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Peyton Jacob - One of the best experts on this subject based on the ideXlab platform.

  • hemodynamic effects of Ephedra free weight loss supplements in humans
    The American Journal of Medicine, 2005
    Co-Authors: Christine A Haller, Neal L Benowitz, Peyton Jacob
    Abstract:

    Abstract Purpose Ephedra-free weight loss dietary supplements containing bitter orange ( Citrus aurantium ), a botanical source of the adrenergic amines synephrine and octopamine, have quickly emerged on consumer markets to replace banned Ephedra products. These supplements may have some of the health risks associated with Ephedra, but studies in humans are lacking. Our aim was to characterize the pharmacokinetics and cardiovascular effects of C. aurantium dietary supplements. Subjects and methods Ten healthy adult nonsmokers participated in a randomized, double-blind, placebo-controlled, three-arm crossover study. Single doses of C. aurantium (Advantra Z) containing 46.9 mg synephrine, Xenadrine EFX, a multi-component formulation containing 5.5 mg synephrine, and placebo were administered with a one-week washout. Results Compared with placebo, Xenadrine EFX but not Advantra Z increased systolic and diastolic blood pressure with peak changes from baseline at 2 hours of 9.6 ± 6.2 mm Hg systolic ( P = 0.047), and 9.1 ± 7.8 mm Hg diastolic ( P = 0.002). Heart rate was increased from baseline at 6 hours compared with placebo (16.7 beats per minute with Xenadrine EFX, P = 0.011; 11.4 beats per minute with Advantra Z, P = 0.031). Dose-adjusted synephrine pharmacokinetics were similar between treatments with t max = 90 min, t 1/2 = 3.0 hours, V/F = 16347 L, and CL/F = 88.9 L/min for Xenadrine EFX. Conclusion Ephedra-free weight loss supplements have significant cardiovascular stimulant actions, similar to Ephedra. These effects are not likely caused by C. aurantium alone, because an eightfold higher dose of synephrine (Advantra Z) had no effect on blood pressure, but may be attributable to caffeine and other stimulants in the multi-component formulation

  • short term metabolic and hemodynamic effects of Ephedra and guarana combinations
    Clinical Pharmacology & Therapeutics, 2005
    Co-Authors: Christine A Haller, Peyton Jacob, Neal L Benowitz
    Abstract:

    Objective Serious adverse health events have been reported with the use of dietary supplements containing Ephedra and guarana. We sought to determine whether repeated dosing and multi-ingredient formulations contribute to the adverse effects of these supplements. Methods In this study, 16 healthy adults (8 women) took 2 doses each of Ephedra-guarana alone, Xenadrine RFA, a multicomponent dietary supplement containing 25 mg Ephedra alkaloids and 200 mg caffeine, or placebo 5 hours apart in a randomized, double-blind, 3-arm crossover study. Results Peak plasma ephedrine levels averaged 130 to 140 ng/mL. Compared with placebo, Xenadrine and Ephedra-guarana significantly increased heart rate (maximum increase, 9.4 ± 8.6 beats/min; P = .002), blood pressure (maximum increase in systolic and diastolic pressure, 11.5 ± 10.7 mm Hg and 7.3 ± 7.4 mm Hg, respectively; P = .015), postprandial glucose concentration (maximum change, 41.0 ± 18.8 mg/dL; P < .0001), and insulin concentration (maximum change, 41.2 ± 47.8 μIU/mL; P = .005). Serum potassium concentrations were significantly decreased by both treatments. Hemodynamic and metabolic changes were observed after both the first and second doses. However, plasma free fatty acid concentrations increased after the first dose only. Xenadrine RFA produced higher increases in glucose concentration than Ephedra-guarana, but no other pharmacodynamic differences between the treatments were found. Conclusions Consumption of 2 doses of Ephedra and guarana supplements, per supplement label recommendations, results in persistent increases in heart rate and blood pressure and unfavorable actions on glucose and potassium homeostasis. Such effects could be detrimental in persons with hypertension, atherosclerosis, or glucose intolerance, conditions that are strongly associated with obesity. Clinical Pharmacology & Therapeutics (2005) 77, 560–571; doi: 10.1016/j.clpt.2005.01.023

  • caffeine herbal Ephedra combination increases resting energy expenditure heart rate and blood pressure
    Clinical and Experimental Pharmacology and Physiology, 2005
    Co-Authors: Matthew D Vukovich, Peyton Jacob, Rana Schoorman, Chris Heilman, Neal L Benowitz
    Abstract:

    SUMMARY 1. The purpose of the present study was to determine whether the consumption of an acute dose of caffeine and Ma Huang increases resting energy expenditure (REE), heart rate (HR) and blood pressure (BP) over a 3 h period. 2. A randomized, double-blind cross-over study was performed evaluating the acute effects of caffeine (150 mg)/herbal Ephedra (Ma Huang; 20 mg Ephedra alkaloids) versus a placebo. A total of eight healthy subjects (four males and four females) with a mean (±SD) age of 23.4 ± 0.8 years (mean ages for males and females: 25.3 ± 0.7 and 22.0 ± 0.7 years, respectively) and 22.5 ± 3.1% body fat (15.7 ± 1.2 and 27.6 ± 3.5% body fat for males and females, respectively) were recruited to the study. Participants were moderate caffeine users (approximately 150–300 mg/day). 3. Subjects reported to the laboratory following a 12 h fast and 48 h of a caffeine-free diet. Resting energy expenditure was measured prior to supplementation and for 15 min every 30 min for 3 h following supplementation. Heart rate and BP were obtained every 15 min. Blood samples were obtained every 30 min following the measurement of REE and analysed for caffeine, ephedrine, free fatty acids and glucose. 4. By 3 h, HR was 22.7 ± 5.5% higher (P < 0.05) than baseline for the caffeine/Ephedra trial compared with 8.9 ± 2.2% higher for the placebo grou. At 3 h, systolic BP was 9.1 ± 2.2% higher (P < 0.05) than baseline for the caffeine/Ephedra trial compared with only 1.9 ± 2.9% different from baseline for the placebo trial. There was no effect of the caffeine/Ephedra combination on diastolic BP. Resting energy expenditure during the last 30 min was 4.5 ± 2.5% higher in the placebo trial and 10.7 ± 2.5% higher (P < 0.05) in the caffeine/Ephedra trial; REE was 8.5 ± 2.0% higher (P < 0.05) in the caffeine/Ephedra trial compared with the placebo trial. Free fatty acids increased over time in the placebo and caffeine/Ephedra trials (from 0.5 ± 0.05 to 0.63 ± 0.05 mEq/L and from 0.48 ± 0.06L to 0.8 ± 0.05 mEq/L, respectively). 5. Caffeine and herbal Ephedra, at doses of 150 mg and 20 mg (ephedrine), respectively, result in a significant elevation in REE, HR and BP. Although significant, the increase in energy expenditure is negligible in terms of weight loss.

  • concentrations of Ephedra alkaloids and caffeine in commercial dietary supplements
    Journal of Analytical Toxicology, 2004
    Co-Authors: Christine A Haller, Minjing Duan, Neal L Benowitz, Peyton Jacob
    Abstract:

    Dietary supplements that contain Ma Huang (Ephedra alkaloids) and guarana (caffeine) are widely marketed and used in the U.S. for weight loss and athletic performance enhancement, despite a lack of adequate research on the pharmacology of these botanical stimulants. We developed and applied a novel liquid chromatography-tandem mass spectrometry (LC-MS-MS) method to quantitate the various Ephedra alkaloids found in dietary supplements that contain Ephedra species. The quantities of ephedrine, pseudoephedrine, norephedrine, norpseudoephedrine, methylephedine, methylpseudoephedrine, and caffeine were determined for 35 commercial dietary supplements and compared with the amounts listed on the product labels. The total Ephedra alkaloid content ranged from 5.97 mg to 29.3 mg per serving. Two supplement brands did not list the quantity of Ephedra alkaloids on the label, and four did not list the amount of caffeine per serving. Of the products tested, 31% contained > 110% of the total Ephedra alkaloids listed on the label, and 6% of the supplements contained 110% of the declared caffeine content. The total Ephedra alkaloid content varied significantly from lot to lot in 5 of 9 products. Three product brands contained proportions of alkaloids that exceeded amounts reported for E. sinica, including one that was 98% ephedrine, one that had 10% norpseudoephedrine, and one that contained an average of 13% methylephedrine. We conclude that product inconsistency is common among some commercially available dietary supplements that contain Ephedra alkaloids and caffeine.

  • determination of Ephedra alkaloid and caffeine concentrations in dietary supplements and biological fluids
    Journal of Analytical Toxicology, 2004
    Co-Authors: Peyton Jacob, Christine A Haller, Minjiang Duan, Margaret Peng, Neal L Benowitz
    Abstract:

    Dietary supplements containing botanical forms of caffeine and Ephedra alkaloids have been widely promoted and used in the U.S. for weight loss and athletic enhancement despite a lack of adequate research on the pharmacology of these botanical stimulants. In order to analyze dietary supplements and perform human pharmacokinetic studies, an analytical approach with good precision and accuracy was needed with sufficient sensitivity to detect very low levels of Ephedra alkaloids. A liquid chromatography-atmospheric pressure chemical ionization (APCI) tandem mass spectrometry (LC-MS-MS) method was developed for quantitating the various ephedrine-group alkaloids found in dietary supplements that contain Ephedra species, and in plasma and urine of persons consuming these supplements. Using this method, low nanogram-per-milliliter concentrations of ephedrine, pseudoephedrine, norephedrine, norpseudoephedrine, methylephedrine, methylpseudoephedrine, and caffeine can be quantitated in a 12-min LC-MS-MS run.

Neal L Benowitz - One of the best experts on this subject based on the ideXlab platform.

  • hemodynamic effects of Ephedra free weight loss supplements in humans
    The American Journal of Medicine, 2005
    Co-Authors: Christine A Haller, Neal L Benowitz, Peyton Jacob
    Abstract:

    Abstract Purpose Ephedra-free weight loss dietary supplements containing bitter orange ( Citrus aurantium ), a botanical source of the adrenergic amines synephrine and octopamine, have quickly emerged on consumer markets to replace banned Ephedra products. These supplements may have some of the health risks associated with Ephedra, but studies in humans are lacking. Our aim was to characterize the pharmacokinetics and cardiovascular effects of C. aurantium dietary supplements. Subjects and methods Ten healthy adult nonsmokers participated in a randomized, double-blind, placebo-controlled, three-arm crossover study. Single doses of C. aurantium (Advantra Z) containing 46.9 mg synephrine, Xenadrine EFX, a multi-component formulation containing 5.5 mg synephrine, and placebo were administered with a one-week washout. Results Compared with placebo, Xenadrine EFX but not Advantra Z increased systolic and diastolic blood pressure with peak changes from baseline at 2 hours of 9.6 ± 6.2 mm Hg systolic ( P = 0.047), and 9.1 ± 7.8 mm Hg diastolic ( P = 0.002). Heart rate was increased from baseline at 6 hours compared with placebo (16.7 beats per minute with Xenadrine EFX, P = 0.011; 11.4 beats per minute with Advantra Z, P = 0.031). Dose-adjusted synephrine pharmacokinetics were similar between treatments with t max = 90 min, t 1/2 = 3.0 hours, V/F = 16347 L, and CL/F = 88.9 L/min for Xenadrine EFX. Conclusion Ephedra-free weight loss supplements have significant cardiovascular stimulant actions, similar to Ephedra. These effects are not likely caused by C. aurantium alone, because an eightfold higher dose of synephrine (Advantra Z) had no effect on blood pressure, but may be attributable to caffeine and other stimulants in the multi-component formulation

  • short term metabolic and hemodynamic effects of Ephedra and guarana combinations
    Clinical Pharmacology & Therapeutics, 2005
    Co-Authors: Christine A Haller, Peyton Jacob, Neal L Benowitz
    Abstract:

    Objective Serious adverse health events have been reported with the use of dietary supplements containing Ephedra and guarana. We sought to determine whether repeated dosing and multi-ingredient formulations contribute to the adverse effects of these supplements. Methods In this study, 16 healthy adults (8 women) took 2 doses each of Ephedra-guarana alone, Xenadrine RFA, a multicomponent dietary supplement containing 25 mg Ephedra alkaloids and 200 mg caffeine, or placebo 5 hours apart in a randomized, double-blind, 3-arm crossover study. Results Peak plasma ephedrine levels averaged 130 to 140 ng/mL. Compared with placebo, Xenadrine and Ephedra-guarana significantly increased heart rate (maximum increase, 9.4 ± 8.6 beats/min; P = .002), blood pressure (maximum increase in systolic and diastolic pressure, 11.5 ± 10.7 mm Hg and 7.3 ± 7.4 mm Hg, respectively; P = .015), postprandial glucose concentration (maximum change, 41.0 ± 18.8 mg/dL; P < .0001), and insulin concentration (maximum change, 41.2 ± 47.8 μIU/mL; P = .005). Serum potassium concentrations were significantly decreased by both treatments. Hemodynamic and metabolic changes were observed after both the first and second doses. However, plasma free fatty acid concentrations increased after the first dose only. Xenadrine RFA produced higher increases in glucose concentration than Ephedra-guarana, but no other pharmacodynamic differences between the treatments were found. Conclusions Consumption of 2 doses of Ephedra and guarana supplements, per supplement label recommendations, results in persistent increases in heart rate and blood pressure and unfavorable actions on glucose and potassium homeostasis. Such effects could be detrimental in persons with hypertension, atherosclerosis, or glucose intolerance, conditions that are strongly associated with obesity. Clinical Pharmacology & Therapeutics (2005) 77, 560–571; doi: 10.1016/j.clpt.2005.01.023

  • caffeine herbal Ephedra combination increases resting energy expenditure heart rate and blood pressure
    Clinical and Experimental Pharmacology and Physiology, 2005
    Co-Authors: Matthew D Vukovich, Peyton Jacob, Rana Schoorman, Chris Heilman, Neal L Benowitz
    Abstract:

    SUMMARY 1. The purpose of the present study was to determine whether the consumption of an acute dose of caffeine and Ma Huang increases resting energy expenditure (REE), heart rate (HR) and blood pressure (BP) over a 3 h period. 2. A randomized, double-blind cross-over study was performed evaluating the acute effects of caffeine (150 mg)/herbal Ephedra (Ma Huang; 20 mg Ephedra alkaloids) versus a placebo. A total of eight healthy subjects (four males and four females) with a mean (±SD) age of 23.4 ± 0.8 years (mean ages for males and females: 25.3 ± 0.7 and 22.0 ± 0.7 years, respectively) and 22.5 ± 3.1% body fat (15.7 ± 1.2 and 27.6 ± 3.5% body fat for males and females, respectively) were recruited to the study. Participants were moderate caffeine users (approximately 150–300 mg/day). 3. Subjects reported to the laboratory following a 12 h fast and 48 h of a caffeine-free diet. Resting energy expenditure was measured prior to supplementation and for 15 min every 30 min for 3 h following supplementation. Heart rate and BP were obtained every 15 min. Blood samples were obtained every 30 min following the measurement of REE and analysed for caffeine, ephedrine, free fatty acids and glucose. 4. By 3 h, HR was 22.7 ± 5.5% higher (P < 0.05) than baseline for the caffeine/Ephedra trial compared with 8.9 ± 2.2% higher for the placebo grou. At 3 h, systolic BP was 9.1 ± 2.2% higher (P < 0.05) than baseline for the caffeine/Ephedra trial compared with only 1.9 ± 2.9% different from baseline for the placebo trial. There was no effect of the caffeine/Ephedra combination on diastolic BP. Resting energy expenditure during the last 30 min was 4.5 ± 2.5% higher in the placebo trial and 10.7 ± 2.5% higher (P < 0.05) in the caffeine/Ephedra trial; REE was 8.5 ± 2.0% higher (P < 0.05) in the caffeine/Ephedra trial compared with the placebo trial. Free fatty acids increased over time in the placebo and caffeine/Ephedra trials (from 0.5 ± 0.05 to 0.63 ± 0.05 mEq/L and from 0.48 ± 0.06L to 0.8 ± 0.05 mEq/L, respectively). 5. Caffeine and herbal Ephedra, at doses of 150 mg and 20 mg (ephedrine), respectively, result in a significant elevation in REE, HR and BP. Although significant, the increase in energy expenditure is negligible in terms of weight loss.

  • concentrations of Ephedra alkaloids and caffeine in commercial dietary supplements
    Journal of Analytical Toxicology, 2004
    Co-Authors: Christine A Haller, Minjing Duan, Neal L Benowitz, Peyton Jacob
    Abstract:

    Dietary supplements that contain Ma Huang (Ephedra alkaloids) and guarana (caffeine) are widely marketed and used in the U.S. for weight loss and athletic performance enhancement, despite a lack of adequate research on the pharmacology of these botanical stimulants. We developed and applied a novel liquid chromatography-tandem mass spectrometry (LC-MS-MS) method to quantitate the various Ephedra alkaloids found in dietary supplements that contain Ephedra species. The quantities of ephedrine, pseudoephedrine, norephedrine, norpseudoephedrine, methylephedine, methylpseudoephedrine, and caffeine were determined for 35 commercial dietary supplements and compared with the amounts listed on the product labels. The total Ephedra alkaloid content ranged from 5.97 mg to 29.3 mg per serving. Two supplement brands did not list the quantity of Ephedra alkaloids on the label, and four did not list the amount of caffeine per serving. Of the products tested, 31% contained > 110% of the total Ephedra alkaloids listed on the label, and 6% of the supplements contained 110% of the declared caffeine content. The total Ephedra alkaloid content varied significantly from lot to lot in 5 of 9 products. Three product brands contained proportions of alkaloids that exceeded amounts reported for E. sinica, including one that was 98% ephedrine, one that had 10% norpseudoephedrine, and one that contained an average of 13% methylephedrine. We conclude that product inconsistency is common among some commercially available dietary supplements that contain Ephedra alkaloids and caffeine.

  • determination of Ephedra alkaloid and caffeine concentrations in dietary supplements and biological fluids
    Journal of Analytical Toxicology, 2004
    Co-Authors: Peyton Jacob, Christine A Haller, Minjiang Duan, Margaret Peng, Neal L Benowitz
    Abstract:

    Dietary supplements containing botanical forms of caffeine and Ephedra alkaloids have been widely promoted and used in the U.S. for weight loss and athletic enhancement despite a lack of adequate research on the pharmacology of these botanical stimulants. In order to analyze dietary supplements and perform human pharmacokinetic studies, an analytical approach with good precision and accuracy was needed with sufficient sensitivity to detect very low levels of Ephedra alkaloids. A liquid chromatography-atmospheric pressure chemical ionization (APCI) tandem mass spectrometry (LC-MS-MS) method was developed for quantitating the various ephedrine-group alkaloids found in dietary supplements that contain Ephedra species, and in plasma and urine of persons consuming these supplements. Using this method, low nanogram-per-milliliter concentrations of ephedrine, pseudoephedrine, norephedrine, norpseudoephedrine, methylephedrine, methylpseudoephedrine, and caffeine can be quantitated in a 12-min LC-MS-MS run.

Catarina Rydin - One of the best experts on this subject based on the ideXlab platform.

  • The chloroplast genome of Ephedra foeminea (Ephedraceae, Gnetales), an entomophilous gymnosperm endemic to the Mediterranean area.
    Mitochondrial DNA Part A, 2015
    Co-Authors: Chen Hou, Niklas Wikström, Catarina Rydin
    Abstract:

    This study presents the chloroplast genome of Ephedra foeminea, an entomophilous gymnosperm, sister to the remaining (wind-pollinated) species of Ephedra (Ephedraceae, Gnetales). Based on the refer ...

  • Reproductive morphology in the Gnetum cuspidatum group (Gnetales) and its implications for pollination biology in the Gnetales
    Plant Ecology and Evolution, 2015
    Co-Authors: Annelie Jörgensen, Catarina Rydin
    Abstract:

    Background and aims - The Gnetales include the extant genera Gnetum, Ephedra and Welwitschia. They are usually functionally dioecious, but male cones often have sterile (but pollination drop-producing) ovules in addition to male units. There are, however, exceptions, i.e. most species of Ephedra and African species of Gnetum. Furthermore, the literature contains conflicting information on the Asian Gnetum cuspidatum. One study states that sterile ovules are present in this species; another that they are absent. The latter also claims that male cones secrete nectar instead, which is interesting because nectar has only been suggested to be present in four gymnosperm species. Here we aim to elucidate whether or not sterile ovules are present in male cones of G. cuspidatum and related taxa, evaluate evidence for nectar being present in gymnosperms and discuss implications for pollination biology. Methods - Male cones from relevant taxa were examined using a dissecting microscope and scanning electron microscopy. Key results - Sterile ovules are present in G. cuspidatum and the related G. macrostachyum, G. microcarpum, G. diminutum and G. loerzingii, but they are minute, hidden among hairs, and easily overlooked. No indications of nectar or nectaries were found and their presence in Asian species of Gnetum is questioned. Conclusions - Insect pollination is probably ancestral in the Gnetales. Like most species of Gnetum, members of the G. cuspidatum group have sterile ovules in male cones, and they can thus attract pollinators to both male and female plants using sweet pollination drops. Although it is possible that these species, in addition, produce extraovular reward for pollinators, we find no such evidence. Instead, it seems plausible that pollination drops have been mistaken for (extraovular) nectar. However, African species of Gnetum have unisexual male cones. Have they developed another means of pollinator reward in male plants or are they wind-pollinated as are their Ephedran analogues?

  • Moonlight pollination in the gymnosperm Ephedra (Gnetales).
    Biology Letters, 2015
    Co-Authors: Catarina Rydin, Kristina Bolinder
    Abstract:

    Most gymnosperms are wind-pollinated, but some are insect-pollinated, and in Ephedra (Gnetales), both wind pollination and insect pollination occur. Little is, however, known about mechanisms and evolution of pollination syndromes in gymnosperms. Based on four seasons of field studies, we show an unexpected correlation between pollination and the phases of the moon in one of our studied species, Ephedra foeminea. It is pollinated by dipterans and lepidopterans, most of them nocturnal, and its pollination coincides with the full moon of July. This may be adaptive in two ways. Many nocturnal insects navigate using the moon. Further, the spectacular reflection of the full-moonlight in the pollination drops is the only apparent means of nocturnal attraction of insects in these plants. In the sympatric but wind-pollinated Ephedra distachya, pollination is not correlated to the full moon but occurs at approximately the same dates every year. The lunar correlation has probably been lost in most species of Ephedra subsequent an evolutionary shift to wind pollination in the clade. When the services of insects are no longer needed for successful pollination, the adaptive value of correlating pollination with the full moon is lost, and conceivably also the trait.

  • Micromorphology of the Seed Envelope of Ephedra L. (Gnetales) and Its Relevance for the Timing of Evolutionary Events
    International Journal of Plant Sciences, 2011
    Co-Authors: Stephanie M. Ickert-bond, Catarina Rydin
    Abstract:

    Abstract Micromorphology of the seed envelope of Ephedra (Gnetales) is known to be variable, but variation patterns have never been systematically documented. We test the usefulness of this feature for species determination and subclade delimitation in Ephedra and investigate the relationship of this character to infrageneric evolutionary patterns. Most species have a basically smooth seed envelope, which in some species appears slightly striate or reticulate due to convex or depressed outer periclinal cell walls. Ephedra rhytidosperma from China and Ephedra torreyana from North America have transverse lamellae formed by the epidermis. A papillate surface is found in respective close relatives of these two species. Micromorphology of the seed envelope is generally not useful for species identification or subclade delineation. The amount of variation is low, and intraspecific variation, which in some cases seems to be correlated with hybridization and/or introgression, complicates species recognition. Furt...

  • The female reproductive unit of Ephedra (Gnetales): comparative morphology and evolutionary perspectives.
    Botanical Journal of the Linnean Society, 2010
    Co-Authors: Catarina Rydin, Anbar Khodabandeh, Peter K. Endress
    Abstract:

    Morphological variation in Ephedra (Gnetales) is limited and confusing from an evolutionary perspective, with parallelisms and intraspecific variation. However, recent analyses of molecular data provide a phylogenetic framework for investigations of morphological traits, albeit with few informative characters in the investigated gene regions. We document morphological, anatomical and histological variation patterns in the female reproductive unit and test the hypothesis that some Early Cretaceous fossils, which share synapomorphies with Ephedra, are members of the extant clade. Results indicate that some morphological features are evolutionarily informative although intraspecific variation is evident. Histology and anatomy of cone bracts and seed envelopes show clade-specific variation patterns. There is little evidence for an inclusion of the Cretaceous fossils in the extant clade. Rather, a hypothesized general pattern of reduction of the vasculature in the Ephedran seed envelope, probably from four vascular bundles in the fossils, to ancestrally three in the living clade, and later to two, is consistent with phylogenetic and temporal analyses, which indicate that extant diversity evolved after the Cretaceous-Tertiary boundary. Notwithstanding striking similarities between living and Cretaceous Ephedra, available data indicate that the Mesozoic diversity went almost entirely extinct in the late Cretaceous causing a bottleneck effect in Ephedra, still reflected today by an extraordinarily low level of genetic and structural diversity.

Masayuki Mikage - One of the best experts on this subject based on the ideXlab platform.

  • a type proanthocyanidins from the stems of Ephedra sinica Ephedraceae and their antimicrobial activities
    Molecules, 2013
    Co-Authors: Xinyu Zang, Masayuki Mikage, Ming-ying Shang, Xuan Wang, Jing Liang, Shao-qing Cai
    Abstract:

    Phytochemical investigation of the n-BuOH-soluble fraction of the EtOH extract of the herbaceous stems of Ephedra sinica, which is known as Ephedrae Herba in Traditional Chinese Medicine, led to the isolation and identification of 12 A-type proanthocyanidins, containing five dimers, two trimers and five tetramers [i.e., (+)-epigallocatechin-(2α→O→7,4α→8)-(-)-catechin, named Ephedrannin D1, a dimer; epigallocatechin-(2α→O→7,4α→8)-epigallocatechin-(4α→8)-catechin (Ephedrannin Tr1), a trimer; and epigallocatechin-(2α→O→7,4α→8)-epigallocatechin-(4α→8)-epigallocatechin-(2α→O→7,4α→8)-gallocatechin, named Ephedrannin Te1, a tetramer). Tetramers composed of gallocatechin are reported for the first time in Ephedraceae. Catechin, epicatechin, gallocatechin, epigallocatechin and four known dimers were also isolated. The structures were elucidated by extensive spectroscopic analysis. The absolute configurations of the 4α linkages, which were confirmed by NOESY and CD experiments, are the outstanding characteristic of most of these isolated A-type proanthocyanidins. The antimicrobial activities of these 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 0.00515–1.38 mM. Compounds 6, 8, 10 and 11 exhibited moderate antimicrobial activities against Canidia albicans.

  • Studies of Ephedra plants in Asia. Part 6: Geographical changes of anatomical features and alkaloids content of Ephedra sinica
    Journal of Natural Medicines, 2009
    Co-Authors: Li-li Wang, Nobuko Kakiuchi, Masayuki Mikage
    Abstract:

    Ephedra sinica Stapf is the main botanical origin of the Chinese herbal drug Mahuang, Ephedra Herb. Eighty-five samples of E. sinica , collected across eastern China, Mongolia, and Buryatia (Russia), were studied anatomically and chemically to elucidate the local variations and the relation between environmental factors and the variations. The results showed that samples grown in more arid conditions tended to have a more sinuous epidermis, more cuticular tubers, and more subepidermal fiber bundles anatomically, and contained more total ephedrine alkaloids. These samples also had a high pseudoephedrine content. These results imply that Ephedra Herb with good quality should be collected from arid fields, and the chemical quality can be estimated by observing the anatomical characteristics.

  • Molecular Analysis and Chemical Evaluation of Ephedra Plants in Mongolia
    Biological & Pharmaceutical Bulletin, 2009
    Co-Authors: Yuki Kitani, Masayuki Mikage, Shu Zhu, Takayuki Omote, Ken Tanaka, Javzan Batkhuu, Chinbat Sanchir, Hirotoshi Fushimi, Katsuko Komatsu
    Abstract:

    Ephedrae herba has been used in traditional Chinese and Japanese (Kampo) medicine from ancient times, with the primary resource being in China. In the present study, a field survey as well as molecular and chemical assessments were conducted on Ephedra plants in Mongolia to clarify whether they could be an alternative resource of the Ephedrae herba used in Japanese Kampo medicine. Ephedra sinica, E. equisetina, E. przewalskii, E. regeliana, E. monosperma and an unknown taxon (ESP) collected in Mongolia were divided into 9 genotypes on the basis of nucleotide sequences of 18S ribosomal RNA (rRNA) gene and trnK gene. E. sinica, E. equisetina, and E. monosperma presented completely identical sequences to the corresponding species from China. The sequences of trnK gene and 18S rRNA gene provide a useful index for identification and taxonomic classification of Mongolian Ephedra plants. Quantitative analysis of 5 ephedrine alkaloids revealed that almost all Mongolian Ephedra plants contained high amounts of total ephedrine alkaloids (TAs, 1.86-4.90%) and a high percentage of pseudoephedrine in TAs differed obviously from the Chinese. E. sinica and E. equisetina found in eastern and central Mongolia, showing total contents of ephedrine and pseudoephedrine higher than 1.43%, were potential new resources of Japanese Pharmacopoeia grade Ephedrae herba.

  • Ephedra resource in Sichuan and Yunnan Provinces 2007.
    Biological & Pharmaceutical Bulletin, 2009
    Co-Authors: Ai Inoko, Nobuko Kakiuchi, Shao-qing Cai, Michiyo Yoshimitsu, Masayuki Mikage
    Abstract:

    Wild Ephedra plants growing near the Tibetan border of Yunnan and Sichuan Provinces and north-central Sichuan were surveyed and their DNA and ephedrine alkaloids content were analyzed. By analysis of internal transcribed spacer 1 (ITS) 1 DNA, E. likiangensis was found to be the dominant species in these regions, which clustered into 2 major groups in the phylogenic tree. Most Ephedra plants in these regions of ordinal size contained ephedrine and pseudoephedrine of more than 0.7%, the requirement for Japanese Pharmacopoeia 15th edition, suggesting that they have potential for crude drug production of Ephedra herbs.

  • Studies on cultivated Ephedra plants in inner mongolia autonomous region and ningxia hui autonomous region
    Biological & Pharmaceutical Bulletin, 2006
    Co-Authors: Nobuko Kakiuchi, Yukimasa Kurita, Shao-qing Cai, Ikumi Nakajima, Changfeng Long, Masayuki Mikage
    Abstract:

    Progression of the desertification in northern China has been causing damage to wild Ephedra plants on which we depend for most of supply of the traditional herbal medicine, "Ma huang." The Chinese government encourages the cultivation of Ephedra plants, and Ephedra fields have been reclaimed in the original Ephedra habitats in recent years. We surveyed 7 Ephedra fields that have been recently developed in the Inner Mongolia Autonomous Region and Ningxia Hui Autonomous Region to collect information on Ephedra plant cultivation, especially pertaining to crop species. Specimens taken from those Ephedra fields were genetically and morphologically analyzed, and their ephedrine alkaloid content was examined. DNA analyses of Ephedra specimens, including DNA sequencing of ITS (internal transcribing sequence of nuclear ribosomal DNA) and trn L/F (intron of trnL and intergenic spacer between the trnL and trnF of chloroplast DNA) region and species-specific amplification of trn L/F were conducted to identify Ephedra species. Based on the results of DNA sequencing and morphological determination, the crops grown in 6 fields ware identified as Ephedra sinica, while co-planting of E. sinica and E. intermedia was found in one field where a higher appearance rate of plants with varied morphology from wild Ephedra plants was observed. Furthermore, direct sequencing of the PCR product of the trn L/F region of some specimens from the field and their species-specific PCR showed ambivalent result. Cloning and sequencing of the PCR product of the trn L/F region of those specimens DNA suggested their heteroplasmy, containing both E. sinica- and E. intermedia-type chloroplasts. On the other hand, the profile of the ephedrine alkaloid content was clearly correlated with the result of direct sequencing of the trn L/F region; the specimens showing the E. sinica-type sequence contained more ephedrine than pseudoephedrine, and the specimens of the E. intermedia-type more pseudoephedrine.

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  • hemodynamic effects of Ephedra free weight loss supplements in humans
    The American Journal of Medicine, 2005
    Co-Authors: Christine A Haller, Neal L Benowitz, Peyton Jacob
    Abstract:

    Abstract Purpose Ephedra-free weight loss dietary supplements containing bitter orange ( Citrus aurantium ), a botanical source of the adrenergic amines synephrine and octopamine, have quickly emerged on consumer markets to replace banned Ephedra products. These supplements may have some of the health risks associated with Ephedra, but studies in humans are lacking. Our aim was to characterize the pharmacokinetics and cardiovascular effects of C. aurantium dietary supplements. Subjects and methods Ten healthy adult nonsmokers participated in a randomized, double-blind, placebo-controlled, three-arm crossover study. Single doses of C. aurantium (Advantra Z) containing 46.9 mg synephrine, Xenadrine EFX, a multi-component formulation containing 5.5 mg synephrine, and placebo were administered with a one-week washout. Results Compared with placebo, Xenadrine EFX but not Advantra Z increased systolic and diastolic blood pressure with peak changes from baseline at 2 hours of 9.6 ± 6.2 mm Hg systolic ( P = 0.047), and 9.1 ± 7.8 mm Hg diastolic ( P = 0.002). Heart rate was increased from baseline at 6 hours compared with placebo (16.7 beats per minute with Xenadrine EFX, P = 0.011; 11.4 beats per minute with Advantra Z, P = 0.031). Dose-adjusted synephrine pharmacokinetics were similar between treatments with t max = 90 min, t 1/2 = 3.0 hours, V/F = 16347 L, and CL/F = 88.9 L/min for Xenadrine EFX. Conclusion Ephedra-free weight loss supplements have significant cardiovascular stimulant actions, similar to Ephedra. These effects are not likely caused by C. aurantium alone, because an eightfold higher dose of synephrine (Advantra Z) had no effect on blood pressure, but may be attributable to caffeine and other stimulants in the multi-component formulation

  • short term metabolic and hemodynamic effects of Ephedra and guarana combinations
    Clinical Pharmacology & Therapeutics, 2005
    Co-Authors: Christine A Haller, Peyton Jacob, Neal L Benowitz
    Abstract:

    Objective Serious adverse health events have been reported with the use of dietary supplements containing Ephedra and guarana. We sought to determine whether repeated dosing and multi-ingredient formulations contribute to the adverse effects of these supplements. Methods In this study, 16 healthy adults (8 women) took 2 doses each of Ephedra-guarana alone, Xenadrine RFA, a multicomponent dietary supplement containing 25 mg Ephedra alkaloids and 200 mg caffeine, or placebo 5 hours apart in a randomized, double-blind, 3-arm crossover study. Results Peak plasma ephedrine levels averaged 130 to 140 ng/mL. Compared with placebo, Xenadrine and Ephedra-guarana significantly increased heart rate (maximum increase, 9.4 ± 8.6 beats/min; P = .002), blood pressure (maximum increase in systolic and diastolic pressure, 11.5 ± 10.7 mm Hg and 7.3 ± 7.4 mm Hg, respectively; P = .015), postprandial glucose concentration (maximum change, 41.0 ± 18.8 mg/dL; P < .0001), and insulin concentration (maximum change, 41.2 ± 47.8 μIU/mL; P = .005). Serum potassium concentrations were significantly decreased by both treatments. Hemodynamic and metabolic changes were observed after both the first and second doses. However, plasma free fatty acid concentrations increased after the first dose only. Xenadrine RFA produced higher increases in glucose concentration than Ephedra-guarana, but no other pharmacodynamic differences between the treatments were found. Conclusions Consumption of 2 doses of Ephedra and guarana supplements, per supplement label recommendations, results in persistent increases in heart rate and blood pressure and unfavorable actions on glucose and potassium homeostasis. Such effects could be detrimental in persons with hypertension, atherosclerosis, or glucose intolerance, conditions that are strongly associated with obesity. Clinical Pharmacology & Therapeutics (2005) 77, 560–571; doi: 10.1016/j.clpt.2005.01.023

  • concentrations of Ephedra alkaloids and caffeine in commercial dietary supplements
    Journal of Analytical Toxicology, 2004
    Co-Authors: Christine A Haller, Minjing Duan, Neal L Benowitz, Peyton Jacob
    Abstract:

    Dietary supplements that contain Ma Huang (Ephedra alkaloids) and guarana (caffeine) are widely marketed and used in the U.S. for weight loss and athletic performance enhancement, despite a lack of adequate research on the pharmacology of these botanical stimulants. We developed and applied a novel liquid chromatography-tandem mass spectrometry (LC-MS-MS) method to quantitate the various Ephedra alkaloids found in dietary supplements that contain Ephedra species. The quantities of ephedrine, pseudoephedrine, norephedrine, norpseudoephedrine, methylephedine, methylpseudoephedrine, and caffeine were determined for 35 commercial dietary supplements and compared with the amounts listed on the product labels. The total Ephedra alkaloid content ranged from 5.97 mg to 29.3 mg per serving. Two supplement brands did not list the quantity of Ephedra alkaloids on the label, and four did not list the amount of caffeine per serving. Of the products tested, 31% contained > 110% of the total Ephedra alkaloids listed on the label, and 6% of the supplements contained 110% of the declared caffeine content. The total Ephedra alkaloid content varied significantly from lot to lot in 5 of 9 products. Three product brands contained proportions of alkaloids that exceeded amounts reported for E. sinica, including one that was 98% ephedrine, one that had 10% norpseudoephedrine, and one that contained an average of 13% methylephedrine. We conclude that product inconsistency is common among some commercially available dietary supplements that contain Ephedra alkaloids and caffeine.

  • determination of Ephedra alkaloid and caffeine concentrations in dietary supplements and biological fluids
    Journal of Analytical Toxicology, 2004
    Co-Authors: Peyton Jacob, Christine A Haller, Minjiang Duan, Margaret Peng, Neal L Benowitz
    Abstract:

    Dietary supplements containing botanical forms of caffeine and Ephedra alkaloids have been widely promoted and used in the U.S. for weight loss and athletic enhancement despite a lack of adequate research on the pharmacology of these botanical stimulants. In order to analyze dietary supplements and perform human pharmacokinetic studies, an analytical approach with good precision and accuracy was needed with sufficient sensitivity to detect very low levels of Ephedra alkaloids. A liquid chromatography-atmospheric pressure chemical ionization (APCI) tandem mass spectrometry (LC-MS-MS) method was developed for quantitating the various ephedrine-group alkaloids found in dietary supplements that contain Ephedra species, and in plasma and urine of persons consuming these supplements. Using this method, low nanogram-per-milliliter concentrations of ephedrine, pseudoephedrine, norephedrine, norpseudoephedrine, methylephedrine, methylpseudoephedrine, and caffeine can be quantitated in a 12-min LC-MS-MS run.