Evaluation of bioaccessibility, metabolic clearance and interaction with xenobiotic receptors (PXR and AhR) of cinnamaldehyde.

Cinnamon is one of the oldest known spices used in various food delicacies and herbal formulations. Cinnamaldehyde is a primary active constituent of cinnamon and substantially contributes to the food additive and medicinal properties of cinnamon. This report deals with cinnamaldehyde bioaccessibility, metabolic clearance, and interaction with human xenobiotic receptors (PXR and AhR).

A Combined Approach for Rapid Dereplication of Herb-Drug Interaction Causative Agents in Botanical Extracts-A Molecular Networking Strategy To Identify Potential Pregnane X Receptor (PXR) Modulators in Yohimbe.

Despite promising preliminary biology, natural products isolation efforts may be confounded when the active compound is not isolated during bioassay-guided purification or classical pharmacognostic research investigations. A more rational isolation procedure connecting the polypharmacology of an herb to its individual constituents must be applied to better detect bioactive molecules before tedious analytical steps are considered. While (yohimbe) has been traditionally used in herbal medicine as a general tonic, an aphrodisiac, a performance enhancer, and an integral part of various dietary supplements, the hydroethanolic extract of yohimbe was identified to possess at least 3-4-fold induction of the pregnane X receptor (PXR) at 30 μg/mL, a key nuclear receptor implicated in adverse interactions, .

Interaction of Phyllanthus amarus extract and its lignans with human xenobiotic receptors, drug metabolizing enzymes and drug transporters.

Ethnopharmacological Relevance: Phyllanthus amarus is ethnomedicinally used to treat gallbladder stones, kidney stones and chronic liver diseases. P. amarus is gaining popularity as an ingredient in many botanical dietary supplements.

Developing a Screening Strategy to Identify Hepatotoxicity and Drug Interaction Potential of Botanicals.

Botanical supplements, herbal remedies, and plant-derived products are used globally. However, botanical dietary supplements are rarely subjected to robust safety testing unless there are adverse reports in post-market surveillance. Botanicals are complex and difficult to assess using current frameworks designed for single constituent substances (e.

The National Center for Natural Products Research (NCNPR) at 30: A Legacy of Pioneering Research in Natural Products and Dietary Supplements.

Since its establishment in 1994, the National Center for Natural Products Research (NCNPR) at the University of Mississippi has made notable contributions to the field of natural product research, coinciding with the passage of the Dietary Supplement Health and Education Act. Over the past three decades, the Center has focused on studying plants, herbs, and other natural materials for applications in medicine, agriculture, and nutraceuticals, particularly in the area of botanical dietary supplements. NCNPR scientists have been actively engaged in developing and improving quality control measures to help ensure the safety of dietary supplements in response to a growing market.

Human quad liver-on-chip system as a tool toward bridging the gap between animals and humans regarding toxicology and pharmacology of a cannabidiol-rich cannabis extract.

Cannabidiol (CBD) is a major phytocannabinoid from . It is currently widely available and widely used in the USA, but despite its rapid progress to market, the pharmacology and toxicology of both CBD and cannabidiol-rich cannabis extracts (CRCE) remain largely unknown. The goals of this study were to investigate the potential of a novel human microphysiological system to emulate CRCE-induced hepatotoxicity and pharmacological properties demonstrated in animal models.

Inter-strain variability in responses to a single administration of the cannabidiol-rich cannabis extract in mice.

Cannabidiol (CBD) has gained widespread popularity; however, its pharmacological and toxicological profiles in the context of human genetic diversity remain largely unexplored. Here, we investigated the variability in metabolism and toxicity of CBD-rich cannabis extract (CRCE) in genetically diverse mouse models: C57BL/6J, B6C3F/J, and NZO/HlLtJ strains. Mice received a single dose of CRCE containing 57.

Clinically Relevant Herb-Drug Interactions: A 30-Year Historical Assessment.

The Dietary Supplement Health and Education Act, a legislative measure ushering in a novel class of complementary healthcare products known as dietary supplements, will mark its 30th anniversary in October 2024. Over this 30-year period, dietary supplement usage evolved from a few hundred products made up mostly of vitamins, minerals, and select botanical extracts to more than 75,000 single- and multi-ingredient products that are now regular staples in the American healthcare system and used by half of all U.S.

Development of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for characterizing pomegranate extract pharmacokinetics in humans.

Pomegranate extracts standardized to punicalagins are a rich source of ellagitannins including ellagic acid (EA). Recent evidence suggests that gut microbiota-derived urolithin (Uro) metabolites of ellagitannins are pharmacologically active. Studies have evaluated the pharmacokinetics of EA, however, little is known about the disposition of urolithin metabolites (urolithin A (UA) and B (UB)).

Evaluation of the Herb-Drug Interaction (HDI) Potential of and Its Major Phytoconstituents.

Ginger is currently one of the most popular herbs commonly added to diverse foods, beverages, and dietary supplements. We evaluated the ability of a well-characterized ginger extract, and several of its phytoconstituents, to activate select nuclear receptors as well as modulate the activity of various cytochrome P450s and ATP-binding cassette (ABC) transporters because phytochemical-mediated modulation of these proteins underlies many clinically relevant herb-drug interactions (HDI). Our results revealed ginger extract activated the aryl hydrocarbon receptor (AhR) in AhR-reporter cells and pregnane X receptor (PXR) in intestinal and hepatic cells.

Screening of medicinal plants for possible herb-drug interactions through modulating nuclear receptors, drug-metabolizing enzymes and transporters.

Ethnopharmacological Relevance: The last three decades have witnessed a surge in popularity and consumption of herbal products. An unintended consequence of such popularity is that chronic consumption of these products can often modulate the functions of various proteins involved in drug disposition and may, in turn, impose risks for herb-drug interactions (HDIs), leading to serious adverse health outcomes. Identifying plants that may give rise to clinically relevant HDIs is essential, and proactive dissemination of such research outcomes is necessary for researchers, clinicians, and average consumers.

Hepatotoxicity due to herbal dietary supplements: Past, present and the future.

Dietary supplements (DS) constitute a widely used group of products comprising vitamin, mineral, and botanical extract formulations. DS of botanical or herbal origins (HDS) comprise nearly 30% of all DS and are presented on the market either as single plant extracts or multi-extract-containing products. Despite generally safe toxicological profiles of most products currently present on the market, rising cases of liver injury caused by HDS - mostly by multi-ingredient and adulterated products - are of particular concern.

Evaluation of the Herb-Drug Interaction Potential of Commonly Used Botanicals on the US Market with Regard to PXR- and AhR-Mediated Influences on CYP3A4 and CYP1A2.

In this study, hydroethanolic extracts of 30 top-selling botanicals (herbs) commonly used as ingredients of herbal dietary supplements in the US were screened for their potential to activate the human pregnane X receptor (hPXR) and human aryl hydrocarbon receptor (hAhR) and to increase the activities of hPXR- and hAhR-regulated drug metabolizing cytochrome P450 enzymes (i.e., CYP3A4 and CYP1A2, respectively).

Safety and Pharmacokinetics of Intranasally Administered Heparin.

Purpose: Intranasally administered unfractionated heparin (UFH) and other sulfated polysaccharides are potential prophylactics for COVID-19. The purpose of this research was to measure the safety and pharmacokinetics of clearance of intranasally administered UFH solution from the nasal cavity.

Methods: Double-blinded daily intranasal dosing in C57Bl6 mice with four doses (60 ng to 60 μg) of UFH was carried out for fourteen consecutive days, with both blood coagulation measurements and subject adverse event monitoring.

Safety and Pharmacokinetics of Intranasally Administered Heparin.

Purpose: Intranasally administered unfractionated heparin (UFH) and other sulfated polysaccharides are potential prophylactics for COVID-19. The purpose of this research was to measure the safety and pharmacokinetics of clearance of intranasally administered UFH solution from the nasal cavity.

Methods: Double-blinded daily intranasal dosing in C57Bl6 mice with four doses (60 ng to 60 μg) of UFH was carried out for fourteen consecutive days, with both blood coagulation measurements and subject adverse event monitoring.

Designing a Clinical Study With Dietary Supplements: It's All in the Details.

A successful randomized clinical trial of the effect of dietary supplements on a chosen endpoint begins with developing supporting data in preclinical studies while paying attention to easily overlooked details when planning the related clinical trial. In this perspective, we draw on our experience studying the effect of an ethanolic extract from L. (termed PMI-5011) on glucose homeostasis as a potential therapeutic option in providing resilience to metabolic syndrome (MetS).

Analytical Challenges and Metrological Approaches to Ensuring Dietary Supplement Quality: International Perspectives.

The increased utilization of metrology resources and expanded application of its' approaches in the development of internationally agreed upon measurements can lay the basis for regulatory harmonization, support reproducible research, and advance scientific understanding, especially of dietary supplements and herbal medicines. Yet, metrology is often underappreciated and underutilized in dealing with the many challenges presented by these chemically complex preparations. This article discusses the utility of applying rigorous analytical techniques and adopting metrological principles more widely in studying dietary supplement products and ingredients, particularly medicinal plants and other botanicals.

Bulbine natalensis (currently Bulbine latifolia) and select bulbine knipholones modulate the activity of AhR, CYP1A2, CYP2B6, and P-gp.

an emerging medicinal herb on the global market with androgenic properties, is often formulated in dietary supplements that promote perceived sexual enhancement. However, to date, comprehensive safety studies of are lacking, particularly those related to its herb-drug interaction potential. The purpose of this study was to assess the inductive and inhibitory effects of extracts and pure compounds of on human cytochrome P-450 isozymes .

Modulation of CYP3A4 and CYP2C9 activity by Bulbine natalensis and its constituents: An assessment of HDI risk of B. natalensis containing supplements.

Background: Bulbine natalensis is an African-folk medicinal plant used as a dietary supplement for enhancing sexual function and muscle strength in males by presumably boosting testosterone levels, but no scientific information is available about the possible herb-drug interaction (HDI) risk when bulbine-containing supplements are concomitantly taken with prescription drugs.

Purpose: This study was aimed to investigate the HDI potential of B. natalensis in terms of the pregnane X receptor (PXR)-mediated induction of major drug-metabolizing cytochrome P450 enzyme isoforms (i.

Safety and Molecular-Toxicological Implications of Cannabidiol-Rich Cannabis Extract and Methylsulfonylmethane Co-Administration.

Cannabidiol (CBD) is a biologically active, non-psychotropic component of whose popularity has grown exponentially in recent years. Besides a wealth of potential health benefits, ingestion of CBD poses risks for a number of side effects, of which hepatotoxicity and CBD/herb-drug interactions are of particular concern. Here, we investigated the interaction potential between the cannabidiol-rich cannabis extract (CRCE) and methylsulfonylmethane (MSM), a popular dietary supplement, in the mouse model.

Medical Foods-A Closer Look at the Menu: A Brief Review and Commentary.

The notion of a medical food-a foodstuff that, by definition, must be obtained and used while under medical supervision, and regulated by the US Food and Drug Administration, is a source of considerable confusion to the lay public as well as many-if not most-in the health professions community. Such restrictions are more often associated with pharmaceutical agents or medical devices. Additionally, specific regulatory aspects of medical foods are overseen by the US Food and Drug Administration, and these specifics appear to overlap with other foods and dietary supplements in terms of requirements and allowances.

Cannabidiol (CBD) in Dietary Supplements: Perspectives on Science, Safety, and Potential Regulatory Approaches.

The proliferation in the last few years of cannabidiol (CBD)-containing products in the U.S. markets has been greatly accelerated by changes in the regulatory environment, and by perceptions of their health benefits and presumed safety.

Content versus Label Claims in Cannabidiol (CBD)-Containing Products Obtained from Commercial Outlets in the State of Mississippi.

Products containing cannabidiol (CBD) are now available throughout the United States, but their quality is oftentimes questionable. The CBD and Δ-tetrahydrocannabinol (THC) content of 25 commercially available hemp oil products, obtained throughout the state of Mississippi, was determined gas chromatography/flame ionization detection (GC/FID). These products were also analyzed for the presence of synthetic cannabinoids using full scan gas chromatography/mass spectrometry (GC/MS).

Potential Probiotic or Trigger of Gut Inflammation - The Janus-Faced Nature of Cannabidiol-Rich Cannabis Extract.

Cannabidiol (CBD) is the major non-psychotropic phytocannabinoid present in . In 2018, Congress designated certain plant material as "hemp," thus removing it from the DEA's list of controlled substances. As a result, CBD-containing hemp extracts and other CBD products are now widely available and heavily marketed, yet their FDA regulatory status is still hotly debated.