Steviol Glycosides from Stevia rebaudiana: An Updated Overview of Their Sweetening Activity, Pharmacological Properties, and Safety Aspects.

This literature-based review synthesizes the available scientific information about steviol glycosides as natural sweeteners and molecules with therapeutic potential. In addition, it discusses the safety concerns regarding human consumption. Steviol glycosides exhibit a superior sweetener proficiency to that of sucrose and are noncaloric, noncariogenic, and nonfermentative. Scientific evidence encourages stevioside and rebaudioside A as sweetener alternatives to sucrose and supports their use based on their absences of harmful effects on human health. Moreover, these active compounds isolated from Stevia rebaudiana possess interesting medicinal activities, including antidiabetic, antihypertensive, anti-inflammatory, antioxidant, anticancer, and antidiarrheal activity. The described bioactivities of steviol glycosides deserve special attention based on their dose dependence and specific pathological situations. Further clinical research is needed to understand underlying mechanisms of action, therapeutic indexes, and pharmacological applications.

Pharmacological Profile, Bioactivities, and Safety of Turmeric Oil.

The pharmacological attributes of turmeric have been extensively described and frequently related to the action of curcuminoids. However, there is also scientific evidence of the contribution of turmeric oil. Since the oil does not contain curcuminoids in its composition, it is crucial to better understand the therapeutic role of other constituents in turmeric. The present review discusses the pharmacokinetics of turmeric oil, pointing to the potential application of its active molecules as therapeutic compounds. In addition, the bioactivities of turmeric oil and its safety in preclinical and clinical studies were revised. This literature-based research intends to provide an updated overview to promote further research on turmeric oil and its constituents.

Interactions of clinical relevance associated with concurrent administration of prescription drug and food or medicinal plants: a systematic review protocol.

BACKGROUND: An inadequate combination of prescription drugs with food or medicinal plants could cause adverse effects in patients or produce negative therapeutic results. Therefore, this generic systematic review protocol aims to identify and synthesize the literature on clinical characteristics and safety issues of these types of pharmacological interactions occurring in children, adolescents, adults, pregnant/lactating women, and older adults. METHODS/DESIGN: This generic protocol follows the stated guidelines from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement. A literature search will be performed in PubMed, Scopus, and Virtual Health Library (VHL) electronic databases from 1960 till present for studies reporting clinical characteristics and safety issues associated with pharmacological interactions occurring between prescription drugs and food or medicinal plants in participants from birth-age to ≥ 65-year-old, including pregnant/lactating women. Lateral searching will be carried out in PubMed via related citation. Two reviewers will carry out an independent evaluation of eligible studies as well as the corresponding data extraction of the selected ones. Subsequently, the methodological quality evaluation of the selected articles will be completed using the corresponding Joanna Briggs Institute Checklists. Moreover, the quality of evidence will be graded according to the criteria of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Working Group. Quantitative research in humans comprising clinical trials and clinical, comparative and, observational studies will be included. The main outcomes of this protocol involve reported potential food-drug and herb-drug interactions, associated safety issues, and adverse reactions along with the generic name of the prescribed drug and the scientific name of the food and medicinal plants involved in these types of pharmacological interactions. Finally, findings extracted from the selected studies will be summarized in a narrative synthesis. DISCUSSION: This generic systematic review protocol seeks to synthesize and critically evaluate current knowledge besides to identify any comprehension gaps in the concurrent administration of prescription drugs with food and herbs. By achieving a better understanding of this topic, this information will allow healthcare professionals to develop useful strategies to recognize, manage, and prevent these types of pharmacological interactions at different age stages, including pregnant/lactating women. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018117308.

Child Development and Nutritional Status in Ecuador.

We assessed the development, nutritional status, and complementary feeding of 12- to 23-month-old children from Cuenca, Ecuador in 2013. Ecuador, an upper-middle-income country, developed a child policy in accordance with World Health Organization (WHO) guidelines. We collected cross-sectional survey data. Child development was assessed using the Integrated Management of Childhood Illness Guide-2011. The nutritional status was defined with WHO Child Growth Standards-2006. We investigated nutrient density, WHO Infant and Young Child Feeding Indicators, and nutrient supplementation intake of the complementary feeding. In all, 11.7% of children had "possible developmental delay," stunting was identified in 29.4% of the children, and 25.3% faced overnutrition (overweight risk/overweight/obesity). The complementary feeding composition can be summarized as having adequate fat, high energy (MJ/day) and protein, and low iron and zinc. Children with "possible developmental delay" received less iron (P < .05) than children with normal development. Overall, 30.4% of children had minimum dietary diversity. A total of 47.7% of children received nutrient supplementation. This epidemiological profile of infants remains a challenge for Ecuador's health programs.

Methylated flavonoids as anti-seizure agents: Naringenin 4',7-dimethyl ether attenuates epileptic seizures in zebrafish and mouse models.

Epilepsy is a neurological disease that affects more than 70 million people worldwide and is characterized by the presence of spontaneous unprovoked recurrent seizures. Existing anti-seizure drugs (ASDs) have side effects and fail to control seizures in 30% of patients due to drug resistance. Hence, safer and more efficacious drugs are sorely needed. Flavonoids are polyphenolic structures naturally present in most plants and consumed daily with no adverse effects reported. These structures have shown activity in several seizure and epilepsy animal models through allosteric modulation of GABAA receptors, but also via potent anti-inflammatory action in the brain. As such, dietary flavonoids offer an interesting source for ASD and anti-epileptogenic drug (AED) discovery, but their pharmaceutical potential is often hampered by metabolic instability and low oral bioavailability. It has been argued that their drug-likeness can be improved via methylation of the free hydroxyl groups, thereby dramatically enhancing metabolic stability and membrane transport, facilitating absorption and highly increasing bioavailability. Since no scientific data is available regarding the use of methylated flavonoids in the fight against epilepsy, we studied naringenin (NRG), kaempferol (KFL), and three methylated derivatives, i.e., naringenin 7-O-methyl ether (NRG-M), naringenin 4',7-dimethyl ether (NRG-DM), and kaempferide (4'-O-methyl kaempferol) (KFD) in the zebrafish pentylenetetrazole (PTZ) seizure model. We demonstrate that the methylated flavanones NRG-DM and NRG-M are highly effective against PTZ-induced seizures in larval zebrafish, whereas NRG and the flavonols KFL and KFD possess only a limited activity. Moreover, we show that NRG-DM is active in two standard acute mouse seizure models, i.e., the timed i.v. PTZ seizure model and the 6-Hz psychomotor seizure model. Based on these results, NRG-DM is proposed as a lead compound that is worth further investigation for the treatment of generalized seizures and drug-resistant focal seizures. Our data therefore highlights the potential of methylated flavonoids in the search for new and improved ASDs.

Insights from zebrafish and mouse models on the activity and safety of ar-turmerone as a potential drug candidate for the treatment of epilepsy.

In a previous study, we uncovered the anticonvulsant properties of turmeric oil and its sesquiterpenoids (ar-turmerone, α-, ß-turmerone and α-atlantone) in both zebrafish and mouse models of chemically-induced seizures using pentylenetetrazole (PTZ). In this follow-up study, we aimed at evaluating the anticonvulsant activity of ar-turmerone further. A more in-depth anticonvulsant evaluation of ar-turmerone was therefore carried out in the i.v. PTZ and 6-Hz mouse models. The potential toxic effects of ar-turmerone were evaluated using the beam walking test to assess mouse motor function and balance. In addition, determination of the concentration-time profile of ar-turmerone was carried out for a more extended evaluation of its bioavailability in the mouse brain. Ar-turmerone displayed anticonvulsant properties in both acute seizure models in mice and modulated the expression patterns of two seizure-related genes (c-fos and brain-derived neurotrophic factor [bdnf]) in zebrafish. Importantly, no effects on motor function and balance were observed in mice after treatment with ar-turmerone even after administering a dose 500-fold higher than the effective dose in the 6-Hz model. In addition, quantification of its concentration in mouse brains revealed rapid absorption after i.p. administration, capacity to cross the BBB and long-term brain residence. Hence, our results provide additional information on the anticonvulsant properties of ar-turmerone and support further evaluation towards elucidating its mechanism of action, bioavailability, toxicity and potential clinical application.

Tanshinone IIA exhibits anticonvulsant activity in zebrafish and mouse seizure models.

Danshen or Chinese red sage (Salvia miltiorrhiza, Bunge) is used by traditional Chinese medicine (TCM) practitioners to treat neurological, cardiovascular, and cerebrovascular disorders and is included in some TCM formulations to control epileptic seizures. In this study, acetonic crude extracts of danshen inhibited pentylenetetrazol (PTZ)-induced seizure activity in zebrafish larvae. Subsequent zebrafish bioassay-guided fractionation of the extract resulted in the isolation of four major tanshinones, which suppressed PTZ-induced activity to varying degrees. One of the active tanshinones, tanshinone IIA, also reduced c-fos expression in the brains of PTZ-exposed zebrafish larvae. In rodent seizure models, tanshinone IIA showed anticonvulsive activity in the mouse 6-Hz psychomotor seizure test in a biphasic manner and modified seizure thresholds in a complex manner for the mouse i.v. PTZ seizure assay. Interestingly, tanshinone IIA is used as a prescription drug in China to address cerebral ischemia in patients. Here, we provide the first in vivo evidence demonstrating that tanshinone IIA has anticonvulsant properties as well.

Anticonvulsant activity of bisabolene sesquiterpenoids of Curcuma longa in zebrafish and mouse seizure models.

Turmeric, obtained from the rhizomes of Curcuma longa, is used in South Asia as a traditional medicine for the treatment of epilepsy. To date, in vivo studies on the anticonvulsant activity of turmeric have focused on its principal curcuminoid, curcumin. However, poor absorption and rapid metabolism have limited the therapeutic application of curcumin in humans. To explore the therapeutic potential of turmeric for epilepsy further, we analyzed its anticonvulsant activity in a larval zebrafish seizure assay. Initial experiments revealed that the anticonvulsant activity of turmeric in zebrafish larvae cannot be explained solely by the effects of curcumin. Zebrafish bioassay-guided fractionation of turmeric identified bisabolene sesquiterpenoids as additional anticonvulsants that inhibit PTZ-induced seizures in both zebrafish and mice. Here, we present the first report of the anticonvulsant properties of bisabolene sesquiterpenoids and provide evidence which warrants further investigation toward the mechanistic understanding of their neuromodulatory activity.