scholarly journals In silico Docking Studies of Antiglycation Activity of Isorhamnetin on Molecular Proteins of Advanced Glycation end Product (AGE) Pathway

2021 ◽  
Vol 14 (4) ◽  
pp. 2299-2306
Author(s):  
Sindhuja A Sindhuja A ◽  
Vimalavathini R Vimalavathini R ◽  
Kavimani S Kavimani S
Keyword(s):  
Radical Scavenging ◽  
Camp Response Element Binding ◽  
Docking Studies ◽  
Hydroxyl Group ◽  
Advanced Glycation ◽  
In Silico Docking ◽  
Advanced Glycation End Product ◽  
Extracellular Signal ◽  
Element Binding Protein ◽  
And Function

Advanced glycation end products (AGEs) are formed excessively in pathological conditions due to non - enzymatic glycation of proteins, lipids or nucleic acids, affecting their structure and function. Isorhamnetin is a naturally occurring flavonoid with anti-inflammatory, anti-oxidant, anti-obesity, anticancer, anti-diabetic and anti-atherosclerosis activity. Structure activity studies of isorhamnetin reveal the presence of hydroxyl group in the B-ring of isorhamnetin may contribute to antiglycation activity. Hence we hypothised that isorhamnetin may have antiglycation activity owing to its structure as well as antioxidant and free radical scavenging activities by modulating various AGE pathway proteins. The aim of our study was to determine the antiglycation activity of isorhamnetin by targeting various molecular proteins of AGE pathway using insilico docking. The structure of isorhamnetin was imported and drawn in Marvin sketch (version 6. 3. 0). Nearly 17 molecular proteins of AGE pathway were docked with isorhamnetin using autodock tools 4.2 (version 1. 5. 6) software. The present study showed that isorhamnetin exhibited good docking profiles with receptor for advanced glycation End product (RAGE), protein kinase B (PKB/Akt2), activating transcription factor4 (ATF4), cAMP response element-binding protein (CREB), extracellular signal regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3-K) and signal transducer and activator of transcription (STAT) indicating it may exert good antiglycation activity by modulating these proteins of AGE pathways. However further invitro and invivo studies are required to establish the antiglycation activity of isorhamnetin.

scholarly journals Synthesis, Bioactivity, Pharmacokinetic and Biomimetic Properties of Multi-Substituted Coumarin Derivatives

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5999
Author(s):  
Annita Katopodi ◽  
Evangelia Tsotsou ◽  
Triantafylia Iliou ◽  
Georgia-Eirini Deligiannidou ◽  
Eleni Pontiki ◽  
...  
Keyword(s):  
Cell Viability ◽  
Oral Absorption ◽  
Radical Scavenging ◽  
Human Keratinocytes ◽  
Docking Studies ◽  
Hydroxyl Group ◽  
Coumarin Derivatives ◽  
In Silico Docking ◽  
A375 Cells

A series of novel multi-substituted coumarin derivatives were synthesized, spectroscopically characterized, and evaluated for their antioxidant activity, soybean lipoxygenase (LOX) inhibitory ability, their influence on cell viability in immortalized human keratinocytes (HaCaT), and cytotoxicity in adenocarcinomic human alveolar basal epithelial cells (A549) and human melanoma (A375) cells, in vitro. Coumarin analogues 4a–4f, bearing a hydroxyl group at position 5 of the coumarin scaffold and halogen substituents at the 3-phenyl ring, were the most promising ABTS•+ scavengers. 6,8-Dibromo-3-(4-hydroxyphenyl)-4-methyl-chromen-2-one (4k) and 6-bromo-3-(4,5-diacetyloxyphenyl)-4-methyl-chromen-2-one (3m) exhibited significant lipid peroxidation inhibitory activity (IC50 36.9 and 37.1 μM). In the DCF-DA assay, the 4′-fluoro-substituted compound 3f (100%), and the 6-bromo substituted compounds 3i (80.9%) and 4i (100%) presented the highest activity. The 3′-fluoro-substituted coumarins 3e and 4e, along with 3-(4-acetyloxyphenyl)-6,8-dibromo-4-methyl-chromen-2-one (3k), were the most potent lipoxygenase (LOX) inhibitors (IC50 11.4, 4.1, and 8.7 μM, respectively) while displaying remarkable hydroxyl radical scavenging ability, 85.2%, 100%, and 92.9%, respectively. in silico docking studies of compounds 4e and 3k, revealed that they present allosteric interactions with the enzyme. The majority of the analogues (100 μΜ) did not affect the cell viability of HaCaT cells, though several compounds presented over 60% cytotoxicity in A549 or A375 cells. Finally, the human oral absorption (%HOA) and plasma protein binding (%PPB) properties of the synthesized coumarins were also estimated using biomimetic chromatography, and all compounds presented high %HOA (>99%) and %PPB (60–97%) values.

scholarly journals Effect of FermentedSpirulina maximaExtract on Cognitive-Enhancing Activities in Mice with Scopolamine-Induced Dementia

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Woon Yong Choi ◽  
Do Hyung Kang ◽  
Hyeon Yong Lee
Keyword(s):  
Escape Latency ◽  
Antioxidant Activities ◽  
Synergistic Effects ◽  
Camp Response Element Binding ◽  
Positive Control ◽  
Initial Increase ◽  
Latency Time ◽  
Bioactive Substances ◽  
Extracellular Signal ◽  
Element Binding Protein

This work provides the first demonstration thatSpirulina maximaextract fermented with the lactic acid bacteriumLactobacillus planetariumHY-08 has the ability to ameliorate scopolamine-induced memory impairment in mice. The fermented extract exhibited good cognitive-enhancing activities, as demonstrated through Morris water maze and passive avoidance experiments: in these tests, the mice administered the fermented extract at a dose of 400 mg/kg exhibited an escape latency time and a latency time of 88.5 and 76.0 sec, respectively, whereas those administered donepezil, which was used as a positive control, showed an escape latency time and a latency time of 81.3 and 83.3 sec, respectively. However, an extract of 200 mg/kg was considered economically feasible for maintaining relatively high memory-improving activities because only a slight difference in activities was found between 200 and 400 mg/kg. The study also provides the first demonstration thatβ-carotene, one of the major bioactive substances inS. maxima, has memory-enhancing activity. A detailed analysis of the mechanism for the cognitive-enhancing activities of the fermented extract revealed that the fermented extract effectively increased the phosphorylation of both extracellular signal-regulated kinases (p-ERK) and p-cAMP response element-binding protein (p-CREB) and sequentially upregulated the expression of brain-derived neurotrophic factor (BDNF), whose signaling pathway responds to a reduction in oxidative stress in the brain. The results indicate that the improved efficacy of the fermented extract was likely due to the synergistic effects ofβ-carotene and other bioactive substances. Therefore, it can be concluded that the fermented extract exerts memory-improving effects in the hippocampus of scopolamine-treated mice through an initial increase in ERK signaling and a sequential induction of the expression of p-CREB and BDNF, and these effects are related to the antioxidant activities ofβ-carotene and other components.

scholarly journals Stimulation of Phosphorylation of ERK and CREB by Phellopterin and Auraptene Isolated from Citrus junos

2014 ◽  
Vol 9 (10) ◽  
pp. 1934578X1400901 ◽  
Author(s):  
Mitsuhiro Nakamura ◽  
Tomoko Suzuki ◽  
Mai Takagi ◽  
Hirotoshi Tamura ◽  
Toshiya Masuda
Keyword(s):  
Camp Response Element Binding ◽  
Long Term Memory ◽  
Camp Response Element ◽  
Extracellular Signal Regulated Kinase ◽  
Cellular Processes ◽  
Extracellular Signal ◽  
Citrus Junos ◽  
Element Binding Protein ◽  
Methyl Ferulate

Bioactive compounds from citrus fruits contribute many benefits to human health. Extracellular signal-regulated kinase (ERK) signaling plays an important role in the regulation of multiple cellular processes. Activation of the ERK-cAMP response element binding protein (CREB) signaling is required for long-term memory formation. In this study, auraptene, phellopterin, thymol, coniferyl alcohol 9-methyl ether and methyl ferulate were isolated from Citrus junos. Among the five compounds isolated, auraptene and phellopterin increased the phosphorylation of ERK and CREB. This study provides, to our knowledge, the first evidence that phellopterin potently stimulates the phosphorylation of ERK and CREB. Phellopterin could be a novel neuroprotective agent.

scholarly journals Extracts ofArtocarpus communisDecreaseα-Melanocyte Stimulating Hormone-Induced Melanogenesis through Activation of ERK and JNK Signaling Pathways

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Yi-Tzu Fu ◽  
Chiang-Wen Lee ◽  
Horng-Huey Ko ◽  
Feng-Lin Yen
Keyword(s):  
Skin Diseases ◽  
Folk Medicine ◽  
Camp Response Element Binding ◽  
Melanin Content ◽  
Agricultural Plant ◽  
Melanocyte Stimulating Hormone ◽  
B16f10 Cells ◽  
Extracellular Signal ◽  
Element Binding Protein ◽  
Stimulating Hormone

Artocarpus communisis an agricultural plant that is also used in folk medicine to prevent skin diseases, including acne and dermatitis. Extracts ofA. communishave been used to effectively inhibit melanogenesis; however, the antimelanogenesis mechanism of these extracts has not yet been investigated. The present study utilized a cell-free tyrosinase assay as well asα-melanocyte stimulating hormone- (-MSH-) induced tyrosinase assay conducted in B16F10 cells, performed a cytotoxicity assay, and determined cellular melanin content to examine the effects of a methanolic extract ofA. communis(ACM) and various organic partition fractions ofA. communison melanogenesis. In addition, we performed western blot analysis to elucidate the mechanism of their antimelanogenesis effect. Our results indicated that, except for the n-hexane extract, ACM and the various partition extracts at noncytotoxic concentrations effectively decreased melanin content and tyrosinase activity by downregulating microphthalmia-associated transcription factor (MITF) and phosphorylated cAMP response element-binding protein (p-CREB). Moreover, ACM and the partition fractions activated phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) to inhibit the synthesis of MITF and finally to decrease melanin production. In conclusion, we suggest that noncytotoxic concentrations of ACM and the various partition fractions may be useful as references for developing skin-lighting agents for use in medicines or cosmetics.

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