Pharmacology Commons^™

Chemical Constituents From A Marine Medicinal Brown Alga-Derived Xylaria Acuta Sc1019, Hsiao-Yang Hsi, Shih-Wei Wang, George Hsiao, Li-Kwan Chang, Yuan-Chung Cheng, Shu-Jung Huang, Yi-Shan Lu, Tzong-Huei Lee

Journal of Food and Drug Analysis

In this study, a marine medicinal brown alga Sargassum cristaefolium-derived fungal strain Xylaria acuta SC1019 was isolated and identified. Column chromatography of the extracts from liquid- and solid-fermented products of the fungal strain was carried out, and led to the isolation of twenty-one compounds. Their structures were characterized by spectroscopic analysis, and the absolute configurations were further established by single X-ray diffraction analysis or modified Mosher’s method as nine previously undescribed compounds, namely xylarilactones A–C (1–3), ent-gedebic acid 8-O-α-D-glucopyranoside (4), 5R-hydroxylmethylmellein 11-O-α-D-glucopyranoside (5), ent …

The Role And Mechanism Of Cinnamaldehyde In Cancer, Jiahua Peng, Xin Song, Wenbin Yu, Yuhan Pan, Yufei Zhang, Hui Jian, Bin He

Journal of Food and Drug Analysis

As cancer continues to rise globally, there is growing interest in discovering novel methods for prevention and treatment. Due to the limitations of traditional cancer therapies, there has been a growing emphasis on investigating herbal remedies and exploring their potential synergistic effects when combined with chemotherapy drugs. Cinnamaldehyde, derived from cinnamon, has gained significant attention for its potential role in cancer prevention and treatment. Extensive research has demonstrated that cinnamaldehyde exhibits promising anticancer properties by modulating various cellular processes involved in tumor growth and progression. However, challenges and unanswered questions remain regarding the precise mechanisms for its effective use as …

Trends And Current Food Safety Regulations And Policies For Functional Foods And Beverages Containing Botanicals, Jarunee Intrasook, Takuji W. Tsusaka, Anil Kumar Anal

Journal of Food and Drug Analysis

Globally, the demand for functional foods and beverages has significantly increased due to socioeconomic changes, particularly in health consciousness to enhance their functionality. Functional ingredients derived from botanicals are widely used because of their phytochemical properties with health benefits. This study aims to (1) review the capabilities and challenges of botanical addition in functional foods, (2) review current policies and regulations for functional foods containing botanicals in the European Union (EU), Canada, Japan, the Republic of Korea, and Thailand, and (3) provide recommendations on effective food safety control measures for better consumer trust and trade facilitation. This critical review was …

Nanoparticles As Antioxidant Agents: A Comprehensive Review, Sulyman Olalekan Ibrahim, Halimat Yusuf Lukman, Fatimat Ronke Abdulkadir, Monsurat Yemisi Bello, Yusuf Oloruntoyin Ayipo, Halimah Funmilayo Babamale, Marili Funmilayo Zubair, Olubunmi Atolani

Al-Bahir

This study seeks to provide a comprehensive overview of the latest progress in the antioxidant properties of nanoparticles. Nanoparticles (NPs) have emerged as a promising tool in several domains of science and industry, including their application as antioxidant agents. The main knowledge gaps seem to be in correctly identifying the make-up of the naturally occurring phytochemicals that give these nano-antioxidants their extraordinary pharmacology and drug-like properties. In many instances, that characterization is done using spectroscopy instrumentation such as fourier-transform Infrared (FT-IR), scanning electron microscope (SEM), and X-ray diffraction analysis (XRD). From literature appraisals, it was discovered that a lot of …

A Drug's Life: The Untapped Potential Of Secondary Pharmacology Studies In Drug Development, Christina Scott

The University of New Hampshire Law Review

The United States Food and Drug Administration has evolved over the past century to regulate new medicine and protect the public from harmful or ineffective drugs. Drug development and testing science have advanced rapidly alongside the FDA’s increased regulation, enabling pharmaceutical companies to assess a drug's potential adverse reactions by studying its reactivity with various proteins called "off-target receptors." Off-target proteins are often screened and reported in the Investigational New Drug Application as a percentage indicating the drug's binding strength to each protein, which suggests the strength of a particular adverse drug effect. Adverse drug effects often lead to unfavorable …

The Multipurpose Dna Repair/Redox Protein Ape1 In Rodent And Human Lewy Body Disease, Kristin Marie Miner

Electronic Theses and Dissertations

Lewy body disorders are a family of neurodegenerative conditions characterized by proteostatic and redox disequilibrium, leading to deposition of the abundant protein α-synuclein in hallmark inclusions and oxidative damage to DNA. Sublethal oxidative DNA damage in neurons is repaired predominantly by the base excision repair pathway, which involves the coordinated activity of several enzymes, including apurinic/apyrimidinic endonuclease 1 (APE1). Despite emerging connections between α-synuclein, oxidative stress, and DNA damage/repair, along with evidence demonstrating the multifunctional nature of APE1, the link between APE1 and α-synuclein has not yet been explored.

Here, we conducted a broad investigation of APE1 in the context …

The Effect Of Novel Microtubule Modulators On Experimental Lewy Body Disease, Anuj S. Jamenis

Electronic Theses and Dissertations

In Lewy body disorders, α-synuclein aggregates are believed to destabilize the microtubular framework. However, microtubules are a challenging therapeutic target, as excessive rigidity or flexibility afforded by microtubule modulators may be neurotoxic. Thus, the objective of the present study was to evaluate dual-acting microtubule- stabilizing/destabilizing agents in cellular and animal models of early-stage Lewy body disease.

In Aim 1 we tested the dual-acting tricylic pyrimido[4,5-b]indole analogs AG161-47 and AG161-41 in an in vitro preformed fibril induced model of Lewy body disease. We found that both compounds reduced preformed fibril-seeded α-synucleinopathy without toxicity in primary hippocampal cultures. AG161-47 subtly impacted microtubule …

Assessment Of In-Vitro And In-Vivo Pre-Clinical Pharmacokinetics Of Epz015666; A Novel Small Molecule For Medulloblastoma Treatment, Pratiksha U. Kshirsagar

Theses & Dissertations

Group 3 medulloblastoma (MB) has the worst prognosis of the MB subgroups associated with elevated MYC expression and a 5-year survival rate of

Quantitation of EPZ was performed on a Shimadzu LC-MS/MS system utilizing electrospray ionization operated in positive mode. The validated assay was linear from 0.2 to 500 ng/mL. Metabolic stability studies demonstrated slow intrinsic clearance of EPZ in mouse and human liver microsomes, suggesting no CYP-mediated metabolism. Additionally, EPZ exhibited low binding affinity to plasma and brain proteins and high apparent permeability across artificial membranes, indicating efficient membrane penetration. Drug transporter studies identified EPZ as a substrate of …

An Ultra Long-Acting Bictegravir Prodrug Nanocrystal With A Shape-Shifting Pharmacokinetic Tail, Mohammad Ullah Nayan

Theses & Dissertations

While antiretroviral therapy (ART) has significantly reduced human immunodeficiency virus type one (HIV-1) co-morbidities and mortality, adherence to daily oral therapy remains a key barrier to all therapeutic and preventative outcomes. Over the past years, the emergence of long-acting (LA) ART has gained considerable enthusiasm amongst people living with HIV (PLWH) and could potentially simplify dosing regimens and improve treatment outcomes. LA ART could also improve drug adherence, reduce viral transmission, and limit viral drug resistance and systemic toxicities. In response to these needs, a combination of two LA injectable nanocrystalline drugs (CABENUVA) was recently approved for bimonthly administration in …

Haloperidol Paradoxical Behavior Induced Cell Proliferation Through Pkb/Akt And Abolished By Mir-Let-7c, Mounira Morgem

Dissertations (2016-Present)

Haloperidol is a typical antipsychotic drug; it is widely used for people with various psychiatric conditions such as schizophrenia, bipolar disorder, major depressive disorder, and dementia. Despite its effectiveness in controlling delusions, hallucinations, agitation, and other disruptive behavioral symptoms in these psychiatric conditions, it has adverse side effects such as extrapyramidal manifestation and endocrinologic and metabolic changes. Initial evidence shows that haloperidol has antitumor properties in several cancer types by inhibiting cell proliferation and inducing apoptosis. However, other reports indicate that haloperidol promotes cell proliferation in other cells, raising concerns about its association with an increased risk of cancer which …

The Role Of B Cell Activation State And Sex In Aryl Hydrocarbon Receptor Mediated Induction Of Chemokine Receptor 9 And Alpha4beta7 Expression In Vitro, Logan Bauerle

Master's Theses

Defense of mucosal tissues from microbial infection and allergy is reliant on continual production of antibodies. The aryl hydrocarbon receptor (AhR) is known to regulate B cell development and is associated with suppression of systemic humoral immunity. Recent attention has been paid to the role of the AhR in altering expression of cell adhesion molecules (CAMs). B cells express CAMs and chemokine receptors to migrate around the body for localized secretion of antibodies. AhR agonists promote B cell migration to the small intestine through upregulation of chemokine receptor 9 (CCR9) and integrin α₄β₇. Both the AhR …

Pipecolic Acid And Novel Insights Into Cerebral Malaria, Akua E. Mensah

Theses and Dissertations

Cerebral malaria (CM), a severe manifestation of Plasmodium infection, prompts our investigation into the nuanced role of pipecolic acid in its pathophysiology. To unravel the molecular intricacies, we conducted in vitro lysine labeling techniques of mice infected with P. berghei ANKA parasites, and human P. falciparum grown in vitro, aiming to discern the impact of Plasmodium on pipecolic acid production. Previous observations indicated an elevation in pipecolic acid levels correlating with neurological decline in children with CM. In our study, confirming elevated pipecolic acid presence in the plasma and brain tissues of CM patients and the animal model of CM, …

The Role Of Extracellular Vesicles And Their Cargo In Intercellular Communication, Chongyu Zhang

Dissertations

Extracellular vesicles (EVs) are membranous vesicles secreted by most cells. They contain lipids, proteins, and nucleic acids, including microRNAs (miRNA), and function in intercellular communication by endocytosis into other cells. EVs in diseased states carry miRNAs and proteins reflective of the changed state of cells and can be endocytosed into other cells to exert regulatory effects. Thus, EVs represent a form of paracrine genetic regulation in health and disease. Myocardial infarction (MI) and pulmonary embolism (PE) are leading causes of cardiovascular deaths worldwide. It is important to develop new diagnostic and therapeutic approaches that could lead to medical advances. Circulating …

Differential Behavioral Responses In Male And Female Mice Lacking Either Rgs2 Or Rgs4 Proteins After Acute Administration Of Antidepressants And Anxiolytics, Hiroyoshi Matsui, Sarah Seeley, Manoranjan S. D'Souza

ONU Student Research Colloquium

The overall objective of the study was to assess the acute behavioral effects of currently used antidepressants and anxiolytics in male and female mice lacking regulator of G protein-signaling (RGS) proteins 2 and 4 and their wild-type counterparts. RGS 2 and 4 proteins negatively modulate signaling pathways of G protein-coupled receptors (GPCRs), which play an important role in mediating the effects of monoamine neurotransmitters such as dopamine, norepinephrine, and serotonin. These neurotransmitters in turn play an important role in the action of antidepressant and anxiolytic medications. The study was undertaken because no studies till date have systematically assessed the behavioral …

Effects Of Kappa Opioid Receptor Manipulation On Methamphetamine-Induced Behavioral Sensitization In Adolescent Male And Female Rats, Hiroyoshi Matsui Mr, Sarah Seeley, Manoranjan S. D'Souza

ONU Student Research Colloquium

Methamphetamine abuse amongst adolescents has been on the rise in the United States. In this study, we assessed the effects of manipulation of KORs on methamphetamine-induced behavioral sensitization in adolescent male and female rats. Methamphetamine-induced behavioral sensitization is an animal model to study methamphetamine addiction. Behavioral sensitization usually occurs in animals who have been treated with methamphetamine followed by a period of withdrawal. It is hypothesized that brain circuits are altered during the period of withdrawal after methamphetamine exposure resulting in sensitized (increased) responses to methamphetamine at the end of the withdrawal period. The experiment was conducted over 28 days. …

The Effect Of The Glucocorticoid Receptor Modulator, Safit, On Acute Stress Reactivity In A Rat Model Of Abusive Head Trauma, Brielle Coe

Tower Health Research Day

No abstract provided.

In Silico Identification Of Small Molecule Agonist Binding Sites On Kcc2, Kenyon Mitchell, Alfred Amendolara, Ruth Hunter, Jaden Miner, Andrew Payne

Annual Research Symposium

Purpose: Potassium-Chloride Cotransporter 2 (KCC2) is a neuronal membrane protein specific to the central nervous system. It is responsible for removing Cl- ions from the intracellular space, maintaining a normal Cl- gradient essential for proper function at inhibitory synapses. Dysregulation causes an upward shift in the Cl- reversal potential resulting in a hyperexcitable state of the postsynaptic neuron. Existing literature indicates that KCC2 may be involved in the addiction pathway of a variety of drugs of abuse, including opioids and alcohol. This makes KCC2 an attractive potential drug target when treating substance use disorders. A novel direct KCC2 agonist, VU0500469, …

Safety Of Potentised Dilutions Of Rhus Toxicodendron In Wistar Albino Rats, Abanti Goswami, Narasimha Kumar Gv, Vara Prasad Saka, Pankaj Gupta, Bibaswan Biswas, Digvijay Verma

Indian Journal of Research in Homoeopathy

Background: Rhus toxicodendron (Rhus tox.) is a well-known homoeopathic medicine used to treat inflammatory disorders supported by historical and modern scientific evidence. Objective: The safety testing of 6C, 30C and 200C potencies of Rhus tox. through acute and sub-acute oral toxicity tests as per the Organisation for Economic Cooperation and Development test guidelines. Methods: For the acute oral toxicity study, Rhus tox. (2000 μL/kg) was administered to rats and observed for 14 days. For the subacute oral toxicity study, Rhus tox. (200 μL/kg) was administered for 28 days and additional recovery groups were included to monitor reversibility, persistence, or delayed …

Pediatric Beta Blocker Therapy: A Comprehensive Review Of Development And Genetic Variation To Guide Precision-Based Therapy In Children, Adolescents, And Young Adults., Mollie Walton, Jonathan B. Wagner

Manuscripts, Articles, Book Chapters and Other Papers

Beta adrenergic receptor antagonists, known as beta blockers, are one of the most prescribed medications in both pediatric and adult cardiology. Unfortunately, most of these agents utilized in the pediatric clinical setting are prescribed off-label. Despite regulatory efforts aimed at increasing pediatric drug labeling, a majority of pediatric cardiovascular drug agents continue to lack pediatric-specific data to inform precision dosing for children, adolescents, and young adults. Adding to this complexity is the contribution of development (ontogeny) and genetic variation towards the variability in drug disposition and response. In the absence of current prospective trials, the purpose of this comprehensive review …

An Acute Herb-Drug Interaction Of Magnoliae Officinalis Cortex With Methotrexate Via Inhibiting Multidrug Resistance-Associated Protein 2, Chung-Ping Yu, Pei-Ying Li, Szu-Yu Chen, Shiuan-Pey Lin, Ying-Chen Chen, Lu-Ching Ho, Yow-Wen Hsieh, Yu-Chi Hou

Journal of Food and Drug Analysis

Magnoliae Officinalis Cortex (MOC), an herbal drug, contains polyphenolic lignans mainly magnolol (MN) and honokiol (HK). Methotrexate (MTX), a critical drug for cancers and autoimmune deseases, is a substrate of multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP). This study investigated the effect of coadministration of MOC on the pharmacokinetics of MTX and relevant mechanisms. Sprague-Dawley rats were orally administered MTX alone and with single dose (2.0 and 4.0 g/kg) and repeated seven doses of MOC (2.0 g/kg thrice daily for 2 days, the 7th dose given at 0.5 h before MTX). The serum concentrations of MTX …