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Garcinia indica (Kokum) and Ilex aquifolium (European Holly)
Published in Azamal Husen, Herbs, Shrubs, and Trees of Potential Medicinal Benefits, 2022
Dicson Sheeja Malar, Mani Iyer Prasanth, Tewin Tencomnao, James Michael Brimson, Anchalee Prasansuklab
Connectivity map approach indicates that UA exhibit inhibitory effect against breast cancer cells by modulating some of the key pathways including PLK1, IKK/NF-κB, and RAF/ERK pathways (Guo et al., 2020). In addition, downregulation of Nrf-2, PI3K/AKT, JNK pathway were also reported (Zhang et al., 2020; Luo et al., 2017; Yeh et al., 2010). UA sensitized the triple negative breast cancer cells to doxorubicin and enhances apoptosis by targeting ZEB1-AS1/miR-186-5p/ABCC1 axis (Lu et al., 2021). ATP-binding cassette transporter C (ABCC1) are transporters that mediates the efflux of drugs from cancer cells, preventing their accumulation and causing chemoresistance. UA inhibits the growth of breast cancer stem-like cells by attenuating sFRP4 mediated Wnt/β-catenin pathway and suppressing miRNA-499a-5p involved in invasion and metastasis (Mandal et al., 2021).
The Role of Platelet-Activating Factor in Endotoxin-Related Disease
Published in Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison, Endotoxin in Health and Disease, 2020
Taco W. Kuijpers, Tom van der Poll
A convincing mechanistic view explaining these phenomena concerning releasability is not available. The multidrug resistance-associated protein (MRP), a 190 kDa product of an ATP-binding cassette transporter gene, has most recently been suggested to have a role in the release of leukotrienes from cells. The endogenous glutathione conjugate of LTC4 had the highest affinity for this transporter. A series of experiments (e.g., photoaffinity labeling and transfection studies) provided evidence that the MRP gene genuinely encodes an ATP-dependent export pump for conjugates of lipophilic compounds with glutathione and several other anionic residues (15). Whether similar “export pumps” are involved in PAF release remains to be clarified.
Niemann-Pick type C disease/cholesterol-processing abnormality
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
The adenosine triphosphatase (ATP)-binding cassette transporter A1 (ABACA1) is also upregulated in response to increased cellular cholesterol, leading to high-density lipoprotein (HDL) particle formation. Mutations in this ABACA1 lead to increased intracellular cholesterol and very low levels of HDL in Tangier disease [90]. Mutations in NPC1 appear to impair also the regulation and activity of ABACA1 [91]. Fibroblasts from patients with NPC disease were shown to have decreased efflux of labeled LDL-cholesterol mediated by apolipoprotein A-I. These fibroblasts also displayed diminished ABCA1 mRNA and protein in both basal and cholesterol stimulated states. Furthermore, 17 of 21 patients studied had low levels of HDL-cholesterol. This observation can provide another diagnostic aid in evaluating children for NPC disease.
Amelioration of Cholesterol Rich diet-induced Impaired Cognition in AD Transgenic Mice by an LXR Agonist TO901317 Is Associated with the Activation of the LXR-β-RXR-α-ABCA1 Transmembrane Transport System and Improving the Composition of Lipid Raft
Published in Experimental Aging Research, 2023
Yang Na, Lin Ke, Zhang Jie, Wang Jinping, Meng Tao, Zhu Jie, Yang Liu, Zhou Yueqin
The brain has a large of cholesterol, its content accounts for 25% of total cholesterol in the human body. Cholesterol cannot be degraded by itself. Excessive cholesterol in the brain is mainly discharged from neurons through ATP-binding cassette transporter transmembrane transport system. In the process of cholesterol transporting, firstly, liver X receptor (LXR) and retinoic X receptor (RXR) bind with each other to form a heterodimer, and then bind to LXRES (LXR reaction element) in the enhancer region of the target gene, so as to regulate the expression of ATP-binding cassette transporter A1 (ABCA1), and promote the efflux of cholesterol, and then reduce the concentration of cholesterol intracellular. A large number of reports have shown that ABCA1 transmembrane cholesterol transport system plays an important role in the precipitation and clearance of Aβ for AD, which provides a new target for drug development and prevention of AD (Tapan et al., 2021) (Sup 1).
An overview of statin-induced myopathy and perspectives for the future
Published in Expert Opinion on Drug Safety, 2020
Dragana Nikolic, Maciej Banach, Roberta Chianetta, Luca Marco Luzzu, Anca Pantea Stoian, Camelia Cristina Diaconu, Roberto Citarrella, Giuseppe Montalto, Manfredi Rizzo
As discussed above, SAMS represents a broad spectrum of disorders from insignificant myalgia to fatal rhabdomyolysis with the frequency ranging from 3–5% in clinical trials to 15–29% in daily clinical practice. However, such large variations can be explained by the definition used. Thus, some authors proposed a scoring system to classify SAMS according to clinical and biochemical criteria [111]. The etiology remains still poorly understood, and most probably, an underlying genetic cause is necessary for overt SAMS. Variants in gene groups that encode proteins involved in i) statin metabolism and distribution (membrane transporters and enzymes; OATP1B1, ATP-binding cassette transporter (ABCA1), multidrug resistance protein (MRP), CYP3A4), ii) CoQ10 production (CoQ10A and B), iii) energy metabolism of muscle tissue (glycogen phosphorylase, muscle associated (PYGM), glucosidase alpha, acid (GAA), carnitine palmitoyltransferase 2 (CPT2)) have been proposed as candidates who can predispose to SAMS. On the other hand, pharmacological properties of the statin molecules (lipophilicity, excretion pathways) and patients’ characteristics influence the likelihood of SAMS development [111]. All these statements are widely revised in the literature and were summarized above.
Surface engineered liposomal delivery of therapeutics across the blood brain barrier: recent advances, challenges and opportunities
Published in Expert Opinion on Drug Delivery, 2019
Saikat Ghosh, Rohan Lalani, Vivek Patel, Subhas Bhowmick, Ambikanandan Misra
The trafficking at molecular and cellular level between systemic circulation and CNS is regulated by BBB serving as an active and dynamic edge. The nervous system and immune system disorders invite functional loss of BBB which is reflected in their pathologies described in Table 2 [187]. In vitro models are very important tool to assess permeation across BBB for CNS therapeutics [188]. In vivo models are accurate and most relevant however they require complex screening procedures with a high cost. In vitro models are developed with an aim to mimic the in vivo physiology. However, there is no model till date which mimics the architecture and functionality of BBB. Validation markers are useful tools to assess in vitro models. The functional tightness of cellular junction is the most important parameter. The permeability markers (sucrose, mannitol, Lucifer yellow) and trans-endothelial electrical resistance are the key measurement of functional tightness. The tight junction proteins like Occludin, Claudin, ZO-I expression also help to estimate the models’ utility. Transferrin receptors are abundantly found in brain endothelial cells therefore their expression is considered as validation marker [189,190]. Moreover, the transporters like ATP binding cassette transporter (ABC) are involved in entry and exit of endogenous as well as exogenous substances therefore. Efflux ratio more than 2 and less than 0.5 indicates efflux and uptake, respectively [189,191].