&lt;p&gt;Synergistic Effect of Tangeretin and Atorvastatin for Colon Cancer Combination Therapy: Targeted Delivery of These Dual Drugs Using RGD Peptide Decorated Nanocarriers&lt;/p&gt;

He, Bei-Bei; Zheng, Nanbo; Li, Zhuanting; Yuan, Zhi

doi:10.2147/dddt.s256636

Cited by 20 publications

(8 citation statements)

References 55 publications

(55 reference statements)

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“…Hence the explicit advancements for tangeretin applications with friendly approach without toxicity can foresee immense research prospects. On the contrary, tangeretin and atorvastatin have utilized nanocarriers for targeted delivery for colon cancer treatment [31]. Henceforth the scienti c therapeutics and nutraceutical potentials of tangeretin research have a long path of excellence in biomedical applications.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and Molecular Docking for Identification of Potential Drug Targets in Tangeretin’s Neuro-Protection

Balasubramani

Arulkumar

Venuvanalingam

et al. 2022

Preprint

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Background Tangeretin obtained from Citrus limonum L. represents the key secondary metabolite amongst other citrus derived polymethoxyflavones eliciting a comprehensive bioactive potential establishing versatility in abating neurodegenerative disorders. Objective The present study was aimed to decipher additional targets and interacting mechanisms for tangeretin in elucidating the neuro-inflammatory profiles through computer aided drug designing and deciphering potential molecular mechanisms. Methods Pharmacokinetic evaluation waswill be performed for ADMET properties comprising Liver Toxicity, Metabolism, blood brain barrier permeability, cardiotoxicity, mitochondrial toxicity, mutagenicity by vNN web server and SWISS-ADME for drug likeliness deriving medicinal properties of tangeretin, comparatively. Polar surface area-based drug assimilatory profiles were catalogued using Molinspiration toolkit for confirming the tangeretin’s bioavailibility and solubility. Extra-precision flexible molecular docking studies was preceded using Glide XP incorporated in Schrödinger, LLC, New York, NY, 2021 for protein (5-Beta-reductase, PLA2, IRAK4, COX-1, COX-2, 5-LOX, NIK) – ligand (tangeretin) interaction assessment. Phylogenetic analysis of the selected protein targets in docking experiments were assessed for closely relatedness by maximum likelihood iterations using MEGA 10.2.6. Further tangeretin-gene targets-interaction assessment was cross-verified in STITCH and SWISSTARGET prediction data for affirming putative drug targets. Results Pharmaokinetic assessment revealed the tangeretin’s role in safety, efficacy and druglike properties based on chemi-informatic profiles. Further selected proteins utilized for flexible docking corresponds to 3KK6, 1CX2 (Cyclooxygenases family), 2B03 (Phospholipase A2), 4IDV (NF-KB-inducing kinase), 6O9D (Interleukin-1 receptor-associated kinase domain) and 3BV7 (steroid 5beta-reductase) that were assessed for binding affinity patterns revealed the efficacy in the order of 5-Beta-reductase > PLA2 > IRAK4 > COX-1 > COX-2 > 5-LOX > NIK. Phylogenetic relatedness proved that 3BV7 posed the ancestral node for rest of the selected proteins emphasizing cascade mechanisms in absorption potentiating additional protein-protein interaction and crosstalk. Comparative gene target analysis revealed two putative potential targets namely AKT1 and CYP1A1. Conclusion Pharmacokinetic based docking assessment and network pharmacology studies pertaining neuro-inflammatory protection are coerced with confirmation of putative targets aiding the safety, efficacy, and efficiency of tangeretin.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and Molecular Docking for Identification of Potential Drug Targets in Tangeretin’s Neuro-Protection

Balasubramani

Arulkumar

Venuvanalingam

et al. 2022

Preprint

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“…Synergistic effects among flavonoid compounds or between flavonoids and chemical drug entities have been described in other fields of biological research; for example, between vicenin-2 and docetaxel for prostate cancer (49), between apigenin and ceftazidime against resistant Enterobacter (50), between catechin, quercetin and epigallocatechin gallate with fluconazole against resistant candida (51), between tangeretin and atorvastatin for colon cancer (52), between hesperidin and diazepam for anxiolysis (53), and between quercetin, gallic acid, and rutin for antioxidant effects (54).…”

Section: Discussionmentioning

confidence: 99%

Vascular interactions of Croton schiedeanus major flavonoids in isolated aortic rings from Wistar rats

Pabón

Ortiz

Ibáñez

2021

Vitae

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Background: Ayanin (3,7,4’-Tri-O-methylquercetin) and 3,7-Di-O-methylquercetin (DMQ) are the main active metabolites isolated by bioguided fractionation from Croton schiedeanus, species known popularly in Colombia as “almizclillo”, which has been studied in experimental models in rats, exerting vasodilator and antihypertensive effects. Also, when the effect of these flavonoids was studied separately, important vasodilation was observed. Objective: To evaluate whether flavonoids from Croton schiedeanus have synergistic vasodilator properties when different combinations are used in isolated aorta rings. Methods: Cumulative concentrations of ayanin (10-8 M - 6x10-5 M or 0.01 μM - 60 μM) were assayed in the absence and presence of an increasing concentration of 3,7-Di-O-methylquercetin (DMQ) (10-8 – 3x10-5 M or 0.01–30 μM) in isolated rings from Wistar rats, pre-contracted with phenylephrine. The concentration-response curve with the maximal effect was compared with that obtained by Croton schiedeanus whole ethanolic extract (10-6 – 3x10-4 g/mL). Also, this combination was assayed in the presence of the nitric oxide synthetase inhibitor L-NAME (10-4 M) and the guanylate cyclase inhibitor methylene blue (10-4 M) to assess the role of the NO/cGMP pathway in this interaction. Results: Ayanin and DMQ display a dual interaction in vascular relaxant response: agonism at higher concentration ranges (10-6 – 3x10-5 M or 1–30 μM) and antagonism at lower concentration ranges (10-8 – 3x10-7 M or 0.01–0.3 μM). The efficacy at the highest concentration was greater than that obtained by the whole extract (Emax: 98.4% vs. 33.9%). This response was decreased but not reverted in the presence of L-NAME and methylene blue. Thus, the vasodilator effect of this combination does not depend entirely on the NO/cGMP cyclic pathway. Conclusion: The combined use of appropriate concentrations of these flavonoids could represent an advantage over Croton schiedeanus whole extract for vasodilator purposes.

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“…First, the poor bioavailability and stability of flavonoids make them difficult to be used as potential chemo‐preventive drugs. To overcome these limitations, the use of nano‐drug delivery systems, such as nanoparticles, liposomes, chitosan, and other carriers, may be a feasible strategy (Bao, Zheng, Li, & Zhi, 2020; Karamchedu, Tunki, Kulhari, & Pooja, 2020). Secondly, flavonoids exert pleiotropic regulatory effects through various mechanisms, and the lack of specificity creates obstacles to their medicinal use.…”

Section: Flavonoids Targeting Lncrna/wnt Axis In Crcmentioning

confidence: 99%

Targeting lncRNA/Wnt axis by flavonoids: A promising therapeutic approach for colorectal cancer

Han

Cao

Guo

et al. 2022

Phytotherapy Research

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Despite the dramatic advances in our understanding of the etiology of colorectal cancer (CRC) in recent decades, effective therapeutic strategies are still urgently needed. Oncogenic mutations in the Wnt/β‐Catenin pathway are hallmarks of CRC. Moreover, long non‐coding RNAs (lncRNAs) as molecular managers are involved in the initiation, progression, and metastasis of CRC. Therefore, it is important to further explore the interaction between lncRNAs and Wnt/β‐Catenin signaling pathway for targeted therapy of CRC. Natural phytochemicals have not toxicity and can target carcinogenesis‐related pathways. Growing evidences suggest that flavonoids are inversely associated with CRC risk. These bioactive compounds could target carcinogenesis pathways of CRC and reduced the side effects of anti‐cancer drugs. The review systematically summarized the progress of flavonoids targeting lncRNA/Wnt axis in the investigations of CRC, which will provide a promising therapeutic approach for CRC and develop nutrition‐oriented preventive strategies for CRC based on epigenetic mechanisms. In the field, more epidemiological and clinical trials are required in the future to verify feasibility of targeting lncRNA/Wnt axis by flavonoids in the therapy and prevention of CRC.

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<p>Synergistic Effect of Tangeretin and Atorvastatin for Colon Cancer Combination Therapy: Targeted Delivery of These Dual Drugs Using RGD Peptide Decorated Nanocarriers</p>

Cited by 20 publications

References 55 publications

Pharmacokinetics and Molecular Docking for Identification of Potential Drug Targets in Tangeretin’s Neuro-Protection

Pharmacokinetics and Molecular Docking for Identification of Potential Drug Targets in Tangeretin’s Neuro-Protection

Vascular interactions of Croton schiedeanus major flavonoids in isolated aortic rings from Wistar rats

Targeting lncRNA/Wnt axis by flavonoids: A promising therapeutic approach for colorectal cancer

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