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*

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*

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*

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

The genus Ephedra of the Ephedraceae family contains more than 60 species of nonflowering seed plants distributed throughout Asia, America, Europe, and North Africa. These Ephedra species have medicinal, ecological, and economic value. This review aims to summarize the chemical constituents and pharmacological activities of the Ephedra species to unveil opportunities for future research. Comprehensive information on the Ephedra species was collected by electronic search (e.g., GoogleScholar, Pubmed, SciFinder, and Web of Science) and phytochemical books. The chemical compounds isolated from the Ephedra species include alkaloids, flavonoids, tannins, polysaccharides, and others. The in vitro and in vivo pharmacological studies on the crude extracts, fractions and few isolated compounds of Ephedra species showed anti-inflammatory, anticancer, antibacterial, antioxidant, hepatoprotective, anti-obesity, antiviral, and diuretic activities. After chemical and pharmacological profiling, current research is focused on the antibacterial and antifungal effects of the phenolic acid compounds, the immunosuppressive activity of the polysaccharides, and the antitumor activity of flavonoids.
Animals ; Anti-Infective Agents ; chemistry ; pharmacology ; Antioxidants ; chemistry ; pharmacology ; Antiviral Agents ; chemistry ; pharmacology ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Ephedra ; chemistry ; Humans

PURPOSEEphedra alata (E. alata) is perennial tough shrub plant that grows in Palestine and other regions. It is used often in folk's medicine for the treatment of various diseases. In this project, E. alata extract was tested for its ability to improve wound and burn healing.

METHODSAn aqueous extract of E. alata was prepared and underwent several phytochemical analyses for the presence of the major classes of phytochemical compounds. After that, a polyethylene glycol-based ointment containing the extract of E. alata was prepared and its wound and burn healing activities were tested in-vivo using an animal model for deep wound and full thickness skin burn. The effect was compared against a placebo ointment. Skin biopsies were evaluated by a blinded clinical histopathologist, in addition to digital analysis.

RESULTSPhytochemical analysis demonstrated the presence of the major classes of phytochemical compounds in the prepared extract including flavonoids, alkaloids, phytosteroids, phenolic compounds, volatile oils and tannins. As compared to placebo ointment, E. alata ointment significantly improved the healing of the wound ulcers, whereas it showed no advantage on the quality of the healing of burn ulcers.

CONCLUSIONE. alata extract is rich in phytochemical compounds and can improve wound healing when applied topically.

Animals ; Burns ; drug therapy ; Disease Models, Animal ; Ephedra ; chemistry ; Male ; Mesocricetus ; Ointments ; Plant Extracts ; analysis ; therapeutic use ; Wound Healing ; drug effects

OBJECTIVEMahuang-Shigao herb-pair is a famous formula composed of Ephedra and Gypsum. The herb-pair is frequently used for treating cold symptoms and bronchial asthma in the clinical practice of Chinese medicine (CM). In the present study, we evaluated evidence for the benefit of combined use of Ephedra and Gypsum by analyzing the antipyretic and anti-asthmatic activities of Ephedra-Gypsum.

METHODSThe antipyretic effects of Ephedra-Gypsum were evaluated in yeast-induced hyperthermia test. Thirty male Wistar rats were randomly divided into 5 groups, including control group, standard aspirin group, and 3 Ephedra- Gypsum groups of different doses (6, 12, 24 g/kg). Ephedra-Gypsum extract and asprin were administered orally 6 h after the injection of yeast solution and body temperature was measured every 1 h for 8 h. The antiasthmatic effects of Ephedra-Gypsum were evaluated using an ovalbumin (OVA)-induced asthmatic rat model. Thirty-six male SD rats were randomly divided into 6 groups. Rats were alternately sensitized and OVA+Al(OH) challenged by exposure to mists of ovalbumin. Ephedra-Gypsum extracts (6, 12, 24 g/kg) or dexamethasone were administered 45 min prior to the allergen challenge for 8 days. Latent period and the weight of wet to dry ratio of lung were determined. In addition, the eosinophils in blood and white blood cell (WBC) were counted by an YZ-Hemavet Analyzer.

RESULTSThe Ephedra-Gypsum extracts at test dose (6, 12, 24 g/kg) significantly and dose-dependently attenuated yeast-induced fever in rats. The Ephedra-Gypsum extracts also prolonged the latent period, reduced OVA-induced increases in eosinophils and WBC, and decreased the wet and dry weight ratio of the lungs in the anti-asthmatic test.

CONCLUSIONSThese findings indicate that the Ephedra-Gypsum extract has antipyretic and anti-asthmatic properties. Hence, the results support additional scientific evidence in prescriptions.

Alkaloids ; analysis ; Animals ; Anti-Asthmatic Agents ; therapeutic use ; Antipyretics ; therapeutic use ; Asthma ; drug therapy ; Calcium Sulfate ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Ephedra ; chemistry ; Fever ; drug therapy ; Lung ; drug effects ; pathology ; Male ; Organ Size ; drug effects ; Ovalbumin ; Plant Extracts ; therapeutic use ; Rats, Sprague-Dawley ; Rats, Wistar

Animals ; Disease Models, Animal ; Ephedra ; chemistry ; Galactosamine ; Lipopolysaccharides ; Liver Failure, Acute ; chemically induced ; drug therapy ; Protective Agents ; pharmacology ; Rats

With a great difference in therapeutic effects of Mahuang (MH, the stems of Ephedra sinica) and Mahuanggen (MHG, the roots of Ephedra sinica), chemical differences between MH and MHG should be investigated. In the present study, gas chromatography-mass spectrometry (GC-MS)-based plant metabolomics was employed to compare volatile oil profiles of MH and MHG. The antioxidant activities of volatile oils from MH and MHG were also compared. 32 differential chemical markers were identified according to the variable importance in the projection (VIP) value of orthogonal partial least squares discriminant analysis (OPLS-DA) and P value of Mann-Whitney test. Among them, chemical markers of tetramethylpyrazine (TMP) and α-terpineol were quantified. Their contents were much higher in most MH samples compared with MHG. The antioxidant assay demonstrated that MH had significantly higher free radical-scavenging activity than MHG. Although MH and MHG derived from the same medicinal plant, there was much difference in their volatile oil profiles. MH samples had significantly higher content of two reported pharmacologically important chemical markers of TMP and α-terpineol, which may account for their different antioxidant activities.
Drugs, Chinese Herbal ; chemistry ; Ephedra sinica ; chemistry ; Gas Chromatography-Mass Spectrometry ; Metabolomics ; Oils, Volatile ; chemistry ; Plant Roots ; chemistry ; Plant Stems ; chemistry

This study is to establish the characteristic HPLC chromatogram of phenols in Ephedrae Herba, from which to pick out the marker peaks, followed by the analysis of the regularity of their distribution and content in the herbaceous stems of Ephedra sinica, E. intermedia and E. equisetina. The HPLC-DAD method for the characteristic chromatogram as well as quantitative analysis was established. The separation was carried out on a YMC-Pack ODS-A column (4.6 mm x 250 mm, 5 µm), eluted with the mobile phases as 0.01% formic acid aqueous solution (A) and acetonitrile (B) in a linear gradient (0-10 min, 17% B; 10-25 min, 17%-19% B; 25- 33 min, 19%-48% B; 33-35 min, 48%-51% B; 35-44 min, 51% B). The flow rate was kept at 1.0 mL · min⁻¹. The column tem- perature was 40 °C, and the detection wavelength was set at 350 nm (0-16 min) and 330 nm (16-44 min). Forty-six batches of collected samples from three official origins of Ephedrae Herba were detected, whose liquid chromatograms proven to be helpful to the differentiation of different origins. With principal component analysis and the analysis of distribution of peak area, twelve key peaks from the chromatogram were discussed in details on their contributions to the characteristics and differences of three official origins of the herb: peak area of peak 10, 11, 12 were found out to be significantly higher in E. equisetina than in other two origins, whose sum (higher than 146 mAU in E. equisetina) was useful for the discrimination between E. equisetina and the other two origins; peak area of 1 and 4 were respectively higher in E. sinica and E. intermedia than in other official origins, indicating their important effect on the differen- tiation of corresponding origins; peak 8 and 9 were picked out as two characteristic common peaks in three official origins of the herb, whose peak area showed little difference among different origins; further, peak area of other key peaks in the chromatogram also showed some difference among three origins, which make contributions to the differentiation of origins as well. Then, four phenols as 2"-O-α- L-rhamnosyl-isovitexin (1), vitexin (2), pollenitin B (5) and herbacetin-7-O-β-D-glucoside (6) were quantitative analyzed with the above-mentioned method, with good linear relationship and accuracy (recoveries in a range of 97.8%-102.5%). The content of the four phenols were firstly reported in Ephedrae Herba from official origins, which were respectively trace-1.55 (1), trace-0.160 (2), trace-0.284 (5) and trace-0.620 (6) mg · g⁻¹ in all of the tested samples. In addition, the content of these phenols showed differences in three official origins, especially 1, whose content in E. sinica [(0.670 ± 0.88) mg ± g⁻¹] were significantly higher than in other two origins (lower than 0.16 mg ± g⁻¹ besides sample Ei-060630-2-2), and 6, whose average content in E. equisetina [(0.260 ± 0.039 2) mg · g⁻¹] were twice as high as in E. sinica [(0.120 ± 0.270) mg · g⁻¹] and E. intermedia [(0.136 ± 0.485) mg g⁻¹], indicating the important effects of the two constituents on the differentiation among three official origins of the herb. The method established for the characteristic HPLC chromatogram and quantitative analysis of phenols was simple and accurate, and the marker constituents selected may provide new guides for the discrimination of official origins as well as the improvement of quality criteria of EphedraeHerba.
Chromatography, High Pressure Liquid ; methods ; Ephedra ; chemistry ; Phenols ; analysis