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Acute and Chronic Effects of Green Oat (Avena sativa) Extract on Cognitive Function and Mood during a Laboratory Stressor in Healthy Adults: A Randomised, Double-Blind, Placebo-Controlled Study in Healthy Humans

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David O. Kennedy,1,* Bernd Bonnländer,2 Stefanie C. Lang,2 Ivo Pischel,3 Joanne Forster,1 Julie Khan,1 Philippa A. Jackson,1 and Emma L. Wightman4

Abstract

Green oat (Avena sativa) extracts contain several groups of potentially psychoactive phytochemicals. Previous research has demonstrated improvements in cognitive function following a single dose of these extracts, but not following chronic supplementation. Additionally, whilst green oat extracts contain phytochemicals that may improve mood or protect against stress, for instance species-specific triterpene saponins, to date this possibility has not been examined. The current study investigated the effects of a single dose and four weeks of administration of a novel, Avena sativa herbal extract (cognitaven®) on cognitive function and mood, and changes in psychological state during a laboratory stressor. The study adopted a dose-ranging, double-blind, randomised, parallel groups design in which 132 healthy males and females (35 to 65 years) received either 430 mg, 860 mg, 1290 mg green oat extract or placebo for 29 days. Assessments of cognitive function, mood and changes in psychological state during a laboratory stressor (Observed Multitasking Stressor) were undertaken pre-dose and at 2 h and 4 h post-dose on the first (Day 1) and last days (Day 29) of supplementation. The results showed that both a single dose of 1290 mg and, to a greater extent, supplementation for four weeks with both 430 mg and 1290 mg green oat extract resulted in significantly improved performance on a computerised version of the Corsi Blocks working memory task and a multitasking task (verbal serial subtractions and computerised tracking) in comparison to placebo. After four weeks, the highest dose also decreased the physiological response to the stressor in terms of electrodermal activity. There were no treatment-related effects on mood. These results confirm the acute cognitive effects of Avena sativa extracts and are the first to demonstrate that chronic supplementation can benefit cognitive function and modulate the physiological response to a stressor.

Keywords: cognition, working memory, brain, stress, phytochemicals, polyphenols, triterpenes, Avena sativa, green oat extract

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1. Introduction

Immature or “green” oat extracts and tinctures, made from the higher aerial parts of oat plants (Avena sativa L.), have a long history of medicinal use, encompassing a number of psychotropic indications, including insomnia and anxiety [1,2,3]. Avena sativa extracts contain a wide range of potentially bioactive secondary metabolite compounds [4] that play ecological roles for the plant [5,6,7]. These consistently include a range of terpenes, including genus-specific triterpene saponin “avenacins”, and a broad spectrum of phenolic acids and polyphenols, the latter including flavonoids and avenanthramides, a group of genus specific atypical phenolic amides [5,6,8,9,10].

These structural groups of phytochemicals include numerous compounds that have been shown to both exert wide ranging cellular and physiological effects and to modulate human brain function [7,11]. On a mechanistic level, polyphenols, including avenanthramides [8], have been shown to interact with diverse components of mammalian cellular signal transduction, including brain-specific direct and indirect interactions with neurotransmitter receptors [11,12,13,14]. Similarly, triterpenes may also modulate neurotransmission via direct receptor interactions [15,16] via inhibition of the enzymes that catalyse the oxidation or hydrolysis of neurotransmitters [7,17,18,19] or via modulation of the functioning of the glucocorticoid and estrogen systems [7,20,21], the latter due to a structural similarity to these triterpene mammalian hormones [7]. These mechanisms potentially underlie the observation of improved cognitive function following polyphenol- and triterpene-rich herbal extracts [22,23,24,25,26,27,28]. In addition, extracts of Avena sativa, including those from an accession of the plant material used to make the current study’s extract [29] have previously been shown to specifically inhibit the enzymes monoamine oxidase B (MAO-B) and phosphodiesterase 4 (PDE4) [30]. This adds the upregulation of monoamine neurotransmitter function to the potential mechanisms of action of this herbal extract.

Direct demonstrations of the effects of Avena sativa extracts include an initial study in rats that demonstrated that the lower of two doses had beneficial effects in terms of responses to stressors, aversive learning and social behaviour [31]. In humans, several placebo-controlled cross-over trials have assessed the effects of single doses of Avena sativa extract. In the first, an electroencephalography (EEG) study, the higher (2500 mg) of two doses of extract resulted in a pattern of modulation of cerebro-electrical activity in the frontal cortex that was interpreted as reflecting an improvement in brain function [32]. In a further study, a single dose of 1600 mg, but not a higher dose of 2400 mg Avena sativa extract improved the performance of a single task (Stroop) completed by 36 elderly participants with poor cognitive function [33]. Subsequently, in a more comprehensive cross-over study involving 45 middle-aged participants, researchers employed a battery of 13 computerised cognitive tasks, and found that the lower of two doses (800 mg/1600 mg) of Avena sativa extract increased the speed of performance across post-dose assessments on a global measure comprising speed of performance data from all of the timed tasks. The same dose was also associated with improvements on a delayed word recall task, an executive function task (Peg and Ball) and the Corsi Blocks spatial working memory task [34].

Only two studies have assessed the effects of chronic supplementation (12 weeks) with Avena sativa extracts. In one study, Wong et al. [35] found that 1500 mg of green oat extract resulted in improved peripheral and cerebral vasodilation as assessed by flow-mediated dilatation, and trans-cranial Doppler during hypercapnia. However, in a further study, the same administration regimen had no effect on a number of cognitive tasks assessing attention/concentration [36]. Regarding these two latter studies, it is of interest to note that the last dose of the intervention was taken a minimum of 18 h prior to the assessment, thus only allowing a measurement of the “pure” chronic effects of the treatments.

To date, there has been no demonstration of chronic cognitive benefits following green oat extracts, and no single investigation of the comparative acute, chronic and superimposed acute/chronic effects of these extracts on brain function. There have also been no human studies that have assessed the effects of green oat extracts on aspects of mood or investigated any potential protection against psychological stress similar to the effects attributed to other “adaptogenic” triterpene-containing herbal extracts.

The current dose-ranging, double-blind, placebo-controlled, parallel-groups study investigated the potential for single doses and extended daily consumption of three ascending doses (430 mg/860 mg/1290 mg) of green oat herbal extract to modulate cognitive function and attenuate the negative shift in psychological state and the physiological responses elicited by a potent novel laboratory stressor (the Observed Multitasking Stressor (OMS)). The study included an assessment of the acute (Day 1 of treatment, 2/4 h post-dose), chronic and acute/chronic superimposed (Day 29, pre-dose, and 2/4 h post-dose) effects of the three doses of green oat extract.

nutrients-12-01598

Reference:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352613/

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Ivermectin – Niacin Research

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A review on phytochemistry and medicinal properties of the genus Achillea

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  • Received 30 Apr 2011; Revised 2 July 2011; Accepted 2 July 2011

1Saeidnia S., *1Gohari AR., 1Mokhber-Dezfuli N, 2 Kiuchi F.
1 Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical
Sciences, Tehran, Iran. 2 Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku,
Tokyo 105-8512, Japan.

Abstract

Achillea L. (Compositae or Asteraceae) is a widely distributed medicinal plant throughout the world and has been used since ancient time. Popular indications of the several species of this genus include treatment of wounds, bleedings, headache, inflammation, pains, spasmodic diseases, flatulence and dyspepsia. Phytochemical investigations of Achillea species have revealed that many components from this genus are highly bioactive. There are many reports on the mentioned folk and traditional effects. Although, the medicinal properties of Achillea plants are recognized worldwide, there are only one review article mainly about the structures of the phytochemical constituents of Achillea. The present paper reviews the medicinal properties of various species of Achillea, which have been examined on the basis of the scientific in vitro, in vivo or clinical evaluations. Various effects of these plants may be due to the presence of a broad range of secondary active metabolites such as flavonoids, phenolic acids, coumarins, terpenoids (monoterpenes, sesquiterpenes, diterpenes, triterpenes) and sterols which have been frequently reported from Achillea species.

Keywords: Achillea, Asteraceae, Bioactive compounds.

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INTRODUCTION

The genus Achillea L. belongs to Asteraceae (Compositae), the largest family of vascular plants. Asteraceaeous plants are distributed throughout the world and most common in the arid and semi-arid regions of subtropical and lower temperate latitudes. Achillea contains around 130 flowering and perennial species and occurs in Europe and temperate areas of Asia and a few grow in North America. These plants typically have hairy and aromatic leaves and flat clusters of small flowers on the top of the stem. Since these flowers have various colors, a number of species are popular garden plants (14). The basic chromosome number of this genus is X=9 and most of the species are diploid with great ecological ranges from desert to water-logged habitats (5).

The name of Achillea is referred to the Achilles in the literary Trojan War of the Iliad who used yarrow to treat the soldiers’ wounds (6). The majority of the Achillea species are as the medicinal plants which have therapeutic applications (4). There are few review papers on the different aspects of Achillea as a noteworthy and medicinal genus. Recently, Si and co-authors (7) published a review article mainly about the structures of phytochemical constituents and a brief section of biological properties of Achillea (7). Literature reviews show that there are many reports on pharmacological, immunological, biological and other therapeutic activities of these valuable herbs which are reviewed in this article.

Traditional usages 

Since Achillea genus is widespread all over the world, its species have been used by local people as folk or traditional herbal medicines. Bumadaran is a popular name for several species of Achillea in Persian language. They are reported as tonic, anti-inflammatory, anti-spasmodic, diaphoretic, diuretic and emmenagogic agents and have been used for treatment of hemorrhage, pneumonia, rheumatic pain and wounds healing in Persian traditional literature (89).

In Spanish-speaking New Mexico and southern Colorado, A. millefolium L. is called plumajillo, or “little feather”, because of the shape of the leaves. Native Americans and early settlers used yarrow for its astringent qualities that made it effective in wound healing and anti-bleeding (10).

Achillea species are the most important indigenous economic plants of Anatolia. Herbal teas prepared from some Achillea species are traditionally used for abdominal pain and flatulence in Turkey (11). Dioscorides also used Achillea for dysentery, whether associated with cholera or other causes, which killed as many soldiers as did steel and lead. In terms of Chinese medicine, Achillea can be said to have three main actions: clear Exterior Wind (diaphoretic), Tonify Deficiency (tonic) and clear Heart Phlegm (anti-hypertention) (12).

Many of these therapeutic usages have been confirmed by new experimental and clinical studies. The consumption of herbal teas from different species of Achillea, especially for treatment of the gastrointestinal tract, is common in folk medicine (13). However, there are still several unknown aspects of Achillea plants that need more attention.

Phytochemical constituents 

Phytochemical investigations of Achillea species have revealed that many components from this genus are highly bioactive. The first anti-spasmodic flavonoids, cynaroside I and cosmosiin II (Scheme 1) were isolated from A. millefolium L. (14), and the first natural proazulene, achillicin III (Scheme 2) was identified from the genus Achillea (15). Literature search shows that the, flavonoids, terpenoids, lignans, amino acid derivatives, fatty acids and alkamides such as p-hydroxyphenethylamide IV (Scheme 2) have been identified in Achillea species. The main constituents of the most species have been previously reviewed (7). Therefore, in this article some other minor or rare compounds and especially their medicinal or industrial usages which have been less described are reviewed. Among them,alkamides, the lipophilic and nitrogen containing compounds, are responsible for insecticide, anti-inflammation and some immunological activities of Achillea and Echinacea plants (16). The genus Achillea comprises flavored species which produce intense essential oils. The volatile oils of Achillea contain monoterpenes as the most representative metabolites. However, there are reports on high levels of sesquiterpenes compared with monoterpenes (1718). There are several pharmacological actions which have been mostly attributed to the presence of azulenogenous sesquiterpene lactones in the essential oil of Achillea. Results of studies have indicated that tetraploid species are accumulating proazulenes such as achillicin III (Scheme 2) (19).Except for the essential oil constituents, yarrow (A. tenuifolia Lam.) seeds consist of the high oil content which is rich in linoleic acid, an essential polyunsaturated fatty acid. This makes yarrow seed as a potential source of edible oil for human consumption (20). Recently, A. millefolium has been introduced as a new source of natural dye for wool dyeing due to the presence of the flavonoids, luteolin V and apigenin VI (Scheme 1). A. millefolium was found to have good agronomic potential as a natural dye in Iran (21). In the plant kingdom, hydroxycinnamoyl conjugates of quinic acid represent common end metabolites of the shikimate-phenylpropanoid pathway, and feruloylcaffeoylquinic acid derivates VII have been isolated only from two species of genus Achillea so far (22). From the aerial parts of Achillea species, proline VIII, stachydrine IX, betonicine X, betaine XI and choline XII have been isolated as the major nitrogen containing compounds (Scheme 2) (2324). Betaines, containing the permanent positive charge on the quaternary ammonium moiety, belong to an important class of naturally occurring compounds that function as compatible solutes or osmoprotectants (25). These compounds have shown immunosuppressive activity in the experimental animals (2627).

DARU-19-173

Reference:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3232110/

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Yerba Mate (Ilex paraguariensis) Beverage: Nutraceutical Ingredient or Conveyor for the Intake of Medicinal Plants? Evidence from Paraguayan Folk Medicine

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Monika Kujawska

Abstract

The use of medicinal plants mixed with yerba mate (Ilex paraguariensis) has been poorly studied in the ethnopharmacological literature so far. The Paraguayan Mestizo people have the longest tradition of using the yerba mate beverage, apart from the indigenous Guarani people. This study analyses the role of yerba mate and medicinal plants in the treatment of illnesses within Paraguayan folk medicine. The research was conducted among 100 Paraguayan migrants living in Misiones, Argentina, in 2014 and 2015. Yerba mate is not considered to be a medicinal plant by its own virtues but is culturally a very important type of medicinal plant intake. Ninety-seven species are employed in hot and cold versions of the yerba mate beverage. The most important species are as follows: Allophylus edulis (highest number of citations), Aristolochia triangularis (highest relative importance value), and Achyrocline flaccida and Achyrocline tomentosa (highest score by Index of Agreement on Species). The plants are used in the treatment of 18 medicinal categories, which include illnesses traditionally treated with plants: digestive system, humoral medicine, and relatively new health conditions such as diabetes, hypertension, and high levels of cholesterol. Newly incorporated medicinal plants, such as Moringa oleifera, are ingested predominantly or exclusively with the mate beverage.

1. Introduction

Yerba mate (Ilex paraguariensis A.St.-Hil., Aquifoliaceae) is a native tree growing in the subtropics of South America, present in Southern Brazil, Northeastern Argentina, Eastern Paraguay, and Uruguay [1]. The yerba mate beverage has been consumed traditionally by Guarani indigenous people since before the conquest of South America by the Spaniards [2]. The commercial potential of this plant was discovered by the Jesuits, who brought wild growing yerba mate into cultivation. Pedro de Montenegro, a Jesuit monk, in his Materia Medica Misionera described the use of the most important species for the Guarani people, in which yerba mate appeared on the top of the list [3]. The Guarani name for yerba mate is ka’a which means “a plant” or “a herb”; hence yerba mate has been considered by this group as the plant par excellence [3]. Yerba mate was also known as Jesuit tea or Paraguayan tea and shipped as such to Europe [2]. With the expulsion of the Jesuits in 1768, the plantations went wild. By this time, the yerba mate beverage was already popular among Mestizo people (of Spanish and Guarani origin). Since the end of the 19th century, it also became a daily beverage for the European migrants who partly colonized Southern Brazil, Northeastern Argentina, and, to a lesser extent, Eastern Paraguay [4]. Nowadays yerba mate is consumed at the rate of more than one litre per day by millions of people in the above-mentioned countries [45]. It plays a very special social role and constitutes a very important form of caffeine intake [245]. Its popularity is also increasing outside South America due to its pharmacological properties, proven to be beneficial to health [467]. It is also a very important drink in Syria and Lebanon due to Syro-Lebanese migration to Argentina in the second half of the 19th century. Many migrants who returned to the Levant in the 1920s took the habit of drinking mate with them [89].

Over the last 20 years there has been an increase in studies of the pharmacologic properties of Ilex paraguariensis, which have been reviewed [46710]. Numerous active compounds have been identified in yerba mate. Phenolic compounds predominate caffeoyl derivatives (caffeic acid, chlorogenic acid) [1112], xanthines (caffeine and theobromine), which are a class of purine alkaloids found in many other plants such as tea and coffee, flavonoids (quercetin, kaempferol, and rutin), and tannins [7]. Numerous triterpenoid saponins have also been identified, including those derived from ursolic acids known as metasaponins [47]. Saponins are responsible for the distinct flavour of yerba mate extracts [7]. Yerba mate also contains minerals (P, Fe, and Ca) and vitamins (C, B1, and B2) [13].

Research on extracts and isolated compounds from yerba mate has provided a number of pharmacological applications. Studies have demonstrated that yerba mate leaves have antioxidant [11], antiobesity [1415], antidiabetic, digestive improvement and cardiovascular properties [1617], and chemopreventative ones (preventing cellular damage that may cause chronic diseases) [18]. The consumption of yerba mate infusion reduces LDL-cholesterol in parallel with an increase in HDL-cholesterol, as observed in studies on humans [19]. Yerba mate extract also reduces acute lung inflammation, as observed in the animal model [4]. Antimicrobial activity of Ilex paraguariensis has been recently studied as well [20].

Some ethnobotanical studies from the south cone of South America report medicinal uses of yerba mate beverage [2122]. Few ethnobotanical and ethnopharmacological studies mention that various medicinal plants are consumed together with the yerba mate beverage by Mestizo and European migrants living in Argentina and Paraguay [2326]. However, very little is known about how medicinal plants are combined with yerba mate beverage by local people. Additionally, medicinal plant use by Paraguayan Mestizo people is poorly documented in the English-language scientific literature, with very few exceptions [232630]. The documentation of medicinal plants and analysis of traditional knowledge related to the yerba mate beverage by Paraguayan Mestizo people is of paramount importance for two reasons: (1) apart from indigenous Guarani peoples, they have the longest tradition of using yerba mate and mixing it with medicinal plants; (2) The Paraguayan people are described in the literature as knowledgeable about medicinal plants [3031]. Nearly 80% of the population of Paraguay consume medicinal plants on a daily basis [30]. However, the relationship between traditional uses and pharmaceutical properties is poorly studied.

The objectives of this contribution were to (1) document and analyse the role of yerba mate in prophylaxis and treatment by Paraguayan Mestizo people; (2) evaluate the role of medicinal plants in yerba mate beverages, and (3) describe the scope of illnesses treated with yerba mate beverage and medicinal plants. Additionally, two questions guided my research and analysis: (1) Does any pattern exist showing that particular illnesses are treated with a hot version of yerba mate beverage and others with a cold one? (2) How receptive is this traditional mode of plant administration to new health challenges and new medicinal plants, previously unknown to the Paraguayan people?

ECAM2018-6849317

Reference:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5872613/

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