scholarly journals Rose Exctracts and In-Vitro Inhibition of SARS-CoV-2 Spike: The Ace-2 Interaction

2021 ◽  
Vol 48 (2) ◽  
pp. 41-44
Author(s):  
M. Arokiaraj ◽  
E. Menesson
Keyword(s):  
Inhibitory Concentration ◽  
Receptor Interaction ◽  
The Novel ◽  
Beneficial Effects ◽  
Therapeutic Benefits ◽  
Dependent Sequence ◽  
The Rose ◽  
Dose Dependent

Abstract Objective The study was performed to evaluate the novel potential of red rose extract to inhibit SARS-CoV-2 spike protein-Ace2 receptor interaction in vitro. Methods ACE2 receptors were His-labelled, and the interaction was studied by chemiluminescence after the addition of anti-His HRP and HRP substrate. The inhibition of SARS-CoV-2 and ACE2 was assessed in a dose-dependent sequence. Results The 50% inhibitory concentration was observed at 0.75 percent v/v of the rose extract, and the 90% inhibition was seen at about 1.8 percent v/v. Steam inhalation or nebulization could be simple methods of delivering rose extracts to the lower respiratory tract and pulmonary tissues. Conclusion Rose extracts have a potential for inhibition of SARS-CoV-2 and ACE2 receptor in vitro, which could add beneficial effects in Covid-19 treatment. Further tests need to be performed to study their therapeutic benefits in vivo.

scholarly journals Modulation of the Neuroprotective and Anti-inflammatory Activities of the Flavonol Fisetin by the Transition Metals Iron and Copper

Antioxidants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1113
Author(s):  
Pamela Maher
Keyword(s):  
Transition Metals ◽  
Neurodegenerative Diseases ◽  
Dependent Manner ◽  
Copper Binding ◽  
Drug Candidates ◽  
Beneficial Effects ◽  
Anti Inflammatory ◽  
Dose Dependent

Alterations occur in the homeostasis of the transition metals iron (Fe2+) and copper (Cu2+) during aging and these are further amplified in neurodegenerative diseases, including Alzheimer’s disease (AD). These observations suggest that the most effective drug candidates for AD might be those that can reduce these alterations. The flavonoid fisetin has both neuroprotective and anti-inflammatory activity both in vitro and in vivo and can bind both iron and copper suggesting that its chelating activity might play a role in its beneficial effects. To test this idea, the effects of iron and copper on both the neuroprotective and anti-inflammatory activities of fisetin were examined. It is shown that while fisetin can reduce the potentiation of cell death by iron and copper in response to treatments that lower glutathione levels, it is much less effective when the metals are combined with other inducers of oxidative stress. In addition, iron but not copper reduces the anti-inflammatory effects of fisetin in a dose-dependent manner. These effects correlate with the ability of iron but not copper to block the induction of the antioxidant transcription factor, Nrf2, by fisetin. In contrast, although the flavanone sterubin also binds iron, the metal has no effect on sterubin’s ability to induce Nrf2 or protect cells from toxic or pro-inflammatory insults. Together, these results suggest that while iron and copper binding could contribute to the beneficial effects of neuroprotective compounds in the context of neurodegenerative diseases, the consequences of this binding need to be fully examined for each compound.

INTERFERENCE OF GESTAGENS AND ANDROGENS WITH RAT UTERINE OESTROGEN RECEPTORS

1978 ◽  
Vol 77 (1) ◽  
pp. 49-55 ◽  
Author(s):  
F. DI CARLO ◽  
G. CONTI ◽  
C. REBOANI
Keyword(s):  
Medroxyprogesterone Acetate ◽  
Binding Capacity ◽  
Inhibitory Effect ◽  
Receptor Interaction ◽  
Plot Analysis ◽  
Specific Receptors ◽  
Dose Dependent ◽  
Intact Rats

The inhibitory effect of some gestagens and calusterone on the binding of oestradiol-17β to its specific uterine receptors has been investigated in intact rats. Progesterone, medrogestone, clogestone, medroxyprogesterone acetate and calusterone reduce the specific oestradiol– receptor interaction in vitro; this effect is dose-dependent and does not differ significantly from one drug to the other. A more relevant decrease in the amount of oestradiol-17β bound to specific receptors has been observed with calusterone. Progesterone, clogestone, medrogestone, medroxyprogesterone acetate and calusterone given orally induce a marked decrease (between 30 and 70% depending on the dose) in the binding capacity of oestradiol-17β to specific uterine receptors in vivo. Results from a Scatchard plot analysis suggest that the interference with the binding of oestradiol-17β caused by both progestogens and calusterone is due to a non-competitive interaction.

scholarly journals Curative Anti-Inflammatory Properties of Chinese Optimized Yinxieling Formula in Models of Parkinson’s Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
RenRong Wei ◽  
Jing OuYang ◽  
WeiXian Lin ◽  
TongXiang Lin
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Models ◽  
Inflammatory Responses ◽  
Killer Cell ◽  
Glial Activation ◽  
Receptor Interaction ◽  
Therapeutic Benefits

Parkinson’s disease (PD) is marked by the progressive degeneration of dopaminergic neurons (DAN) accompanied by glial activation. Thus, inhibiting glial activation that occurs during this disease could be an effective method for treating PD. Optimized Yinxieling Formula (OYF), a Chinese medicinal formula, which is used to efficiently treat autoimmune disease psoriasis, has been proved to display potential immunomodulatory effects in inflammation-associated diseases. This study assessed the therapeutic benefits of OYF on glial-mediated neuroinflammation and neuroprotection in PD models in vitro and in vivo. First, the results showed that OYF significantly suppresses LPS-induced proinflammatory cytokine secretion and attenuates the overall inflammatory responses in BV-2 cells. Second, in vivo studies confirm that while the validity of our MPTP-induced PD mouse models possesses activated glia and significant neurobehavioral dysfunction, pretreatment with OYF prevents glial activation and ameliorates movement dysfunction in the MPTP-induced PD mouse models as evaluated by the pole and rotarod tests. Third, transcriptomic analyses were carried out to reveal the underlying molecular mechanism of the OYF treatment. Sixteen pathways were significantly upregulated in the OYF-treated PD model mice, including the cytokine-cytokine receptor interaction, cell adhesion molecules, coagulation, and complement cascades. Fifteen pathways were significantly downregulated in the OYF-treated PD model mice, such as the natural killer cell mediated cytotoxicity, hematopoietic cell lineage, phagosome, and others. These pathways share direct or indirect features of immunomodulation, suggesting that the physiological effects of OYF involve key roles of immune and inflammation regulations. Therefore, we prove that OYF is a useful immunomodulatory formula in developing prevention and treatment methods for neurodegenerative disease PD.

scholarly journals Hormonal regulation of the novel adipocytokine visfatin in 3T3-L1 adipocytes

2005 ◽  
Vol 185 (3) ◽  
pp. R1-R8 ◽  
Author(s):  
Susan Kralisch ◽  
Johannes Klein ◽  
Ulrike Lossner ◽  
Matthias Bluher ◽  
Ralf Paschke ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Hormonal Regulation ◽  
The Novel ◽  
Insulin Mimetic ◽  
The Metabolic Syndrome ◽  
Tnf Α ◽  
Core Components ◽  
Dose Dependent

Recently, visfatin was characterized as a novel adipo-cytokine that is upregulated in obesity and exerts insulin-mimetic effects in various tissues. To clarify expression and regulation of this adipocytokine, visfatin mRNA was measured by quantitative real-time reverse transcription-polymerase chain reaction in 3T3-L1 adipocytes during adipogenesis and after treatment with various hormones known to alter insulin sensitivity. Visfatin expression was about 6-fold higher in 3T3-L1 adipocytes in vitro as compared with epididymal fat in vivo and increased during adipogenic conversion more than 3-fold. Interestingly, 100 nM dexamethasone significantly increased visfatin mRNA by almost 1.5-fold. In contrast, 500 ng/ml growth hormone (GH), 10 ng/ml tumor necrosis factor (TNF) α, and 10 μM isoproterenol downregulated visfatin expression by 45%, 36%, and 43% respectively. Insulin did not influence synthesis of this adipocytokine. The effects of dexamethasone, GH, TNFα and isoproterenol were time- and dose-dependent. Furthermore, activation of Gs-protein-coupled pathways by forskolin and cholera toxin was sufficient to significantly downregulate visfatin mRNA. Taken together, our results show a differential regulation of visfatin mRNA by insulin resistance-inducing hormones, supporting the view that this adipo-cytokine might be an interesting novel candidate linking core components of the metabolic syndrome such as obesity and insulin resistance.

scholarly journals Treatment with sodium butyrate has therapeutic benefits for Machado-Joseph disease through the induction of autophagy

2021 ◽  
Author(s):  
Maxinne Watchon ◽  
Katherine J. Robinson ◽  
Luan Luu ◽  
Kristy C. Yuan ◽  
Albert Lee ◽  
...  
Keyword(s):  
Sodium Butyrate ◽  
Trinucleotide Repeat ◽  
Swimming Performance ◽  
Protein Aggregates ◽  
Dependent Manner ◽  
Beneficial Effects ◽  
Therapeutic Benefits ◽  
Machado Joseph Disease

AbstractMachado-Joseph disease (MJD) is a fatal neurodegenerative disease caused by expansion of the trinucleotide repeat region within the ATXN3/MJD gene. Mutation of ATXN3 causes formation of neurotoxic ataxin-3 protein aggregates, neurodegeneration and motor deficits. Here we investigated the therapeutic potential of sodium butyrate (SB), the sodium salt of butyric acid, a metabolite naturally produced by gut microbiota, on cultured SH-SY5Y cells and transgenic zebrafish expressing human ataxin-3 containing 84 glutamine (Q) residues to model MJD. MJD SH-SY5Y cells were found to contain ataxin-3 oligomeric species and protein aggregates. Interestingly, treatment with SB decreased the size of detergentinsoluble ataxin-3 aggregates in vitro. Further investigation revealed that SB treatment increased activity of the autophagy protein quality control pathway in the MJD cells and decreased presence of ataxin-3 oligomers in an autophagy-dependent manner. Treatment with SB was also beneficial in vivo through induction of autophagy and improving swimming performance in transgenic MJD zebrafish. Co-treating the MJD zebrafish with SB and chloroquine, an autophagy inhibitor, prevented the beneficial effects of SB, suggesting that the improved swimming performance was autophagy-dependent. Furthermore, intraperitoneal injection of SB to wild type mice resulted in increased levels of neuronal LC3B levels, indicating induction of autophagy within the brain. Collectively, our findings suggest that SB can induce activity of the autophagy pathway and can produce beneficial effects in vitro and in vivo. We propose that treatment with sodium butyrate warrants further investigation for the treatment of neurodegenerative diseases underpinned by proteinopathy mechanisms, including MJD.

Soluble Thrombomodulin Purified from Human Urine Exhibits a Potent Anticoagulant Effect In Vitro and In Vivo

1995 ◽  
Vol 73 (05) ◽  
pp. 805-811 ◽  
Author(s):  
Yasuo Takahashi ◽  
Yoshitaka Hosaka ◽  
Hiromi Niina ◽  
Katsuaki Nagasawa ◽  
Masaaki Naotsuka ◽  
...  
Keyword(s):  
Human Urine ◽  
Specific Activity ◽  
Anticoagulant Activity ◽  
Rabbit Lung ◽  
Soluble Thrombomodulin ◽  
Molecular Weights ◽  
Dose Dependent Fashion ◽  
Dose Dependent

SummaryWe examined the anticoagulant activity of two major molecules of soluble thrombomodulin purified from human urine. The apparent molecular weights of these urinary thrombomodulins (UTMs) were 72,000 and 79,000, respectively. Both UTMs showed more potent cofactor activity for protein C activation [specific activity >5,000 thrombomodulin units (TMU)/mg] than human placental thrombomodulin (2,180 TMU/mg) and rabbit lung thrombomodulin (1,980 TMU/mg). The UTMs prolonged thrombin-induced fibrinogen clotting time (>1 TMU/ml), APTT (>5 TMU/ml), TT (>5 TMU/ml) and PT (>40 TMU/ml) in a dose-dependent fashion. These effects appeared in the concentration range of soluble thrombomodulins present in human plasma and urine. In the rat DIC model induced by thromboplastin, administration of UTMs by infusion (300-3,000 TMU/kg) restored the hematological abnormalities derived from DIC in a dose-dependent fashion. These results demonstrate that UTMs exhibit potent anticoagulant and antithrombotic activities, and could play a physiologically important role in microcirculation.

Novel Phospholipid-Based Labrasol Nanomicelles Loaded Flavonoids for Oral Delivery with Enhanced Penetration and Anti-Brain Tumor Efficiency

2020 ◽  
Vol 17 (3) ◽  
pp. 229-245
Author(s):  
Gang Wang ◽  
Junjie Wang ◽  
Rui Guan
Keyword(s):  
Drug Delivery ◽  
Brain Tumor ◽  
Oral Delivery ◽  
Safe Delivery ◽  
Drug Delivery Vehicles ◽  
Therapeutic Benefits ◽  
Delivery Vehicles ◽  
The Brain

Background: Owing to the rich anticancer properties of flavonoids, there is a need for their incorporation into drug delivery vehicles like nanomicelles for safe delivery of the drug into the brain tumor microenvironment. Objective: This study, therefore, aimed to prepare the phospholipid-based Labrasol/Pluronic F68 modified nano micelles loaded with flavonoids (Nano-flavonoids) for the delivery of the drug to the target brain tumor. Methods: Myricetin, quercetin and fisetin were selected as the initial drugs to evaluate the biodistribution and acute toxicity of the drug delivery vehicles in rats with implanted C6 glioma tumors after oral administration, while the uptake, retention, release in human intestinal Caco-2 cells and the effect on the brain endothelial barrier were investigated in Human Brain Microvascular Endothelial Cells (HBMECs). Results: The results demonstrated that nano-flavonoids loaded with myricetin showed more evenly distributed targeting tissues and enhanced anti-tumor efficiency in vivo without significant cytotoxicity to Caco-2 cells and alteration in the Trans Epithelial Electric Resistance (TEER). There was no pathological evidence of renal, hepatic or other organs dysfunction after the administration of nanoflavonoids, which showed no significant influence on cytotoxicity to Caco-2 cells. Conclusion: In conclusion, Labrasol/F68-NMs loaded with MYR and quercetin could enhance antiglioma effect in vitro and in vivo, which may be better tools for medical therapy, while the pharmacokinetics and pharmacodynamics of nano-flavonoids may ensure optimal therapeutic benefits.

Phenolic Acids Exert Anticholinesterase and Cognition-Improving Effects

2018 ◽  
Vol 15 (6) ◽  
pp. 531-543 ◽  
Author(s):  
Dominik Szwajgier ◽  
Ewa Baranowska-Wojcik ◽  
Kamila Borowiec
Keyword(s):  
Phenolic Acids ◽  
Ex Vivo ◽  
Amyloid Β ◽  
Inhibitory Effect ◽  
In Vivo Studies ◽  
Amyloid Β Peptide ◽  
Beneficial Effects ◽  
Aβ Fibrils

Numerous authors have provided evidence regarding the beneficial effects of phenolic acids and their derivatives against Alzheimer's disease (AD). In this review, the role of phenolic acids as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is discussed, including the structure-activity relationship. In addition, the inhibitory effect of phenolic acids on the formation of amyloid β-peptide (Aβ) fibrils is presented. We also cover the in vitro, ex vivo, and in vivo studies concerning the prevention and treatment of the cognitive enhancement.

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