Stable, Monodisperse, and Highly Cell-Permeating Nanocochleates from Natural Soy Lecithin Liposomes

(1) Background: Andrographolide (AN), the main diterpenoid constituent of Andrographis paniculata, has a wide spectrum of biological activities. The aim of this study was the development of nanocochleates (NCs) loaded with AN and based on phosphatidylserine (PS) or phosphatidylcholine (PC), cholesterol and calcium ions in order to overcome AN low water solubility, its instability under alkaline conditions and its rapid metabolism in the intestine. (2) Methods: The AN-loaded NCs (AN–NCs) were physically and chemically characterised. The in vitro gastrointestinal stability and biocompatibility of AN–NCs in J77A.1 macrophage and 3T3 fibroblasts cell lines were also investigated. Finally, the uptake of nanocarriers in macrophage cells was studied. (3) Results: AN–NCs obtained from PC nanoliposomes were suitable nanocarriers in terms of size and homogeneity. They had an extraordinary stability after lyophilisation without the use of lyoprotectants and after storage at room temperature. The encapsulation efficiency was 71%, while approximately 95% of AN was released in PBS after 24 h, with kinetics according to the Hixson–Crowell model. The in vitro gastrointestinal stability and safety of NCs, both in macrophages and 3T3 fibroblasts, were also assessed. Additionally, NCs had extraordinary uptake properties in macrophages. (4) Conclusions: NCs developed in this study could be suitable for both AN oral and parental administration, amplifying its therapeutic value.

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Tamarix articulata (T. articulata) - An Important Halophytic Medicinal Plant with Potential Pharmacological Properties

Current Pharmaceutical Biotechnology ◽

10.2174/1389201020666190318120103 ◽

2019 ◽

Vol 20 (4) ◽

pp. 285-292 ◽

Cited By ~ 5

Author(s):

Abdullah M. Alnuqaydan ◽

Bilal Rah

Keyword(s):

Medicinal Plant ◽

Biological Activities ◽

Wide Spectrum ◽

Biological Properties ◽

In Vivo Model ◽

Drug Candidate ◽

Phytochemical Analysis ◽

Pharmacological Properties

Background:Tamarix Articulata (T. articulata), commonly known as Tamarisk or Athal in Arabic region, belongs to the Tamaricaece species. It is an important halophytic medicinal plant and a good source of polyphenolic phytochemical(s). In traditional medicines, T. articulata extract is commonly used, either singly or in combination with other plant extracts against different ailments since ancient times.Methods:Electronic database survey via Pubmed, Google Scholar, Researchgate, Scopus and Science Direct were used to review the scientific inputs until October 2018, by searching appropriate keywords. Literature related to pharmacological activities of T. articulata, Tamarix species, phytochemical analysis of T. articulata, biological activities of T. articulata extracts. All of these terms were used to search the scientific literature associated with T. articulata; the dosage of extract, route of administration, extract type, and in-vitro and in-vivo model.Results:Numerous reports revealed that T. articulata contains a wide spectrum of phytochemical(s), which enables it to have a wide window of biological properties. Owing to the presence of high content of phytochemical compounds like polyphenolics and flavonoids, T. articulata is a potential source of antioxidant, anti-inflammatory and antiproliferative properties. In view of these pharmacological properties, T. articulata could be a potential drug candidate to treat various clinical conditions including cancer in the near future.Conclusion:In this review, the spectrum of phytochemical(s) has been summarized for their pharmacological properties and the mechanisms of action, and the possible potential therapeutic applications of this plant against various diseases discussed.

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α-Glucosidase Inhibition, Antioxidant and Docking Studies of Hydroxycoumarins and their Mono and Bis O-alkylated/acetylated Analogs

Letters in Drug Design & Discovery ◽

10.2174/1570180814666170602081941 ◽

2018 ◽

Vol 15 (2) ◽

pp. 127-135 ◽

Cited By ~ 3

Author(s):

Parvesh Singh ◽

Nomandla Ngcoya ◽

Ramgopal Mopuri ◽

Nagaraju Kerru ◽

Neha Manhas ◽

...

Keyword(s):

In Silico ◽

Biological Activities ◽

Wide Spectrum ◽

Radical Scavenging Activity ◽

Radical Scavenging ◽

Catalytic Site ◽

Docking Simulations ◽

In Silico Docking ◽

Anti Oxidant

Background: Diabetes Mellitus (DM) is a complex metabolic disease illustrated by abnormally high levels of plasma glucose or hyperglycaemia. Accordingly, several α-glucosidase inhibitors have been developed for the treatment of diabetes and other degenerative disorders. While, a coumarin ring has the privilege to represent numerous natural and synthetic compounds with a wide spectrum of biological activities e.g. anti-cancer, anti-HIV, anti-viral, anti-malarial, anti-microbial, anti-convulsant, anti-hypertensive properties. Besides this, coumarins have also shown potential to inhibit α-glucosidase leading to a generation of new promising antidiabetic agents. However, the testing of O-substituted coumarins for α-glucosidase inhibition has evaded the attention of medicinal chemists. Methods: For O-alkylation/acetylation reactions, the hydroxyl coumarins (A-B) initially activated by K2CO3 in dry DMF were reacted with variedly substituted haloalkanes at room temperature under nitrogen. The synthesized compounds were tested for their α-glucosidase (from Saccharomyces cerevisiae) inhibitory activity and anti-oxidant activity using DPPH radical scavenging activity. In silico docking simulations were conducted using CDocker module in DS (Accelrys) to explore the binding modes of the representative compounds in the catalytic site of α-glucosidase. Results: All the coumarin analogues (A1, B1, A2-A10, B2-B8) including their precursors (A-B) were evaluated for their in vitro α-glucosidase inhibition using acarbose as a standard inhibitor. All the mono O-alkylated coumarins (except A1) showed significant (p <0.05) α-glucosidase inhibition relative to the hydroxyl coumarin (A) with IC50 values ranging between 11.084±0.117 to 145.24± 29.22 µg/mL. Compound 7-(benzyloxy)-4, 5-dimethyl-2H-chromen-2-one (A9) bearing a benzyl group (Ph-CH2-) at position 7 showed a remarkable (p <0.05) increase in the activity (IC50 = 11.084±0.117 µg/mL), almost four-fold more than acarbose (IC50 = 40.578±5.999 µg/mL). The introduction of –NO2 group dramatically improved the anti-oxidant activity of coumarin, while the O-alkylation/acetylation decreased the activity. Conclusion: The present study describes the synthesis of functionalized coumarins and their evaluation for α-glucosidase inhibition and antioxidant activity under in vitro conditions. Based on IC50 data, the mono O-alkylated coumarins were observed to be stronger inhibitors of α-glucosidase with respect to their bis O-alkylated analogues. Coumarin (A9) bearing O-benzyloxy group displayed the strongest α-glucosidase inhibition, even higher than the standard inhibitor acarbose. The coumarin (A10) bearing –NO2 group showed the highest anti-oxidant activity amongst the synthesized compounds, almost comparable to the ascorbic acid. Finally, in silico docking simulations revealed the role of hydrogen bonding and hydrophobic forces in locking the compounds in catalytic site of α-glucosidase.

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Effect of guaianolides in the meiosis reinitiation of amphibian oocytes

Zygote ◽

10.1017/s0967199416000265 ◽

2016 ◽

Vol 25 (1) ◽

pp. 10-16 ◽

Cited By ~ 2

Author(s):

J. Zapata-Martínez ◽

G. Sánchez-Toranzo ◽

F. Chaín ◽

C.A.N. Catalán ◽

M.I. Bühler

Keyword(s):

Biological Activities ◽

Wide Spectrum ◽

Sesquiterpene Lactones ◽

Inhibitory Effect ◽

Biological Molecules ◽

Plant Metabolites ◽

Major Mechanism ◽

Bufo Arenarum ◽

Asteraceae Family

SummarySesquiterpene lactones (STLs) are a large and structurally diverse group of plant metabolites generally found in the Asteraceae family. STLs exhibit a wide spectrum of biological activities and it is generally accepted that their major mechanism of action is the alkylation of the thiol groups of biological molecules. The guaianolides is one of various groups of STLs. Anti-tumour and anti-migraine effects, an allergenic agent, an inhibitor of smooth muscle cells and of meristematic cell proliferation are only a few of the most commonly reported activities of STLs. In amphibians, fully grown ovarian oocytes are arrested at the beginning of meiosis I. Under stimulus with progesterone, this meiotic arrest is released and meiosis progresses to metaphase II, a process known as oocyte maturation. There are previous records of the inhibitory effect of dehydroleucodin (DhL), a guaianolide lactone, on the progression of meiosis. It has been also shown that DhL and its 11,13-dihydroderivative (2H-DhL; a mixture of epimers at C-11) act as blockers of the resumption of meiosis in fully grown ovarian oocytes from the amphibian Rhinella arenarum (formerly classified as Bufo arenarum). The aim of this study was to analyze the effect of four closely related guaianolides, i.e., DhL, achillin, desacetoxymatricarin and estafietin as possible inhibitors of meiosis in oocytes of amphibians in vitro and discuss some structure–activity relationships. It was found that the inhibitory effect on meiosis resumption is greater when the lactone has two potentially reactive centres, either a α,β–α′,β′-diunsaturated cyclopentanone moiety or an epoxide group plus an exo-methylene-γ-lactone function.

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Optimization and characterization of poly(lactic-co-glycolic acid) nanoparticles loaded with astaxanthin and evaluation of anti-photodamage effect in vitro

Royal Society Open Science ◽

10.1098/rsos.191184 ◽

2019 ◽

Vol 6 (10) ◽

pp. 191184 ◽

Cited By ~ 5

Author(s):

Fangbin Hu ◽

Weikang Liu ◽

Liuliu Yan ◽

Fanhui Kong ◽

Kun Wei

Keyword(s):

Electron Microscopy ◽

Glycolic Acid ◽

Water Solubility ◽

Skin Diseases ◽

Biological Activities ◽

Drug Loading ◽

Synthesis Method ◽

Hacat Cells ◽

Scanning Calorimetry

Astaxanthin is a xanthophyll carotenoid with high beneficial biological activities, such as antioxidant function and scavenging oxygen free radicals, but its application is limited because of poor water solubility and low bioavailability. Here, we prepared and optimized poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with astaxanthin using the emulsion solvent evaporation technique and investigated the anti-photodamage effect in HaCaT cells. The four-factor three-stage Box–Behnken design was used to optimize the nanoparticle formulation. The experimental determination of the optimal nanoparticle size was 154.4 ± 0.35 nm, the zeta potential was 22.07 ± 0.93 mV, encapsulation efficiency was 96.42 ± 0.73% and drug loading capacity was 7.19 ± 0.12%. The physico-chemical properties of the optimized nanoparticles were characterized by dynamic light scattering, scanning electron microscopy, transmission electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, differential scanning calorimetry and thermo-gravimetric analyser. In vitro study exhibited the excellent cell viability and cellular uptake of optimized nanoparticles on HaCaT cells. The anti-photodamage studies (cytotoxicity assay, reactive oxygen species content and JC-1 assessment) demonstrated that the optimized nanoparticles were more effective and safer than pure astaxanthin in HaCaT cells. These results suggest that our PLGA-coated astaxanthin nanoparticles synthesis method was highly feasible and can be used in cosmetics or the treatment of skin diseases.

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Extracellular MIF, but not its homologue D-DT, promotes fibroblast motility independent of its receptor CD74/CD44

Journal of Cell Science ◽

10.1242/jcs.217356 ◽

2020 ◽

pp. jcs.217356

Author(s):

Paweł Szczęśniak ◽

Tamara Henke ◽

Suada Fröhlich ◽

Uwe Plessmann ◽

Henning Urlaub ◽

...

Keyword(s):

Actin Cytoskeleton ◽

Biological Activities ◽

Wide Spectrum ◽

Oxidoreductase Activity ◽

Dopachrome Tautomerase ◽

Associated Proteins ◽

Signalling Transduction ◽

Thiol Protein

Macrophage migration inhibitory factor (MIF) and its homologue D-dopachrome tautomerase (D-DT) are ubiquitous, pro-inflammatory cytokines with chemokine-like functions that coordinate a wide spectrum of biological activities like migration. Here, we biotin-tagged intracellular MIF/D-DT in vivo to identify important cytosolic interactors and found a plethora of actin cytoskeleton-associated proteins. While the CD74/CD44 receptor complex is essential for signalling transduction in fibroblasts by extracellular MIF/D-DT, our interactome data rather suggested direct effects. We thus investigated whether MIF/D-DT can modulate cell migration independent of CD74/CD44. To differentiate between receptor- and non-receptor-mediated motility, we treated fibroblasts that are deficient in CD74 and CD44 or that express both proteins with recombinant MIF/D-DT. Interestingly, only MIF could stimulate chemokinesis in the presence or absence of CD74/CD44. The pro-migratory effects of MIF depended on lipid raft/caveolae-mediated but not clathrin-mediated endocytosis, on its tautomerase activity and, likely, on its thiol protein oxidoreductase activity. As MIF treatment restrained actin polymerisation in vitro our findings establish a new intracellular role for MIF/D-DT in driving cell motility by modulating the actin cytoskeleton.

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Formulation of More Efficacious Curcumin Delivery Systems Using Colloid Science: Enhanced Solubility, Stability, and Bioavailability

Molecules ◽

10.3390/molecules25122791 ◽

2020 ◽

Vol 25 (12) ◽

pp. 2791 ◽

Cited By ~ 1

Author(s):

Bingjing Zheng ◽

David Julian McClements

Keyword(s):

Water Solubility ◽

Biological Activities ◽

Anticancer Activities ◽

Potential Health ◽

Colloid Science ◽

Enhanced Solubility ◽

Alkaline Conditions ◽

Low Toxicity ◽

Neutral Conditions ◽

Bioactive Constituent

Curcumin is a bioactive constituent isolated from turmeric that has historically been used as a seasoning, pigment, and herbal medicine in food. Recently, it has become one of the most commonly studied nutraceuticals in the pharmaceutical, supplement, and food areas because of its myriad of potential health benefits. For instance, it is claimed to exhibit antioxidant, anti-inflammatory, antimicrobial, antiparasite, and anticancer activities when ingested as a drug, supplement, or food. Toxicity studies suggest that it is safe to consume, even at relatively high levels. Its broad-spectrum biological activities and low toxicity have meant that it has been widely explored as a nutraceutical ingredient for application in functional foods. However, there are several hurdles that formulators must overcome when incorporating curcumin into commercial products, such as its low water solubility (especially under acidic and neutral conditions), chemical instability (especially under neutral and alkaline conditions), rapid metabolism by enzymes in the human body, and limited bioavailability. As a result, only a small fraction of ingested curcumin is actually absorbed into the bloodstream. These hurdles can be at least partially overcome by using encapsulation technologies, which involve trapping the curcumin within small particles. Some of the most commonly used edible microparticles or nanoparticles utilized for this purpose are micelles, liposomes, emulsions, solid lipid particles, and biopolymer particles. Each of these encapsulation technologies has its own benefits and limitations for particular product applications and it is important to select the most appropriate one.

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In vitro and in vivo activities of flavonoids – apigenin, baicalin, chrysin, scutellarin – in regulation of hypertension – a review for their possible effects in pregnancy-induced hypertension

Herba Polonica ◽

10.2478/hepo-2019-0001 ◽

2019 ◽

Vol 65 (1) ◽

pp. 55-70 ◽

Cited By ~ 1

Author(s):

Marcin Ożarowski ◽

Radosław Kujawski ◽

Przemysław Ł. Mikołajczak ◽

Karolina Wielgus ◽

Andrzej Klejewski ◽

...

Keyword(s):

Ex Vivo ◽

Biological Activities ◽

Wide Spectrum ◽

Chemical Compounds ◽

New Drugs ◽

Future Application ◽

Mediators Of Inflammation ◽

And Function

Summary Flavonoids and their conjugates are the most important group of natural chemical compounds in drug discovery and development. The search for pharmacological activity and new mechanisms of activity of these chemical compounds, which may inhibit mediators of inflammation and influence the structure and function of endothelial cells, can be an interesting pharmacological strategy for the prevention and adjunctive treatments of hypertension, especially induced by pregnancy. Because cardiovascular diseases have multi-factorial pathogenesis these natural chemical compounds with wide spectrum of biological activities are the most interesting source of new drugs. Extracts from one of the most popular plant used in Traditional Chinese Medicine, Scutellaria baicalensis Georgi could be a very interesting source of flavonoids because of its exact content in quercetin, apigenin, chrysin and scutellarin as well as in baicalin. These flavonoids exert vasoprotective properties and many activities such as: anti-oxidative via several pathways, anti-in-flammatory, anti-ischaemic, cardioprotective and anti-hypertensive. However, there is lack of summaries of results of studies in context of potential and future application of flavonoids with determined composition and activity. Our review aims to provide a literature survey of in vitro, in vivo and ex vivo pharmacological studies of selected flavonoids (apigenin, chrysin and scutellarin, baicalin) in various models of hypertension carried out in 2008–2018.

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Oral Bioavailability Enhancement and Anti-Fatigue Assessment of the Andrographolide Loaded Solid Dispersion

International Journal of Molecular Sciences ◽

10.3390/ijms21072506 ◽

2020 ◽

Vol 21 (7) ◽

pp. 2506 ◽

Cited By ~ 1

Author(s):

Ching-Chi Yen ◽

Yu-Kai Liang ◽

Chao-Pei Cheng ◽

Mei-Chich Hsu ◽

Yu-Tse Wu

Keyword(s):

Dissolution Rate ◽

Solid Dispersion ◽

Oral Bioavailability ◽

Water Solubility ◽

Biological Activities ◽

Wide Spectrum ◽

Amorphous State ◽

Vehicle Group ◽

Time To Exhaustion ◽

Pharmacokinetic Studies

Andrographolide (AG), a major diterpene lactone isolated from Andrographis paniculata (Burm. f.) Nees (Acanthaceae), possesses a wide spectrum of biological activities. However, its poor water solubility and low bioavailability limit its clinical application. Therefore, this study aimed to develop a solid dispersion (SD) formulation to increase the aqueous solubility and dissolution rate of AG. Different drug-polymer ratios were used to prepare various SDs. The optimized formulation was characterized for differential scanning calorimetry, Fourier transform infrared spectroscopy, and powder X-ray diffraction. The analysis indicated that the optimized SD enhanced AG solubility and dissolution rates by changing AG crystallinity to an amorphous state. The dissolution behaviors of the optimum SD composed of an AG-polyvinylpyrrolidone K30-Kolliphor EL ratio of 1:7:1 (w/w/w) resulted in the highest accumulated dissolution (approximately 80%). Pharmacokinetic studies revealed that Cmax/dose and the AUC/dose increased by 3.7-fold and 3.0-fold, respectively, compared with AG suspension. Furthermore, pretreatment using the optimized AG-SD significantly increased the swimming time to exhaustion by 1.7-fold and decreased the plasma ammonia level by 71.5%, compared with the vehicle group. In conclusion, the optimized AG-SD formulation appeared to effectively improve its dissolution rate and oral bioavailability. Moreover, the optimized AG-SD provides a promising treatment against physical fatigue.

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SYNTHESIS, CHARACTERIZATION AND IN VITRO STUDY OF ANTIBACTERIAL, ANTIFUNGAL ACTIVITIES OF SOME NOVEL DIHYDROPYRIMIDINTHIONE DERIVATIVES

Latin American Applied Research - An international journal ◽

10.52292/j.laar.2014.454 ◽

2014 ◽

Vol 44 (4) ◽

pp. 289-293

Author(s):

S. BALUJA ◽

S. CHANDA ◽

R. BHALODIA ◽

R. TALAVIYA

Keyword(s):

Biological Activities ◽

Wide Spectrum ◽

In Vitro Study ◽

Dimethyl Formamide ◽

Mass Spectral Data ◽

Antifungal Activities ◽

Mass Spectral ◽

Antibacterial And Antifungal Activities ◽

Antibacterial And Antifungal

Dihydropyrimidinthione is an important class of heterocyclic compounds which exhibits wide spectrum of biological activities. In the present study, some bio-active dihydropyrimidinthione derivatives have been synthesized and their characterization was done by IR, NMR and mass spectral data. The antibacterial and antifungal activities of synthesized compounds have also been studied in N,N-dimethyl formamide and Dimethyl sulfoxide.

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CXCL14 Overexpression Attenuates Sepsis-Associated Acute Kidney Injury by Inhibiting Proinflammatory Cytokine Production

Mediators of Inflammation ◽

10.1155/2020/2431705 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Jing Lv ◽

Zhi-Lin Wu ◽

Zheng Gan ◽

Ping Gui ◽

Shang-Long Yao

Keyword(s):

Acute Kidney Injury ◽

Serum Creatinine ◽

Cytokine Production ◽

Biological Activities ◽

Wide Spectrum ◽

Macrophage Polarization ◽

Cecal Ligation ◽

Kidney Injury ◽

M1 Macrophage

CXCL14 is a relatively novel chemokine with a wide spectrum of biological activities. The present study was designed to investigate whether CXCL14 overexpression attenuates sepsis-associated acute kidney injury (AKI) in mice. Sepsis model has been established by cecal ligation and puncture (CLP). CLP induced AKI in mice as assessed by increased renal neutrophil gelatinase-associated lipocalin (NGAL) expression and serum creatinine levels. We found that renal CXCL14 expression in the kidney was significantly decreased at 12 hours after CLP. Correlation analysis demonstrated a negative association between renal CXCL14 expression and AKI markers including serum creatinine and renal NGAL. Moreover, CXCL14 overexpression reduced cytokine (TNF-α, IL-6, and IL-1β) production and NGAL expression in the kidney and decreased serum creatinine levels. In vivo and in vitro experiments found that CXCL14 overexpression inhibited M1 macrophage polarization but increased M2 polarization. Together, these results suggest that CXCL14 overexpression attenuates sepsis-associated AKI probably through the downregulation of macrophages-derived cytokine production. However, further studies are required to elucidate the underlying mechanism.

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