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Applied and Environmental Microbiology Mar 2020The Gram-positive soil bacterium sp. strain TS-15 (DSM 32400), which is capable of metabolizing ephedrine as a sole source of carbon and energy, was isolated. According...
The Gram-positive soil bacterium sp. strain TS-15 (DSM 32400), which is capable of metabolizing ephedrine as a sole source of carbon and energy, was isolated. According to 16S rRNA gene sequences and comparative genomic analysis, sp. TS-15 is closely related to Distinct from all known physiological paths, ephedrine metabolism by sp. TS-15 is initiated by the selective oxidation of the hydroxyl function at the α-C atom, yielding methcathinone as the primary degradation product. Rational genome mining revealed a gene cluster potentially encoding the novel pathway. Two genes from the cluster, which encoded putative short-chain dehydrogenases, were cloned and expressed in The obtained enzymes were strictly NAD dependent and catalyzed the oxidation of ephedrine to methcathinone. Pseudoephedrine dehydrogenase (PseDH) selectively converted ()-(+)-pseudoephedrine and ()-(+)-ephedrine to ()- and ()-methcathinone, respectively. Ephedrine dehydrogenase (EDH) exhibited strict selectivity for the oxidation of the diastereomers (,)-(-)-ephedrine and (,)-(-)-pseudoephedrine. sp. TS-15 is a newly isolated bacterium with the unique ability to degrade ephedrine isomers. The initiating steps of the novel metabolic pathway are described. sp. TS-15 and its isolated ephedrine-oxidizing enzymes have potential for use in decontamination and synthetic applications.
Topics: Arthrobacter; Biodegradation, Environmental; Ephedrine; Escherichia coli; Gene Expression Regulation, Bacterial; Genes, Bacterial; Micrococcaceae; Microorganisms, Genetically-Modified; Multigene Family; Pseudoephedrine; Stereoisomerism
PubMed: 31900306
DOI: 10.1128/AEM.02487-19 -
Journal of Natural Medicines Jul 2016It is generally accepted that the primary pharmacological activities and adverse effects of Ephedra Herb are caused by ephedrine alkaloids. Interestingly, our research...
It is generally accepted that the primary pharmacological activities and adverse effects of Ephedra Herb are caused by ephedrine alkaloids. Interestingly, our research shows that Ephedra Herb also has ephedrine alkaloid-independent pharmacological actions, such as c-MET inhibitory activity. This study describes the preparation of an ephedrine alkaloids-free Ephedra Herb extract (EFE) by ion-exchange column chromatography, as well as in vitro and in vivo evaluation of its pharmacological actions and toxicity. We confirmed that EFE suppressed hepatocyte growth factor (HGF)-induced cancer cell motility by preventing both HGF-induced phosphorylation of c-Met and its tyrosine kinase activity. We also investigated the analgesic effect of EFE. Although the analgesic effect of Ephedra Herb has traditionally been attributed to pseudoephedrine, oral administration of EFE reduced formalin-induced pain in a dose-dependent manner in mice. Furthermore, we confirmed the anti-influenza virus activity of EFE by showing inhibition of MDCK cell infection in a concentration-dependent manner. All assessments of toxicity, even after repeated oral administration, suggest that EFE would be a safer alternative to Ephedra Herb. The findings described here suggest that EFE has c-Met inhibitory action, analgesic effect, and anti-influenza activity, and that it is safer than Ephedra Herb extract itself. Therefore, EFE could be a useful pharmacological agent.
Topics: Alkaloids; Analgesics; Antineoplastic Agents; Ephedra; Ephedrine; Humans; Influenza, Human
PubMed: 26943796
DOI: 10.1007/s11418-016-0979-z -
Obesity Research Nov 1995When given as a supplement to an energy restricted diet the sympathomimetic agent ephedrine, in combination with methylxanthines such as caffeine, improves fat loss by... (Clinical Trial)
Clinical Trial Review
When given as a supplement to an energy restricted diet the sympathomimetic agent ephedrine, in combination with methylxanthines such as caffeine, improves fat loss by dual actions: a central suppression of appetite and peripheral stimulation of energy expenditure covered by fat oxidation. Mean weight loss was found to be 16.6 kg after 6 months when E+C was given as an adjuvant to an efficient hypoenergetic diet, which was 3.4 kg higher than in the placebo group. An additional 24 weeks treatment with E+C prevented relapse. In the first weeks of treatment E+C offset the hypotensive effect of energy restriction and weight loss, but the effect was transient, and after 8 weeks blood pressures were indistinguishable from those of the placebo group. E+C has no adverse effect on glucose and lipid metabolism, but has been shown to prevent the decline in HDL-cholesterol caused by weight loss. In a comparative trial the weight loss produced by E+C was similar to that of dexfenfluramine. More research on sympathomimetics and methylxanthines should be carried out to identify combinations with improved efficiency and safety. Moreover, more long-term trials and studies in males are required.
Topics: Appetite Depressants; Body Temperature Regulation; Caffeine; Ephedrine; Humans; Obesity; Sympathomimetics
PubMed: 8697055
DOI: 10.1002/j.1550-8528.1995.tb00224.x -
Phytotherapy Research : PTR May 2016Obesity and overweight are major health issues. Exercise and calorie intake control are recognized as the primary mechanisms for addressing excess body weight. Naturally... (Review)
Review
Obesity and overweight are major health issues. Exercise and calorie intake control are recognized as the primary mechanisms for addressing excess body weight. Naturally occurring thermogenic plant constituents offer adjunct means for assisting in weight management. The controlling mechanisms for thermogenesis offer many intervention points. Thermogenic agents can act through stimulation of the central nervous system with associated adverse cardiovascular effects and through metabolic mechanisms that are non-stimulatory or a combination thereof. Examples of stimulatory thermogenic agents that will be discussed include ephedrine and caffeine. Examples of non-stimulatory thermogenic agents include p-synephrine (bitter orange extract), capsaicin, forskolin (Coleus root extract), and chlorogenic acid (green coffee bean extract). Green tea is an example of a thermogenic with the potential to produce mild but clinically insignificant undesirable stimulatory effects. The use of the aforementioned thermogenic agents in combination with other extracts such as those derived from Salacia reticulata, Sesamum indicum, Lagerstroemia speciosa, Cissus quadrangularis, and Moringa olifera, as well as the use of the carotenoids as lutein and fucoxanthin, and flavonoids as naringin and hesperidin can further facilitate energy metabolism and weight management as well as sports performance without adverse side effects. © 2016 The Authors Phytotherapy Research published by John Wiley & Sons Ltd.
Topics: Caffeine; Capsaicin; Central Nervous System Stimulants; Chlorogenic Acid; Ephedrine; Humans; Obesity; Overweight; Synephrine; Tea; Thermogenesis
PubMed: 26856274
DOI: 10.1002/ptr.5583 -
British Journal of Anaesthesia May 2023Off-label use of medications in paediatric anaesthesia is common practice, owing to the relative paucity of evidence-based dosing regimens in children. Well-performed...
Off-label use of medications in paediatric anaesthesia is common practice, owing to the relative paucity of evidence-based dosing regimens in children. Well-performed dose-finding studies, especially in infants, are rare and urgently needed. Unanticipated effects can result when paediatric dosing is based on adult parameters or local traditions. A recent dose-finding study on ephedrine highlights the uniqueness of paediatric dosing in comparison with adult dosing. We discuss the problems of off-label medication use and the lack of evidence for various definitions of hypotension and associated treatment strategies in paediatric anaesthesia. What is the aim of treating hypotension associated with anaesthesia induction: restoring the MAP to awake baseline values or elevating it above a provisional hypotension threshold?
Topics: Adult; Infant; Humans; Child; Ephedrine; Vasoconstrictor Agents; Anesthesia, Spinal; Hypotension; Anesthesia, Obstetrical
PubMed: 36906461
DOI: 10.1016/j.bja.2023.02.007 -
Biological & Pharmaceutical Bulletin 2019The analgesic effect of Ephedra Herb (EH) is believed to be derived from the anti-inflammatory action of pseudoephedrine (Pse). We recently reported that ephedrine...
The analgesic effect of Ephedra Herb (EH) is believed to be derived from the anti-inflammatory action of pseudoephedrine (Pse). We recently reported that ephedrine alkaloids-free EH extract (EFE) attenuates formalin-induced pain to the same level as that achieved by EH extract (EHE), which suggests that the analgesic effect of EH may not be due to ephedrine alkaloids (EAs). To examine the contribution of EAs to the analgesic effect of EH, mice were injected with formalin to induce a biphasic pain reaction (first phase, 0-5 min; second phase, 10-45 min) at various time points after oral administration of the following test drugs: ephedrine (Eph), Pse, "authentic" EHE from Tsumura & Co. (EHE-Ts), EFE, and EHE that was used as the source of EFE (EHE-To). Biphasic pain was suppressed at 30 min after administration of Eph, EHE-Ts, and EHE-To. At 6 h after administration of EFE, EHE-To, and Pse-and at 4 to 6 h after administration of EHE-Ts-only second-phase pain was suppressed; however, the effect of Pse at 6 h was not significant. These results suggested that EHE has a biphasic analgesic effect against biphasic formalin-induced pain: in the first phase of analgesia (30 min after administration), biphasic pain is suppressed by Eph; in the second phase of analgesia (4-6 h after administration), second-phase pain is alleviated by constituents other than EAs, although Pse may partially contribute to the relief of second-phase pain.
Topics: Administration, Oral; Analgesics; Animals; Disease Models, Animal; Ephedra; Ephedrine; Male; Mice, Inbred Strains; Pain; Pain Measurement; Plant Extracts; Pseudoephedrine; Rotarod Performance Test; Time Factors
PubMed: 31474713
DOI: 10.1248/bpb.b19-00260 -
Forensic Science International Oct 2023Manufacture and recreational use of methamphetamine can result in widespread chemical contamination throughout a property. Hydrogen peroxide (HO)-based cleaning products...
Manufacture and recreational use of methamphetamine can result in widespread chemical contamination throughout a property. Hydrogen peroxide (HO)-based cleaning products have shown success against a number of chemical contaminants including agents of chemical warfare, and biological contaminants such as anthrax. They are considered to be environmentally friendly and economically viable and, as such, are used by many companies within the methamphetamine decontamination industry. The oxidative decontamination of methamphetamine and ephedrine hydrochloride was investigated in this current study, employing a commercially available HO-based decontamination product, Bio-Oxygen® Chem Decon. Methamphetamine and ephedrine were observed to degrade following pseudo-first order kinetics of (1.9 ± 0.4) × 10 min and (2.2 ± 0.3) × 10 min, respectively. Major oxidation products identified through GC-MS analyses were phenylacetone oxime (from methamphetamine) and benzaldehyde (from ephedrine). LC-MS analysis revealed the presence of a number of N-oxygenated intermediates which allowed for the elucidation of an N-oxidation decomposition pathway reminiscent of flavin-containing monooxygenase enzymes. Using this information, further targeted research can be performed to understand the behaviour and persistence of these reaction products and accurate assessments can be achieved to estimate their impact on the exposure risks associated with chemical decontamination of amphetamine-type stimulants (ATS).
Topics: Ephedrine; Methamphetamine; Peroxides; Hydrogen Peroxide; Decontamination
PubMed: 37690396
DOI: 10.1016/j.forsciint.2023.111816 -
Obesity Research Nov 1995Pharmacological treatment of obesity has been neglected as a viable therapeutic option for many years. Recent long term studies with combinations of obesity drugs gives... (Review)
Review
Pharmacological treatment of obesity has been neglected as a viable therapeutic option for many years. Recent long term studies with combinations of obesity drugs gives promise that drugs may play a role in weight maintenance, which classically has been the most difficult aspect of treating obesity. Currently available obesity drugs include centrally acting adrenergic agents and serotonin agonists. Drugs still in development include a lipase inhibitor that produces fat malabsorption, a combined adrenergic-serotonergic reuptake inhibitor, various gut-central nervous system peptides, and a number of beta-3 agonists. Any of these obesity drugs given alone produces modest weight loss, and for most, weight loss continues for as long as medication is given. The most successful drug regimens to date are combinations of phentermine and fenfluramine or of ephedrine, caffeine, and/or aspirin. The former combination produces reduction in body weight and complications of obesity for 2 to almost 4 years in clinical trials to date. More research is needed to document long term efficacy and particularly the long term safety of these and other combinations.
Topics: Adrenergic Agents; Appetite Depressants; Benzocaine; Drug Therapy, Combination; Ephedrine; Fenfluramine; Humans; Obesity; Phentermine; Phenylpropanolamine; Serotonin Agents
PubMed: 8697049
DOI: 10.1002/j.1550-8528.1995.tb00218.x -
American Journal of Physiology.... Jan 2007The global prevalence of obesity has increased considerably in the last decade. Tools for obesity management, including caffeine, ephedrine, capsaicin, and green tea... (Review)
Review
The global prevalence of obesity has increased considerably in the last decade. Tools for obesity management, including caffeine, ephedrine, capsaicin, and green tea have been proposed as strategies for weight loss and weight maintenance, since they may increase energy expenditure and have been proposed to counteract the decrease in metabolic rate that is present during weight loss. A combination of caffeine and ephedrine has shown to be effective in long-term weight management, likely due to different mechanisms that may operate synergistically, e.g., respectively inhibiting the phosphodiesterase-induced degradation of cAMP and enhancing the sympathetic release of catecholamines. However, adverse effects of ephedrine prevent the feasibility of this approach. Capsaicin has been shown to be effective, yet when it is used clinically it requires a strong compliance to a certain dosage, that has not been shown to be feasible yet. Also positive effects on body-weight management have been shown using green tea mixtures. Green tea, by containing both tea catechins and caffeine, may act through inhibition of catechol O-methyl-transferase, and inhibition of phosphodiesterase. Here, the mechanisms may also operate synergistically. In addition, tea catechins have antiangiogenic properties that may prevent development of overweight and obesity. Furthermore, the sympathetic nervous system is involved in the regulation of lipolysis, and the sympathetic innervation of white adipose tissue may play an important role in the regulation of total body fat in general.
Topics: Animals; Body Weight; Caffeine; Capsaicin; Central Nervous System Stimulants; Energy Metabolism; Ephedrine; Humans; Obesity; Tea; Thermogenesis
PubMed: 16840650
DOI: 10.1152/ajpregu.00832.2005 -
The Journal of Toxicological Sciences 2023Pulmonary fibrosis is a lethal and progressive pulmonary disorder in human beings. Ephedrine is a compound isolated from Ephedra and plays a regulatory role in...
Pulmonary fibrosis is a lethal and progressive pulmonary disorder in human beings. Ephedrine is a compound isolated from Ephedra and plays a regulatory role in inflammatory response. This study focused on the anti-pulmonary fibrosis effect of ephedrine and its potential molecular mechanism. After a mouse model of pulmonary fibrosis was established through bleomycin (BLM) induction, the survival percentage, body weight, and pulmonary index were measured. Hematoxylin-eosin staining and Masson's trichrome staining for lung tissues were performed to observe the pathological alterations. The viability of lung epithelial BEAS-2B cells, intracellular production of reactive oxygen species, and the levels of pro-inflammatory cytokines were examined by cell counting kit-8 assays, 2',7'-dichlorofluorescein diacetate (DCF-DA) staining, and enzyme-linked immunosorbent assay, respectively. Immunofluorescence staining was performed to determine E-cadherin and vimentin expression after BLM or ephedrine treatment. The mRNA and protein levels of cytokeratin-8, E-cadherin, α-SMA, and vimentin were subjected to quantitative polymerase chain reaction and immunoblotting. Experimental results revealed that ephedrine treatment rescued the repressive impact of BLM on BEAS-2B cell viability, and ephedrine inhibited BLM-induced overproduction of reactive oxygen species and inflammatory response in BEAS-2B cells. Additionally, ephedrine suppressed epithelial-mesenchymal transition (EMT) process stimulated by BLM treatment, as demonstrated by the reduced α-SMA and vimentin levels together with the increased cytokeratin-8 and E-cadherin levels in BLM + Ephedrine group. In addition, ephedrine inhibited NF-κB and activated Nrf-2 signaling in BLM-treated BEAS-2B cells. Moreover, ephedrine ameliorated pulmonary fibrosis in BLM-induced mice and improved the survival of model mice. In conclusion, ephedrine attenuates BLM-evoked pulmonary fibrosis by repressing EMT process via blocking NF-κB signaling and activating Nrf-2 signaling, suggesting that ephedrine might become a potential anti-pulmonary fibrosis agent in the future.
Topics: Mice; Humans; Animals; Pulmonary Fibrosis; NF-kappa B; Bleomycin; Ephedrine; Keratin-8; Vimentin; Reactive Oxygen Species; Epithelial-Mesenchymal Transition; Lung; Cadherins
PubMed: 37778983
DOI: 10.2131/jts.48.547