Bromelain: Unveiling its Potential as a Natural Anti-Inflammatory Agent through Effective Binding to Apoptosis-associated Speck-like Containing CARD (ASC)

1. Introduction

The Apoptosis-associated speck-like containing CARD (ASC), also known as PYCARD, is a crucial adapter molecule in inflammatory processes. Its primary role involves the formation of inflammasomes, multiprotein complexes that activate caspases, leading to inflammation and programmed cell death. ASC comprises PYD and CARD domains, facilitating interactions with similar domains in other proteins for inflammasome assembly[1,2,3]. While inflammasome activation is vital for the immune response against infections and cell damage, excessive activation can contribute to chronic inflammatory, autoimmune, or metabolic diseases. Consequently, understanding and regulating ASC and inflammasome activity are significant areas of research for potential therapeutic interventions in inflammation-related disorders[4,5]. The aim of this concise investigation is to examine the interplay between Apoptosis-associated speck-like containing CARD (ASC) and Bromelain through computational methods.Bromelain, known for its capacity to modulate inflammatory states, is composed of enzymes with proteolytic activity primarily extracted from pineapple stems[6,7,8].

The computational method employed to scrutinize potential binding and interactions between ASC and Bromelain at a molecular level was the HDOCK Server.

Broadly speaking, this is a protein-protein or protein-DNA/RNA docking approach based on a hybrid algorithm, incorporating template-based modeling and ab initio free docking[9,10].

Comprehending these interactions may offer insights into how Bromelain could impact ASC-mediated processes, such as inflammasome assembly and inflammation. Given Bromelain's recognized anti-inflammatory properties, investigating its influence on ASC through computational approaches may enhance our understanding of its therapeutic potential in modulating inflammatory responses.

2. Material and Methods

The HDOCK server was employed to predict the binding complexes between two molecules, specifically proteins represented by PDB Code 6U7D (Bromelain precursor used as the receptor) and PDB Code 2KN6 (Apoptosis-associated speck-like protein containing a CARD in CHAIN A used as the ligand). This prediction was carried out using a hybrid docking strategy.

3. Results and Discussion

The objective of this brief study is to explore the interaction between Apoptosis-associated speck-like containing CARD (ASC) and Bromelain using computational methods. Bromelain, recognized for its ability to regulate inflammatory states, is a group of enzymes with proteolytic activity primarily extracted from pineapple stems[6,7,8].

The computational method employed for the analysis of potential binding and interactions between ASC and Bromelain at a molecular level was the HDOCK Server [9,10]. The primary findings are presented in Figure 1, illustrating the outcomes of the interaction study. Table 1 provides the docking results by the HDOCK Server, demonstrating an excellent docking score and potential affinity between Bromelain and Apoptosis-associated speck-like containing CARD. Additionally, Table 2, Table 3, Table 4 and Table 5 outlines the residues at the interface between the two targets.

4. Conclusions

This theoretical study presents a novel perspective on the potential anti-inflammatory properties of Bromelain, a natural agent extracted from pineapple stems. The investigation delves into Bromelain's binding capabilities with Apoptosis-associated speck-like containing CARD (ASC), a pivotal adapter molecule implicated in inflammatory processes and inflammasome formation. This study unveils molecular interactions that may underpin Bromelain's therapeutic potential in modulating inflammatory responses.