Abstract
Spice-rich recipes are referred to as “functional foods” because they include a variety of bioactive chemicals that have health-promoting properties, in addition to their nutritional value. Using pharmacoinformatics-based analysis, we explored the relevance of bioactive chemicals found in Rasam (a South Indian cuisine) against oxidative stress-induced human malignancies. The Rasam is composed of twelve main ingredients, each of which contains a variety of bioactive chemicals. Sixty-six bioactive compounds were found from these ingredients, and their structures were downloaded from Pubchem. To find the right target via graph theoretical analysis (mitogen-activated protein kinase 6 (MAPK6)) and decipher their signaling route, a network was built. Sixty-six bioactive compounds were used for in silico molecular docking study against MAPK6 and compared with known MAPK6 inhibitor drug (PD-173955). The top four compounds were chosen for further study based on their docking scores and binding energies. In silico analysis predicted ADMET and physicochemical properties of the selected compounds and were used to assess their drug-likeness. Molecular dynamics (MD) simulation modelling methodology was also used to analyse the effectiveness and safety profile of selected bioactive chemicals based on the docking score, as well as to assess the stability of the MAPK6-ligand complex. Surprisingly, the discovered docking scores against MAPK6 revealed that the selected bioactive chemicals exhibit varying binding ability ranges between − 3.5 and − 10.6 kcal mol−1. MD simulation validated the stability of four chemicals at the MAPK6 binding pockets, including Assafoetidinol A (ASA), Naringin (NAR), Rutin (RUT), and Tomatine (TOM). According to the results obtained, fifty of the sixty-six compounds showed higher binding energy (− 6.1 to − 10.6 kcal mol−1), and four of these compounds may be used as lead compounds to protect cells against oxidative stress-induced human malignancies.
Highlights
Spice-rich recipes are referred to as “functional foods” because they include a variety of bioactive chemicals that have health-promoting properties, in addition to their nutritional value
The protein mitogen activated protein kinase 6 (MAPK6)/extracellular signal-regulated kinase 3 (ERK3) was identified as a potential drug target based on the centrality measure and its threshold values
This study looked at the antioxidant properties of bioactive chemicals found in the south Indian cuisine, Rasam against oxidative stress-induced human malignancies
Summary
Spice-rich recipes are referred to as “functional foods” because they include a variety of bioactive chemicals that have health-promoting properties, in addition to their nutritional value. Increased levels of intracellular ROS beyond a certain threshold cause down regulation of cellular antioxidant pathways and enzyme systems, resulting in malignant transformation via various molecular targets such as nuclear factor-B (NF-B), nuclear factor E2 (erythroid-derived 2)-related factor 2 (Nrf2), Kelch likeECH-associated protein 1 (Keap1), mitogen-activated protein kinases (MAPKs) and phosphoinositide 3-kinase (PI3K)[12]. The MAPKs are a class of serine/threonine protein kinases that play important roles in controlling extracellular signaling into a wide range of cellular processes[13]. Based on their structure and functions, they are classified into conventional and atypical MAPKs. Conventional MAPKs, such as, extracellular signal–regulated kinase (ERK) 1/2 and p38 isoforms (α, β, γ, and δ), and atypical MAPKs are ERK3/4 and ERK7/814. MAPK6 interacts with and phosphorylates steroid receptor coactivator 3 (SRC-3), an oncogenic protein overexpressed in multiple human cancers at the amino acid residue, serine 857 (S857)[17]
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