Animal Cell Membranes Research Articles

TRPV4-A Multifunctional Cellular Sensor Protein with Therapeutic Potential.

Transient receptor potential vanilloid (TRPV) channel proteins belong to the superfamily of TRP proteins that form cationic channels in the animal cell membranes. These proteins have various subtype-specific functions, serving, for example, as sensors for pain, pressure, pH, and mechanical extracellular stimuli. The sensing of extracellular cues by TRPV4 triggers Ca2+-influx through the channel, subsequently coordinating numerous intracellular signaling cascades in a spatio-temporal manner. As TRPV channels play such a wide role in various cellular and physiological functions, loss or impaired TRPV protein activity naturally contributes to many pathophysiological processes. This review concentrates on the known functions of TRPV4 sensor proteins and their potential as a therapeutic target.

A PDZ-kinase allosteric relay mediates Par complex regulator exchange.

The Par complex polarizes the plasma membrane of diverse animal cells using the catalytic activity of atypical Protein Kinase C (aPKC) to pattern substrates. Two upstream regulators of the Par complex, Cdc42 and Par-3, bind separately to the complex to influence its activity in different ways. Each regulator binds a distinct member of the complex, Cdc42 to Par-6 and Par-3 to aPKC, making it unclear how they influence one another's binding. Here we report the discovery that Par-3 binding to aPKC is regulated by aPKC autoinhibition and link this regulation to Cdc42 and Par-3 exchange. The Par-6 PDZ domain activates aPKC binding to Par-3 via a novel interaction with the aPKC kinase domain. Cdc42 and Par-3 have opposite effects on the Par-6 PDZ-aPKC kinase interaction: while the Par-6 kinase domain interaction competes with Cdc42 binding to the complex, Par-3 binding is enhanced by the interaction. The differential effect of Par-3 and Cdc42 on the Par-6 PDZ interaction with the aPKC kinase domain forms an allosteric relay that connects their binding sites and is responsible for the negative cooperativity that underlies Par complex polarization and activity.

Unexpected asymmetric distribution of cholesterol and phospholipids in equilibrium model membranes

Lipid compositional asymmetry across the leaflets of the plasma membrane is a ubiquitous feature in eukaryotic cells. How this asymmetry is maintained is thought to be primarily controlled by active transport of lipids between leaflets. This strategy is facilitated by the fact that long tail phospholipids and sphingolipids diffuse through the lipid bilayer slowly – taking many hours or days. However, a lipid like cholesterol – which is the most abundant lipid in the plasma membrane of animal cells – has been harder to pin-point in terms of its favored side. In the present work we show that when a saturated lipid is added to a mix of the unsaturated lipid palmitoyl-oleoyl-phosphatidylcholine (POPC) and cholesterol, both cholesterol and the long tail phospholipids organize asymmetrically across the membrane’s leaflets naturally. In these extruded unilamellar vesicles, most cholesterol as well as the saturated lipid – dipalmitoylphosphatidylcholine (DPPC) or sphingomyelin (SM) – segregated to the inner leaflet while POPC preferentially localized in the outer leaflet. This asymmetric arrangement generated a slight phospholipid number imbalance favoring the outer leaflet and thus opposite to where cholesterol and the saturated lipids preferentially partitioned. These results were obtained using Magic Angle Spinning (MAS) NMR in combination with Small Angle Neutron Scattering (SANS) using isotope labeling to differentiate lipid species. We suggest that sidedness in membranes can be driven by thermodynamic processes. In addition, our MAS NMR results show that the lower bound for cholesterol’s flip-flop half-time at 45°C is 10ms, which is at least two orders of magnitude slower than current MD simulations predict. This result stands in stark contrast to previous work that suggested that cholesterol’s flip-flop half-time at 37°C has an upper bound of 10ms.

Side-chain-engineered fluorescent dyes for 3D and long-term dynamic tracking of the plasma membrane in living cells

The plasma membrane involves in many important biological events such as cell fusion and programmed cell death, but most of current plasma membrane probes cannot meet the requirement of long-term specific anchoring to the plasma membrane. Herein, we propose a molecular side-chain engineering strategy to modulate the long-term imaging performance of fluorescent dyes to the plasma membrane by regulating the cell permeability and anchoring ability. A series of FMR dyes with different lengths of side chains were designed and synthesized, and their transmembrane behaviours and staining performance were evaluated in living HeLa cells. We found that short-chain and medium-chain FMR dyes have excellent cell permeability without the labeling ability to the plasma membrane while the long-chain FMR dyes specifically stain the plasma membrane and can be firmly anchored to the plasma membrane for a long period of time. These long-chain FMR dyes have high stain specificality to the plasma membrane, and C10-FMR can be anchored to the plasma membrane of living cells for 2 h, which enables it to continuously monitor dynamic changes of the plasma membrane. The three-dimensional precision imaging of various cells was achieved using C10-FMR, which provides an opportunity to obtain complete information on the three-dimensional spatial morphology of the plasma membrane. The PEG-induced cell fusion of chicken red blood cells and H2O2-induced apoptosis of HeLa cells were monitored by real-time tracking of dynamic changes of the plasma membrane during these processes, which provide solid examples to prove the usefulness of these fluorescent dyes as long-term imaging tools. This work validates the hypothesis that cell permeability of membrane dyes can be readily regulated by tuning the side chains, and provides the effective design strategy of fluorescent dyes for 3D and long-term dynamic tracking of the plasma membrane of diverse animal cells.

HepG2 cells undergo regulatory volume decrease by mechanically induced efflux of water and solutes.

This study challenges the conventional belief that animal cell membranes lack a significant hydrostatic gradient, particularly under anisotonic conditions, as demonstrated in the human hepatoma cell line HepG2. The Boyle van't Hoff (BvH) relation describes volumetric equilibration to anisotonic conditions for many cells. However, the BvH relation is simple and does not include many cellular components such as the cytoskeleton and actin cortex, mechanosensitive channels, and ion pumps. Here we present alternative models that account for mechanical resistance to volumetric expansion, solute leakage, and active ion pumping. We found the BvH relation works well to describe hypertonic volume equilibration but not hypotonic volume equilibration. After anisotonic exposure and return isotonic conditions cell volumes were smaller than their initial isotonic volume, indicating solutes had leaked out of the cell during swelling. Finally, we observed HepG2 cells undergo regulatory volume decrease at both 20°C and 4°C, indicating regulatory volume decrease to be a relatively passive phenomenon and not driven by ion pumps. We determined the turgor-leak model, which accounts for mechanical resistance and solute leakage, best fits the observations found in the suite of experiments performed, while other models were rejected.

Impact of cholesterol on the structure and phase separation of DPPC Langmuir monolayers: Experiments and simulations

Cholesterol is a lipid that plays a key role mainly in the plasma membrane of animal cells, determining their structural and mechanical properties. While Langmuir monolayers have been a traditional model for studying these membranes, they may not fully capture microscopic phenomena. We studied mixed Langmuir monolayers of DPPC and cholesterol in various proportions, using a Langmuir trough for surface compression isotherms and micro-Brewster Angle Microscopy (MicroBAM) for imaging. Furthermore, atomistic Molecular Dynamics (MD) simulations were used to examine molecular distributions, geometric conformations, and emergence of a gas phase in the monolayers. Both experimental and simulation results were compared to obtain a comprehensive understanding. The results reveal strong attraction between DPPC tails and cholesterol, increasing monolayer stiffness and density. These interactions align the lipid tails more perpendicularly to the water surface, effectively minimizing their projected area and preventing tail entanglement. Consequently, the reduced flexibility triggers a phase separation in the monolayer at smaller areas per lipid, with low-density voids and denser regions, as observed in both MicroBAM and simulations. These outcomes emphasize the critical role of cholesterol in biological membranes. Finally, the consistency of MD simulations with experiments validate them as a valuable tool for investigating lipid monolayer behavior.

Melatonin Mitigates Lead-Induced Oxidative Stress and Modifies Phospholipid Profile in Tobacco BY-2 Suspension Cells.

Many studies have shown that melatonin (an indoleamine) is an important molecule in plant physiology. It is known that this indoleamine is crucial during plant stress responses, especially by counteracting secondary oxidative stress (efficient direct and indirect antioxidant) and switching on different defense plant strategies. In this report, we present exogenous melatonin's potential to protect lipid profile modification and membrane integrity in Nicotiana tabacum L. line Bright Yellow 2 (BY-2) cell culture exposed to lead. There are some reports of the positive effect of melatonin on animal cell membranes; ours is the first to report changes in the lipid profile in plant cells. The experiments were performed in the following variants: LS: cells cultured on unmodified LS medium-control; (ii) MEL: BY-2 cells cultured on LS medium with melatonin added from the beginning of culture; (iii) Pb: BY-2 cells cultured on LS medium with Pb2+ added on the 4th day of culture; (iv) MEL+Pb: BY-2 cells cultured on LS medium with melatonin added from the start of culture and stressed with Pb2+ added on the 4th day of culture. Lipidomic analysis of BY-2 cells revealed the presence of 40 different phospholipids. Exposing cells to lead led to the overproduction of ROS, altered fatty acid composition and increased PLD activity and subsequently elevated the level of phosphatidic acid at the cost of dropping the phosphatidylcholine. In the presence of lead, double-bond index elevation, mainly by higher quantities of linoleic (C18:2) and linolenic (C18:3) acids in the log phase of growth, was observed. In contrast, cells exposed to heavy metal but primed with melatonin showed more similarities with the control. Surprisingly, the overproduction of ROS caused of lipid peroxidation only in the stationary phase of growth, although considerable changes in lipid profiles were observed in the log phase of growth-just 4 h after lead administration. Our results indicate that the pretreatment of BY-2 with exogenous melatonin protected tobacco cells against membrane dysfunctions caused by oxidative stress (lipid oxidation), but also findings on a molecular level suggest the possible role of this indoleamine in the safeguarding of the membrane lipid composition that limited lead-provoked cell death. The presented research indicates a new mechanism of the defense strategy of plant cells generated by melatonin.

The Effects of the Magnetic Drinking Water in Poultry: a Review

Good water quality and cleanliness increase water intake. This could lead to improved performance and reduce health problems of the flock in livestock. It does not require extra energy consumption and easy installation when a permanent magnet is used. Exposure of the water to a magnetic field changes the water’s properties including raising pH, and dissolved oxygen, and the number of water molecules decreases to a smaller cluster leading to better absorption of water into the animal cell membranes. There are many results in poultry field that magnetized drinking water increases water consumption and feed intake, body weight gain, feed conversion ratio and meat quality of broilers, also it enhances egg production traits for laying hens. In addition, it improves hatchability, bioavailability, immunity and decreases mortality. This review aims to explain the existing literature on the influence the application of magnetic drinking water on the performance and health parameters of poultry.

Anticancer activity and other biomedical properties of β-sitosterol: Bridging phytochemistry and current pharmacological evidence for future translational approaches.

Sterols, including β-sitosterol, are essential components of cellular membranes in both plant and animal cells. Despite being a major phytosterol in various plant materials, comprehensive scientific knowledge regarding the properties of β-sitosterol and its potential applications is essential for scholarly pursuits and utilization purposes. β-sitosterol shares similar chemical characteristics with cholesterol and exhibits several pharmacological activities without major toxicity. This study aims to bridge the gap between phytochemistry and current pharmacological evidence of β-sitosterol, focusing on its anticancer activity and other biomedical properties. The goal is to provide a comprehensive understanding of β-sitosterol's potential for future translational approaches. A thorough examination of the literature was conducted to gather relevant information on the biological properties of β-sitosterol, particularly its anticancer therapeutic potential. Various databases were searched, including PubMed/MedLine, Scopus, Google Scholar, and Web of Science using appropriate keywords. Studies investigating the effects of β-sitosterol on different types of cancer were analyzed, focusing on mechanisms of action, pharmacological screening, and chemosensitizing properties. Modern pharmacological screening studies have revealed the potential anticancer therapeutic properties of β-sitosterol against various types of cancer, including leukemia, lung, stomach, breast, colon, ovarian, and prostate cancer. β-sitosterol has demonstrated chemosensitizing effects on cancer cells, interfering with multiple cell signaling pathways involved in proliferation, cell cycle arrest, apoptosis, survival, metastasis invasion, angiogenesis, and inflammation. Structural derivatives of β-sitosterol have also shown anti-cancer effects. However, research in the field of drug delivery and the detailed mode of action of β-sitosterol-mediated anticancer activities remains limited. β-sitosterol, as a non-toxic compound with significant pharmacological potential, exhibits promising anticancer effects against various cancer types. Despite being relatively less potent than conventional cancer chemotherapeutics, β-sitosterol holds potential as a safe and effective nutraceutical against cancer. Further comprehensive studies are recommended to explore the biological properties of β-sitosterol, including its mode of action, and develop novel formulations for its potential use in cancer treatment. This review provides a foundation for future investigations and highlights the need for further research on β-sitosterol as a potent superfood in combating cancer.

Structural Reorganization of Cell Membrane Models Caused by the Anticancer Antibiotic Doxorubicin

The molecular mechanisms of the interaction of anticancer antibiotic doxorubicin with lipid cell membrane models have been investigated using grazing incidence X-ray diffraction (XRD) and X-ray reflectivity (XRR). The model systems were monolayers of four types of phospholipids, related to the main components of animal cell membranes. New information on the processes of damage of phospholipid monolayer lattice caused by doxorubicin is obtained. It is established that the action of doxorubicin on anionic phospholipid monolayers is determined by the electrostatic interaction: positively charged doxorubicin molecules are incorporated between negatively charged phospholipid functional groups. In the case of neutral phospholipids the key role belongs to the hydrophobic interaction: doxorubicin molecules are coordinated with phospholipid hydrocarbon tails in disordered regions.

Disrupting actin filaments enhances glucose-stimulated insulin secretion independent of the cortical actin cytoskeleton

Just under the plasma membrane of most animal cells lies a dense meshwork of actin filaments called the cortical cytoskeleton. In insulin-secreting pancreatic β cells, a long-standing model posits that the cortical actin layer primarily acts to restrict access of insulin granules to the plasma membrane. Here we test this model and find that stimulating β cells with pro-secretory stimuli (glucose and/or KCl) has little impact on the cortical actin layer. Chemical perturbations of actin polymerization, by either disrupting or enhancing filamentation, dramatically enhance glucose-stimulated insulin secretion. Using scanning electron microscopy, we directly visualize the cortical cytoskeleton, allowing us to validate the effect of these filament-disrupting chemicals. We find the state of the cortical actin layer does not correlate with levels of insulin secretion, suggesting filament disruptors act on insulin secretion independently of the cortical cytoskeleton.

Antioxidant Interactions between Citrus Fruit Carotenoids and Ascorbic Acid in New Models of Animal Cell Membranes.

The regular consumption of citrus fruits by humans has been associated with lower incidence of chronic-degenerative diseases, especially those mediated by free radicals. Most of the health-promoting properties of citrus fruits derive from their antioxidant content of carotenoids and ascorbic acid (ASC). In the current work we have investigated the scavenging (against hydroxyl radical) and quenching capacities (against singlet oxygen) of four different carotenoid extracts of citrus fruits in the presence or absence of ASC (μM range) in organic solvent, aqueous solution, micelles and in an innovative biomimicking liposomal system of animal cell membrane (AML). The fruits of four varieties of citrus were selected for their distinctive carotenoid composition (liquid chromatography characterization): 'Nadorcott' mandarin and the sweet oranges 'Valencia late', 'Ruby Valencia' and 'Pinalate' mutant. The quenching activity of citrus carotenoids strongly depended on the biological assemblage: freely diffusible in organic solvent, 'Ruby Valencia' carotenoids (containing lycopene) showed the highest quenching activity, whereas 'Nadorcott' mandarin extracts, rich in β-cryptoxanthin, prevailed in micellar systems. Interestingly, the addition of 10 μM ASC significantly increased the quenching activity of all citrus extracts in micelles: 'Valencia' orange (+53%), 'Pinalate' (+87%), 'Ruby' (4-fold higher) and 'Nadorcott' mandarins (+20%). Accurate C11-BODIPY581/591 fluorescence assays showed solid scavenging activities of all citrus extracts against AML oxidation: 'Valencia' (-61%), 'Pinalate' (-58%) and 'Ruby' oranges (-29%), and 'Nadorcott' mandarins (-70%). Indeed, all four citrus extracts tested here have balanced antioxidant properties; extracts from the 'Nadorcott' mandarin slightly prevailed overall, due, at least in part, to its high content of β-cryptoxanthin. This study depicts some of the antioxidant interactions between citrus fruit carotenoids and ascorbic acid in models of animal cell membranes and reinforces the contribution of them in promoting health benefits for humans.

Type IV P-Type ATPases: Recent Updates in Cancer Development, Progression, and Treatment.

Adaptations of cancer cells for survival are remarkable. One of the most significant properties of cancer cells to prevent the immune system response and resist chemotherapy is the altered lipid metabolism and resulting irregular cell membrane composition. The phospholipid distribution in the plasma membrane of normal animal cells is distinctly asymmetric. Lipid flippases are a family of enzymes regulating membrane asymmetry, and the main class of flippases are type IV P-type ATPases (P4-ATPases). Alteration in the function of flippases results in changes to membrane organization. For some lipids, such as phosphatidylserine, the changes are so drastic that they are considered cancer biomarkers. This review will analyze and discuss recent publications highlighting the role that P4-ATPases play in the development and progression of various cancer types, as well as prospects of targeting P4-ATPases for anti-cancer treatment.

Use of a Short, In-Class Drawing Activity to Assess Student Understanding of Core Concepts of the Cell Membrane in an Undergraduate Physiology Course.

Students in an animal physiology course are required to have completed prerequisite cell biology and genetics courses that include discussion of basic properties and functions of the cell membrane. However, while many students remember basic information about membrane structure, they often have difficulty relating that structure to membrane functions, such as vesicular transport, active transport, osmosis, and current flow across the membrane. To better understand what students recall about the cell membrane, students were given an open-ended prompt to draw what they know about the structure and function of the animal cell membrane. This activity was repeated 1-2 weeks after finishing discussion of the cell membrane in class, with an emphasis on the concepts of membrane transport and a related core concept, flow along gradients. Student responses were analyzed using the conceptual framework for the "cell membrane" core concept published by Michael and Modell. Prior to covering this content in class, the majority of submissions included representation of the cell membrane as a phospholipid bilayer, and a high percentage also included membrane proteins or the fluid mosaic model. Similar percentages of students included these concepts in the post-coverage drawing. However, other components of the conceptual framework were included less frequently or not at all prior to covering the content in class, but improved dramatically afterwards. This activity provides information about what students recall from prior coursework and which concepts need to be revisited, and it can provide a complementary assessment of student understanding of core concept of the cell membrane.

A dual functional polypeptide with antibacterial and anti-inflammatory properties for the treatment of periodontitis

Periodontitis has been reported as the sixth most prevalent disease in human beings. This destructive disease is closely related to systemic diseases. Existing local drug delivery systems for periodontitis suffer from poor antibacterial effect and drug resistance. Inspired by the pathogenesis of periodontitis, we implemented a strategy to construct a dual functional polypeptide LL37-C15, which exhibited remarkable antibacterial effect against P. gingivalis and A. actinomycetemcomitans. In addition, LL37-C15 inhibits the release of pro-inflammatory cytokines by controlling the inflammatory pathway and reversing macrophage M1. Furthermore, the anti-inflammatory effect of LL37-C15 was also verified in vivo in a periodontitis rat model through the morphometry and histological observations of alveolar bone, hematoxylin-eosin, and Trap staining in gingival tissue. The results of molecular dynamics simulations showed that LL37-C15 could selectively destroy the bacterial cell membrane and protect the animal cell membrane in a self-destructive manner. The results showed that the polypeptide LL37-C15, as a novel promising therapeutic agent, exhibited a great potential for the periodontitis management. What's more, this dual functional polypeptide provides a promising strategy for building a multifunctional therapeutic platform against the inflammation and other diseases.

Cholesterol-substituted 3,4-ethylenedioxythiophene (EDOT-MA-cholesterol) and Poly(3,4-ethylenedioxythiophene) (PEDOT-MA-cholesterol)

Cholesterol is a rigid, crystalline, non-polar natural substance that exists in animal blood and cell membranes. Some of its derivatives are known to form ordered liquid crystalline mesophases under suitable conditions. In this work, we carefully examined the influence of cholesterol substitution on the characteristics of 3,4-ethylenedioxythiophene (EDOT-MA-cholesterol) and its corresponding polymer poly(3,4-ethylenedioxythiophene) (PEDOT-MA-cholesterol) synthesized by both chemical and electrochemical polymerization. We found evidence for an ordered lamellar (smectic-like) structure in the EDOT-MA-cholesterol monomer by differential scanning calorimetry (DSC), polarized optical microscopy (POM), and X-ray diffraction techniques. The ordered phase was observed to form on cooling from the isotropic melt at about 80 °C. Due to the insulating and bulky cholesterol side group on the EDOT monomer, we found that there was a maximum charge density for electrodeposition at ∼ 0.155 C.cm−2. A series of electrodepositions were performed from 0 to 0.155 C.cm−2 for probing the change of the charge transport with more charges used for the electrodeposition. We found that the impedance increased in the high-frequency range (above 104 Hz) and decreased in the low-frequency range (below 102 Hz). Three equivalent circuit models were proposed for fitting impedance data at different charge densities for a better understanding of the film growth process. The suppressed cyclic voltammogram (CV) of PEDOT-MA-cholesterol showed that the charge storage capability was essentially eliminated in the thickest films. The limited doping of the films was corroborated by their diminished electrochromic behavior, polaron-dominating absorption in UV-vis, overoxidized S 2p X-ray Photoelectron Spectroscopy (XPS) signal of electrodeposited films, and proton Nuclear Magnetic Resonance (1H NMR) of chemically polymerized samples. Dense film morphologies were confirmed by scanning electron microscopy (SEM). Grazing incident X-ray diffraction (GIWAXS) indicated the disrupted stacking of conjugated chains, which correlated with the decreased conductivity of the PEDOT-MA-cholesterol films. The measurement of the electrical conductivity gave a value of around 3.30 × 10−6 S.cm−1 which is about six orders of magnitude lower than has been seen in PEDOT (∼3 S.cm-1).

Membrane Models and Experiments Suitable for Studies of the Cholesterol Bilayer Domains.

Cholesterol (Chol) is an essential component of animal cell membranes and is most abundant in plasma membranes (PMs) where its concentration typically ranges from 10 to 30 mol%. However, in red blood cells and Schwann cells, PMs Chol content is as high as 50 mol%, and in the PMs of the eye lens fiber cells, it can reach up to 66 mol%. Being amphiphilic, Chol molecules are easily incorporated into the lipid bilayer where they affect the membrane lateral organization and transmembrane physical properties. In the aqueous phase, Chol cannot form free bilayers by itself. However, pure Chol bilayer domains (CBDs) can form in lipid bilayer membranes with the Chol content exceeding 50 mol%. The range of Chol concentrations surpassing 50 mol% is less frequent in biological membranes and is consequently less investigated. Nevertheless, it is significant for the normal functioning of the eye lens and understanding how Chol plaques form in atherosclerosis. The most commonly used membrane models are unilamellar and multilamellar vesicles (MLVs) and supported lipid bilayers (SLBs). CBDs have been observed directly using confocal microscopy, X-ray reflectometry and saturation recovery electron paramagnetic resonance (SR EPR). Indirect evidence of CBDs has also been reported by using atomic force microscopy (AFM) and fluorescence recovery after photobleaching (FRAP) experiments. The overall goal of this review is to demonstrate the advantages and limitations of the various membrane models and experimental techniques suitable for the detection and investigation of the lateral organization, function and physical properties of CBDs.

Efficacy of TurmiZn, a Metallic Complex of Curcuminoids-Tetrahydrocurcumin and Zinc on Bioavailability, Antioxidant, and Cytokine Modulation Capability

Complexes of curcumin with metals have shown much-improved stability, solubility, antioxidant capability, and efficacy when compared to curcumin. The present research investigates the relative bioavailability, antioxidant, and ability to inhibit inflammatory cytokine production of a curcuminoid metal chelation complex of tetrahydrocurcumin-zinc-curcuminoid termed TurmiZn. In vitro uptake assay using pig intestinal epithelial cells showed that TurmiZn has an ~3-fold increase (p ≤ 0.01) in uptake compared to curcumin and a ~2-fold increase (p ≤ 0.01) over tetrahydrocurcumin (THC). In a chicken model, an oral 1-g dose of TurmiZn showed a ~2.5-fold increase of a specific metabolite peak compared to curcumin (p = 0.004) and a ~3-fold increase compared to THC (p = 0.001). Oral doses (5 g/Kg) of TurmiZn in rats also showed the presence of curcumin and THC metabolites in plasma, indicating bioavailability across cell membranes in animals. Determination of the antioxidant activity by a 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) radical scavenging assay indicated that TurmiZn was about 13x better (p ≤ 0.0001) than curcumin and about 4X better (p ≤ 0.0001) than THC, in reducing free radicals. In vitro experiments further showed significant (p ≤ 0.01) reductions of lipopolysaccharide (LPS)-induced proinflammatory cytokines such as interleukin (IL) IL-6, IL-8, IL-15, IL-18, and tumor necrosis factor (TNF)-alpha, while showing a significant (p ≤ 0.01) increase of granulocyte-macrophage colony-stimulating factor (GM-CSF) in dog kidney cells. In vivo cytokine modulations were also observed when TurmiZn was fed for 6 weeks to newborn chickens. TurmiZn reduced IL-1 and IL-6, but significantly reduced (p ≤ 0.01) IL-10 levels while there was a concurrent significant (p = 0.02) increase in interferon gamma compared to controls. Overall, these results indicate that TurmiZn has better bioavailability and antioxidant capability than curcumin or THC and has the ability to significantly modulate cytokine levels. Thus, TurmiZn could be an excellent candidate for a novel ingredient that can be incorporated into food and supplements to help overall health during the aging process.

A concerted mechanism involving ACAT and SREBPs by which oxysterols deplete accessible cholesterol to restrict microbial infection.

Most of the cholesterol in the plasma membranes (PMs) of animal cells is sequestered through interactions with phospholipids and transmembrane domains of proteins. However, as cholesterol concentration rises above the PM's sequestration capacity, a new pool of cholesterol, called accessible cholesterol, emerges. The transport of accessible cholesterol between the PM and the endoplasmic reticulum (ER) is critical to maintain cholesterol homeostasis. This pathway has also been implicated in the suppression of both bacterial and viral pathogens by immunomodulatory oxysterols. Here, we describe a mechanism of depletion of accessible cholesterol from PMs by the oxysterol 25-hydroxycholesterol (25HC). We show that 25HC-mediated activation of acyl coenzyme A: cholesterol acyltransferase (ACAT) in the ER creates an imbalance in the equilibrium distribution of accessible cholesterol between the ER and PM. This imbalance triggers the rapid internalization of accessible cholesterol from the PM, and this depletion is sustained for long periods of time through 25HC-mediated suppression of SREBPs and continued activation of ACAT. In support of a physiological role for this mechanism, 25HC failed to suppress Zika virus and human coronavirus infection in ACAT-deficient cells, and Listeria monocytogenes infection in ACAT-deficient cells and mice. We propose that selective depletion of accessible PM cholesterol triggered by ACAT activation and sustained through SREBP suppression underpins the immunological activities of 25HC and a functionally related class of oxysterols.

β-sitosterol in Various Pathological Conditions: An Update

Abstract: Phytosteroids are biologically active compounds found naturally in herb plasma membranes, with a chemical composition similar to animal plasma membrane cholesterol. It can be found in almost all fats abundant plant’s diets. One of the vital phytosterols is β-sitosterol which has several biological activities. It has been proved in various in-vivo and in-vitro research in which β-sitosterol stabilized several physiological activities like as antioxidant, CNS activity (like anti-alzheimer, anxiolytic and sedative effects, CNS depressant activity), lipid-lowering effects (like nonalcoholic fatty liver disease), antidiabetic, anti-inflammatory and analgesic effects, anticancer and immunomodulatory, protective effects in pulmonary fibrosis, wound healing effects and anti-viral and COVID-19 activity. The experimental research on β-sitosterol shows that it can be used as a nutritional supplement to combat variousexisting diseases. In this review, we are highlighting the most significant pharmacological action of β-sitosterol on the basis of available literature.