITPR2, GNAS, and NLGN4Y in oligodendrocytes as key genes. NLGN4Y was the only gene shared by the three glia and was identified as the biomarker for the gender specificity of AD. Gene-transcription factor (TF)-miRNA coregulatory network identified key regulators for NLGN4Y and its target TCMs. Ecklonia kurome Okam (Kunbu) and Herba Ephedrae (Mahuang) were identified, and the effects of the active ingredients on AD were displayed. Finally, enrichment analysis of Kunbu and Mahuang suggested that they might act as therapeutic candidates for gender specificity of AD.

Effects of nutrient conditions to stem photosynthesis and growth in Ephedra intermedia (Ephedraceae)

ABSTRACT Ephedra intermedia Schrenk et C.A.Meyer (Ephedraceae, Gnetales, Gymnospermae) contains ephedrine and pseudoephedrine, and has been used as Ephedra herb, a traditional medicine. Instead of degenerated leaves, photosynthetic assimilation is performed in their stems. Recently domestic cultivation of this species has been required, but relevant nutrient conditions for cultivation remain uncertain. In this study, we examined stem photosynthetic parameters in E. intermedia plants grown under different nutrient conditions in order to clarify relationships between the photosynthetic parameters and growth in their stems. Also, we examined whether the regulation of two photosystems of the photosynthetic electron transport system in E. intermedia stems is similar to that of angiosperm leaves. We cultivated E. intermedia plants under various nutrient conditions with different levels of nitrogen (N), and regularly measured CO2 assimilation rates, parameters of the photosynthetic electron transport system, and growth of E. intermedia stems. The stem growth was better under the condition with the additional ordinary chemical fertilizer compared to those with urea or magnesium lime. The seasonal changes were observed in the CO2 assimilation rates, Y(II), the quantum yield of photosystem II (PSII), and Y(ND), the non-photochemical yield due to donor side limitations in photosystem I (PSI). However, these parameters differed between nutrient conditions to small extents, and were not related to stem growth. Therefore, the measured parameters of photosynthesis could not explain the difference in stem growth between nutrient conditions. Although the photosynthetic parameters seasonally changed, the tight relationships between Y(ND), the PSI parameter, and Y(II) or Y(NPQ), the PSII parameters, were found throughout the seasons. These relationships between two photosystems in stems of gymnosperm E. intermedia were as the same as those in angiosperm leaves, although a flavodiiron protein can function as the electron sink in the stems of E. intermedia. This balance between two photosystems may be regulated by the system dependent on the thylakoid lumen pH, which may lead to the protection of two photosystems throughout the seasons.

Screening of natural inhibitors against peptidyl arginine deiminase 4 from herbal extracts by a high-performance liquid chromatography ultraviolet-visible based method

Peptidyl arginine deiminase 4 (PAD4) is an important biocatalytic enzymes involved in the conversion of protein arginine to citrulline, its dysregulation has a great impact on many physiological processes. Recently, PAD4 has emerged as a potential therapeutic target for the treatment of various diseases including rheumatoid arthritis (RA). Traditional Chinese Medicines (TCMs), also known as herbal plants, have gained great attention by the scientific community due to their good therapeutic performance and far fewer side effects observed in the clinical treatment. However, limited researches have been reported to screen natural PAD4 inhibitors from herbal plants. The color developing reagent (COLDER) or fluorescence based methods have been widely used in PAD4 activity assay and inhibitor screening. However, both methods measure the overall absorbance or fluorescence in the reaction solution, which are easy to be affected by the background interference due to colorful extracts from herbal plants. In this study, a simple, and robust high-performance liquid chromatography ultraviolet-visible (HPLC-UV) based method was developed to determine PAD4 activity. The proposed strategy was established based on COLDER principle, while used hydrophilic l-arginine instead of hydrophobic N-benzoyl-l-arginine ethyl ester (BAEE) as a new substrate to determine PAD4 inhibition activity of herbal extracts. The herbal extracts and PAD4 generated hydrophobic l-citrulline were successfully separated by the HPLC, and the developed method was optimized and validated with a known PAD4 inhibitor (GSK484) in comparison with COLDER assay. The IC50 value of GSK484 measured by HPLC-UV method was 153 nM, and the detection limit of the citrulline was 0.5 nmol, respectively, with a linear range of 0.5 nmol to 20 nmol. The IC50 value of the HPLC-UV method was improved by nearly three times compared with COLDER assay (527 nM), and the results indicated the reliability of PAD4 inhibition via HPLC-UV method. The inhibitory effect against PAD4 were fast and accurately screened for the twenty-four extracts from eight herbs. Among them, Ephedra Herba extracts showed significant inhibitory activity against the PAD4 with the IC50 values of three extracts (ethanol, ethyl acetate and water) ranging from 29.11 μg/mL to 41.36 μg/mL, which may help researchers to discover novel natural compounds holding high PAD4 inhibition activity.

Antiviral effect of alkaloids-free Ephedra Herb extract on respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) is a major cause of respiratory tract infection in children. Despite decades of efforts, no effective therapies are available. We recently reported that extracts of Ephedra Herb and Cinnamon Bark interacted with the G attachment protein of RSV to inhibit infectivity. The present in vitro study aimed to investigate the antiviral effect of ephedrine alkaloids-free Ephedra Herb extract (EFE), which is characterized by free of harmful effects of ephedrine alkaloids in Ephedra Herb, on experimental RSV infection. Infection of RSV into A549 cells simultaneously with EFE resulted the significant reduction of RSV RNA, viral protein, and viral titers after the incubation of the cells. We found that RSV attachment to the cell surface was inhibited both in the presence of EFE and when RSV particles were pre-treated with EFE. We also found that EFE specifically interacted with the central conserved domain of RSV G protein by surface plasmon resonance, demonstrating that specific binding of G protein to the cellular receptor was inhibited by EFE. Another mechanism was found in which a higher concentration of EFE inhibited the viral load immediately after the viral entry into host cells, suggesting the inhibition of viral RNA replication. These results demonstrate that EFE worked against RSV infection through multiple antiviral mechanisms, a unique feature of this crude drug extract.

Deciphering the mechanism of Ephedra Herba-Armeniacae Semen Amarum herb pairs on COVID-19 by integrated network pharmacology and bioinformatics

BackgroundEffective prevention of COVID-19 is vital for impeding the current pandemic. Our study is devoted to investigating the targets of Ephedra Herba (EH)-Armeniacae Semen Amarum (ASA) herb pairs on COVID-19 and identifying the signature genes. MethodsFirstly, the active constituents and corresponding targets of EH-ASA were separately obtained through Traditional Chinese Medicine System Pharmacology Database (TCMSP) and UniProt KB database. We searched the Gene Expression Omnibus (GEO) database to identify the differentially expressed genes (DEGs) for COVID-19 and intersected the targets with DEGs to retrieve common genes. Subsequently, the Protein-Protein Interaction (PPI) network and weighted gene coexpression network analysis (WCGNA) were carried out to discover the genes related to COVID-19, which was combined with DEGs performed the GO and KEGG enrichment analysis to investigate the pathogenesis of COVID-19. The receiver operating characteristic curve (ROC) and molecular docking were ultimately exerted to verify the precision and stability of the screened genes. ResultsThere were 42 active compounds of the EH-ASA corresponding to 200 targets, including Luteolin, Glycyrol, Glabridin, and Quercetin. Also, 548 DEGs were filtered out, and 74 common genes were obtained after the intersection. In addition, 358 genes associated with COVID-19 were identified through the WGCNA method, mainly involved in Human T-cell leukemia virus one infection and IL-17 signaling pathway, etc. At last, three signature genes were obtained, containing ESR1, IL2, and NFKBIA, and the ROC of these three genes was 1.000, 0.967, and 0.967, respectively, which illuminated the accuracy of the results. Also, molecular docking indicated that the main chemical constituents of the EH-ASA had a good affinity with COVID-19. ConclusionEH-ASA herb pairs may play a preventive and therapeutic role in COVID-19 through the three characteristic genes, ESR1, IL2, and NFKBIA.

Evaluation of the Influence of Genetic and Environmental Factors on the Ephedrine Alkaloids Content of Ephedra sinica.

Ephedra herb, a dried terrestrial stem of Ephedra sinica, is used in traditional Japanese medicine (Kampo) and Chinese medicine to treat the common cold, headaches, bronchial asthma, and nasal inflammation. E. sinica predominantly contains two ephedrine alkaloids-(-)-ephedrine and (+)-pseudoephedrine-which are crucial for its medicinal effects. This study aimed to reveal the influence of genetic and environmental factors on ephedrine alkaloids content using statistical genetic analyses. To evaluate the influence of genetic factors on ephedrine alkaloids content, 25 clonal lines were cultivated in Ibaraki and the broad-sense heritability of the traits was estimated. The heritabilities of (-)-ephedrine, (+)-pseudoephedrine, and "total alkaloids" (TA) content were 0.871, 0.969, and 0.865, respectively. The heritabilities of ephedrine alkaloids content were high. To evaluate the influence of environmental factors on ephedrine alkaloids content, four clonal lines which have different genotypes were cultivated in three locations (Ibaraki, Shizuoka, and Yamanashi prefectures). The effects of genotype (G), location (L), and genotype by environment (G × E) interactions on ephedrine alkaloids content were found to be significant (p < 0.05) by two-way ANOVA, and, in particular, the genotypic effects were found to be the largest. Our results indicate that the ephedrine alkaloids content in E. sinica is under relatively strong genetic control and remains stable under various environments. These findings suggest that E. sinica with a higher and stable ephedrine alkaloids content could be cultivated in different locations through selective breeding.

The combination of Ephedrae herba and coixol from Coicis semen attenuate adiposity via glucocorticoid receptor regulation

The enhanced therapeutic effects and mechanisms of certain herbal combination in various herbal prescriptions are mostly unclear. A combination of two herbs, namely Ephedrae herba (EH) and Coicis semen (CS), has been commonly prescribed for obesity. In our previous work, the combination of EH and CS was studied using network pharmacological approach to predict its pharmacological targets and in vitro experiments to evaluate its efficacy on obesity. Although we demonstrated enhanced anti-adiposity effects of the combination on matured adipocytes, the molecular mechanisms and contributing compounds underlying the effects of EH-CS combination on adiposity or adipogenesis were not fully elucidated. The current study adopted integrated bioinformatics analysis to precisely validate potential targets of EH-CS by screening differentially expressed genes (DEGs) of morbid obesity patients from NCBI gene expression omnibus (GEO). Based on the functional cluster analysis of down-regulated DEGs, the anti-adipogenesis mechanism of EH-CS combination was speculated with KEGG enrichment analysis. Furthermore, we investigated the combinational effects of EH and coixol, or stigmasterol, the two compounds in CS which were expected to have main beneficial effects in metabolic diseases. Moreover, distinct effect of the combination on transcriptional activity of glucocorticoid receptor (GR) was investigated using electrophoretic mobility shift assay (EMSA). The EH-CS combination was predicted to modulate down-regulated genes which are involved in KEGG pathways crucial to metabolic disease in morbidly obese individuals. The combination of EH with CS compounds significantly increased the phosphorylation of acetyl-coA carboxylase (ACC), AMP-activated protein kinase (AMPK), and protein kinase B (AKT) in 3T3-L1 cells and decreased intracellular lipid accumulation. The two CS compounds significantly increased the anti-adipogenesis/lipogenesis effects of EH by inhibiting the gene expression levels. Finally, the combination of EH and coixol inhibited dexamethasone-induced GR translocation to the nucleus and transcriptional binding activity in adipocytes. The combination of EH and CS could be considered a therapeutic strategy for treating metabolic diseases, including obesity.

Herbal combinations against COVID-19: A network pharmacology, molecular docking and dynamics study

ObjectiveThe aim of this study is to identify molecules from traditional Chinese medicine (TCM) with potential activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants. MethodsWe applied the Apriori algorithm to identify important combinations of herbs in the TCM prescriptions for the treatment of coronavirus disease 2019 (COVID-19). Then, we explored the active components and core targets using network pharmacology. In addition, the molecular docking approach was performed to investigate the interaction of these components with the main structural and non-structural proteins, as well as the mutants. Furthermore, their stability in the binding pockets was further evaluated with the molecular dynamics approach. ResultsA combination of Amygdalus Communis Vas., Ephedra Herba and Scutellaria baicalensis Georgi was selected as the important herbal combination, and 11 main components and 20 core targets against COVID-19 were obtained. These components, including luteolin, naringenin, stigmasterol, baicalein, and so on, were the potentially active compounds against COVID-19. The binding affinity of these compounds with the potential targets was as high as the positive controls. Among them, baicalein could interfere with multiple targets simultaneously, and it also interfered with the interaction between spike protein and angiotensin-converting enzyme 2 receptor. Additionally, almost all the systems reached stability during dynamics simulation. ConclusionThe combination of A. communis, Ephedra Herba and S. baicalensis was the most important herbal combination for the treatment of COVID-19. Baicalein may be a potential candidate against SARS-CoV-2 and its variants.Please cite this article as: Song JB, Zhao LQ, Wen HP, Li YP. Herbal combinations against COVID-19: A network pharmacology, molecular docking and dynamics study. J Integr Med. 2023;21(6):593–604.

Integrative Korean Medicine Treatment for Obesity and Overweight in Children and Adolescents: A Multicenter Retrospective Chart Review Study.

Integrative Korean medicine treatment (IKM), including herbal medicine (HM) and acupuncture, has been widely used for obesity and overweight in children and adolescents in South Korea. We investigated the real-world usage status and the potential effect of the IKM for obesity and overweight in children and adolescents. Multicenter medical charts were retrospectively reviewed of obese and overweight children and adolescents who visited Korean medicine institutions with the goal of weight control for the first time and received IKM, to analyze the usage status and effect of IKM. We defined IKM responders as those with an improved obesity grade on the body mass index (BMI) percentile and analyzed their characteristics. Medical charts of 209 patients (183 obese and 26 overweight) with a mean age of 11.45 years were examined. Patients visited the institution a mean of 5.95 times, and HM alone and HM plus acupuncture were frequently used IKM. HM was prescribed to 205 patients, 167 of whom received an HM prescription containing Ephedrae Herba. An HM of the decoction type was prescribed to 189 patients, and the average treatment duration was 76.54 days. After IKM, the percentile and z-score of BMI and weight significantly declined and height percentile and z-score were significantly enhanced, without serious adverse events. In the IKM responders, age, and the proportion of girls and overweight were significantly higher, and the percentile and z-score of height, weight, and BMI were significantly lower. This is the first study to examine the real-world usage of IKM for obesity and overweight in children and adolescents. A significant improvement in obesity-related outcome measures after IKM, illustrated the potential effect of IKM.

Use of Chinese herbal medicines for acute cough in China: An online survey

IntroductionAnti-microbial resistance is a complex and evolving global public health threat. Promoting effective alternative treatments is an important way to reduce the unnecessary use of antibiotics. This study aimed to identify the use of treatments for acute cough in China, including Chinese herbal medicines (CHMs) and their association with avoidance of antibiotics and participants’ reported clinical recovery. MethodsAn online retrospective treatment outcome survey was conducted. Retrospective clinical information was collected on participants who either were experiencing acute cough, or had experienced acute cough in the last 3 months. Participants were recruited through WeChat (a QR code or a link to the online survey), using snowball sampling. We analysed the usage of different CHMs, changes in symptoms as measured by Likert scales and subsequent use of antibiotics. ResultsA total of 25,583 participants completed the online questionnaire, covering all 34 province-level administrative units in China. Respondents had a median age of 25 years (73.5%, aged 18–39). Most respondents reported sputum (65.8%). Nearly half of the participants (45.3%) reported using antibiotics, 39.4% using CHMs, 27.1% and 20.9% using non-antibiotic Western medications and home remedies respectively. Fewer participants took antibiotics after taking CHMs (14.4%), compared to those who started with home remedies (17.6%), or non-antibiotic Western medications (24.5%). The recommendation of doctors (62.4%) and pharmacies (32.1%) were the most common reason for choosing CHMs. Participant-reported clinical recovery was similar (same median of 4 on a 1–5 Likert self-rating scale) regardless of type of CHM. The five CHMs associated with the lowest proportions of subsequent antibiotic use were individualised Chinese herbal formulae, Xiao Qing Long granule, Xian Zhu Li liquid, Chuan Bei Pi Pa Gao and Shi Wu Wei Long Dan Hua pill. The most commonly used herbs in the Chinese patent medicines were Glycyrrhizae radix et rhizome, Platycodonis radix, Pinelliae rhizome, Armeniacae semen amarum, Ephedrae herba, and Citri reticulatae pericarpium. ConclusionAlmost 40% of participants with acute cough used CHMs. The proportion of participants who subsequently used antibiotics after CHMs was lower than other treatments. CHMs have a potential role for symptom relief thus reducing antibiotic use.

Integrative traditional Chinese medicine treatment for children with obstructive sleep apnea

PurposeObstructive sleep apnea (OSA) is a chronic disease that affects 1%–6% of children. Our study aims to explore the effectiveness and clinical characteristics of integrative Traditional Chinese Medicine (ITCM) for pediatric OSA. Materials and methodsIn this retrospective cohort study, we assessed differences of polysomnography (PSG) parameters and clinical characteristics between 2009 and 2020. Children <12 years old diagnosed with OSA (n = 508) were included and were categorized into ITCM cohort, western medicine (WM) cohort ,and surgery cohort. Outcomes were apnea-hypopnea index (AHI), respiratory disturbance index (RDI), and body mass index (BMI). ResultsThere were 56 (11%), 324 (63.8%), and 128 (25.2%) patients in the ITCM, WM, and surgery cohorts. Among 17, 26, and 33 patients in the ITCM, WM, and surgery cohorts underwent follow-up PSG studies, respectively. In the ITCM follow-up cohort, AHI were significantly reduced (9.59 to 5.71, p < 0.05). BMI significantly increased in the WM follow-up cohort (19.46 to 20.50, p < 0.05) and the surgery follow-up cohort (18.04 to 18.85, p < 0.01). Comparing ITCM to WM cohort, a significant difference was found between the changes in RDI (ITCM: −6.78, WM: 0.51, p < 0.05) after treatment. Among ITCM follow-up cohort, the most prescribed TCM formula was Forsythia and Laminaria Combination. The most prescribed TCM herb was Ephedrae Herba. ConclusionsITCM therapy can significantly reduce RDI and control BMI. We identified potential TCM treatments for pediatric OSA. Further study of the pharmacological mechanisms and clinical efficacy is warranted.

A Modified 1H-NMR Quantification Method of Ephedrine Alkaloids in Ephedrae Herba Samples.

A previous 1H-NMR method allowed the quantification of ephedrine alkaloids; however, there were some disadvantages. The cyclized derivatives resulted from the impurities of diethyl ether were identified and benzene was selected as the better extraction solvent. The locations of ephedrine alkaloids were confirmed with 2D NMR. Therefore, a specific 1H-NMR method has been modified for the quantification of ephedrine alkaloids. Accordingly, twenty Ephedrae Herba samples could be classified into three classes: (I) E. sinica-like species; (II) E. intermedia-like species; (III) others (lower alkaloid contents). The results indicated that ephedrine and pseudoephedrine are the major alkaloids in Ephedra plants, but the concentrations vary greatly determined by the plant species and the collection locations.