scholarly journals Aldose Reductase Inhibitory Activity of Compounds from  Zea maysL.

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Tae Hyeon Kim ◽  
Jin Kyu Kim ◽  
Young-Hee Kang ◽  
Jae-Yong Lee ◽  
Il Jun Kang ◽  
...  
Keyword(s):  
Zea Mays ◽  
Aldose Reductase ◽  
Inhibitory Activity ◽  
Diabetes Complications ◽  
Therapeutic Agent ◽  
Competitive Inhibition ◽  
Therapeutic Potential ◽  
High Concentration ◽  
Etoh Extract ◽  
Bioassay Guided Fractionation

Aldose reductase (AR) inhibitors have a considerable therapeutic potential against diabetes complications and do not increase the risk of hypoglycemia. Through bioassay-guided fractionation of an EtOH extract of the kernel from purple corn (Zea maysL.), 7 nonanthocyanin phenolic compounds (compound1–7) and 5 anthocyanins (compound8–12) were isolated. These compounds were investigated by rat lens aldose reductase (RLAR) inhibitory assays. Kinetic analyses of recombinant human aldose reductase (rhAR) were performed, and intracellular galactitol levels were measured. Hirsutrin, one of 12 isolated compounds, showed the most potent RLAR inhibitory activity (IC50, 4.78 μM). In the kinetic analyses using Lineweaver-Burk plots of 1/velocity and 1/substrate concentration, hirsutrin showed competitive inhibition against rhAR. Furthermore, hirsutrin inhibited galactitol formation in rat lens and erythrocytes sample incubated with a high concentration of galactose; this finding indicates that hirsutrin may effectively prevent osmotic stress in hyperglycemia. Therefore, hirsutrin derived fromZea maysL. may be a potential therapeutic agent against diabetes complications.

scholarly journals Anti-Acetylcholinesterase Alkaloids from Annona glabra Leaf

2015 ◽  
Vol 10 (6) ◽  
pp. 1934578X1501000
Author(s):  
Shoei-Sheng Lee ◽  
Dong-Yi Wu ◽  
Sheng-Fa Tsai ◽  
Chien-Kuang Chen
Keyword(s):  
Inhibitory Activity ◽  
Spectroscopic Analysis ◽  
Etoh Extract ◽  
Bioassay Guided Fractionation ◽  
Annona Glabra

Bioassay guided fractionation and separation of the EtOH extract of Annona glabra leaf against acetylcholinesterse led to the characterization of 15 alkaloids. Among them, (–)-actinodaphnine (2) and (–)-(6a S,7 R)-7-hydroxyactinodaphnine (9) are new aporphines, although (+)-2 and (±)-2 have been found in several plants. Their structures were established by spectroscopic analysis. (-)-Anolobine (5) and (-)-roemeroline (8) showed moderate inhibitory activity against eel acetylcholinesterase with IC50 values of 22.4 and 26.3 μM, respectively.

Rat lens aldose reductase inhibitory activity of Aralia continentalis

Planta Medica ◽  
2016 ◽  
Vol 81 (S 01) ◽  
pp. S1-S381
Author(s):  
JP Rodriguez ◽  
S Cho ◽  
J Lee ◽  
KH Lee ◽  
T Jin ◽  
...  
Keyword(s):  
Aldose Reductase ◽  
Inhibitory Activity ◽  
Aralia Continentalis ◽  
Rat Lens Aldose Reductase

From Ocean to Bedside: the Therapeutic Potential of Molluscan Hemocyanins

2018 ◽  
Vol 25 (20) ◽  
pp. 2292-2303 ◽  
Author(s):  
Negar Talaei Zanjani ◽  
Monica Miranda Saksena ◽  
Fariba Dehghani ◽  
Anthony L. Cunningham
Keyword(s):  
Antiviral Activity ◽  
Clinical Efficacy ◽  
Mechanism Of Action ◽  
Therapeutic Agent ◽  
Marine Invertebrates ◽  
Therapeutic Potential ◽  
Biological Functions ◽  
Anticancer Properties ◽  
Mechanistic Understanding

Hemocyanins are large and versatile glycoproteins performing various immunological and biological functions in many marine invertebrates including arthropods and molluscs. This review discusses the various pharmacological applications of mollusc hemocyanin such as antiviral activity, immunostimulatory and anticancer properties that have been reported in the literature between the years 2000 and 2016. Emphasis is placed on a better mechanistic understanding of hemocyanin as a therapeutic agent. Elucidation of the mechanism of action is essential to improve the clinical efficacy and for a better understanding of some endogenous immunological functions of this complex glycoprotein.

Review of Medicinal Plants and their Compounds for Aldose Reductase Inhibitory Activity

2018 ◽  
Vol 15 (7) ◽  
pp. 796-812
Author(s):  
Saliha Bouknana ◽  
Mohamed Bouhrim ◽  
Hayat Ouassou ◽  
Mohamed Bnouham
Keyword(s):  
Medicinal Plants ◽  
Aldose Reductase ◽  
Inhibitory Activity

Synthesis and Investigation of Therapeutic Potential of Isoform-Specific HDAC8 Inhibitors for the Treatment of Cutaneous T Cell Lymphoma

2019 ◽  
Vol 19 (7) ◽  
pp. 916-934 ◽  
Author(s):  
Appavoo Umamaheswari ◽  
Ayarivan Puratchikody ◽  
Natarajan Hari
Keyword(s):  
Side Effects ◽  
Inhibitory Activity ◽  
Hydroxamic Acid ◽  
Histone Deacetylase Inhibitors ◽  
Therapeutic Potential ◽  
In Vitro Assays ◽  
Normal Cells ◽  
Standard Drug ◽  
In Silico Studies ◽  
Hdac8 Inhibitors

Background:The available treatment option for any type of cancer including CTCL is chemotherapy and radiation therapy which indiscriminately persuade on the normal cells. One way out for selective destruction of CTCL cells without damaging normal cells is the use of histone deacetylase inhibitors (HDACi). Despite promising results in the treatment of CTCL, these HDACi have shown a broadband inhibition profile, moderately selective for one HDAC class but not for a particular isotype. The prevalence of drug-induced side effects leaves open a narrow window of speculation that the decreased therapeutic efficacy and observed side effects may be most likely due to non specific HDAC isoform inhibition. The aim of this paper is to synthesis and evaluates HDAC8 isoform specific inhibitors.Methods:Based on the preliminary report on the design and in silico studies of 52 hydroxamic acid derivatives bearing multi-substituent heteroaromatic rings with chiral amine linker, five compounds were shortlisted and synthesized by microwave assisted approach and high yielding synthetic protocol. A series of in vitro assays in addition to HDAC8 inhibitory activity was used to evaluate the synthesised compounds.Results:Inhibitors 1e, 2e, 3e, 4e and 5e exerted the anti-proliferative activities against CTCL cell lines at 20- 100 µM concentrations. Both the pyrimidine- and pyridine-based probes exhibited μM inhibitory activity against HDAC8. The pyrimidine-based probe 1e displayed remarkable HDAC8 selectivity superior to that of the standard drug, SAHA with an IC50 at 0.1µM.Conclusion:Our study demonstrated that simple modifications at different portions of pharmacophore in the hydroxamic acid analogues are effective for improving both HDAC8 inhibitory activity and isoform selectivity. Potent and highly isoform-selective HDAC8 inhibitors were identified. These findings would be expedient for further development of HDAC8-selective inhibitors.

scholarly journals Therapeutic Features and Updated Clinical Trials of Mesenchymal Stem Cell (MSC)-Derived Exosomes

2021 ◽  
Vol 10 (4) ◽  
pp. 711
Author(s):  
Byung-Chul Lee ◽  
Insung Kang ◽  
Kyung-Rok Yu
Keyword(s):  
Clinical Trials ◽  
Therapeutic Agent ◽  
Therapeutic Potential ◽  
Therapeutic Option ◽  
Treatment Options ◽  
Genetic Material ◽  
Experimental Models ◽  
Attractive Alternative ◽  
Cell Based Therapy ◽  
Cellular Rejection

Identification of the immunomodulatory and regenerative properties of mesenchymal stem cells (MSCs) have made them an attractive alternative therapeutic option for diseases with no effective treatment options. Numerous clinical trials have followed; however, issues such as infusional toxicity and cellular rejection have been reported. To address these problems associated with cell-based therapy, MSC exosome therapy was developed and has shown promising clinical outcomes. MSC exosomes are nanosized vesicles secreted from MSCs and represent a non-cellular therapeutic agent. MSC exosomes retain therapeutic features of the cells from which they originated including genetic material, lipids, and proteins. Similar to MSCs, exosomes can induce cell differentiation, immunoregulation, angiogenesis, and tumor suppression. MSC exosomes have therefore been employed in several experimental models and clinical studies. Here, we review the therapeutic potential of MSC-derived exosomes and summarize currently ongoing clinical trials according to disease type. In addition, we propose several functional enhancement strategies for the effective clinical application of MSC exosome therapy.

scholarly journals The HGR motif is the antiangiogenic determinant of vasoinhibin: implications for a therapeutic orally active oligopeptide

Angiogenesis ◽  
2021 ◽  
Author(s):  
Juan Pablo Robles ◽  
Magdalena Zamora ◽  
Lourdes Siqueiros-Marquez ◽  
Elva Adan-Castro ◽  
Gabriela Ramirez-Hernandez ◽  
...  
Keyword(s):  
Therapeutic Agent ◽  
Clinical Evidence ◽  
Therapeutic Potential ◽  
Peripartum Cardiomyopathy ◽  
Loss Of Function ◽  
Functional Determinant ◽  
Melanoma Tumor ◽  
Linear Motif ◽  
Anti Cancer ◽  
Orally Active

AbstractThe hormone prolactin acquires antiangiogenic and antivasopermeability properties after undergoing proteolytic cleavage to vasoinhibin, an endogenous prolactin fragment of 123 or more amino acids that inhibits the action of multiple proangiogenic factors. Preclinical and clinical evidence supports the therapeutic potential of vasoinhibin against angiogenesis-related diseases including diabetic retinopathy, peripartum cardiomyopathy, rheumatoid arthritis, and cancer. However, the use of vasoinhibin in the clinic has been limited by difficulties in its production. Here, we removed this barrier to using vasoinhibin as a therapeutic agent by showing that a short linear motif of just three residues (His46-Gly47-Arg48) (HGR) is the functional determinant of vasoinhibin. The HGR motif is conserved throughout evolution, its mutation led to vasoinhibin loss of function, and oligopeptides containing this sequence inhibited angiogenesis and vasopermeability with the same potency as whole vasoinhibin. Furthermore, the oral administration of an optimized cyclic retro-inverse vasoinhibin heptapeptide containing HGR inhibited melanoma tumor growth and vascularization in mice and exhibited equal or higher antiangiogenic potency than other antiangiogenic molecules currently used as anti-cancer drugs in the clinic. Finally, by unveiling the mechanism that obscures the HGR motif in prolactin, we anticipate the development of vasoinhibin-specific antibodies to solve the on-going challenge of measuring endogenous vasoinhibin levels for diagnostic and interventional purposes, the design of vasoinhibin antagonists for managing insufficient angiogenesis, and the identification of putative therapeutic proteins containing HGR.

scholarly journals Development of Novel Indole-Based Bifunctional Aldose Reductase Inhibitors/Antioxidants as Promising Drugs for the Treatment of Diabetic Complications

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 2867
Author(s):  
Lucia Kovacikova ◽  
Marta Soltesova Prnova ◽  
Magdalena Majekova ◽  
Andrej Bohac ◽  
Cimen Karasu ◽  
...  
Keyword(s):  
Aldose Reductase ◽  
Diabetic Complications ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Biological Activities ◽  
In Vivo Models ◽  
Aldose Reductase Inhibitors ◽  
Reductase Inhibitors ◽  
Promising Therapeutic Approach

Aldose reductase (AR, ALR2), the first enzyme of the polyol pathway, is implicated in the pathophysiology of diabetic complications. Aldose reductase inhibitors (ARIs) thus present a promising therapeutic approach to treat a wide array of diabetic complications. Moreover, a therapeutic potential of ARIs in the treatment of chronic inflammation-related pathologies and several genetic metabolic disorders has been recently indicated. Substituted indoles are an interesting group of compounds with a plethora of biological activities. This article reviews a series of indole-based bifunctional aldose reductase inhibitors/antioxidants (ARIs/AOs) developed during recent years. Experimental results obtained in in vitro, ex vivo, and in vivo models of diabetic complications are presented. Structure–activity relationships with respect to carboxymethyl pharmacophore regioisomerization and core scaffold modification are discussed along with the criteria of ‘drug-likeness”. Novel promising structures of putative multifunctional ARIs/AOs are designed.

From mesenchymal stem cells and stromal cells - from bench to bedside

2019 ◽  
Vol 1 (1) ◽  
pp. 36-39
Author(s):  
Bernd Giebel ◽  
Verena Börger ◽  
Mario Gimona ◽  
Eva Rohde
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Stromal Cells ◽  
Therapeutic Agent ◽  
Therapeutic Potential ◽  
Therapeutic Effects ◽  
Cell Replacement ◽  
Beneficial Effects ◽  
Promising Tool

Human mesenchymal stem/stromal cells (MSCs) represent a promising tool in regenerative medicine. Until now, almost one thousand NIH-registered clinical trials investigated their immunomodulatory and pro-regenerative therapeutic potential in various diseases. Despite controversial reports regarding the efficacy of MSC-treatments, MSCs appear to exert their beneficial effects in a paracrine manner rather than by cell replacement. In this context, extracellular vesicles (EVs), such as exosomes and microvesicles, seem to induce the MSCs’ therapeutic effects. Here, we briefly illustrate the potential of MSC-EVs as therapeutic agent of the future.

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