Shegan Mahuang Decoction has been used in clinical practice for thousands of years, and is a classical formula for treating asthma and other respiratory diseases, with the effects of ventilating lung, dispersing cold, and relieving cough and asthma. This paper summarized the history, clinical application and mechanism of Shegan Mahuang Decoction, and predicted its quality markers(Q-markers) based on the "five principles" of Q-markers. The results suggested that irisflorentin, tectoridin, tectorigenin, irigenin, ephedrine, pseudoephedrine, asarinin, methyleugenol, shionone, epifriedelanol, tussilagone, 6-gingerol, trigonelline, cavidine, schizandrin, and schizandrin B could be used as Q-markers of Shegan Mahuang Decoction, which provided a basis for the quality control and subsequent research and development of Shegan Mahuang Decoction.
Humans ; Ephedra sinica ; Drugs, Chinese Herbal/pharmacology* ; Asthma/drug therapy* ; Lung ; Cough/drug therapy*

This study aims to investigate mechanism of "Ephedrae Herba-Descurainiae Semen Lepidii Semen" combination(MT) in the treatment of bronchial asthma based on network pharmacology and in vivo experiment, which is expected to lay a theoretical basis for clinical application of the combination. First, the potential targets of MT in the treatment of bronchial asthma were predicted based on network pharmacology, and the "Chinese medicine-active component-target-pathway-disease" network was constructed, followed by Gene Oncology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the potential targets. Molecular docking was used to determine the binding activity of key candidate active components to hub genes. Ovalbumin(OVA, intraperitoneal injection for sensitization and nebulization for excitation) was used to induce bronchial asthma in rats. Rats were classified into control group(CON), model group(M), dexamethasone group(DEX, 0.075 mg·kg~(-1)), and MT(1∶1.5) group. Hematoxylin and eosin(HE), Masson, and periodic acid-Schiff(PAS) staining were performed to observe the effect of MT on pathological changes of lungs and trachea and goblet cell proliferation in asthma rats. The levels of transforming growth factor(TGF)-β1, interleukin(IL)6, and IL10 in rat serum were detected by enzyme-linked immunosorbent assay(ELISA), and the mRNA and protein levels of mitogen-activated protein kinase 8(MAPK8), cyclin D1(CCND1), IL6, epidermal growth factor receptor(EGFR), phosphatidylinositol 3-kinase(PI3 K), and protein kinase B(Akt) by qRT-PCR and Western blot. Network pharmacology predicted that MAPK8, CCND1, IL6, and EGFR were the potential targets of MT in the treatment of asthma, which may be related to PI3 K/Akt signaling pathway. Quercetin and β-sitosterol in MT acted on a lot of targets related to asthma, and molecular docking results showed that quercetin and β-sitosterol had strong binding activity to MAPK, PI3 K, and Akt. In vivo experiment showed that MT could effectively alleviate the symptoms of OVA-induced asthma rats, improve the pathological changes of lung tissue, reduce the production of goblet cells, inhibit the inflammatory response of asthma rats, suppress the expression of MAPK8, CCND1, IL6, and EGFR, and regulate the PI3 K/Akt signaling pathway. Therefore, MT may relieve the symptoms and inhibit inflammation of asthma rats by regulating the PI3 K/Akt signaling pathway, and quercetin and β-sitosterol are the candidate active components.
Animals ; Asthma/drug therapy* ; Cyclin D1 ; Dexamethasone/adverse effects* ; Drug Combinations ; Drugs, Chinese Herbal/therapeutic use* ; Eosine Yellowish-(YS)/adverse effects* ; Ephedra ; ErbB Receptors ; Hematoxylin/therapeutic use* ; Interleukin-10 ; Interleukin-6 ; Mitogen-Activated Protein Kinase 8/therapeutic use* ; Molecular Docking Simulation ; Network Pharmacology ; Ovalbumin/adverse effects* ; Periodic Acid/adverse effects* ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt/metabolism* ; Quercetin ; RNA, Messenger ; Rats

To study the molecular mechanism of Mahuang Lianqiao Chixiaodou Decoction in the treatment of eczema by means of network pharmacology and molecular docking. First, the TCMSP database was used to excavate the active ingredient of each drug in Mahuang Lianqiao Chixiaodou Decoction and predict its target, and the Uniprot database was used to standardize the names of target proteins, in order to obtain the disease targets of eczema through GeneCards, OMIM, PharmGkb, DrugBank and other databases. And next, the potential targets on which drug targets and disease targets work together were selected to make a Venn diagram, the Cytoscape 3.6.1 software was used to screen out and construct the "active ingredient-core targets" network. STRING database was used to construct a protein-protein interaction(PPI) network, and the R language was used to perform GO enrichment analysis and KEGG pathway analysis. Finally, the molecular docking verification of main active ingredients and core targets of the drug was performed by AutoDock software. The study showed that 74 active ingredients and 103 targets of Mahuang Lianqiao Chixiaodou Decoction for the treatment of eczema were screened. The main active ingredients included quercetin, luteolin, wogonin, kaempferol, and the main targets included PTGS1, ESR1, PPARG, and MAPK3. In addition, eight key targets, including MAPK8, MAPK3, JUN, MAPK14, TP53, MAPK1, ESR1 and RELA, were calculated by PPI network. GO enrichment analysis involved 2 024 biological processes, 81 cell components, and 140 molecular functions. KEGG pathway enrichment analysis was performed to screen out 158 eczema-related pathways, which mainly acted on AGE-RAGE signaling pathway, IL-17 signaling pathway, virus-related pathways, and the results of molecular docking showed that the main active compounds could respectively bind to representative targets and exhibit a good affinity. The study proved that the treatment of eczema with Mahuang Lianqiao Chixiaodou Decoction involved multiple signaling pathways and biological processes, and the combination of main active ingredients(such as quercetin, luteolin, wogonin, kaempferol) and key targets(such as MAPK8, MAPK3, JUN, MAPK14, TP53, MAPK1, ESR1, RELA) may be one of the important mechanisms of action.
Drugs, Chinese Herbal/pharmacology* ; Eczema ; Ephedra sinica ; Humans ; Molecular Docking Simulation ; Technology

Adult ; Body Temperature/drug effects* ; COVID-19/pathology* ; Drug Therapy, Combination ; Drugs, Chinese Herbal/therapeutic use* ; Ephedra sinica/chemistry* ; Female ; Fever/pathology* ; Glycyrrhiza/chemistry* ; Humans ; Indoles/administration & dosage* ; Male ; Medicine, Chinese Traditional/methods* ; Middle Aged ; Phytotherapy/methods* ; Pneumonia, Viral/pathology* ; Radiography, Thoracic ; SARS-CoV-2/drug effects*

This study aimed to establish the HPLC characteristic chromatogram and content determination method for index components with the primary standard substances of the classical prescription Mahuang Decoction, and to provide data basis for the establishment of its quality standard and the development and utilization of compound preparations. First, HPLC was used to establish the material reference chromatograms of Mahuang Decoction, and 15 batches of standard samples of Mahuang Decoction were determined. Their similarity was calculated by the median method. Secondly, the content of the standard substances was determined and a simplecontent determination method was established by HPLC. Relevant methodology was investigated, and the extraction ratio, index component transfer rate and moisture content of 15 batches of primary standard samples were calculated. The results showed that the two sets of HPLC methods had their own characteristics. The six chromatographic peaks identified from the 10 common peaks in the former characteristic chromatogram covered all the herbal medicines in the standard substances, which can better indicate the quality characteristics of the standard substances of Mahuang Decoction. The latter method(content determination method) was simple and practical, so it was suitable for establishing the quality standard of its compound preparation. Two sets of methods were jointly used to evaluate the quality of 15 batches of Mahuang Decoction. The results were as follows: the similarity of 15 batches of samples was greater than 0.90; the average extraction ratio was 18.1%; the average moisture content was 9.7%; the average content and transfer rate of the standard ingredients ephedrine hydrochloride and total pseudoephedrine hydrochloride were 2.3% and 26.7% respectively, and the average content and transfer rate of amygdalin were 2.2% and 48.3% respectively. None of the data showed dispersion(beyond 70%-130% of the mean value), which met the application data requirements for the substance standards of ancient classical Chinese herbal compound preparations(draft for comments). Based on the above research, the primary substance quality standard of Mahuang Decoction was established in order to provide reference for the development and research of the compound preparation of Mahuang Decoction.
Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; Ephedra sinica ; Prescriptions ; Quality Control ; Reference Standards

To investigate the antipyretic effect of active components of Mahuang Decoction in febrile rats, and explore its correlation with pharmacokinetics at different time points. The feverished rat models were induced by dry yeast, and intragastrically administered with the effective components of Mahuang Decoction with different orthogonal compatibility ratios. At different time points after administration, body temperature was measured; blood was taken from orbital vena plexus, and the contents of interleukin-6(IL-6), interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α) in rat serum were determined with the kits. Combined with the pharmacokinetic data of the seven effective components in Mahuang Decoction, PK-PD(pharmacokinetics-pharmacodynamics) data fitting was conducted by using the analysis method of non-atrioventricular model, and then the pharmacodynamic parameters were calculated to determine the optimal binding model. The results showed that the effective components of Mahuang Decoction inhibited the release of heat-causing factors IL-6, IL-1β and TNF-α, and reduced the increase of body temperature. There was a significant lag between drug effect and blood drug concentration, which was consistent with Sigmoid-E_(max) model. The model fitting value showed a good correlation with mea-sured data, which could be used to evaluate and predict the correlation between PK and PD in Mahuang Decoction, and further applied to the multiple-indicator and multiple-effect study of PK-PD in other compound traditional Chinese medicines.
Animals ; Antipyretics/therapeutic use* ; Drugs, Chinese Herbal/therapeutic use* ; Ephedra sinica/chemistry* ; Fever/drug therapy* ; Interleukin-1beta/blood* ; Interleukin-6/blood* ; Medicine, Chinese Traditional ; Rats ; Tumor Necrosis Factor-alpha/blood*

There is often the risk of confusing pollen grains with helminth eggs from archaeological sites. Thousands to millions of pollen grains can be recovered from archaeological burial sediments that represent past ritual, medication and environment. Some pollen grain types can be similar to parasite eggs. Such a confusion is represented by the diagnosis of enterobiasis in ancient Iran. The authors of this study confused a joint-pine (Ephedra spp.) pollen grain with a pinworm egg. This paper describes the specific Ephedra pollen morphology that can be confused with pinworm eggs.
Adolescent ; Archaeology ; Burial ; Diagnosis ; Eggs ; Enterobiasis ; Enterobius ; Ephedra ; Female ; Helminths ; Humans ; Iran ; Ovum ; Parasites ; Pollen

The herbal formula, DF-02, consisting of Ephedra intermedia and Rheum palmatum are used for the treatment of the metabolic diseases such as obesity and liver fibrosis in Korean local clinics. We aimed to develop the simultaneous analytical conditions for four standards, (+)-pseudoephedrine (PSEP) and (−)-ephedrine (EP) for E. intermedia, and aloe-emodin (AE) and chrysophanol (CP) for R. palmatum using HPLC-UV techniques. The validated conditions yielded the high precision (relative standard deviation (RSD) < 3.65%) and the recoveries (94 – 106%) using the calibration curves with high linearity (R² > 0.9994). As a result, four standards of DF-02 were simultaneously determined under the developed method, which will be utilized for the quality control or evaluation of DF-02 and many herbal preparations containing E. intermedia and R. palmatum.
Calibration ; Chromatography, High Pressure Liquid ; Ephedra ; Liver Cirrhosis ; Metabolic Diseases ; Methods ; Obesity ; Plant Preparations ; Quality Control ; Rheum

In the present paper,after the febrile rat model was prepared by injecting yeast,orthogonally compatible effective components from prescription drugs of Mahuang Decoction( Ephedra sinica total alkaloids,Cinnamomum cassia essential oil,amygdalin,Glycyrrhiza uralensis total flavonoids+G. uralensis total saponins) with nine different dosage ratios were given by gavage administration.The plasma concentrations of main active ingredients including ephedrine hydrochloride,pseudoephedrine hydrochloride,methylephedrine hydrochloride,cinnamic acid,amygdalin,liquritin and glycyrrhizin at different time points were analyzed by liquid chromatograph mass spectrometer( LC-MS). Based on the pharmacokinetic parameters of non-compartmental model,the area under curve of total quantum( AUCt) and the mean chromatographic retention time of total quantum( MRTt) were further calculated,in order to evaluate the effect of compatibility on the total statistical moment parameters. The results showed that the pharmacokinetic characteristics of main active components in febrile rats were significantly different after treatment with orthogonally compatibility of E. sinica total alkaloids,C.cassia essential oil,amygdalin,G. uralensis total flavonoids and G. uralensis total saponins. Orthogonal analysis confirmed that different compatibility components had different effects on the total statistical moment parameters. The contribution of effective components of Mahuang Decoction to AUCtwas as follows in a descending order: E. sinica total alkaloids>C. cassia essential oil>amygdalin>G. uralensis total flavonoids+G. uralensis total saponin,while the contribution to MRTtwas: E. sinica total alkaloids >G. uralensis total flavonoids+G. uralensis total saponin>amygdalin>C. cassia essential oil. The E. sinica total alkaloid had the greatest effects on both of the above parameters,and the optimal combination was A_3B_3C_2D_1 for AUCt,and A_1B_1C_1D_1 for MRTt.
Animals ; Drugs, Chinese Herbal ; pharmacokinetics ; Ephedra sinica ; chemistry ; Glycyrrhiza uralensis ; chemistry ; Oils, Volatile ; pharmacokinetics ; Phytochemicals ; pharmacokinetics ; Rats

Ephedra is a classic herb in traditional Chinese medicine( TCM). The new effects of ephedra were gradually found,and the contraindications of the drug were broken in later ages. Because the principles of expanded application were not well elucidated,it is difficult to use in the clinical flexibility. Based on the characteristics of ephedra and its classic clinical application,the authors summarized the possible principles of clinical application of ephedra and the drug property and pharmacological characteristics of ephedra.Studies showed that ephedrine substances are an important material basis for the efficacy of ephedra,and its adrenergic action is the pharmacological basis of its efficacy. It is the key to grasp the autonomic function and the interaction between sympathetic/adrenal medulla and adrenal cortex for the clinical application of ephedra. The authors discussed the principles of clinical application of ephedra and the effects of processing of ephedra. Finally,the authors put forward the basic research process of clinical application of drugs,and provide ideas for the inheritance and further development of TCM experience.
Ephedra/chemistry* ; Ephedrine/pharmacology* ; Medicine, Chinese Traditional ; Plant Extracts ; Plants, Medicinal/chemistry*