Identiﬁcation of 2,4-Di-tert-butylphenol (2,4-DTBP) as the Major Contributor of Anti-colon cancer Activity of Active Chromatographic Fraction of Parkia javanica (Lamk.) Merr. Bark Extract

Saha, Partha; Sharma, Dipshikha; Dash, Suvakanta; Dey, Kumar Saurav; Sil, Samir Kumar

doi:10.13005/bpj/2609

Cited by 2 publications

(1 citation statement)

References 28 publications

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“… 14 In this therapeutic quest, nature's vast arsenal of molecules has often been the starting point for the identification of efficacious drug candidates, mainly attributed to their innate pharmacological properties and favourable safety profiles. 15 In this vast natural repository, 2,4‐ditert‐butylphenol (2,4‐DTBP), a lipophilic phytocompound, 16 , 17 , 18 , 19 stands out with its plethora of biological activities that span from antioxidant, 20 , 21 anti‐inflammatory 22 and antimicrobial 23 , 24 , 25 , 26 , 27 to notable anti‐cancer properties. 28 However, a distinct knowledge gap persists in understanding how 2,4‐DTBP modulates the activities of Bcl‐2 and Survivin, especially in the context of CRC cell proliferation and apoptotic responses.…”

Section: Introductionmentioning

confidence: 99%

Targeted inhibition of colorectal cancer proliferation: The dual‐modulatory role of 2,4‐DTBP on anti‐apoptotic Bcl‐2 and Survivin proteins

Saha,

Hegde,

Chakraborty

et al. 2024

J Cellular Molecular Medi

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The anti‐apoptotic proteins, Bcl‐2 and Survivin, are consistently overexpressed in numerous human malignancies, notably in colorectal cancer. 2,4‐Di‐tert‐butylphenol (2,4‐DTBP) is a naturally occurring phenolic compound known for its diverse biological activities, including anti‐cancer properties. The mechanism behind 2,4‐DTBP‐induced inhibition of cell proliferation and apoptosis in human colorectal cancer cells, specifically regarding Bcl‐2 and Survivin, remains to be elucidated. In this study, we employed both in silico and in vitro methodologies to underpin this interaction at the molecular level. Molecular docking demonstrated a substantial binding affinity of 2,4‐DTBP towards Bcl‐2 (ΔG = −9.8 kcal/mol) and Survivin (ΔG = −5.6 kcal/mol), suggesting a potential inhibitory effect. Further, molecular dynamic simulations complemented by MM‐GBSA calculations confirmed the significant binding of 2,4‐DTBP with Bcl‐2 (dGbind = −54.85 ± 6.79 kcal/mol) and Survivin (dGbind = −32.36 ± 1.29 kcal/mol). In vitro assays using HCT116 colorectal cancer cells revealed that 2,4‐DTBP inhibited proliferation and promoted apoptosis in both a dose‐ and time‐dependent manner. Fluorescence imaging and scanning electron microscopy illustrated the classical features associated with apoptosis upon 2,4‐DTBP exposure. Cell cycle analysis through flow cytometry highlighted a G1 phase arrest and apoptosis assay demonstrated increased apoptotic cell population. Notably, western blotting results indicated a decreased expression of Bcl‐2 and Survivin post‐treatment. Considering the cytoprotective roles of Bcl‐2 and Survivin through the inhibition of mitochondrial dysfunction, our findings of disrupted mitochondrial bioenergetics, characterized by reduced ATP production and oxygen consumption, further accentuate the functional impairment of these proteins. Overall, the integration of in silico and in vitro data suggests that 2,4‐DTBP holds promise as a therapeutic agent targeting Bcl‐2 and Survivin in colorectal cancer.

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Section: Introductionmentioning

confidence: 99%

Targeted inhibition of colorectal cancer proliferation: The dual‐modulatory role of 2,4‐DTBP on anti‐apoptotic Bcl‐2 and Survivin proteins

Saha,

Hegde,

Chakraborty

et al. 2024

J Cellular Molecular Medi

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Parkia javanica Edible Pods Reveal Potential as an Anti-Diabetic Agent: UHPLC-QTOF-MS/MS-Based Chemical Profiling, In Silico, In Vitro, In Vivo, and Oxidative Stress Studies

Sarkar,

Chakrabarti,

Bhaumik

et al. 2024

Pharmaceuticals

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According to the World Health Organization, over 422 million people worldwide have diabetes, with the majority residing in low- and middle-income countries. Diabetes causes 1.5 million fatalities a year. The number of diabetes cases and its prevalence have progressively increased over the last few decades. This study aims to determine the phytochemicals in the edible part of Perkia javanica, predict their α-glucosidase inhibitory potential, one of the promising targets for diabetes, and then carry out in vitro and in vivo studies. The phytochemicals present in the n-butanol fraction of the methanol extract of P. javanica pods were analyzed using UHPLC-QTOF-MS/MS (Ultra-High-Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry). The UHPLC-QTOF analysis revealed the presence of 79 different compounds in the n-butanol fraction. Among these, six compounds demonstrated excellent binding affinities with α-glucosidase, surpassing the performance of two standard inhibitors, Miglitol and Voglibose. In vitro α-glucosidase inhibitory activities were assessed by the n-butanol fraction, followed by in vivo studies. According to the in vitro study, the inhibitory efficiency against α-glucosidase was determined to have an IC50 value of 261.9 µg/mL. The in vivo findings revealed a significant reduction in blood glucose levels in Swiss albino mice treated with the same extract, decreasing from 462.66 mg/dL to 228.66 mg/dL. Additionally, the extract significantly increased the activity of the enzymes catalase and superoxide dismutase (SOD) and decreased the amount of malondialdehyde (MDA) in the liver and kidney tissue. The predicted physicochemical parameters indicated that most of the compounds would be excreted from the body after inhibition in the small intestine without being absorbed. Considering the low cost and wide availability of raw materials, P. javanica pods can serve as a good food supplement that may help prevent type 2 diabetes management.

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Identiﬁcation of 2,4-Di-tert-butylphenol (2,4-DTBP) as the Major Contributor of Anti-colon cancer Activity of Active Chromatographic Fraction of Parkia javanica (Lamk.) Merr. Bark Extract

Cited by 2 publications

References 28 publications

Targeted inhibition of colorectal cancer proliferation: The dual‐modulatory role of 2,4‐DTBP on anti‐apoptotic Bcl‐2 and Survivin proteins

Targeted inhibition of colorectal cancer proliferation: The dual‐modulatory role of 2,4‐DTBP on anti‐apoptotic Bcl‐2 and Survivin proteins

Parkia javanica Edible Pods Reveal Potential as an Anti-Diabetic Agent: UHPLC-QTOF-MS/MS-Based Chemical Profiling, In Silico, In Vitro, In Vivo, and Oxidative Stress Studies

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