Multiomics Identification of Potential Targets for Alzheimer Disease and Antrocin as a Therapeutic Candidate

Wu, Alexander T.H.; Lawal, Bashir; Li, Wei; Wen, Ya; Tzeng, David T.W.; Lo, Wen Cheng

doi:10.3390/pharmaceutics13101555

Cited by 24 publications

(16 citation statements)

References 76 publications

(83 reference statements)

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“…Furthermore, several van der Waals forces were found around the ligand backbones with the respective amino acid residues of receptors binding pockets would create strong cohesive environments, that stabilizes the receptor–ligand complexes. 75–77 Compared to epicatechin and procyanidin B2, the standard drugs acarbose and nicotinic acid demonstrated lower binding affinities to their respective receptors ( Figures 6 and 7 ). Altogether, our molecular docking analysis revealed that both epicatechin and procyanidin B2 has molecular properties to interact efficiently with cholinesterase, α-amylase and α-glucosidase, suggesting that these compounds are the bioactive components that could be responsible for the biological activities of AESTL reported in this study.…”

Section: Discussionmentioning

confidence: 97%

Sterculia tragacantha Lindl Leaf Extract Ameliorates STZ-Induced Diabetes, Oxidative Stress, Inflammation and Neuronal Impairment

Onikanni¹,

Lawal²,

Olusola³

et al. 2021

JIR

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Background Sterculia tragacantha is a medicinal plant commonly used in the western part of Nigeria, for managing diabetes mellitus. However, there is a dearth of scientific information on the antidiabetic and neuroprotective properties of the plant. Methods The in silico, in vitro and in vivo models were used to evaluate the antioxidants, antidiabetic, anti-inflammatory and neuroprotective potential of aqueous extract of Sterculia tragacantha leaf (AESTL) in streptozotocin (STZ)-induced diabetic rats. Thirty (30) male albino rats (155.34±6.33 g) were intraperitoneal injected with 40 mg/kg of freshly prepared streptozotocin and were divided into 5 groups (A-E) of 6 animals each. Groups A–D were treated with 0, 150 and 300 mg/kg of AESTL, and 200 mg/kg body weight of metformin respectively, while group E serve as the normal control. Results The results of in vitro analysis revealed dose-dependent antioxidant activities; ABTS (IC 50 = 63.03±2.57 μg/mL), DPPH (117.49±2.35 μg/mL), FRAP (15.19±0.98 mmol/100g), TAC (43.38±0.96 mg/100g), hypoglycaemic effect; α-amylase (IC 50 = 77.21±4.35 μg/mL) and α-glucosidase (IC 50 = 443.25±12.35), and anti-cholinesterase; AChE (IC 50 = 113.07±3.42 μg/mL) and BChE (IC 50 = 87.50±4.32 μg/mL) activities of AESTL. In vivo study revealed dose-dependent hypoglycemic effect and body weight improvement in rats treated with the AESTL. In addition, AESTL improved the antioxidant status and attenuated STZ-induced dysregulations of Na + -K + -ATPase, cholinesterases and neurotransmitters in the brain tissue of experimental rats. The results also demonstrated that AESTL could regulate anti-inflammatory response via inhibition of COX-2/NO signaling axis in the brain of diabetic rats. Molecular docking analysis revealed that epicatechin and procyanidin B2, the bioactive compounds from AESTL, docked well to the binding cavities of acetylcholinesterase, butyrylcholinesterase, α-amylase and α-glucosidase with binding affinities ranges between –8.0 and –11.4 kcal/mol, suggesting that these compounds are the bioactive component that could be responsible for the antidiabetic and neuroprotective activities of AESTL. Conclusion The results of the present study strongly suggested that the AESTL extract could be very useful for halting diabetes progression and its associated neuroinflammation complications.

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Section: Discussionmentioning

confidence: 97%

Sterculia tragacantha Lindl Leaf Extract Ameliorates STZ-Induced Diabetes, Oxidative Stress, Inflammation and Neuronal Impairment

Onikanni¹,

Lawal²,

Olusola³

et al. 2021

JIR

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“…Studies have shown that the AMPA receptor (GRIA4) was significantly up-regulated in the hippocampus of patients with AD ( Jacob et al, 2007 ). MAP2K4 was exhibited brain-specific gene and to play essential roles in the regulation of cell proliferation in AD ( Wu et al, 2021 ), while MAP2K4 was related with the condition and prognosis of endometrial carcinoma ( Zhang et al, 2022 ). ITPR1 ( Seo et al, 2020 ) and GABBR2 ( Yin et al, 2021 ) may be associated with AD, and prostate cancer ( Choi et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Transcriptome analysis reveals potential marker genes for diagnosis of Alzheimer’s disease and vascular dementia

Wang

Tao

et al. 2022

Front. Genet.

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Alzheimer’s disease (AD) and vascular dementia (VD) are the two most common forms of dementia, share similar symptoms, and are sometimes difficult to distinguish. To investigate the potential mechanisms by which they differ, we identified differentially expressed genes in blood and brain samples from patients with these diseases, and performed weighted gene co-expression network analysis and other bioinformatics analyses. Weighted gene co-expression network analysis resulted in mining of different modules based on differences in gene expression between these two diseases. Enrichment analysis and generation of a protein-protein interaction network were used to identify core pathways for each disease. Modules were significantly involved in cAMP and AMPK signaling pathway, which may be regulated cell death in AD and VD. Genes of cAMP and neurotrophin signaling pathways, including ATP1A3, PP2A, NCEH1, ITPR1, CAMKK2, and HDAC1, were identified as key markers. Using the least absolute shrinkage and selection operator method, a diagnostic model for AD and VD was generated and verified through analysis of gene expression in blood of patients. Furthermore, single sample gene set enrichment analysis was used to characterize immune cell infiltration into brain tissue. That results showed that infiltration of DCs and pDCs cells was increased, and infiltration of B cells and TFH cells was decreased in the brain tissues of patients with AD and VD. In summary, classification based on target genes showed good diagnostic efficiency, and filled the gap in the diagnostic field or optimizes the existing diagnostic model, which could be used to distinguish between AD and VD.

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“…The 3D structures of sitagliptin (CID: 4369359), PNU-74654 (CID:9836739), and crizotinib (CID:116250) were retrieved from the pubchem database ( accessed on 22 October 2021), in the spatial data file (SDF) format, and consequently converted to PDB file format using the PyMOL visualization tool [ 61 ] ( accessed on 22 October 2021), while the crystal structures of DPP4 (PDB:2ONC), CTNNB1 (PDB:1JDH), and MET (PDB:3DKF) were downloaded from the protein database (PDB), ( accessed on 22 October 2021), in PDF file format. File preparation for molecular docking was as described in previous studies [ 62 , 63 , 64 ]. Using autodock software, an in silico molecular docking tool [ 65 ], all PDB files were converted to PDBQT file formats, and docking was accordingly performed using autodock, as described previously [ 66 , 67 ].…”

Section: Methodsmentioning

confidence: 99%

Identification of DPP4/CTNNB1/MET as a Theranostic Signature of Thyroid Cancer and Evaluation of the Therapeutic Potential of Sitagliptin

Cheng

Batiha

et al. 2022

Biology

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In recent years, the incidence of thyroid cancer has been increasing globally, with papillary thyroid cancer (PTCa) being the most prevalent pathological type, accounting for approximately 80% of all cases. Although PTCa has been regarded to be slow growing and has a good prognosis, in some cases, PTCa can be aggressive and progress despite surgery and radioactive iodine treatment. In addition, most cancer treatment drugs have been shown to be cytotoxic and nonspecific to cancer cells, as they also affect normal cells and consequently cause harm to the body. Therefore, searching for new targets and therapies is required. Herein, we explored a bioinformatics analysis to identify important theranostic markers for THCA. Interestingly, we identified that the DPP4/CTNNB1/MET gene signature was overexpressed in PTCa, which, according to our analysis, is associated with immuno-invasive phenotypes, cancer progression, metastasis, resistance, and unfavorable clinical outcomes of thyroid cancer cohorts. Since most cancer drugs were shown to exhibit cytotoxicity and to be nonspecific, herein, we evaluated the anticancer effects of the antidiabetic drug sitagliptin, which was recently shown to possess anticancer activities, and is well tolerated and effective. Interestingly, our in silico molecular docking results exhibited putative binding affinities of sitagliptin with DPP4/CTNNB1/MET signatures, even higher than standard inhibitors of these genes. This suggests that sitagliptin is a potential THCA therapeutic, worthy of further investigation both in vitro and in vivo and in clinical settings.

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Multiomics Identification of Potential Targets for Alzheimer Disease and Antrocin as a Therapeutic Candidate

Cited by 24 publications

References 76 publications

Sterculia tragacantha Lindl Leaf Extract Ameliorates STZ-Induced Diabetes, Oxidative Stress, Inflammation and Neuronal Impairment

Sterculia tragacantha Lindl Leaf Extract Ameliorates STZ-Induced Diabetes, Oxidative Stress, Inflammation and Neuronal Impairment

Transcriptome analysis reveals potential marker genes for diagnosis of Alzheimer’s disease and vascular dementia

Identification of DPP4/CTNNB1/MET as a Theranostic Signature of Thyroid Cancer and Evaluation of the Therapeutic Potential of Sitagliptin

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