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Asian Pacific Journal of Cancer... Jun 2024Molecular docking is a key tool in structural molecular biology and computer-assisted drug design. Oral carcinogenesis is a complex, multistep process in which genetic...
OBJECTIVE
Molecular docking is a key tool in structural molecular biology and computer-assisted drug design. Oral carcinogenesis is a complex, multistep process in which genetic events within signal transduction pathways governing normal cellular physiology are quantitatively or qualitatively altered. There are various molecular targets like Cyclin D and PI3k- alpha Ras Binding Domain receptor protein involved in the pathogenesis of Oral Squamous Cell Carcinoma. The aim of the study is to demonstrate the computer aided drug design to identify a potent natural molecule for targeting cyclin D4 and PI3K RAS binding protein.
MATERIALS AND METHODS
Target selection (Cyclin D1 and PI3K-alpha Ras Binding Domain receptor) was done and structures were derived from protein data bank. Ligands (Apigenin, Chrysoeriol and Luteolin) selection was done and structure derived. Final docking was performed by Autodock.
RESULTS
From the docking results it can be seen that luteolin has the highest binding energy (-5.45) with the Cyclin D receptor molecule followed by Chrysoeriol (-4.99) and Apigenin (-4.96). The binding energies of the ligands against PI3K-alpha Ras Binding Domain receptors were Apigenin (-4.51), Chrysoeriol (-4.6) and Luteolin (-4.56).
CONCLUSION
The study concludes that all the three selected ligands possess high binding energy with both the target proteins involved in carcinogenesis with highest binding energy possessed by Luteolin against the Cyclin D receptor and by Chrysoeriol against PI3K-RAS binding protein. Thus their activity can be utilized to derive potential Anti-cancer therapeutic drugs.
Topics: Humans; Molecular Docking Simulation; Mouth Neoplasms; Phytochemicals; Ligands; Biomarkers, Tumor; Cyclin D1; Apigenin; Carcinoma, Squamous Cell; Luteolin; Computer Simulation
PubMed: 38918669
DOI: 10.31557/APJCP.2024.25.6.2069 -
Chemical Composition, Nutritional Value, Antioxidative, and Anti-inflammatory Activities of Cladode.ACS Omega Jun 2024The cactus family plant has been used in folk medicine for a long time. In this work, chemical composition and its antioxidative and anti-inflammatory properties were...
The cactus family plant has been used in folk medicine for a long time. In this work, chemical composition and its antioxidative and anti-inflammatory properties were investigated. Our results showed that is highly rich in fibers and minerals. The present study assessed the levels of polyphenol contents and antioxidant and in vivo anti-inflammatory activities. The highest phenolic compounds and antioxidant activity were observed in the methanolic extract. Concerning the qualitative analysis, nine phenolic and organic acids were identified and quantified by high-performance liquid chromatography (HPLC). Luteolin-7-Glu (4.25 μg/g), apigenin-7-Glu (3.15 μg/g), and catechin (2.85 μg/g) were identified as major phenolic compounds. The predominant fatty acids detected by gas chromatography (GC) coupled to a flame ionization detector were linoleic and linolenic acids (35.11%). A factorial design plan was used to determine the effect of temperature, agitation speed, and maceration period on phenolic contents. , the methanol extract from showed anti-inflammatory activity. The computational modeling reveals that compounds bind VEGF, IL-6, and TNF-α with high binding scores that reach -8.7 kcal/mol and establish significant molecular interactions with some key residues that satisfactorily explain both and findings. These data indicate that cladode powder could be potentially useful in pharmaceutical and food applications.
PubMed: 38911808
DOI: 10.1021/acsomega.4c04330 -
Biomedicine & Pharmacotherapy =... Jun 2024Apigenin, a natural bioflavonoid, is reported as an anti-diabetic agent since it possesses the ability to inhibit α-glucosidase activity, cause stimulation of insulin...
AIM
Apigenin, a natural bioflavonoid, is reported as an anti-diabetic agent since it possesses the ability to inhibit α-glucosidase activity, cause stimulation of insulin action and secretion, manage ROS, and prevent diabetes complications. Apigenin was identified as a new insulin secretagogue that enhances glucose-stimulated insulin secretion and seems like a better antidiabetic drug candidate. Here we explored the insulinotropic mechanism(s) of apigenin in vitro in mice islets and in vivo in diabetic rats.
METHODS
Size-matched pancreatic islets were divided into groups and incubated in the presence or absence of apigenin and agonists or antagonists of major insulin signaling pathways. The secreted insulin was measured by ELISA. The intracellular cAMP was estimated by cAMP acetylation assay. The acute and chronic effects of apigenin were evaluated in diabetic rats.
RESULTS
apigenin dose-dependently enhanced insulin secretion in isolated mice islets, and its insulinotropic effect was exerted at high glucose concentrations distinctly different from glibenclamide. Furthermore, apigenin amplified glucose-induced insulin secretion in depolarized and glibenclamide-treated islets. Apigenin showed no effect on intracellular cAMP concentration; however, an additive effect was observed by apigenin in both forskolin and IBMX-induced insulin secretion. Interestingly, H89, a PKA inhibitor, and U0126, a MEK kinase inhibitor, significantly inhibited apigenin-induced insulin secretion; however, no significant effect was observed by using ESI-05, an epac2 inhibitor. Apigenin improved glucose tolerance and increased glucose-stimulated plasma insulin levels in diabetic rats. Apigenin also lowered blood glucose in diabetic rats upon chronic treatment.
CONCLUSION
Apigenin exerts glucose-stimulated insulin secretion by modulating the PKA-MEK kinase signaling cascade independent of K-ATP channels.
PubMed: 38906017
DOI: 10.1016/j.biopha.2024.116986 -
Molecules (Basel, Switzerland) Jun 2024Gilli is a rare annual wild herb grown in Libya. It belongs to the Apiaceae family, which is one of the largest flowering plant families. Plants of this family are... (Comparative Study)
Comparative Study
Gilli is a rare annual wild herb grown in Libya. It belongs to the Apiaceae family, which is one of the largest flowering plant families. Plants of this family are outstanding sources of various secondary metabolites with various biological activities. A UPLC-ESI-MS/MS analysis of different extracts of in vivo and in vitro tissues of together with the fruit extract of the cultivated plant in both ionization modes was carried out for the first time in the current study. Our results reveal the tentative identification of eighty-seven compounds in the tested extracts, including thirty-two phenolic acids and their derivatives; thirty-seven flavonoid glycosides and aglycones of apigenin, luteolin, diosmetin, myricetin and quercetin, containing glucose, rhamnose, pentose and/or glucuronic acid molecules; seven anthocyanins; six tannins; three acetylenic compounds; and three nitrogenous compounds. The tentative identification of the above compounds was based on the comparison of their retention times and ESI-MS/MS fragmentation patterns with those previously in the literature. For this Apiaceae plant, our results confirm the presence of a wide array of secondary metabolites with reported biological activities. This study is among the first ones to shed light on the phytoconstituents of this rare plant.
Topics: Plant Extracts; Tandem Mass Spectrometry; Spectrometry, Mass, Electrospray Ionization; Chromatography, High Pressure Liquid; Secondary Metabolism; Flavonoids; Methanol; Apiaceae; Fruit
PubMed: 38893577
DOI: 10.3390/molecules29112694 -
Molecules (Basel, Switzerland) Jun 2024Apigenin, a naturally derived flavonoid, is increasingly being acknowledged for its potential therapeutic applications, especially in oncology. This research explores...
Apigenin, a naturally derived flavonoid, is increasingly being acknowledged for its potential therapeutic applications, especially in oncology. This research explores apigenin's capacity to modulate cancer cell viability, emphasizing its roles beyond its minimal antioxidant activity attributed to its basic molecular structure devoid of hydroxyl groups. We investigated apigenin's effects on two breast cancer cell lines, estrogen-dependent MCF-7 and non-estrogen-dependent MDA-MB-231 cells. Our findings reveal that apigenin exerts a dose-dependent cytotoxic and anti-migratory impact on these cells. Interestingly, both apigenin and doxorubicin-a standard chemotherapeutic agent-induced lipid droplet accumulation in a dose-dependent manner in MDA-MB-231 cells. This phenomenon was absent in MCF-7 cells and not evident when doxorubicin and apigenin were used concurrently, suggesting distinct cellular responses to these treatments that imply that their synergistic effects might be mediated through mechanisms unrelated to lipid metabolism. A further chemoinformatics analysis indicated that apigenin and doxorubicin might interact primarily at the level of ATP-binding cassette (ABC) transporter proteins, with potential indirect influences from the AKT and MYC signaling pathways. These results highlight the importance of understanding the nuanced interactions between apigenin and conventional chemotherapeutic drugs, as they could lead to more effective strategies for cancer treatment. This study underscores apigenin's potential as a modulator of cancer cell dynamics through mechanisms independent of its direct antioxidant effects, thereby contributing to the development of flavonoid-based adjunct therapies in cancer management.
Topics: Humans; Apigenin; Doxorubicin; Breast Neoplasms; Female; Cell Line, Tumor; Cell Survival; MCF-7 Cells; Cell Movement; Signal Transduction; Cell Proliferation; Drug Synergism
PubMed: 38893482
DOI: 10.3390/molecules29112603 -
Molecules (Basel, Switzerland) May 2024var. (Lamiaceae) is widely used not only as an oil or a spice, but also as a traditional medicine to treat colds, coughs, fever, and indigestion. As an ongoing effort,...
var. (Lamiaceae) is widely used not only as an oil or a spice, but also as a traditional medicine to treat colds, coughs, fever, and indigestion. As an ongoing effort, luteolin-7--diglucuronide (), apigenin-7--diglucuronide (), and rosmarinic acid () isolated from var. were investigated for their anti-adipogenic and thermogenic activities in 3T3-L1 cells. Compound exhibited a strong inhibition against adipocyte differentiation by suppressing the expression of and over 52.0% and 45.0%, respectively. Moreover, inhibited the expression of those genes in a dose-dependent manner [: 41.7% (5 µM), 62.0% (10 µM), and 81.6% (50 µM); : 13.8% (5 µM), 18.4% (10 µM), and 37.2% (50 µM)]. On the other hand, the var. water extract showed moderate thermogenic activities. Compounds and also induced thermogenesis in a dose-dependent manner by stimulating the mRNA expressions of , , and . Moreover, an LC-MS/MS chromatogram of the extract was acquired using UHPLC-MS and it was analyzed by feature-based molecular networking (FBMN) and the Progenesis QI software (version 3.0). The chemical profiling of the extract demonstrated that flavonoids and their glycoside derivatives, including those isolated earlier as well as rosmarinic acid, are present in var. .
Topics: Mice; Perilla frutescens; Animals; Plant Extracts; 3T3-L1 Cells; Depsides; Anti-Obesity Agents; Cinnamates; Rosmarinic Acid; Adipogenesis; Adipocytes; Cell Differentiation; Obesity; Thermogenesis
PubMed: 38893341
DOI: 10.3390/molecules29112465 -
Foods (Basel, Switzerland) May 2024Herbal teas have attracted attention as functional beverages containing luteolin and apigenin, which exhibit antioxidant and anti-inflammatory effects. The objective of...
Herbal teas have attracted attention as functional beverages containing luteolin and apigenin, which exhibit antioxidant and anti-inflammatory effects. The objective of this study was to develop a sensitive online automated method to determine these flavones' contents in herbal teas using in-tube solid-phase microextraction (IT-SPME) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). These compounds were extracted and concentrated by IT-SPME using a Supel Q PLOT capillary column and then separated and detected within 6 min using a CAPCELL PAK C18 MG III analytical column and a negative electrospray ionization-mode multiple-reaction monitoring system by LC-MS/MS. The detection limits ( = 3) for luteolin and apigenin were 0.4 and 0.8 pg mL, respectively, and the calibration curves were linear in the range of 2-2000 pg mL with correlation coefficients above 0.9995, and intra-day and inter-day precisions with relative standard deviations below 2.9 and 3.6% ( = 6), respectively. The luteolin and apigenin in herbal tea were quantified using IT-SPME/LC-MS/MS following the acid hydrolysis of their glycosides. Among the 10 herbal teas tested, luteolin was detected in peppermint and sage at concentrations of 375 and 99 µg mL, respectively, while apigenin was detected in German chamomile at 110 µg mL, which were higher than in the other herbal teas. The method is expected to be a useful method for evaluating the efficacy of luteolin and apigenin in herbal teas as functional beverages.
PubMed: 38890915
DOI: 10.3390/foods13111687 -
RSC Advances Jun 2024This study explored the flavonoid-rich extract of beetroot ( L.) for type 2 diabetes mellitus (T2D) and Alzheimer's disease (AD) dual therapy by using and molecular...
This study explored the flavonoid-rich extract of beetroot ( L.) for type 2 diabetes mellitus (T2D) and Alzheimer's disease (AD) dual therapy by using and molecular simulation studies. Flavonoid-rich extracts of fruit were evaluated for their antidiabetic and anti-alzheimic activities. Molecular docking and dynamic simulation were performed to identify potential bioactive flavonoids with dual therapeutic effects on T2D and AD. Flavonoid-rich extracts of fruit (IC = 73.062 ± 0.480 μg mL) had moderate activity against α-amylase compared to the standard acarbose (IC = 27.104 ± 0.270 μg mL). Compared with acarbose, flavonoid-rich extracts of fruit had appreciable activity against α-glucosidase (IC = 17.389 ± 0.436 μg mL) (IC = 37.564 ± 0.620 μg mL). For AChE inhibition, flavonoid-rich extracts of fruit exhibited ( < 0.0001) inhibitory activity (IC = 723.260 ± 5.466 μg mL), albeit weaker than that of the standard control, galantamine (IC = 27.950 ± 0.122 μg mL). Similarly, flavonoid-rich extracts of fruit showed considerable ( < 0.0001) inhibitory effects on BChE (IC = 649.112 ± 0.683 μg mL). In contrast, galantamine (IC = 23.126 ± 0.683 μg mL) is more potent than the extracts of fruit. Monoamine oxidase (MAO) activity increased in FeSO-induced brain damage. In contrast, flavonoid-rich extracts of fruit protected against Fe-mediated brain damage by suppressing MAO activity in a concentration-dependent manner. HPLC-DAD profiling of the extracts identified quercetrin, apigenin, rutin, myricetin, iso-quercetrin, -coumaric acid, ferulic acid, caffeic acid, and gallic acid. Molecular docking studies revealed quercetrin, apigenin, rutin, iso-queretrin, and myricetin were the top docked bioactive flavonoids against the five top target proteins (α-amylase, α-glucosidase AchE, BchE, and MAO). Molecular dynamic simulations revealed that the complexes formed remained stable over the course of the simulation. Collectively, the findings support the prospect of flavonoid-rich extracts of root functioning as a dual therapy for T2D and AD.
PubMed: 38887650
DOI: 10.1039/d4ra03638g -
ACS Omega Jun 2024Apigenin, a flavonoid, is reported to have multiple health benefits including cancer prevention; this study evaluates the drug likeliness and Swiss ADME properties of...
Apigenin, a flavonoid, is reported to have multiple health benefits including cancer prevention; this study evaluates the drug likeliness and Swiss ADME properties of apigenin. Apoptosis, which is a key hallmark of cancer, is associated with the deregulation of the balance between proapoptotic proteins and antiapoptotic proteins such as BCL-2,BCL-xl, BFL-1, BCL-w, BRAG-16, and MCL-1. The docking studies of apigenin with the mentioned proteins was performed to identify the interactions between the ligand and proteins, which suggested that apigenin was able to bind to most of the proteins similar to the inhibitory molecules of its native structure. A remarkable reduction in the total energy after energy minimization of apigenin-antiapoptotic protein complexes suggested increased stability of the docked complexes. The same complexes were found to be stable over a 10 ns period of molecular simulation at 300 K. These findings advocated the study to evaluate apigenin's potential to inhibit the HeLa cells at 5, 10, and 15 μM concentrations in the clonogenic assay. Apigenin inhibited the colony-forming ability of HeLa cells in a dose-dependent manner over a fortnight. Light microscopy of the treated cells displayed the morphological evidence characteristic of apoptosis in HeLa cells such as blebbing, spike formation, cytoplasmic oozing, and nuclear fragmentation. Thus, these results clearly indicate that apigenin may be used as a potential chemopreventive agent in cervical cancer management.
PubMed: 38882173
DOI: 10.1021/acsomega.4c01300 -
Translational Cancer Research May 2024Apigenin is a natural flavonoid compound with proven antitumor activity. However, its precise underlying pharmacological mechanism remains unclear. Oxaliplatin (OXA) is...
BACKGROUND
Apigenin is a natural flavonoid compound with proven antitumor activity. However, its precise underlying pharmacological mechanism remains unclear. Oxaliplatin (OXA) is commonly utilized for cancer treatment as a platinum-based chemotherapy drug. However, the utilization of low-dose OXA carries the risk of inducing epithelial-mesenchymal transition (EMT) in cancer cells and promoting tumor metastasis, thereby giving rise to potential side effects. The purpose of this study is to investigate the synergistic inhibitory effect of apigenin and OXA and its potential mechanism.
METHODS
HSC-3 cells of oral squamous carcinoma cells (OSCCs) were divided into control, apigenin-treated and co-treated groups. A wound healing assay was conducted to assess alterations in cellular motility and migration, an invasion assay was performed to assess invasiveness, and a three-dimensional culture assay was employed to evaluate angiogenic capacity. Cultured cells were utilized for total DNA extraction, followed by reverse transcription. Relative RNA levels were obtained, and quantitative polymerase chain reaction (qPCR) analysis was conducted to assess the efficiency of LINC00857 expression.
RESULTS
The administration of a low dose of OXA promoted the migratory, invasive, and angiogenic capabilities of HSC-3 cells, while also regulating EMT-associated molecular markers to facilitate the process of EMT. The inhibitory impact on OSCC proliferation was enhanced by the synergistic effect of apigenin and OXA. Furthermore, the tumor-promoting effects induced by low-dose OXA were notably suppressed through LINC00857.
CONCLUSIONS
Evidence from this study indicates that apigenin can effectively suppress the metastasis of OSCC cancer cells induced by low-dose OXA through inhibiting the level of LINC00857, suggesting a promising therapeutic strategy.
PubMed: 38881938
DOI: 10.21037/tcr-23-2335