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1.
BMC Complement Med Ther ; 24(1): 103, 2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38414023

ABSTRACT

BACKGROUND: Natural health products (NHP) are an important part of the healthcare system. They are mainly non-prescription and sold over the counter, which requires active decision making by the consumer. Within the framework of the Complementary and Alternative Healthcare Model, this study aims to identify factors that influence NHP usage, in particular related to concentration and cognition (CC), a topic that concerns all ages and social classes within the population. METHODS: Data were collected by means of a representative online survey (n = 1,707) in Germany in April 2022. Three user groups were defined: NHPCC users, who used NHP for CC (12 month prevalence); nCC-NHP users, who used NHP but not for CC indications (12 month prevalence); and past NHP users, who have used NHP but not within the previous 12 months. Independent influencing variables were categorized into predisposing, enabling, need, and health service use factors. Data were analyzed with descriptive statistics, inferential statistics, and binary logistic regression models to compare NHPCC users to nCC-NHP users (model 1) and to past NHP users (model 2). RESULTS: A higher share of NHPCC and nCC-NHP users compared to past NHP users were women, self-medicated with NHP, and used information about NHP provided by health professionals or on product. Their openness-to-change value orientation was more pronounced than of past users. Compared to nCC-NHP and past NHP users, the probability of being an NHPCC user increased if an individual had more difficulties in daily attention and memory performance, made use of health professionals and literature to seek information about NHP, and used NHP for health support and illness prevention. Additionally, a female gender, NHP self-medication, and having higher values of self-transcendence were significant indicators for NHPCC usage compared to past NHP usage. CONCLUSION: NHP manufacturers, health professionals, and policymakers should be aware of the factors that lead to NHP consumption decisions and consider them in the development and optimization of healthcare strategies as well as in the marketing and communication strategies of companies producing NHP, in particular for CC. The current study can contribute to characterizing the target groups and to defining the aims and communication channels of such campaigns.


Subject(s)
Biological Products , Humans , Female , Male , Delivery of Health Care , Surveys and Questionnaires , Germany , Cognition
2.
J Pharm Policy Pract ; 16(1): 134, 2023 Nov 03.
Article in English | MEDLINE | ID: mdl-37924079

ABSTRACT

BACKGROUND: Health supplements and natural products are widely used by the general public to support physical function and prevent disease. Additionally, with the advent of e-commerce, these products have become easily accessible to the general public. Although several theoretical models have been used to explain the use of health supplements and natural products, empirical evidence on how consumers make decisions to purchase online health supplements and natural products remains limited. METHODS: In this study, a grounded theory approach was used to develop a substantive theoretical model with the aim of investigating the decision-making process of consumers when purchasing health supplements and natural products online. Malaysian adult consumers who had purchased these products via the Internet were either purposively or theoretically sampled. A total of 18 virtual in-depth interviews (IDIs) were conducted to elicit participants' experiences and priorities in relation to this activity. All the IDIs were audio-recorded and transcribed verbatim. The data were analysed using open coding, focus coding and theoretical coding. The analytical interpretations and theoretical concepts were recorded in research memos. RESULTS: Consumers' decisions to purchase a health supplement or natural product over the Internet are based on a series of assessments regarding the perceived benefits and risks of this activity, which may be related to the product or the process. In the online marketplace, consumers attempt to choose products, online sellers, sales platforms and/or purchase mechanisms with lower perceived risk, which ultimately enhances their confidence in five elements related to the purchase: (1) product effectiveness, (2) product safety, (3) purchase convenience, (4) fair purchase and (5) online security. Consumers take an acceptable level of risk to purchase these products online, and this acceptable level is unique to each individual and is based on their perception of having control over the potential consequences if the worst-case scenario occurs. CONCLUSIONS: In this study, a substantive theoretical model is developed to demonstrate how consumers decide to purchase online health supplements and natural products by accepting an acceptable level of risk associated with the product or process. The emerging model is potentially transferable to other populations in similar contexts.

3.
BMC Complement Med Ther ; 23(1): 372, 2023 Oct 21.
Article in English | MEDLINE | ID: mdl-37865731

ABSTRACT

BACKGROUND: Respiratory diseases (RD) can challenge healthcare systems around the globe. Natural health products (NHPs) are popular complementary and alternative medicine options for health issues concerning non-fatal RD. Little is known about the characteristics of the users of RD-NHPs and about their NHP consumption behavior during the Covid-19 pandemic in Germany. METHODS: A representative online survey was conducted in Germany in 2022. 1707 participants were classified based on having used NHPs for RD within the previous 12 months, having used NHPs but not for RD within the previous 12 months and not having used NHPs. Data were analyzed using descriptive and inferential statistical methods as well as a multinomial logistic regression model. RESULTS: Users of RD-NHPs within the previous 12 months were more likely to be employed and to consult pharmacists more often for non-fatal health issues than individuals who did not take RD-NHPs. RD-NHP users were more likely to suffer from a Covid-19 infection and to have children living in the same household than other NHP users. Compared to non-NHP users, RD-NHP users were more likely to be female, highly educated and have stronger openness-to-change value orientations. Vaccination-related behavior was no indicator of RD-NHP usage. Most RD-NHP users took NHPs in self-medication. Few reported informing their practitioner about their self-medication. Drugstores were the most visited supply source for NHPs during the pandemic, followed by pharmacies. Common information sources regarding NHPs were the products themselves and pharmacists. CONCLUSION: This study emphasized the important role of NHPs as a popular prevention and treatment option for RD. RD-NHPs were more likely used by individuals who were employed, who suffered from a RD and who consult pharmacists for non-fatal health issues. The importance of product information and pharmacies as information sources should be considered to make communication strategies about safe self-medication options with RD-NHPs more effective, which could help to reduce the burden of health facilities regarding non-fatal RD. To improve and develop future pandemic-control strategies, health professionals and policy makers should consider NHP usage behavior and provide critical information about chances and risks of self-medicated NHP consumption.


Subject(s)
Biological Products , COVID-19 , Complementary Therapies , Child , Humans , Female , Male , Pandemics , Biological Products/therapeutic use , COVID-19/epidemiology , Germany/epidemiology
4.
Article in English | WPRIM | ID: wpr-996790

ABSTRACT

@#Aim and design: This systematic review aimed to estimate the prevalence of online natural health products (NHPs) purchases among consumers. Data Sources: Four databases (PubMed, Science Direct, Scopus and Web of Sciences) were searched for articles published up to July 1, 2021. Review Method: Studies included were those reporting the prevalence of online NHPs purchases, those excluded were case reports, commentaries, letters, editorials, review articles, theses and non-English studies. The risk of bias of selected studies was assessed using the Joanna Briggs Institute’s checklist, and the pooled prevalence of online NHPs purchases was generated using the random-effect model. Results: A total of 30 studies were included in the meta-analysis, representing a total of 40,535 respondents. The pooled prevalence of online NHPs purchases was estimated at 7.60% (95% CI: 5.49, 10.01). Prevalence was higher in studies conducted in recent years, among physically active populations and when sports nutrition was included within the scope of NHPs. More than half of the selected studies have a moderate risk of bias, and considerable heterogeneity was observed across the selected studies. Conclusion and Impact: Online purchases of NHPs are not common among consumers, but they have become more common in recent years. A wide range of NHPs were investigated across studies, which may have contributed to the considerable heterogeneity reported in this review. It is suggested that future studies investigating online NHPs purchases consider reporting individual prevalence statistics specific to each NHP type, to facilitate meaningful comparisons between studies.

5.
Saudi Pharm J ; 29(5): 361-368, 2021 May.
Article in English | MEDLINE | ID: mdl-34135662

ABSTRACT

Commiphora myrrha (Nees) Engl. (C. myrrha) resin is the most Middle Eastern herbal medicine used against numerous diseases. After being decocted or macerated, this resin is widely consumed among Saudi Arabian patients who are already under prescribed medication. Despite its popularity, no studies have been reported on potential modulation effects of these resin extracts on drug metabolism. Therefore, we studied C. myrrha resin extracts on the expression of cytochrome P450 (CYP) drug-metabolizing isoenzyme in human hepatocellular carcinoma cell line HepG2. The C. myrrha extracts were prepared by sonication and boiling, resembling the most popular traditional preparations of maceration and decoction, respectively. Both boiled and sonicated aqueous extracts were fingerprinted using high-performance liquid chromatography equipped with ultra-violet detector (HPLC-UVD). The viability of HepG2 cells treated with these aqueous extracts was determined using CellTiter-Glo® assay in order to select the efficient and non-toxic resin extract concentrations for phase-I metabolic CYP isoenzyme expression analysis. The isoenzyme gene and protein expression levels of CYP 2C8, 2C9, 2C19, and 3A4 were assessed using reverse transcription-quantitative polymerase chain reaction and Western blot technologies. The HPLC-UVD fingerprinting revealed different chromatograms for C. myrrha boiled and sonicated aqueous extracts. Both aqueous extracts were toxic to HepG2 cells when tested at concentrations exceeding 150 µg/ml of the dry crude extract. The CYP 2C8, 2C9, and 2C19 mRNA expression levels increased up to 4.0-fold in HepG2 cells treated with either boiled or sonicated C. myrrha aqueous extracts tested between 1 and 30 µg/ml, as compared with the untreated cells. However, CYP3A4 mRNA expression level exceeded the 2.0-fold cutoff when the cells were exposed to 30 µg/ml of C. myrrha extracts. The up-regulation of CYP mRNA expression levels induced by both boiled and sonicated C. myrrha aqueous extracts was confirmed at the CYP protein expression levels. In conclusion, both sonicated and boiled C. myrrha aqueous extracts modulate CYP 2C8, 2C9, 2C19, and 3A4 gene expression at clinically-relevant concentrations regardless of preparation methods. Further in vitro and in vivo experiments are required for CYP isoenzyme activity assessment and the establishment of herb-drug interaction profile for these traditional medicinal resin extracts.

6.
Int J Mol Sci ; 21(22)2020 Nov 11.
Article in English | MEDLINE | ID: mdl-33187200

ABSTRACT

Most cancer therapeutics, such as tubulin-targeting chemotherapy drugs, cause cytotoxic, non-selective effects. These harmful side-effects drastically reduce the cancer patient's quality of life. Recently, researchers have focused their efforts on studying natural health products (NHP's) which have demonstrated the ability to selectively target cancer cells in cellular and animal models. However, the major hurdle of clinical validation remains. NHP's warrant further clinical investigation as a therapeutic option since they exhibit low toxicity, while retaining a selective effect. Additionally, they can sensitize cancerous cells to chemotherapy, which enhances the efficacy of chemotherapeutic drugs, indicating that they can be utilized as supplemental therapy. An additional area for further research is the investigation of drug-drug interactions between NHP's and chemotherapeutics. The objectives of this review are to report the most recent results from the field of anticancer NHP research, and to highlight the most recent advancements in possible supplemental therapeutic options.


Subject(s)
Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Biological Products/pharmacology , Biological Products/therapeutic use , Neoplasms/drug therapy , Animals , Drug Interactions , Humans
7.
Nutrients ; 12(6)2020 Jun 19.
Article in English | MEDLINE | ID: mdl-32575480

ABSTRACT

The lack of effective treatment for chronic discomfort without negative side effects highlights the need for alternative treatments. Pain Bloc-R is a natural health product composed of vitamins B6, B12, D, white willow bark extract, Angelica root extract, acetyl L-carnitine HCl, caffeine, L-theanine, Benfotiamine, and L-tetrahydropalmatine. The objective of this study was to compare the effects of Pain Bloc-R, acetaminophen, and placebo on unresolved aches and discomfort as assessed by the brief pain inventory (BPI) and modified Cornell musculoskeletal discomfort questionnaires. This randomized, double-blind, placebo-controlled, crossover study consisted of three 7-day periods with Pain Bloc-R, acetaminophen, or placebo, each separated by a 7-day washout. Twenty-seven healthy adults (ages 22-63 years) were randomized to receive the three interventions in different sequences. The BPI "pain at its worst" scores were significantly lower when participants took Pain Bloc-R than when they took acetaminophen (21.8% vs. 9.8% decrease, p = 0.026) after seven days of supplementation. Pain Bloc-R achieved a significant improvement in the "pain at its least" score, significantly decreased the interference of discomfort in walking, and significantly decreased musculoskeletal discomfort total scores (34%, p = 0.040) after seven days. In a post hoc subgroup analysis based on age and gender, male participants ≤45 years taking Pain Bloc-R reported significant reductions in pain severity and pain interference vs. acetaminophen. Pain Bloc-R performed as well as acetaminophen in managing unresolved non-pathological pain in otherwise healthy individuals.


Subject(s)
Berberine Alkaloids/therapeutic use , Caffeine/therapeutic use , Chronic Pain/drug therapy , Pain Management/methods , Plant Extracts/therapeutic use , Thiamine/analogs & derivatives , Vitamins/therapeutic use , Acetylcarnitine , Adult , Angelica , Cross-Over Studies , Double-Blind Method , Drug Combinations , Female , Glutamates/therapeutic use , Humans , Hydrochloric Acid/therapeutic use , Male , Middle Aged , Plant Bark , Plant Roots , Salix , Sex Factors , Thiamine/therapeutic use , Treatment Outcome , Vitamin B 12/therapeutic use , Vitamin B 6/therapeutic use , Vitamin D/therapeutic use , Young Adult
8.
Phytochem Anal ; 31(1): 68-80, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31389645

ABSTRACT

INTRODUCTION: Commercial cranberry supplements provide a low-sugar alternative to juices and sweetened fruit consumed for health benefits, but their phytochemical composition and associated biological activity varies depending on the source material and post-harvest processing. Proton nuclear magnetic resonance (1 H-NMR) is a rapid and environmentally friendly method of generating metabolic profiles of plant materials that may be used to authenticate cranberry products. OBJECTIVE: The 1 H NMR-based chemometrics were used to characterise variations in metabolic profiles of cranberry supplements in comparison to a whole cranberry powder reference standard. MATERIALS AND METHODS: The secondary metabolite profiles of nine commercial cranberry supplements were compared to a whole cranberry powder reference standard, using 1 H-NMR with Bruker AssureNMR software and principal component analysis (PCA). Content of selected triterpenoids and organic acids was determined by quantitative NMR. Total proanthocyanidins and anthocyanins were determined by established methods. RESULTS: PCA of 1 H-NMR spectra showed overlap between the cranberry standard and three supplements, but most products varied substantially in metabolic profile. Metabolites contributing to the observed variance include citric acid and cranberry peel constituents ursolic acid, oleanolic acid and hyperoside. Ursolic, oleanolic, citric, quinic and malic acids were readily determined by quantitative 1 H-NMR in the whole cranberry standard, but were below detection limits in many supplements. Proanthocyanidin and flavonoid content in several products was minimal or below detection limits. CONCLUSION: The 1 H-NMR chemometrics found significant variation in composition of characteristic cranberry metabolites among commercial preparations, reinforcing the need for reliable industry standards.


Subject(s)
Vaccinium macrocarpon , Fruit , Magnetic Resonance Spectroscopy , Metabolomics , Plant Extracts
9.
Biomedicines ; 7(3)2019 Aug 24.
Article in English | MEDLINE | ID: mdl-31450579

ABSTRACT

Herbal teas are becoming popular as functional beverages due to their various health promotional properties. This study aimed at assessing 13 hot water infusions (HWIs) from different herbs against streptococcal pharyngitis (strep throat). Licorice root exhibited the lowest minimum inhibitory concentrations (MIC) of 1.56 mg/mL, followed by barberry root, thyme, and oregano flowering shoots, with a MIC of 3.13 mg/mL. At their respective minimum bactericidal concentrations (MBC), licorice showed the bactericidal effect on S. pyogenes within 12 h after exposure while others need 24 h for a similar outcome. The HWIs exhibited inhibitory activity on biofilm formation, ranging from 1.56 to 6.25 mg/mL, which confirmed by ruptured cells or clusters of dead cell debris observed in scanning electron microscope (SEM). Overall, non-toxic concentrations of efficacious HWIs from licorice root, barberry root, thyme, and oregano flowering shoots may provide potential sources for developing herbal teas or biomedicine for the management of S. pyogenes infections.

10.
Pharmacol Res ; 139: 228-242, 2019 01.
Article in English | MEDLINE | ID: mdl-30227261

ABSTRACT

The majority of brain injuries that lead to cerebral palsy, developmental disability, and mental health disorders have their onset in utero. These lifelong conditions come with great economic and emotional burden as they impact function in nearly all domains of affected individuals' lives. Unfortunately, current therapeutic options are limited. There remains a focus on rescue, rehabilitation, and regeneration after the injury has occurred, rather than aiming to prevent the initial injury. Prevention would imply treating the mother during pregnancy to alter the fetal environment and in turn, treat the fetus. Fear of harming the developing fetus remains as a result of errors of the past such as the release of thalidomide. In this review, we outline evidence from animal studies and clinical trials that have explored maternal dietary supplementation with natural health products (including nutraceuticals and functional foods) for perinatal brain injury prevention. Namely, we discuss magnesium sulphate, creatine, choline, melatonin, resveratrol and broccoli sprouts/sulforaphane. Although clinical trials have only been completed in this realm for magnesium sulphate, results in animal models have been promising, suggesting that this is a productive avenue for further research. Natural health products may provide safe, effective, affordable, and easily accessible prevention of fetal brain injury and resulting lifelong disabilities.


Subject(s)
Brain Injuries/prevention & control , Dietary Supplements , Neuroprotective Agents/therapeutic use , Animals , Child , Female , Humans , Pregnancy
11.
Nutrients ; 10(1)2018 Jan 04.
Article in English | MEDLINE | ID: mdl-29300341

ABSTRACT

Many of the scientific and regulatory challenges that exist in research on the safety, quality and efficacy of dietary supplements are common to all countries as the marketplace for them becomes increasingly global. This article summarizes some of the challenges in supplement science and provides a case study of research at the Office of Dietary Supplements at the National Institutes of Health, USA, along with some resources it has developed that are available to all scientists. It includes examples of some of the regulatory challenges faced and some resources for those who wish to learn more about them.


Subject(s)
Biomedical Research/legislation & jurisprudence , Dietary Supplements , Health Policy/legislation & jurisprudence , Animals , Biomedical Research/standards , Consumer Product Safety/legislation & jurisprudence , Dietary Supplements/adverse effects , Dietary Supplements/classification , Dietary Supplements/standards , Government Regulation , Humans , Policy Making , Quality Control , Risk Assessment , Terminology as Topic
12.
Musculoskeletal Care ; 15(4): 345-349, 2017 12.
Article in English | MEDLINE | ID: mdl-28052563

ABSTRACT

OBJECTIVES: To describe the self-reported use of natural health products (NHPs) and identify characteristics that predict selected NHP use in rheumatology patients. METHODS: We conducted a cross-sectional survey of consecutive rheumatology patients in two major clinics in Edmonton, Alberta. Survey items included demographic data, rheumatologic diagnoses, prescribed medications, NHPs, and information regarding patients' use of NHPs. Selected NHPs of interest - defined to include joint-specific products, oils with putative joint benefits, and other non-vitamin, non-mineral products - were classified by 2 reviewers. The characteristics of selected NHP users and non-users were compared using chi-squared and ANOVA tests, followed by multivariable-adjusted logistic regression. RESULTS: 1063 patients completed the survey (response rate = 36%, mean age 53 [sd 15], 70% female). 36% of respondents reported using one or more of a wide range of selected NHPs (mean 1.8, range 1-9). The most common source of NHP recommendations for selected NHP users were physicians (42%). Significant predictors of selected NHP use were: being female (aOR 1.41, 95%CI [1.05-1.90], p = 0.02), having a post-secondary degree (aOR 1.60 [1.15-2.22], p = 0.005), and the number of non-rheumatic medications (aOR 1.08 [ 1.00-1.15], p = 0.03) and NSAIDs (aOR 1.32 [1.06, 1.63], p = 0.01). Similar findings were observed among only inflammatory arthritis patients. CONCLUSIONS: Our study confirms the frequent use of selected NHPs, possibly to mitigate persistent symptoms of rheumatologic illness. Rheumatologists appear to be trusted sources of advice and recommendations on NHP use and should provide balanced counselling for their patients.


Subject(s)
Dietary Supplements/statistics & numerical data , Rheumatic Diseases/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Antirheumatic Agents/therapeutic use , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Rheumatology , Young Adult
13.
J Clin Sleep Med ; 13(2): 275-281, 2017 Feb 15.
Article in English | MEDLINE | ID: mdl-27855744

ABSTRACT

STUDY OBJECTIVES: Melatonin is an important neurohormone, which mediates circadian rhythms and the sleep cycle. As such, it is a popular and readily available supplement for the treatment and prevention of sleep-related disorders including insomnia and jet lag. This study quantified melatonin in 30 commercial supplements, comprising different brands and forms and screened supplements for the presence of serotonin. METHODS: A total of 31 supplements were analyzed by ultraperformance liquid chromatography with electrochemical detection for quantification of melatonin and serotonin. Presence of serotonin was confirmed through analysis by ultraperformance liquid chromatography with mass spectrometry detection. RESULTS: Melatonin content was found to range from -83% to +478% of the labelled content. Additionally, lot-to-lot variable within a particular product varied by as much as 465%. This variability did not appear to be correlated with manufacturer or product type. Furthermore, serotonin (5-hydroxytryptamine), a related indoleamine and controlled substance used in the treatment of several neurological disorders, was identified in eight of the supplements at levels of 1 to 75 µg. CONCLUSIONS: Melatonin content did not meet label within a 10% margin of the label claim in more than 71% of supplements and an additional 26% were found to contain serotonin. It is important that clinicians and patients have confidence in the quality of supplements used in the treatment of sleep disorders. To address this, manufacturers require increased controls to ensure melatonin supplements meet both their label claim, and also are free from contaminants, such as serotonin. COMMENTARY: A commentary on this article appears in this issue on page 163.


Subject(s)
Biological Products/analysis , Dietary Supplements/analysis , Melatonin/analysis , Serotonin/analysis , Biological Products/chemistry , Chromatography, Liquid , Electrochemical Techniques , Mass Spectrometry , Melatonin/chemistry , Serotonin/chemistry
14.
Oncotarget ; 7(45): 73080-73100, 2016 Nov 08.
Article in English | MEDLINE | ID: mdl-27564258

ABSTRACT

Dandelion extracts have been studied extensively in recent years for its anti-depressant and anti-inflammatory activity. Recent work from our lab, with in-vitro systems, shows the anti-cancer potential of an aqueous dandelion root extract (DRE) in several cancer cell models, with no toxicity to non-cancer cells. In this study, we examined the cancer cell-killing effectiveness of an aqueous DRE in colon cancer cell models. Aqueous DRE induced programmed cell death (PCD) selectively in > 95% of colon cancer cells, irrespective of their p53 status, by 48 hours of treatment. The anti-cancer efficacy of this extract was confirmed in in-vivo studies, as the oral administration of DRE retarded the growth of human colon xenograft models by more than 90%. We found the activation of multiple death pathways in cancer cells by DRE treatment, as revealed by gene expression analyses showing the expression of genes implicated in programmed cell death. Phytochemical analyses of the extract showed complex multi-component composition of the DRE, including some known bioactive phytochemicals such as α-amyrin, ß-amyrin, lupeol and taraxasterol. This suggested that this natural extract could engage and effectively target multiple vulnerabilities of cancer cells. Therefore, DRE could be a non-toxic and effective anti-cancer alternative, instrumental for reducing the occurrence of cancer cells drug-resistance.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Plant Extracts/pharmacology , Plant Roots/chemistry , Signal Transduction/drug effects , Taraxacum/chemistry , Animals , Apoptosis/drug effects , Caspases/metabolism , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Disease Models, Animal , Energy Metabolism/drug effects , Gene Expression Profiling , Humans , Membrane Potential, Mitochondrial/drug effects , Mice , Reactive Oxygen Species/metabolism , Signal Transduction/genetics , Xenograft Model Antitumor Assays
15.
Phytochemistry ; 117: 373-379, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26164238

ABSTRACT

In our previous study, Abies balsamea (L.) Mill., a plant used in Cree traditional medicine, had a strong effect on the regulation of glucose homeostasis in liver cells. This study aimed to isolate and identify its active constituents using a bioassay-guided fractionation approach as well as to elucidate their mechanism(s) of action. The effect of the crude extract and its constituents was evaluated on the activity of Glucose-6-Phosphatase (G6Pase) and Glycogen Synthase (GS) and phosphorylation of three kinases, AMP-activated protein kinase (AMPK), Akt and Glycogen Synthase Kinase-3 (GSK-3). Three compounds, abietic acid, dehydroabietic acid and squalene, were isolated from the most active fraction in the bioassays (hexane). The compounds were able to decrease the activity of G6Pase and to stimulate GS. Their effect on G6Pase activity involved both Akt and AMPK phosphorylation with significant correlations between insulin-dependent and -independent pathways and the bioassay. In addition, the compounds were able to stimulate GS through GSK-3 phosphorylation with a significant correlation between the signaling pathway and the bioassay. Dehydroabietic acid stood out for its strongest effect in all the experiments close to that of the crude extract. These compounds may have potential applications in the treatment of type 2 diabetes and insulin resistance.


Subject(s)
Abies/chemistry , Abietanes/pharmacology , Glucose/metabolism , Liver/drug effects , Squalene/pharmacology , Abietanes/isolation & purification , Animals , Cell Line, Tumor/drug effects , Drug Evaluation, Preclinical/methods , Glycogen Synthase/metabolism , Homeostasis/drug effects , Humans , L-Lactate Dehydrogenase/metabolism , Liver/metabolism , Medicine, Traditional , Phosphorylation/drug effects , Plant Extracts/chemistry , Plant Extracts/pharmacology , Rats , Squalene/isolation & purification
16.
Can J Physiol Pharmacol ; 92(9): 758-64, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25140794

ABSTRACT

The mode of action of the anxiolytic medicinal plant Souroubea sympetala was investigated to test the hypothesis that extracts and the active principle act at the pharmacologically important GABAA-benzodiazepine (GABAA-BZD) receptor. Leaf extracts prepared by ethyl acetate extraction or supercritical extraction, previously determined to have 5.54 mg/g and 6.78 mg/g of the active principle, betulinic acid, respectively, reduced behavioural parameters associated with anxiety in a rat model. When animals were pretreated with the GABAA-BZD receptor antagonist flumazenil, followed by the plant extracts, or a more soluble derivative of the active principle, the methyl ester of betulinic acid (MeBA), flumazenil eliminated the anxiety-reducing effect of plant extracts and MeBA, demonstrating that S. sympetala acts via an agonist action on the GABAA-BZD receptor. An in vitro GABAA-BZD competitive receptor binding assay also demonstrated that S. sympetala extracts have an affinity for the GABAA-BZD receptor, with an EC50 value of 123 µg/mL (EtOAc leaf extract) and 154 µg/mL (supercritical CO2 extract). These experiments indicate that S. sympetala acts at the GABAA-BZD receptor to elicit anxiolysis.


Subject(s)
Anti-Anxiety Agents/therapeutic use , Anxiety/drug therapy , GABA Agonists/therapeutic use , Plant Extracts/therapeutic use , Receptors, GABA-A/metabolism , Triterpenes/therapeutic use , Animals , Anti-Anxiety Agents/pharmacology , Anxiety/psychology , Flumazenil/pharmacology , GABA Agonists/pharmacology , GABA Antagonists/pharmacology , Male , Phytotherapy , Plant Bark/chemistry , Plant Extracts/pharmacology , Plant Leaves/chemistry , Plants, Medicinal , Rats, Sprague-Dawley , Triterpenes/pharmacology
17.
Phytomedicine ; 21(4): 435-42, 2014 Mar 15.
Article in English | MEDLINE | ID: mdl-24252333

ABSTRACT

We tested the hypothesis that alkamides from Echinacea exert antifungal activity by disrupting the fungal cell wall/membrane complex. Saccharomyces cerevisiae cells were treated separately with each of seven synthetic alkamides found in Echinacea extracts. The resulting cell wall damage and cell viability were assessed by fluorescence microscopy after mild sonication. Membrane disrupting properties of test compounds were studied using liposomes encapsulating carboxyfluorescein. Negative controls included hygromycin and nourseothricin (aminoglycosides that inhibit protein synthesis), and the positive control used was caspofungin (an echinocandin that disrupts fungal cell walls). The results show that yeast cells exposed to sub-inhibitory concentrations of each of the seven alkamides and Echinacea extract exhibit increased frequencies of cell wall damage and death that were comparable to caspofungin and significantly greater than negative controls. Consistent with effects of cell wall damaging agents, the growth inhibition by three representative alkamides tested and caspofungin, but not hygromycin B, were partially reversed in sorbitol protection assays. Membrane disruption assays showed that the Echinacea extract and alkamides have pronounced membrane disruption activity, in contrast to caspofungin and other controls that all had little effect on membrane stability. A Quantitative Structure-Activity Relationship (QSAR) analysis was performed to study the effect of structural substituents on the antifungal activity of the alkamides. Among the set studied, diynoic alkamides showed the greatest antifungal and cell wall disruption activities while an opposite trend was observed in the membrane disruption assay where the dienoic group was more effective. We propose that alkamides found in Echinacea act synergistically to disrupt the fungal cell wall/membrane complex, an excellent target for specific inhibition of fungal pathogens. Structure-function relationships provide opportunities for synthesis of alkamide analogs with improved antifungal activities.


Subject(s)
Antifungal Agents/analysis , Cell Membrane/drug effects , Cell Wall/drug effects , Echinacea/chemistry , Polyunsaturated Alkamides/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Microbial Sensitivity Tests , Plant Extracts/pharmacology , Polyunsaturated Alkamides/chemistry , Quantitative Structure-Activity Relationship , Saccharomyces cerevisiae
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