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1.  SOMA AS ENERGIZER-CUM-EUPHORIANT, VERSUS SURA, AN INTOXICANT 
Ancient Science of Life  1984;3(3):161-168.
Specific features of Soma plant are implict from various references in Rigveda enabling its identity as ephedra. Its juice is an energizer – cum – euphoriant contrary to the intoxicant sura. Sura is beer prepared from barely malt. Soma is the juice of ephedra rich in ephedrine which is antisomnalent. At least one use of soma has never been substituted, as the drink of longevity for a newly born child.
PMCID: PMC3331558  PMID: 22557400
2.  EVOLUTION OF EPHEDRA AS THE SOMA OF RIGVEDA 
Ancient Science of Life  1982;2(2):93-97.
In Rigveda Soma is an evergreen plant, with thousand stalks yellow hued bestowing auspicious energy. Resembling yellow fibres of hemp ephedra was rained in Chlnoso Ho-Ma, Yellow-hemp. It was Sanskritized as Soma. Being an energizer-cum-euphoriant its juice was consumed thrice daily. Finally it became a drug of longevity, rejuvenation and resurrection even god Soma. As drug it was substituted by Rasayana promisiig rejuvenation but also salvation. Soma with Water and Fire constitutes the proto-cosmology of Rigveda.
PMCID: PMC3336717  PMID: 22556961
3.  Phylogeographic Evidence for a Link of Species Divergence of Ephedra in the Qinghai-Tibetan Plateau and Adjacent Regions to the Miocene Asian Aridification 
PLoS ONE  2013;8(2):e56243.
The Qinghai-Tibetan Plateau (QTP) has become one of the hotspots for phylogeographical studies due to its high species diversity. However, most previous studies have focused on the effects of the Quaternary glaciations on phylogeographical structures and the locations of glacial refugia, and little is known about the effects of the aridization of interior Asia on plant population structure and speciation. Here the chloroplast DNA (cpDNA) trnT-trnF and trnS-trnfM sequences were used to investigate the differentiation and phylogeographical history of 14 Ephedra species from the QTP and northern China, based on a sampling of 107 populations. The phylogeographical analysis, together with phylogenetic reconstruction based on combined four cpDNA fragments (rbcL, rpl16, rps4, and trnS-trnfM), supports three main lineages (eastern QTP, southern QTP, and northern China) of these Ephedra species. Divergence of each lineage could be dated to the Middle or Late Miocene, and was very likely linked to the uplift of the QTP and the Asian aridification, given the high drought and/or cold tolerance of Ephedra. Most of the Ephedra species had low intraspecific variation and lacked a strong phylogeographical structure, which could be partially attributed to clonal reproduction and a relatively recent origin. In addition, ten of the detected 25 cpDNA haplotypes are shared among species, suggesting that a wide sampling of species is helpful to investigate the origin of observed haplotypes and make reliable phylogeographical inference. Moreover, the systematic positions of some Ephedra species are discussed.
doi:10.1371/journal.pone.0056243
PMCID: PMC3571962  PMID: 23418542
4.  Effect of extractions from Ephedra sinica Stapf on hyperlipidemia in mice 
The aim of the present study was to investigate the hypolipidemic and antioxidant potential of ephedra extractions in diet-induced hyperlipidemic mice. Mice were fed a diet high in fat to establish the hyperlipidemic model. A total of 48 mice were randomly divided into six groups, which included the normal control, model control, positive control, ephedra alkaloid, ephedra polysaccharide and ephedra non-alkaloid groups. Intragastric administration of the respective treatments was provided continuously for four weeks and the body weight was recorded weekly. The total levels of cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and malondialdehyde (MDA), and the activity levels of superoxide dismutase (SOD), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum were recorded. In addition, changes in liver morphology and organ coefficients (ratio of organ to body weight) were evaluated, while the acute toxicity reactions of ephedra extractions were investigated using the modified Spearman-Karber method. Compared with the mice in the model control group, the weight, liver coefficient, serum levels of TC, TG and MDA, and activities of ALT and AST were significantly lower (P<0.05) in the mice in the ephedra non-alkaloid group. However, the level of HDL-C and the activity of SOD were markedly higher (P<0.05). Fatty degeneration of the liver in the ephedra alkaloid and non-alkaloid groups was notably improved compared with the model control group. The mean lethal dose (LD50) of ephedra alkaloids was 610 mg/kg, and the maximum tolerated dose of oral ephedra non-alkaloids in the mice was 367.5-fold larger than the clinical dosage in humans. In conclusion, ephedra non-alkaloids have therapeutic potential for the treatment of hyperlipidemia, since they are able to improve lipid metabolism and are relatively safe for use under the maximum tolerated dose.
doi:10.3892/etm.2014.2117
PMCID: PMC4280985  PMID: 25574244
ephedra alkaloids; ephedra polysaccharides; ephedra non-alkaloids; hyperlipidemia; acute toxicity
5.  Chengia laxispicata gen. et sp. nov., a new ephedroid plant from the Early Cretaceous Yixian Formation of western Liaoning, Northeast China: evolutionary, taxonomic, and biogeographic implications 
Background
The extant Gnetales include three monotypic families, namely, Ephedraceae (Ephedra), Gnetaceae (Gnetum), and Welwitschiaceae (Welwitschia), all of which possess compound female cones that comprise a main axis and 1 to multiple pairs/whorls of bracts subtending a female reproductive unit or having lower pairs/whorls of bracts sterile. However, the evolutionary origin of such a reproductive architecture in Gnetales is controversial in the light of the competing anthophyte versus gnetifer hypotheses of seed plant relationships. Hence, macrofossils demonstrating the structure of compound female cones of the Gnetales should be important to decipher the early evolution of the order.
Results
A new ephedroid plant Chengia laxispicata gen. et sp. nov. is described from the Early Cretaceous Yixian Formation of western Liaoning, Northeast China. The fossil represents a part of a leafy shooting system with reproductive organs attached. The main shoot bears internodes and swollen nodes, from which lateral branches arise oppositely. Reproductive organs consist of female spikes terminal to twigs or axillary to linear leaves. Spikes are loosely arranged, having prominent nodes and internodes. Bracts of the spikes are decussately opposite and comprise 4—8 pairs of bracts. Each bract subtends an ellipsoid seed. Seeds are sessile, with a thin outer envelope and a distal micropylar tube.
Conclusions
Chengia laxispicata gen. et sp. nov. provides a missing link between archetypal fertile organs in the crown lineage of the Gnetales and compound female cones of the extant Ephedraceae. Combined with a wealth of Ephedra and ephedroid macrofossils from the Early Cretaceous, we propose a reduction and sterilization hypothesis that the female cone of the extant Ephedraceae may have stemmed from archetypal fertile organs in the crown lineage of the Gnetales. These have undergone sequentially intermediate links similar to female cones of Cretaceous Siphonospermum, Chengia, and Liaoxia by reduction and sterilization of the lower fertile bracts, shortenings of internodes and peduncles as well as loss of reproductive units in all inferior bracts. The basal family Ephedraceae including Ephedra of the extant Gnetales was demonstrated to have considerable diversity by the Early Cretaceous, so an emended familial diagnosis is given here. The Jehol Biota in Northeast China and adjacent areas contains a plethora of well-preserved macrofossils of Ephedra and ephedroids that show different evolutionary stages including primitive and derived characters of Ephedraceae, so Northeast China and adjacent areas may represent either the centre of origination or one of the centres for early diversification of the family.
doi:10.1186/1471-2148-13-72
PMCID: PMC3626868  PMID: 23530702
Biogeography; Chengia; Early Cretaceous; Ephedraceae; Ephedroid; Evolution; Female cone; Gnetales; Jehol biota; Reduction and sterilization hypothesis; Yixian Formation
6.  Ephedra and Its Application to Sport Performance: Another Concern for the Athletic Trainer? 
Journal of Athletic Training  2001;36(4):420-424.
Objective:
The ma huang herb, otherwise known as ephedra, has gained widespread popularity as an ergogenic supplement. With the sympathomimetic alkaloid ephedrine as its primary active ingredient, ma huang is marketed to reduce fatigue; increase strength, power, and speed; decrease reaction time; and improve body composition. Although numerous side effects have been associated with the use of ma huang, its popularity in athletes continues to grow. This review provides rationale for the ergogenic claims regarding ma huang and compares and contrasts those claims with data from scientifically controlled investigations.
Data Sources:
MEDLINE and SPORT Discus were searched from 1970 to 2000 using the key words ma huang, ephedra, and ephedrine in combination with humans, exercise, performance, and side effects.
Data Synthesis:
Ephedrine has been used alone or in combination with other drugs as an effective weight-loss agent. The weight loss has been attributed to thermogenic and lipolytic effects which, in combination with the central nervous system stimulating effects, have also resulted in its use as an ergogenic aid. Most of the scientific data, however, do not support manufacturers' ergogenic claims, and numerous side effects have been associated with ephedrine use. Thus, the safety and efficacy of ma huang as an ergogenic supplement must be questioned.
Conclusions/Recommendations:
It appears that the risks associated with the use of ma huang far outweigh any possible ergogenic benefits. Thus, it is extremely important that athletic trainers educate athletes on these issues so they can continue to perform at an optimum level in a safe and healthy manner.
PMCID: PMC155439  PMID: 16558668
ma huang; ephedrine; ergogenic aid; performance enhancement
7.  The Earliest Fleshy Cone of Ephedra from the Early Cretaceous Yixian Formation of Northeast China 
PLoS ONE  2013;8(1):e53652.
Bracts of female cones of extant gymnosperm Ephedra (Joint fir) are either colorful and fleshy (section Ephedra), or dry-winged and membranous (section Alatae), or dry and coriaceous (section Asarca), which have played a crucial role in long-distance seed dispersal that is responsible for a wide distribution of the genus in semiarid and arid areas of Eurasia, North Africa, North America, and South America. Recent molecular systematic studies on Ephedra have suggested that the fleshy bracts in character evolution may be plesiomorphic relative to the dry, membranous and coriaceous bracts. However, little is known about when the fleshy bracts of Ephedra have made their debut in the geological past. Herein, we describe a novel, fleshy bract-bearing female cone macrofossil from the Early Cretaceous (ca. 120—125 Ma) Yixian Formation in Liaoning, northeastern China. This cone bears three ellipsoid seeds subtended by only one whorl of fleshy bracts. Each seed has a thin outer envelope and an inner integument that extends upward and passes through the opening of the outer envelope, forming a thin and straight micropylar tube. Such a syndrome shows the closest similarity to an extant triovulate species Ephedra intermedia in the section Ephedra, but the latter bears a whorl of terminal fertile bracts and more than one whorl of inferior sterile bracts, and a thick outer envelope. Hence, we establish a new fossil species Ephedra carnosa. Our discovery provides the first direct macrofossil evidence for the previous molecular systematics of Ephedra, implying that the origin of fleshy bracts in Ephedra should not have been later than that of the membranous and coriaceous bracts by at least the Early Cretaceous.
doi:10.1371/journal.pone.0053652
PMCID: PMC3544918  PMID: 23341964
8.  Deep Sequencing of Plant and Animal DNA Contained within Traditional Chinese Medicines Reveals Legality Issues and Health Safety Concerns 
PLoS Genetics  2012;8(4):e1002657.
Traditional Chinese medicine (TCM) has been practiced for thousands of years, but only within the last few decades has its use become more widespread outside of Asia. Concerns continue to be raised about the efficacy, legality, and safety of many popular complementary alternative medicines, including TCMs. Ingredients of some TCMs are known to include derivatives of endangered, trade-restricted species of plants and animals, and therefore contravene the Convention on International Trade in Endangered Species (CITES) legislation. Chromatographic studies have detected the presence of heavy metals and plant toxins within some TCMs, and there are numerous cases of adverse reactions. It is in the interests of both biodiversity conservation and public safety that techniques are developed to screen medicinals like TCMs. Targeting both the p-loop region of the plastid trnL gene and the mitochondrial 16S ribosomal RNA gene, over 49,000 amplicon sequence reads were generated from 15 TCM samples presented in the form of powders, tablets, capsules, bile flakes, and herbal teas. Here we show that second-generation, high-throughput sequencing (HTS) of DNA represents an effective means to genetically audit organic ingredients within complex TCMs. Comparison of DNA sequence data to reference databases revealed the presence of 68 different plant families and included genera, such as Ephedra and Asarum, that are potentially toxic. Similarly, animal families were identified that include genera that are classified as vulnerable, endangered, or critically endangered, including Asiatic black bear (Ursus thibetanus) and Saiga antelope (Saiga tatarica). Bovidae, Cervidae, and Bufonidae DNA were also detected in many of the TCM samples and were rarely declared on the product packaging. This study demonstrates that deep sequencing via HTS is an efficient and cost-effective way to audit highly processed TCM products and will assist in monitoring their legality and safety especially when plant reference databases become better established.
Author Summary
Chemicals derived from plants and animals are widely used in traditional Chinese medicine (TCM), and it is commonplace for remedies to contain a complex list of ingredients. Due to their heterogeneous origins, and subsequent processing into pills and powders, it can be difficult for the biological origin of ingredients within each remedy to be reliably determined. In this study, we have, for the first time, used a second-generation DNA sequencing method to analyse TCM remedies and determine their animal and plant composition. Using this deep-sequencing approach we identified plant species that are known to contain toxic chemicals and identified animal DNA from species that are currently endangered and protected by international laws. Consumers need to be made aware of legal and health safety issues that surround TCMs before adopting them as a treatment option. More widespread testing of complementary medicines using the DNA methods developed herein represents an efficient and cost-effective way to audit their composition.
doi:10.1371/journal.pgen.1002657
PMCID: PMC3325194  PMID: 22511890
9.  Former Diversity of Ephedra (Gnetales): Evidence from Early Cretaceous Seeds from Portugal and North America 
Annals of Botany  2006;98(1):123-140.
• Background and Aims The extant species of the seed plant group Gnetales (Ephedra, Gnetum and Welwitschia) have been considered a remnant of a much greater, now extinct, diversity due to the pronounced differences in form and ecology among the genera. Until recently, this hypothesis has not been supported by evidence from the fossil record. This paper adds to the expanding information on Gnetales from the Early Cretaceous and describes coalified seeds from Barremian-Albian localities in Portugal and USA.
• Methods The fossils were extracted from sediment samples by sieving in water. Adhering mineral matrix was removed by chemical treatment. Seeds were investigated using light and scanning electron microscopy. Morphology and anatomy of the seeds were documented and compared with those of extant species.
• Key Results The fossils share characters with extant Ephedra, for example papillae on the inner surface of the seed envelope and in situ polyplicate pollen grains that shed the exine during germination. They differ from extant Ephedra seeds in morphological and anatomical details as well as in their smaller size. Two new species of Ephedra are described together with one species assigned to a new genus of Gnetales. Other Ephedra-like seeds, for which pollen and critical morphological details are currently unknown, are also present in the samples.
• Conclusions These Cretaceous seeds document that key reproductive characters and pollen germination processes have remained unchanged within Ephedra for about 120 million years or more. There is sufficient variety in details of morphology to suggest that a diversity of Ephedra and Ephedra-like species were present in the Early Cretaceous flora. Their presence in Portugal and eastern North America indicates that they were widespread on the Laurasian continent. The fossil seeds are similar to seeds of Erdtmanithecales and this supports the previously suggested relationship between Erdtmanithecales and Gnetales.
doi:10.1093/aob/mcl078
PMCID: PMC2803531  PMID: 16675607
Early Cretaceous; Ephedra; Erdtmanispermum; Erdtmanithecales; Eucommiidites; fossil pollen; fossils; Gnetales; Portugal; Potomac Group; seeds
10.  A new Early Cretaceous relative of Gnetales: Siphonospermum simplex gen. et sp. nov. from the Yixian Formation of Northeast China 
Background
Knowledge on fossil and evolutionary history of the Gnetales has expanded rapidly; Ephedra and ephedroids as well as the Gnetum-Welwitschia clade are now well documented in the Early Cretaceous. However, hypotheses on evolutionary relationships among living and fossil species are hampered by restricted knowledge of morphological variation in living groups and recent studies indicate that gnetalean diversity and character evolution may be more complex than previously assumed and involve additional extinct groups (Bennettitales, Erdtmanithecales and unassigned fossil taxa).
Results
Here we describe a new fossil related to Gnetales, Siphonospermum simplex from the Early Cretaceous Yixian Formation, an impression/compression of a reproductive shoot. The slender main axis bears one pair of opposite and linear leaves with primary parallel venation. The reproductive units are ovoid, without supporting bracts and borne on one median and two lateral branches. The most conspicuous feature of the fossil is the long, thread-like micropylar tube formed by the integument. Each ovule is surrounded by two different layers representing one or two seed envelopes; an inner sclerenchymatous layer and an outer probably parenchymatous layer.
Conclusions
The vegetative and reproductive features of Siphonospermum simplex exclude a relationship to any other group than the Gnetales. A combination of opposite phyllotaxis, linear leaves and ovules surrounded by seed envelope(s) and with a long exposed micropylar tube are known only for extant and extinct Gnetales. Siphonospermum simplex constitutes a new lineage within the Gnetales. Its morphology cannot be directly linked to any previously known plant, but the organization of the reproductive units indicates that it belongs to the Gnetum-Welwitschia clade. Based on the absence of cone bracts and the inferred histology of the seed envelope(s) it could be related to Gnetum, however, there are also affinities with the ephedran lineage, some of which are likely plesiomorphic features, others perhaps not. Phylogeny and character evolution in the Bennettitales, Erdtmanithecales and Gnetales are currently only partly understood and under debate; the exact systematic position of Siphonospermum simplex, i.e., its position within the Gnetales, cannot be resolved with certainty.
doi:10.1186/1471-2148-10-183
PMCID: PMC2900273  PMID: 20565755
11.  A systematic review of the efficacy and safety of herbal medicines used in the treatment of obesity 
This review focuses on the efficacy and safety of effective herbal medicines in the management of obesity in humans and animals. PubMed, Scopus, Google Scholar, Web of Science, and IranMedex databases were searched up to December 30, 2008. The search terms were “obesity” and (“herbal medicine” or “plant”, “plant medicinal” or “medicine traditional”) without narrowing or limiting search elements. All of the human and animal studies on the effects of herbs with the key outcome of change in anthropometric measures such as body weight and waist-hip circumference, body fat, amount of food intake, and appetite were included. In vitro studies, reviews, and letters to editors were excluded. Of the publications identified in the initial database, 915 results were identified and reviewed, and a total of 77 studies were included (19 human and 58 animal studies). Studies with Cissus quadrangularis (CQ), Sambucus nigra, Asparagus officinalis, Garcinia atroviridis, ephedra and caffeine, Slimax (extract of several plants including Zingiber officinale and Bofutsushosan) showed a significant decrease in body weight. In 41 animal studies, significant weight loss or inhibition of weight gain was found. No significant adverse effects or mortality were observed except in studies with supplements containing ephedra, caffeine and Bofutsushosan. In conclusion, compounds containing ephedra, CQ, ginseng, bitter melon, and zingiber were found to be effective in the management of obesity. Attention to these natural compounds would open a new approach for novel therapeutic and more effective agents.
doi:10.3748/wjg.15.3073
PMCID: PMC2705729  PMID: 19575486
Animal; Herbal medicine; Human; Obesity
12.  PA01.57. A comparative study of Siddha & Ayurveda medication system of India 
Ancient Science of Life  2012;32(Suppl 1):S107.
Purpose:
As it is well served with the same Aryan and Dravidian primarily in India has developed two cultures to protect human health and resources to suit your needs individually developed treatment methods. Who stated in Ayurveda and Siddha. Ayurveda is expanding, but Siddha could not get into the main stream. Received medical science has Siddha valuable sources resulting from human community is deprived vast majority of today. Received medical science has Siddha purpose of this study contain the main stream in is.
Method:
History of Aryan and Dravidian cultures, History of Indian Sciences, Rigvedas, Atharvavedas, Sangamsahitya, Charaksaamhita, Shaiva Shakta Tantra etc and public mythics present study were used as the sources.
Result:
The study found that the difficulty of language of obtaining siddha was not included in the main stream of Indian medication., Then the formulas of Siddha therapeutics, the global medical science not only the rich are able to.
Conclusion:
The study also the conclusion of this study is that Indian society during the long evolutionary journey Aryan and Dravidian cultures as Siddha and Ayurveda are also mixed in their experiences and medical sources interchange wealthy have been themselves but its originality is maintained. Which consists in the fact that the botanical worlds where Ayurveda Himalayas while the original basis Siddha medicinal seaside minerals suit their environment, chemicals, and herbs the original base. Siddha medicine even today in the poisons, minerals, and ease of purification methods are available, whose use in the current upgrade medical science and is helpful in advancement and enrichment revealed that development and use of drugs in the locality, culture and the environment is essential to keep in mind.
PMCID: PMC3800860
13.  Determination of Ephedrine Alkaloids in Botanicals and Dietary Supplements by HPLC-UV 
Journal of AOAC International  2004;87(1):1-14.
An international collaborative study was conducted of a high-performance liquid chromatography (HPLC)-UV method for the determination of the major (ephedrine [EP] and pseudoephedrine [PS]) and minor (norephedrine [NE], norpseudoephedrine [NP], methylephedrine [ME], and methylpseudoephedrine [MP]) alkaloids in selected dietary supplements representative of the commercially available products. Ten collaborating laboratories determined the ephedrine-type alkaloid content in 8 blind replicate samples. Five products contained ephedra ground herb or ephedra extract. These 5 products included ground botanical raw material of Ephedra sinica, a common powdered extract of Ephedra sinica, a finished product containing only Ephedra sinica ground botanical raw material, a complex multicomponent dietary supplement containing Ma Huang, and a high-protein chocolate flavored drink mix containing Ma Huang extract. In addition, collaborating laboratories received a negative control and negative control spiked with ephedrine alkaloids at high and low levels for recovery studies. Test extracts were treated to solid-phase extraction using a strong-cation exchange column to help remove interferences. The HPLC analyses were performed on a polar-embedded phenyl column using UV detection at 210 nm. Repeatability relative standard deviations (RSDr) ranged from 0.64–3.0% for EP and 2.0–6.6% for PS, excluding the high protein drink mix. Reproducibility relative standard deviations (RSDR) ranged from 2.1–6.6% for EP and 9.0–11.4% for PS, excluding the high protein drink mix. Recoveries ranged from 84.7–87.2% for EP and 84.6–98.2% for PS. The data developed for the minor alkaloids are more variable with generally unsatisfactory HORRATS(i.e., >2). However, since these alkaloids generally add little to the total alkaloid content of the products, the method gives satisfactory results in measuring total alkaloid content (RSDr 0.85–3.13%; RSDR 2.03–10.97%, HORRAT 0.69–3.23, exclusive of the results from the high protein drink). On the basis of these results, the method is recommended for Official First Action for determination of EP and PS in dietary supplements exclusive of the high protein drinks.
PMCID: PMC2584348  PMID: 15084081
14.  Determination of Ephedra Alkaloids by Liquid Chromatography/Tandem Mass Spectrometry 
Journal of AOAC International  2003;86(3):471-475.
In conjunction with an AOAC Task Group on dietary supplements, a liquid chromatography/tandem mass spectrometry (LC–MS/MS) method was validated for measurement of 6 major alkaloids in raw ephedra sinica herb, ephedra extracts, ephedra tablets, complex dietary supplements containing ephedra, and a high-protein drink mix containing ephedra. The amount of ephedrine-type alkaloids present was determined by LC with mass selective detection. Six replicates of each matrix were analyzed on 3 separate occasions. The presence of 6 ephedrine-type alkaloids was detected at a level >0.5 μg/g based on a 0.5 g sample. The standard curve range for this assay is from 0.02 to 1.0 μg/mL. Appropriate dilutions covered a wide range of specific alkaloid concentrations. The calibration curves for all 6 analytes had correlation coefficients >0.995.
PMCID: PMC2586890  PMID: 12852561
15.  Combined Effects of Ephedrine-Containing Dietary Supplements, Caffeine, and Nicotine on Morphology and Ultrastructure of Rat Hearts 
Journal of Caffeine Research  2012;2(3):123-132.
Cigarette smokers have an increased risk for coronary artery disease. Nicotine present in cigarettes can adversely affect the cardiovascular system via stimulation of both sympathetic and parasympathetic neurons. Caffeine, another cardiovascular and central nervous system (CNS) stimulant, is commonly found in Ephedra and Ephedra-free dietary supplements. These caffeine-containing supplements also have been linked to cardiovascular toxicities. Although no longer on the U.S market, Ephedra-containing supplements are another source of cardiovascular and CNS stimulants, namely the ephedrine alkaloids. Together caffeine, nicotine, and ephedrine can individually stress the cardiovascular system, and an overlap of these agents is predicted in smokers and dieters. To understand the collective effects of these stimulants on the heart morphology and ultrastructure, rats were exposed to synthetic combinations of nicotine (0.2 mg/kg/day), ephedrine (0–30 mg/kg/day), and/or caffeine (0–24 mg/kg/day) as well as an extract from a caffeine-containing Ephedra supplement (Metabolife 356). After exposure for 3 days, the hearts were removed and examined for hypersensitivity myocarditis and myocardial necrosis. None of the drugs tested alone affected heart tissue morphology, nor were atypical cardiac cells observed. However, in combination, significant interactions were found between caffeine and ephedrine; the interventricular septum was most susceptible, with a significant increase in atypical cardiac cells observed. Nicotine pretreatment caused greater susceptibility to cardiotoxicity associated with combinations of caffeine + ephedrine or Metabolife, particularly in the left ventricle wall. These results indicate that sympathomimetic combinations present in Ephedra supplements may have produced cardiotoxicity reported in consumers of these products. Moreover, the presence of nicotine exacerbates these toxic effects.
doi:10.1089/jcr.2012.0021
PMCID: PMC3621369  PMID: 24761270
16.  Variable Wood Formation and Adaptation to the Alpine Environment of Ephedra pachyclada (Gnetales: Ephedraceae) in the Mustang District, Western Nepal 
Annals of Botany  2007;100(2):315-324.
Background and Aims
Plants of Ephedra normally have vessels, but are known to become nearly vessel-less in some alpine localities. Previous studies implied that wood formation in Ephedra differs fundamentally from that in dicotyledons in which vessel-bearing and vessel-less taxa are systematically distinct. Using E. pachyclada in the Mustang district of Nepal, growing in an altitudinal range of over 2000 m, variation in wood formation and adaptation to alpine environment was studied in this normally vessel-bearing species.
Methods
Variation in wood anatomy and wood formation was observed with conventional optical microscopy. The lengths of three kinds of tracheary elements were measured and statistically analysed against habitat altitude and plant size of the individuals studied.
Key Results
In E. pachyclada three kinds of tracheary elements, vessel elements, tracheids and fibre-tracheids, were nearly equal in length within individuals showing no elongation after differentiation from cambial initials. Tracheary element lengths among individuals had a negative correlation with altitude and a positive correlation with plant size. Multivariate analyses showed that altitude has a stronger correlation with tracheary element lengths than plant height or stem diameter. Moreover, several individuals from high elevations completely lacked vessels, and vessel formation fluctuated even in individuals from lower elevations.
Conclusions
Wood anatomical trends in E. pachyclada are considered as an adaptation to extremely dry conditions in high mountains. Fluctuation in vessel formation in individuals from low elevations indicated that vessels differentiate only when their lateral expansion is allowed. These results showed that E. pachyclada has a different system of wood formation from dicotyledons and supported the opinion that the wood structure of Gnetales is fundamentally different from that of angiosperms.
doi:10.1093/aob/mcm111
PMCID: PMC2735324  PMID: 17576659
Ephedra pachyclada; Gnetales; habitat altitude; plant height; stem diameter; tracheary element length; vessel loss; wood formation
17.  Total Phenolic Contents and Antioxidant Capacities of Selected Chinese Medicinal Plants 
Antioxidant capacities of 56 selected Chinese medicinal plants were evaluated using the Trolox equivalent antioxidant capacity (TEAC) and ferric reducing antioxidant power (FRAP) assays, and their total phenolic content was measured by the Folin-Ciocalteu method. The strong correlation between TEAC value and FRAP value suggested that the antioxidants in these plants possess free radical scavenging activity and oxidant reducing power, and the high positive correlation between antioxidant capacities and total phenolic content implied that phenolic compounds are a major contributor to the antioxidant activity of these plants. The results showed that Dioscorea bulbifera, Eriobotrya japonica, Tussilago farfara and Ephedra sinica could be potential rich sources of natural antioxidants.
doi:10.3390/ijms11062362
PMCID: PMC2904921  PMID: 20640157
medicinal plant; phenolic content; antioxidant capacity
18.  Ephedra Use in a Select Group of Adolescent Athletes 
Ephedra-containing dietary supplements are consumed to improve sports performace, but may carry risks of cardiac and neurological adverse events. Little is known of their use by young athletes. Our aim was to determine the prevalence and patterns of ephedra use among high school athletes. An anonymous survey was performed in Rochester, Minnesota on high school athletes who participated in fall sports during 2003-04. Parental consent was obtained for athletes under age 18 years. Surveys were distributed at preparticipation examinations and in- school survey stations. The response rate to the survey was 68.2%, or 311 respondents out of a possible 456 with consent (or 26% of all 1197 athletes eligible prior to the consent process). Seven of 311 (2.3%) respondents used dietary supplements containing ephedra. Only one of seven users (14.3%) knew that the supplements they used contained ephedra. Ephedra use was more common in boys (five) than girls (two). Ephedra use was only found in 17 and 18-year-olds. The most common sports among ephedra users were football, track and field, and weightlifting. This study suggests that Ephedra use was infrequent among the young athletes in this population. However, ephedra users were generally unaware that the dietary supplements they consumed contained ephedra. Users were more likely to participate in football, track and field, and weightlifting. Ephedra users were likely to obtain supplements from their peers, and were largely uninformed of the content of their supplements.
Key PointsEphedra is an herbal stimulant used as an ergogenic aide.Adolescent ephedra users most commonly obtain it from their friends.Adolescent athletes are likely to take ephedra unknowningly.
PMCID: PMC3842141  PMID: 24353458
Ephedrine; sports; supplements; performance enhancement, ergogenic
19.  Alcohol Consumption at Midlife and Successful Ageing in Women: A Prospective Cohort Analysis in the Nurses' Health Study 
PLoS Medicine  2011;8(9):e1001090.
Using the Nurses' Health Study, Qi Sun and colleagues examine whether moderate alcohol intake is associated with overall health and well-being among women who survive to older age.
Background
Observational studies have documented inverse associations between moderate alcohol consumption and risk of premature death. It is largely unknown whether moderate alcohol intake is also associated with overall health and well-being among populations who have survived to older age. In this study, we prospectively examined alcohol use assessed at midlife in relation to successful ageing in a cohort of US women.
Methods and Findings
Alcohol consumption at midlife was assessed using a validated food frequency questionnaire. Subsequently, successful ageing was defined in 13,894 Nurses' Health Study participants who survived to age 70 or older, and whose health status was continuously updated. “Successful ageing” was considered as being free of 11 major chronic diseases and having no major cognitive impairment, physical impairment, or mental health limitations. Analyses were restricted to the 98.1% of participants who were not heavier drinkers (>45 g/d) at midlife. Of all eligible study participants, 1,491 (10.7%) achieved successful ageing. After multivariable adjustment of potential confounders, light-to-moderate alcohol consumption at midlife was associated with modestly increased odds of successful ageing. The odds ratios (95% confidence interval) were 1.0 (referent) for nondrinkers, 1.11 (0.96–1.29) for ≤5.0 g/d, 1.19 (1.01–1.40) for 5.1–15.0 g/d, 1.28 (1.03–1.58) for 15.1–30.0 g/d, and 1.24 (0.87–1.76) for 30.1–45.0 g/d. Meanwhile, independent of total alcohol intake, participants who drank alcohol at regular patterns throughout the week, rather than on a single occasion, had somewhat better odds of successful ageing; for example, the odds ratios (95% confidence interval) were 1.29 (1.01–1.64) and 1.47 (1.14–1.90) for those drinking 3–4 days and 5–7 days per week in comparison with nondrinkers, respectively, whereas the odds ratio was 1.10 (0.94–1.30) for those drinking only 1–2 days per week.
Conclusions
These data suggest that regular, moderate consumption of alcohol at midlife may be related to a modest increase in overall health status among women who survive to older ages.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
People have always drunk alcoholic beverages but throughout history there have been arguments about the risks and benefits of beer, wine, and spirits. It is clear that excessive alcohol use—heavy drinking (an average of more than two drinks per day for men or more than one drink per day for women; in the US, a “drink” is defined as 15 g of alcohol or, roughly speaking, a can of beer or a small glass of wine) or binge drinking (five or more drinks on a single occasion for men; 4 or more drinks at one time for women)—is harmful. It causes liver damage and increases the risk of developing some types of cancer. It contributes to depression and violence and interferes with relationships. And it is often implicated in fatal traffic accidents. However, in contrast to these and other harms associated with excessive alcohol use, moderate alcohol consumption seems to reduce the risk of specific diseases such as heart disease, stroke, and cognitive decline (deterioration in learning, reasoning, and perception).
Why Was This Study Done?
Although people who drink moderate amounts of alcohol have a reduced risk of premature death compared to abstainers or heavy drinkers, it is not known whether moderate alcohol consumption is associated with overall health among ageing populations. In many countries, elderly people are an increasingly large part of the population, so it is important to know how moderate alcohol consumption affects their well-being. In this study, the researchers examine the effect of alcohol consumption at midlife on successful ageing among the participants of the Nurses' Health Study. The researchers study the effect of midlife alcohol consumption because the chronic conditions that affect elderly people develop slowly and it is likely that factors in earlier life determine health in later life. Successful ageing is defined as being free of major chronic diseases such as cancer and heart disease, and having no major cognitive impairment, physical impairment, or mental health problems. The Nurses' Health Study enrolled 121,700 female registered nurses in 1976 to investigate the long-term effects of oral contraceptive use but has provided insights into many aspects of health and disease.
What Did the Researchers Do and Find?
The researchers assessed the alcohol consumption of the study participants at midlife (average age 58 years) from food frequency questionnaires completed in 1980 and 1984. Successful ageing for 13,984 participants who survived past 70 years was assessed by analyzing biennial health status questionnaires and cognitive function test results. One tenth of the women achieved successful ageing. After allowing for other factors that might affect their health such as smoking, women who drank light or moderate amounts of alcohol had a modestly increased chance of successful ageing compared to nondrinkers. For example, compared to nondrinkers, women who drank 5–15 g of alcohol per day (between one-third and one drink per day) had about a 20% higher chance of successful ageing. Independent of total alcohol intake, women who drank alcohol regularly had a better chance of successful ageing than occasional drinkers. Thus, compared to nondrinkers, women who drank five to seven days a week had nearly a 50% greater chance of successful ageing whereas women who drank only one or two days a week had a similar likelihood of successful ageing.
What Do These Findings Mean?
These findings suggest that regular, moderate consumption of alcohol at midlife may be related to a modest increase in overall health among women who survive to older ages. Because this is an observational study, it is possible that the women who drank moderately share other unknown characteristics that are actually responsible for their increased chance of successful ageing. Moreover, because all the study participants were women and most had European ancestry, these findings cannot be applied to men or to other ethnic groups. Nevertheless, these findings provide support for the 2010 US Department of Agriculture dietary guidelines, which state that consumption of up to one alcoholic drink per day for women and up to two alcoholic drinks per day for men may provide health benefits. Importantly, they also suggest that drinking alcohol regularly in moderation rather than occasional heavy drinking may be associated with a greater likelihood of successful ageing.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001090.
The US National Institute on Alcohol Abuse and Alcoholism has detailed information about alcohol and its effects on health, including a fact sheet on women and alcohol and a booklet entitled Alcohol, a woman's health issue
The US Centers for Disease Control and Prevention has a website on alcohol and public health
The UK National Health Service Choices website provides detailed information about drinking and alcohol, including how to calculate consumption
The Nutrition Source, a website maintained by the Department of Nutrition at Harvard School of Public Health, has an article entitled Alcohol: balancing risks and benefits
MedlinePlus provides links to many other resources on alcohol and on seniors' health
Details of the Nurses' Health Study are available
The 2010 US Department of Agriculture dietary guidelines are available
doi:10.1371/journal.pmed.1001090
PMCID: PMC3167795  PMID: 21909248
20.  STEMI in a 24-Year-Old Man after Use of a Synephrine-Containing Dietary Supplement 
Texas Heart Institute Journal  2009;36(6):586-590.
Billions of dollars are spent annually in the United States in the largely unregulated market of dietary supplements. Many of these supplements are marketed as weight-loss and athletic-performance-enhancement products. The association of various ephedra-containing products with adverse cardiovascular events has led to a ban on the sale of these products by the U.S. Food and Drug Administration. The result has been the emergence of new formulations marketed for weight loss and athletic-performance enhancement that are “ephedra-free” but contain other sympathomimetic substances, the safety of which has not been established.
We present the case of a previously healthy 24-year-old man who presented with an ST-segment-elevation myocardial infarction (STEMI) within hours of taking the ephedra-free product Nutrex Lipo-6x®. Emergent coronary angiography revealed the presence of extensive, diffuse thrombus in the left anterior descending coronary artery. The patient had no risk factors for coronary artery disease or myocardial infarction; this includes the absence of a hypercoagulable state and the absence of a history of illicit drug use. This case of STEMI—associated as it is with the use of a synephrine-containing product by a person without risk factors for coronary artery disease—is to our knowledge the 1st reported in the literature. We discuss the patient's evaluation and clinical course, and we review the literature with respect to synephrine-containing dietary supplements. On the basis of synephrine's chemical composition and mechanism of action, we propose a direct association between this patient's use of Nutrex Lipo-6x® and his STEMI.
PMCID: PMC2801940  PMID: 20069086
Citrus/adverse effects; coronary vasospasm/complications/etiology; dietary supplements/adverse effects/poisoning; myocardial infarction/chemically induced; plant preparations; synephrine; weight loss/drug effects; United States Food and Drug Administration
21.  A BRIEF ACCOUNT OF THE FRACTIONS OF SOMA 
Ancient Science of Life  1990;9(4):207-208.
Soma was originally Sauma as the Sanskrit form of the Avesta name Haoma. It is a loan word from the Chinese term, Hao-Ma, fire coloured hempior fibrous items like hemp and also coloured yellow with a tinge of brown. The Aryans as hunters took its juice as anti-fatigue drink. It was extolled as panacea and even as drink of longevity. The plant and its stalks were crushed between stones to produce juice. There arose different fractions and these have been given in a regular chart here.
PMCID: PMC3331339  PMID: 22557699
22.  Buried in Sands: Environmental Analysis at the Archaeological Site of Xiaohe Cemetery, Xinjiang, China 
PLoS ONE  2013;8(7):e68957.
Palynomorphs extracted from the mud coffins and plant remains preserved at the archaeological site of Xiaohe Cemetery (Cal. 3980 to 3540 years BP) in Lop Nur Desert of Xinjiang, China were investigated for the reconstruction of the ancient environments at the site. The results demonstrate that the Xiaohe People lived at a well-developed oasis, which was surrounded by extensive desert. The vegetation in the oasis consisted of Populus, Phragmites, Typha and probably of Gramineae, while the desert surrounding the oasis had some common drought-resistant plants dominated by Ephedra, Tamarix, Artemisia and Chenopodiaceae. This present work provides the first data of the environmental background at this site for further archaeological investigation.
doi:10.1371/journal.pone.0068957
PMCID: PMC3718815  PMID: 23894382
23.  Central nervous system stimulants and sport practice 
British Journal of Sports Medicine  2006;40(Suppl 1):i16-i20.
Background and objectives
Central nervous system (CNS) stimulants may be used to reduce tiredness and increase alertness, competitiveness, and aggression. They are more likely to be used in competition but may be used during training to increase the intensity of the training session. There are several potential dangers involving their misuse in contact sports. This paper reviews the three main CNS stimulants, ephedrine, amfetamine, and cocaine, in relation to misuse in sport.
Methods
Description of the pharmacology, actions, and side effects of amfetamine, cocaine, and ephedrine.
Results
CNS stimulants have psychotropic effects that may be perceived to be ergogenic. Some are prescription drugs, such as Ephedra alkaloids, and there are issues regarding their appropriate therapeutic use. Recently attention has been given to their widespread use by athletes, despite the lack of evidence regarding any ergogenic or real performance benefit, and their potentially serious side effects. Recreational drugs, some of which are illegal (cocaine, amfetamines), are commonly used by athletes and cause potential ergolytic effects. Overall, these drugs are important for their frequent use and mention in anti‐doping laboratories statistics and the media, and their potentially serious adverse effects.
Conclusions
Doping with CNS stimulants is a real public health problem and all sports authorities should participate in its prevention. Dissemination of information is essential to prevent doping in sport and to provide alternatives. Adequate training and education in this domain should be introduced.
doi:10.1136/bjsm.2006.027557
PMCID: PMC2657493  PMID: 16799095
stimulants; amphetamine; cocaine; ephedrine; doping; sport
24.  Isolation of antibacterial compounds from Quercus dilatata L. through bioassay guided fractionation 
Background
Four medicinal plants (Chrozophora hierosolymitana Spreng, Chrysanthemum leucanthemum L., Ephedra gerardiana Wall. ex Stapf, and Quercus dilatata L.) used by indigenous healers to treat various infectious diseases were selected for the present study. The major objective of the present study was isolation and characterization of antimicrobial components from the crude plant extracts using bioassay guided fractionation.
Methods
Seven methanolic extracts of the four plants were screened to identify any antimicrobial agents present in them. The active crude plant extract was fractionated first by solvent partitioning and then by HPLC. Characterization of the active fractions was done by using spectrophotometer.
Results
All the seven methanolic extracts showed low antifungal activity, however, when these extracts were tested for antibacterial activity, significant activity was exhibited by two extracts. The extract of aerial parts of Q. dilatata was most active and therefore, was selected for further analysis. Initially fractionation was done by solvent-solvent partitioning and out of six partitioned fractions, ethanol fraction was selected on the basis of results of antibacterial activity and phytochemical analysis. Further, fractionation was carried out by RP- HPLC and purified active subfractions were characterized by comparing their absorption spectra with that of the known natural products isolated from the plants of Quercus genus.
Discussion and conclusion
The results suggest that this is the first report of the isolated antibacterial compounds from this genus.
doi:10.1186/1476-0711-11-11
PMCID: PMC3416653  PMID: 22554280
Absorption spectrum; Antibacterial activity; Phytochemical analysis; RP-HPLC analysis; Solvent partitioning
25.  Geographical Inequalities in Use of Improved Drinking Water Supply and Sanitation across Sub-Saharan Africa: Mapping and Spatial Analysis of Cross-sectional Survey Data 
PLoS Medicine  2014;11(4):e1001626.
Using cross-sectional survey data, Rachel Pullan and colleagues map geographical inequalities in use of improved drinking water supply and sanitation across sub-Saharan Africa.
Please see later in the article for the Editors' Summary
Background
Understanding geographic inequalities in coverage of drinking-water supply and sanitation (WSS) will help track progress towards universal coverage of water and sanitation by identifying marginalized populations, thus helping to control a large number of infectious diseases. This paper uses household survey data to develop comprehensive maps of WSS coverage at high spatial resolution for sub-Saharan Africa (SSA). Analysis is extended to investigate geographic heterogeneity and relative geographic inequality within countries.
Methods and Findings
Cluster-level data on household reported use of improved drinking-water supply, sanitation, and open defecation were abstracted from 138 national surveys undertaken from 1991–2012 in 41 countries. Spatially explicit logistic regression models were developed and fitted within a Bayesian framework, and used to predict coverage at the second administrative level (admin2, e.g., district) across SSA for 2012. Results reveal substantial geographical inequalities in predicted use of water and sanitation that exceed urban-rural disparities. The average range in coverage seen between admin2 within countries was 55% for improved drinking water, 54% for use of improved sanitation, and 59% for dependence upon open defecation. There was also some evidence that countries with higher levels of inequality relative to coverage in use of an improved drinking-water source also experienced higher levels of inequality in use of improved sanitation (rural populations r = 0.47, p = 0.002; urban populations r = 0.39, p = 0.01). Results are limited by the quantity of WSS data available, which varies considerably by country, and by the reliability and utility of available indicators.
Conclusions
This study identifies important geographic inequalities in use of WSS previously hidden within national statistics, confirming the necessity for targeted policies and metrics that reach the most marginalized populations. The presented maps and analysis approach can provide a mechanism for monitoring future reductions in inequality within countries, reflecting priorities of the post-2015 development agenda.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Access to a safe drinking-water supply (a water source that is protected from contamination) and to adequate sanitation facilities (toilets, improved latrines, and other facilities that prevent people coming into contact with human urine and feces) is essential for good health. Unimproved drinking-water sources and sanitation are responsible for 85% of deaths from diarrhea and 1% of the global burden of disease. They also increase the transmission of parasitic worms and other neglected tropical diseases. In 2000, world leaders set a target of reducing the proportion of the global population without access to safe drinking water and basic sanitation to half of the 1990 level by 2015 as part of Millennium Development Goal (MDG) 7 (“Ensure environmental sustainability”; the MDGs are designed to improve the social, economic, and health conditions in the world's poorest countries). Between 1990 and 2010, more than 2 billion people gained access to improved drinking-water sources and 1.8 billion gained access to improved sanitation. In 2011, 89% of the world's population had access to an improved drinking-water supply, 1% above the MDG target, and 64% had access to improved sanitation (the MDG target is 75%).
Why Was This Study Done?
Despite these encouraging figures, the WHO/UNICEF Joint Monitoring Programme for Water Supply and Sanitation (JMP) estimates that, globally, 768 million people relied on unimproved drinking-water sources, 2.5 billion people did not use an improved sanitation facility, and more than 1 billion people (15% of the global population) were defecating in the open in 2011. The JMP estimates for 2011 also reveal national and sub-national inequalities in drinking-water supply and sanitation coverage but a better understanding of geographic inequalities is needed to track progress towards universal coverage of access to improved water and sanitation and to identify the populations that need the most help to achieve this goal. Here, the researchers use cross-sectional household survey data and modern statistical approaches to produce a comprehensive map of the coverage of improved drinking-water supply and improved sanitation at high spatial resolution for sub-Saharan Africa and to investigate geographic inequalities in coverage. Cross-sectional household surveys collect health and other information from households at a single time-point, including data on use of safe water and improved sanitation.
What Did the Researchers Do and Find?
The researchers extracted data on reported household use of an improved drinking-water supply (for example, a piped water supply), improved sanitation facilities (for example, a flushing toilet), and open defecation from 138 national household surveys undertaken between 1991 and 2012 in 41 countries in sub-Saharan Africa. They developed statistical models to fit these data and used the models to estimate coverage at the district (second administrative) level across sub-Saharan Africa for 2012. For ten countries, the estimated coverage of access to improved drinking water at the district level within individual countries ranged from less than 25% to more than 75%. Within-country ranges of a similar magnitude were estimated for coverage of access to improved sanitation (21 countries) and for open defecation (16 countries). Notably, rural households in the districts with the lowest coverage of access to improved water supply and sanitation within a country were 1.5–8 times less likely to access improved drinking water, 2–18 times less likely to access improved sanitation, and 2–80 times more likely to defecate in the open than rural households in districts with the best coverage. Finally, countries with high levels of inequality in improved drinking-water source coverage also experienced high levels of inequality in improved sanitation coverage.
What Do These Findings Mean?
These findings identify important geographic inequalities in the coverage of access to improved water sources and sanitation that were previously hidden within national statistics. The accuracy of these findings depends on the accuracy of the data on water supplies and sanitation provided by household surveys, on the researchers' definitions for improved water supplies and sanitation, and on their statistical methods. Nevertheless, these findings confirm that, to achieve universal coverage of access to improved drinking-water sources and sanitation, strategies that target the areas with the lowest coverage are essential. Moreover, the maps and the analytical approach presented here provide the means for monitoring future reductions in inequalities in the coverage of access to improved water sources and sanitation and thus reflect a major priority of the post-2015 development agenda.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001626.
A PLOS Medicine Collection on water and sanitation is available
The World Health Organization (WHO) provides information on water, sanitation, and health (in several languages)
The WHO/UNICEF Joint Monitoring Programme for Water Supply and Sanitation is the official United Nations mechanism tasked with monitoring progress toward MDG7, Target 7B; the JMP 2013 update report is available online (also available in French and Spanish through the JMP website)
The sub-national predictions resulting from this study and the final sub-national maps are available as a resource for researchers and planners
doi:10.1371/journal.pmed.1001626
PMCID: PMC3979660  PMID: 24714528

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