Integrative traditional Chinese medicine treatment for children with obstructive sleep apnea.

Purpose: Obstructive 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 methods: In 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). Results: There 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. Conclusions: ITCM 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.

Comparison of ephedrine and pseudoephedrine contents in 34 Kampo extracts containing Ephedrae Herba used clinically in Japan.

Ephedrae Herba is among the important crude drugs prescribed in Kampo medicine for the treatment of cold, flue, rhinitis, nasal congestion, cough, and asthma. The active ingredients of Ephedrae Herba, ephedrine (E) and pseudoephedrine (PE), are potent sympathomimetic compounds that stimulate α-, ß1-, and ß2-adrenoceptors resulting in dilatation and alleviation of nasal mucosal hyperemia. Hypertension, palpitations, insomnia, and dysuria are the main adverse effects of E and PE, which can be avoided by determining the actual contents of these alkaloids in Kampo extracts containing Ephedrae Herba. However, the extraction efficiencies of E and PE from Ephedrae Herba contained in Kampo formulas in combination with other crude drugs remain unknown. Therefore, we comprehensively determined the E and PE contents of 34 Kampo extracts containing Ephedrae Herba used clinically in Japan. The E and PE contents per daily dosage in Kampo extracts were generally proportional to the compounding amount of Ephedrae Herba. In contrast, the extraction efficiencies of E or PE were not constant and not influenced by the pH of the extracts. We assume that the extraction efficiencies of E and PE may be independently affected by other constituent crude drugs. Thus, it is necessary to investigate the cause and mechanism in the future. In conclusion, these results show that the E and PE content of each Kampo formulation can be estimated from the compounding amount of Ephedrae Herba. Therefore, the amount of Ephedrae Herba should be carefully considered to ensure the safe use of Kampo formulations containing Ephedrae Herba.

Ephedrae Herba: A Review of Its Phytochemistry, Pharmacology, Clinical Application, and Alkaloid Toxicity.

Ephedrae Herba (Ephedra), known as "MaHuang" in China, is the dried straw stem that is associated with the lung and urinary bladder meridians. At present, more than 60 species of Ephedra plants have been identified, which contain more than 100 compounds, including alkaloids, flavonoids, tannins, sugars, and organic phenolic acids. This herb has long been used to treat asthma, liver disease, skin disease, and other diseases, and has shown unique efficacy in the treatment of COVID-19 infection. Because alkaloids are the main components causing toxicity, the safety of Ephedra must be considered. However, the nonalkaloid components of Ephedra can be effectively used to replace ephedrine extracts to treat some diseases, and reasonable use can ensure the safety of Ephedra. We reviewed the phytochemistry, pharmacology, clinical application, and alkaloid toxicity of Ephedra, and describe prospects for its future development to facilitate the development of Ephedra.

Ephedrae herba: A comprehensive review of its traditional uses, phytochemistry, pharmacology, and toxicology.

ETHNOPHARMACOLOGICAL RELEVANCE: Ephedrae herba (called Mahuang in China) is the dried herbaceous stem of Ephedra sinica Stapf, Ephedra intermedia Schrenk et C. A. Mey., and Ephedra equisetina Bge. Ephedrae herba has a long history of use as an herb, and it was originally recorded in Sheng Nong's herbal classic. Ephedrae herba has also been widely used as both medicine and food. In the clinic, Ephedrae herba is commonly used for treating colds, bronchial asthma, nasal congestion, and other diseases. AIM OF REVIEW: This review aims to provide a systematic summary on the traditional use, chemical constituents, pharmacological effects, clinical applications, quality control, toxicology, and pharmacokinetics of Ephedrae herba to provide a theoretical basis for further reasonable development of Ephedrae herba in clinical practice and creation of new drugs. MATERIALS AND METHODS: Information on Ephedrae herba was gathered from various sources, including the scientific databases including CNKI, PubMed, SciFinder and ScienceDirect, classical books on traditional Chinese herbal medicine, Ph.D. and M.Sc. dissertations; Baidu Scholar; and from different professional websites. RESULTS: Ephedrae herba is distributed in regions of China and other areas. Ephedra and its compound preparations can be used for colds, bronchial asthma, nasal congestion and other diseases. Approximately 281 chemical constituents have been isolated from Ephedrae herba, including alkaloids, flavonoids, tannins, polysaccharides, volatile oils, organic acids, and other compounds. Among these constituents, alkaloids and volatile oils are the most abundant and represent the major bioactive constituents. Ephedrae herba possesses multiple pharmacological activities, including diuretic effect, anti-allergic effect, blood pressure regulatory, anti-inflammatory effect, anti-oxidation effect and anti-viral effects. Ephedrine hydrochloride and pseudoephedrine hydrochloride are generally selected as indicators for the quantitative determination of Ephedrae herba. The maximum dosage of Ephedrae herba should not exceed 10 g. If overused, adverse reactions such as palpitations, sweating, irritability and insomnia will occur. CONCLUSIONS: Ephedrae herba is an ancient herbal medicine with a broad spectrum of pharmacological activities that has been used for thousands of years in China. It is one of the most commonly used herbal components of the TCM formulas. Hydrochloride and pseudoephedrine are the major bioactive constituents. However, there is a need to further understand the mechanisms of active components of Ephedrae herba. Future studies should perform an in-depth analyses of the pharmacokinetics and mechanisms of toxicity of Ephedrae herba. Quality standards should be developed to correspond to the various application methods to ensure the efficacy of drugs in actual treatment.

Evaluating the behavior and principle of deep eutectic solvent on ephedrine-type alkaloid extraction from Ephedrae Herba.

In this study, deep eutectic solvent (DES), as a new green solvent, was used to extract bioactive alkaloids from Ephedrae Herba using supersonic extraction. In a variety of tested hydrophilic and hydrophobic DESs, DES composed of choline chloride and xylitol was proved to be the most efficient solvent. Factors affecting extraction efficiency, including the mole ratio of hydrogen bond acceptor/hydrogen bond donor, water contention, and solid/liquid ratio, were optimized individually. Under optimal conditions, the yield of ephedrine (EP) and pseudoephedrine obtained using this new method was 14.24 and 4.32 mg/g, respectively, which was higher than that using the traditional solvent (acidified water and methanol). Furthermore, the extraction mechanism of DES and EP was investigated using molecular dynamics simulation study. Structural properties such as radial distribution functions and average number of hydrogen bonds were then computed. The results showed that hydrogen bonds and van der Waals forces are important driving forces of extraction; in addition, the hydrogen bonds between the Cl atom of choline chloride and N atom of EP played a dominant part in the extraction process. Based on the extraction principle, the extraction method using choline chloride as extraction solvent was also discussed.

Ephedrae Herba polysaccharides inhibit the inflammation of ovalbumin induced asthma by regulating Th1/Th2 and Th17/Treg cell immune imbalance.

AIMS: This study aimed to investigate the anti-asthma effects of Ephedrae Herba polysaccharides (PE) and possible mechanisms related to immune inflammatory response. METHODS: An asthma model was established in rats using ovalbumin (OVA). Seventy rats were randomly assigned to five groups: control, model, dexamethasone (DEX, 0.075 mg/kg), low dose polysaccharides (LPE, 137.71 mg/kg) and high dose polysaccharides (HPE, 275.42 mg/kg). The cough and asthma were used to evaluate the basic state of asthmatic rats. Histological studies were evaluated by hematoxylin and eosin (H&E), Masson, and periodic acid-schiff (PAS) staining. The levels of interferon-γ (IFN-γ), interleukin (IL)-4, immunoglobulin E (IgE), tumor necrosis factor α (TNF-α), and IL-17A in bronchoalveolar lavage fluid (BALF), and the levels of transforming growth factor ß1 (TGF-ß1), IL-6, and IL-10 in serum were detected by enzyme-linked immunosorbent assay (ELISA). The mRNA levels of Ifn-γ, Il-4, Tgf-ß1, Il-6, Il-10, Tnf-α, Il-13, and Il-17a were evaluated by quantitative real-time reverse transcription (qRT)-PCR. The dendritic cell (DCs), T helper cell (Th), natural killer cell (NK), regulatory T cell (Treg), and Th17 cells in blood, the lymphocytes, macrophages and neutrophils in spleen, and cell apoptosis and reactive oxygen species (ROS) in lung were analysed by flow cytometry (FCM). Immunohistochemistry (IHC) was used to stain DCs (CD11c+, CD86+, and CD80+), macrophages (CD68+), and neutrophils (MPO+) in the spleen and lung. The protein levels of IL-17A, CD11c, CD86, and CD80 in lung were measured by western blot. RESULTS: Our study demonstrated that PE could effectively improve the symptoms of asthmatic rats, ameliorate the lung pathological injury, inhibit inflammation, apoptosis and oxidative stress, regulate the levels of macrophages, neutrophils, DCs, NK, Thc, Treg and Th17 cells. CONCLUSION: PE could collectively inhibit the inflammation, apoptosis and ROS in asthma rats induced by OVA via regulating Th1/Th2 and Th17/Treg cell immune imbalance.

[Mechanism of "Ephedrae Herba-Descurainiae Semen Lepidii Semen" combination in treatment of bronchial asthma based on network pharmacology and experimental verification].

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)-ß1, 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 ß-sitosterol in MT acted on a lot of targets related to asthma, and molecular docking results showed that quercetin and ß-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 ß-sitosterol are the candidate active components.

Molecular Networking, Network Pharmacology, and Molecular Docking Approaches Employed to Investigate the Changes in Ephedrae Herba before and after Honey-Processing.

Raw Ephedrae herba (REH) and honey-processed Ephedrae herba (HEH) were the different decoction pieces of Ephedrae herba (EH). Honey-processing that changes REH into HEH has been shown to relieve cough and asthma to a synergistic extent. However, the chemical markers and the synergistic mechanism of HEH need to be further studied. In this study, the ultra-high performance liquid chromatography coupled with hybrid quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS) and molecular networking (MN) were used to investigate the chemical composition of REH and HEH, which led to the identification of 92 compounds. A total of 38 differential chemical markers for REH and HEH were identified using principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Network pharmacology suggests that the synergistic effect of HEH in relieving cough and asthma may be due to 31 differential chemical markers acting through 111 biological targets. Among them, four compounds and two targets probably played an important role based on the results of molecular docking. This study enriched our knowledge about the chemical composition of REH and HEH, as well as the synergistic mechanism of HEH.

The position of Ephedrae herba in the Western medicine / Az Ephedrae herba helye a nyugati orvoslásban.

Összefoglaló. A Magyar és az Európai Hypertonia Társaság legújabb ajánlásában a gyógyszer okozta szekunder hypertoniák gyakoribb okai között szerepel az Ephedra - csikófark (kínai nevén Mahuang) fajok drogjának (Ephedrae herba) felhasználása is. Összefoglaló közleményünk célja az Ephedra nemzetségbe tartozó, a gyógyászatban is felhasznált, a VIII. Magyar Gyógyszerkönyvben és a Kínai Gyógyszerkönyvben szereplo hivatalos fajoknak a részletes bemutatása. Betekintést nyújtunk történetükbe, továbbá leírjuk a bennük található vegyületek farmakológiai tulajdonságait és azok hatásait. Ismertetjük elonyeiket, mellékhatásaikat és lehetséges gyógyszerkölcsönhatásaikat. Ezenkívül feltárjuk fogyasztó- és testsúlycsökkento szerként való használatukat, étrend-kiegészítoként történo alkalmazásuk betiltásának okát, valamint tárgyaljuk a doppinglistán való szereplésük magyarázatát is. Ezzel párhuzamosan kitérünk az Ephedra fajok orvosi gyakorlatban betöltött szerepére is: rendeltetésszeru használatuk során a fitoterápiában - foleg kombinációban alkalmazva - számos jótékony hatás érheto el, de fontos hangsúlyozni óvatos használatukat és felismerni lehetséges mellékhatásaikat. Orv Hetil. 2022; 163(9): 343-349. Summary. The Hungarian and the European Society of Hypertension guidelines mention Ephedrae herba, the drug of Ephedra species (in Chinese "Mahuang") as one of the causes of secondary hypertension. The aim of our summary is to characterize the Ephedra species used in medicine (based on the VIII. Hungarian and the Chinese Pharmacopoeia), describe their history and their components alongside with possible pharmacological effects, benefits, side-effects, and interactions with other drugs. We demonstrate the herb's history from being a popular weight-loss product to being prohibited as a dietary supplement and citing it in the World Anti-Doping Agency's list. At the same time, we explain the role of the Ephedra species in the everyday medical practice. It is important to know their benefits in detail as used in combination with other herbs in phytotherapy, and recognize their possible side effects. Orv Hetil. 2022; 163(9): 343-349.

Herbal Textual Research on Ephedrae Herba in Famous Classical Formulas / 中国实验方剂学杂志

Ephedrae Herba is a commonly used medicine for dispersing wind and cold， which has a long medicinal history. By referring to the herbal literature， medical books and prescription books， this paper intends to carry out herbal textual research on the name， origin， medicinal part， producing area， harvesting and processing methods of Ephedrae Herba in famous classical formulas， in order to provide the basis for the development of relevant famous classical formulas. According to textual research， the main base of ancient Ephedrae Herba was Ephedra sinica. The medicinal part is the herbaceous stems of Ephedrae Herba. Before the Northern and Southern dynasties， the origin of the records was Jindi and Hedong， which is now Shanxi province. In the Northern and Southern dynasties and later generations， the producing area expanded， and now it is mainly distributed in Hebei， Shanxi， Shaanxi， Inner Mongolia， Gansu， Liaoning and other places， among which Inner Mongolia is the main producing area. The harvesting and processing methods in the past dynasties are to harvest the stems in autumn， dry them in the shade or air to 70%-80% dry， and then dry them in the sun. The processing methods in the past dynasties mainly include removing the knots， wine-fried， honey-fried， processing with vinegar and so on， at present， only honey-fried is still in use. Based on the research results， it is suggested that Ephedrae Herba in famous classical formulas should be selected the dry herbaceous stems of E. sinica. If the processing requirements are not indicated， it is suggested to use raw products of Ephedrae Herba.

Non-ephedrine constituents from the herbaceous stems of Ephedra sinica.

Three new flavonoids, ephedroside A (1), ephedroside B (2), ephedroside C (3), together with fifty-four known compounds 4-57 were isolated from the EtOH extract of the herbaceous stems of Ephedra sinica. The structures of these compounds were elucidated by spectroscopic techniques, as well as by comparison with literature data. Thirty-eight of these compounds were isolated from the genus Ephedra for the first time. The antimicrobial activities of eight compounds were tested by measuring the minimum inhibitory concentrations (MIC) against bacteria (both Gram positive and Gram negative) and fungi, and were found to be in the range of 0.105-0.926 mM. Among them, compound 2 showed the best antimicrobial activity against Pseudomonas aeruginosa with MIC value of 0.105 mM.

Inhibitory activity of flavonoids from Ephedrae Herba on hypoxia signaling in PANC-1 cells and the evaluation of their mechanisms.

Pancreatic cancer is a lethal disease with a very poor prognosis. Recent reports indicate that hypoxia signaling mediated by hypoxia-inducible factor (HIF) contributes to the progression of pancreatic cancer. Therefore, elucidating the inhibitor of hypoxia signaling may lead to the development of a candidate for new anticancer agents. During our screening program for HIF inhibitor from crude drug extracts, new acylated kaempferol glycosides, kaempferol 3-O-[4″-(E)-p-coumaroyl-3″-O-dihydroxypalmityl] rhamnoside (1) and kaempferol 3-O-[4″-(E)-p-coumaroyl-2″-O-dihydroxypalmityl] rhamnoside (2), were isolated from an acetone extract of Ephedrae Herba, together with eight known flavonol glycosides (3-10). The structures of novel compounds 1 and 2 were elucidated based on spectroscopic and chemical analyses. Using a cell-based HRE-driven luciferase reporter assay in a PANC-1 pancreatic cancer cell line, we found that these compounds demonstrated potent inhibitory activity on hypoxia signaling with IC50 values of 18.0 ± 0.6 and 13.3 ± 2.2 µM, respectively. Mechanistically, 2 reduced the amount of HIF-1α protein in the nuclear at 30 µM via the ubiquitin-proteasome pathway with no effect on the nuclear translocation of HIF proteins from cytosol and subsequently decreased Glut1 mRNA. These results indicate that 2 inhibits hypoxia signaling through a mechanism involving the reduction of HIF-1α protein levels and Glut1 mRNA and may have anti-pancreatic cancer effects.

One-pot discriminant LC/MS quantitative analysis of ephedrine and pseudoephedrine using Finger Masher and their distribution in the aerial stems of Ephedra plants.

A discriminant LC/MS quantitative analysis of ephedrine (EP) and pseudoephedrine (PEP) in Ephedrae herba was performed. Aerial parts of three Ephedra species were separated into internodes and extracted using Finger Masher with minimum loss. The contents of EP and PEP were measured by LC/MS/MS using the multiple reaction monitoring (MRM) method. Their contents in old-year branches were lower than those current-year branches and tended to be higher in the middle part than in the tip of each branch. The content ratio of EP and PEP was reversed in some branches depending on their extent of growth. In E. sinica, the contents were low at the first internode closest to the central main stem at each branch. The contents drastically increased from the second internode and were highest at the third internode. There was a strong correlation between the internode distance and alkaloid (EP + PEP) contents. The distribution of alkaloids in one internode was examined and the results showed that the part closest to the node had the lowest contents.

Herb pair of Ephedrae Herba-Armeniacae Semen Amarum alleviates airway injury in asthmatic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Ephedrae Herba (EH, Ephedra sinica Stapf.) and Armeniacae Semen Amarum (ASA, Prunus armeniaca L. var. ansu Maxim.) have been used to treat asthma, cold, fever, and cough in China for thousands of years. AIM OF THE STUDY: In this study, we aimed to investigate the optimal ratio of EH and ASA compatibility (EAC) to reduce airway injury in asthmatic rats and its possible mechanism. METHODS: Rats were sensitized with a mixture of acetylcholine chloride and histamine bisphosphate 1 h before sensitization by intragastric administration of EAC or dexamethasone or saline for 7 days. Subsequently, the ultrastructure of rat airway epithelial tissue changes, apoptosis of the airway epithelial cells, and the expression of mRNA and protein of EGRF and Bcl-2 were detected. RESULTS: Transmission electron microscope: EAC (groups C and E) had the most prominent effect on repairing airway epithelial cells' ultrastructural changes in asthmatic rats. TUNEL: dexamethasone and EAC (groups B、C、E and F) inhibited the apoptosis of airway epithelial cells in asthmatic rats (P < 0.05). In situ hybridization: EAC (group E) inhibited the overexpression of EGFR and Bcl-2 mRNA (P < 0.05).Western Blotting: EAC (groups A、B、C、E and F) inhibited the upregulation of airway epithelial EGFR and Bcl-2 protein expression (P < 0.01). CONCLUSIONS: Our findings indicate that EAC can inhibit abnormal changes in airway epithelial structure and apoptosis of airway epithelial cells, thereby alleviating airway injury. In this study, the best combination of EH and ASA to alleviate airway epithelial injury in asthmatic rats was group E (EH: ASA = 8: 4.5).

Ephedrae Herba in combination with herbal medicine (Zhizichi decoction and Phellodendri Cortex) for weight reduction: a case series.

BACKGROUNDS: Ephedrae Herba is widely used to treat obesity. There is a concern for adverse events (AEs) using it and we need to develop strategies to attenuate it without its effectiveness for weight-reducing potential. We investigated the effects of a combination of Ephedra Herba with Zhizichi decoction and Phellodendri Cortex (Anmyungambi (AMGB) decoction) in reducing the incidence of Ephedra Herba-related AEs. METHODS: We performed a retrospective chart review from a clinical case series of patients visiting the Jaonmi Korean Medicine Clinic (Seoul, Korea). The inclusion criteria was patients who were prescribed AMGB decoction, (containing Ephedrae Herba, Phellodendri Cortex, and Zhizichi decoction [Gardeniae Fructus, and Glycine Semen Preparata] in different proportions) for weight reduction. Exclusion of Phellodendri Cortex in the original AMGB preparation was allowed; conventional medications, acupuncture, and dietary supplements were not allowed. The primary outcome was absolute weight loss at the end of treatment. RESULTS: Twenty-seven patients (6 men and 21 women), aged 18-75 years (mean age, 42.6 ± 11.1 years) and the average treatment duration was 39.4 days. Absolute weight loss at the end of treatment was 4.49 ± 2.40 kg. Fifteen patients lost more than 5% weight (55.6%). Treatment >45 days resulted in significantly greater weight loss compared to treatment <30 days (p < 0.001). Not severe AEs were reported in 16 patients including constipation, fatigue, etc. CONCLUSION: A combination of Ephedra Herba with Zhizichi decoction and Phellodendri Cortex may be a safe and effective treatment for weight reduction in obese and overweight patients.

Molecular docking combined with network pharmacology to study molecular mechanism of Guizhi Shaoyao Zhimu Decoction in treatment of rheumatoid arthritis / 中草药

Objective: To predict the active constituents and targets of Guizhi Shaoyao Zhimu Decoction (GSZD) in the treatment of rheumatoid arthritis by using molecular docking and network pharmacology, and to analyze the effect of multi component-multi target-multi pathway combined with the theory of compatibility of TCM prescriptions. Methods: The main chemical constituents of nine kinds of Chinese herbal medicines (Cinnamomi Ramulus, Paeoniae Radix Alba, Anemarrhenae Rhizoma, Glycyrrhizae Radix et Rhizoma, Ephedrae Herba, Zingiberis Rhizoma Recens, Atractylodis Macrocephalae Rhizoma, Saposhnikoviae Radix and Aconiti Lateralis Radix Praeparata) were collected from TCMSP, TCM-Datebas@Taiwan and PubChen Compound database. The protein targets to the treatment of rheumatoid arthritis are found through DrugBank and TTD databases and uploaded to the String online database to build the network relationship of protein interaction. Appropriate crystal structures of protein targets were downloaded from PDB database, and molecular docking between compounds and targets was performed by using Discovery studio 4.5.0 software. A drug-compound-target visualization network was constructed by using Cytoscape 3.6.1 software to elucidate the main mechanism of GSZD against rheumatoid arthritis. Results: The results of molecular docking showed that there were 316 potential anti-arthritis active components in GSZD, acting on 26 targets, among which MAPK1, ZADH2, P38, AKR1C2, DHODH, CA2, MMP3, MMP9, RANKL, and other proteins were the main targets. Biological function and pathway analysis indicated that the mechanism of GSZD mainly involved in bone absorption (28%), histone kinase activity (20%), peptide tyrosine phosphorylation (20%), prostaglandin metabolism (12%), and other biological processes. The main pathway was osteoclast differentiation (94.12%). Conclusion: In this study, molecular docking combined with network pharmacology was used to study the pharmacodynamic material basis and molecular mechanism of GSZD in the treatment of rheumatoid arthritis from the perspective of multi-target and multi-approach, providing reference and basis for better clinical use.

Analysis of Chemical Components of Anti-allergic Asthma Active Fractions in Alkaloids-free Part of Ephedrae Herba / 中国药房

OBJECTIVE：To provide reference for elucidating the anti-allergic asthma constituents in alkaloids-free part of Ephedrae Herba. METHODS ：Ephedrae Herba was extracted with 85％ ethanol and n-heptane，and then subjected to solid-phase extraction（filler AC 18）for pretreatment to enrich alkaloids-free part from the extract of Ephedrae Herba. HPLC method was adopted，and alkaloids-free fractions of Ephedrae Herba were performed on Unitary C 18 column and Eclipse XDB-C 18 column. Using high expression G protein coupled-receptor 35（GPR35 receptor）in HT- 29 cell as target ，GPR35 receptor agonist zaprinast （1 μmol/L）as positive control ，DMR response value as the detection index ，the agonistic and desensitizing activity of each fraction（100 μg/mL）on GPR 35 receptor was screened by label-free integrated pharmacological method ，so as to screen active anti-allergic asthma fraction. HPLC-Q-TOF-MS method was used to identify the chemical composition of the selected active fractions. RESULTS ：The alkaloids-free part of Ephedrae Herba was divided into two parts ，involving the precipitated part before solid phase extraction and the 95％ methanol elution part ；from them ，20 fractions were screened. Among them ，the precipitated fraction F 1.5-F1.10 and 95％ methanol eluted fraction F 2.5-F2.10 had a strong agonistic activity on GPR 35 receptor；at the same time，GPR35 receptor agonist zaprinast showed a relatively strong desensitization activity. The signal intensity of DMR induced by F1.5-F1.10 in the precipitated part of HT- 29 cells was even higher than that of reference drug zaprinast. By HPLC-Q-TOF-MS analysis，24 chemical components were identified from active fractions ，involving 14 flavonoids，2 volatile oils ，7 organic carboxylic acids ，1 anthraquinones. CONCLUSIONS ：The alkaloid-free part of Ephedrae Herba is mainly flavonoids and has anti-allergic asthma activity.

Quality marker identification based on standard decoction of differently processed materials of Ephedrae Herba.

ETHNOPHARMACOLOGICAL RELEVANCE: The quality control of Traditional Chinese medicine (TCM) is a scientific problem and an industrial issue, which hampers the development of evidence based TCM. The concept of quality markers (Q-markers) is proposed and has been applied to the quality evaluation of TCM based on its clinical efficacy. However, more specific methods are needed to put this idea into practice. The standard decoction is a representative of decoction used in clinical practice and it can be used for the discovery of Q-markers related to the clinical efficacy of TCM. AIM OF THE STUDY: In this study, a systemic strategy was established to discover Q-markers related to the clinical efficacy of TCM Ephedrae Herba (EH), dried stem of Ephedra sinica Stapf. The different processed materials of EH have different clinical applications, though originating from the same medicinal herb. MATERIALS AND METHODS: The standard decoction of each of the processed materials was prepared and a 1HNMR metabolomics approach and total polysaccharide analysis were used to identify potential Q-markers related to the different clinical applications of EH. Correlation analysis was made of the measured biological activity and the holistic chemical profile. RESULTS: The results showed that total polysaccharides and alkaloids were Q-markers for EH preparations. CONCLUSION: This study demonstrates that the standard decoction is a reasonable research objective to explore chemical markers that correlate with the clinical efficacy of TCM.

Analysis of medication patterns of Chinese patent medicine for cough / 中草药

To reveal the medication patterns of Chinese patent medicine in the treatment of cough based on the analysis of the patent status of Chinese materia medica (CMM) in the field of cough control in nearly 20 years. Patents of Chinese patent medicine in the treatment of cough were systematically searched in SIPO Platform and CNKI, association analysis and network analysis of high-frequency medicines were used to reveal the medication patterns of Chinese patent medicine in the treatment of cough with software Clementine 12.0. The results showed that Chinese medicine with highest frequency in 316 formulas was Glycyrrhizae Radix et Rhizoma, the other Chinese herbs with higher frequency were Platycodonis Radix, Ephedrae Herba, Citri Reticulatae Pericarpium, Pinelliae Rhizoma, etc. The main categories were the medicines used to treat cough and asthma, as well as to reduce phlegm. The commonly used herbal pairs were Glycyrrhizae Radix et Rhizoma-Platycodonis Radix, Glycyrrhizae Radix et Rhizoma-Citri Reticulatae Pericarpium, Pinelliae Rhizoma-Glycyrrhizae Radix et Rhizoma, Ephedrae Herba-Glycyrrhizae Radix et Rhizoma, etc. It was concluded that the medication patterns of Chinese patent medicine in the treatment of cough can be revealed based on the analysis of the herbal frequency, herbal pairs, association rules, and the network of high-frequency medicines and the theory of traditional Chinese medicine, so as to provide reference evidences for clinical medication.