Peptide Human Neutrophil Elastase Inhibitors from Natural Sources: An Overview

Abstract

Elastases are a broad group of enzymes involved in the lysis of elastin, the main component of elastic fibres. They are produced and released in the human body, mainly by neutrophils and the pancreas. The imbalance between elastase activity and its endogenous inhibitors can cause different illnesses due to their excessive activity. The main aim of this review is to provide an overview of the latest advancements on the identification, structures and mechanisms of action of peptide human neutrophil elastase inhibitors isolated from natural sources, such as plants, animals, fungi, bacteria and sponges. The discovery of new elastase inhibitors could have a great impact on the pharmaceutical development of novel drugs through the optimization of the natural lead compounds. Bacteria produce mainly cyclic peptides, while animals provide for long and linear amino acid sequences. Despite their diverse natural sources, these elastase inhibitors show remarkable IC50 values in a range from nM to μM values, thus representing an interesting starting point for the further development of potent bioactive compounds on human elastase enzymes.

Standardised Sonneratia apetala Buch.-Ham. fruit extract inhibits human neutrophil elastase and attenuates elastase-induced lung injury in mice

“…Though a large number of synthetic drugs undergo clinical trials, only Sivelestat (ONO-5046) is approved in Japan as human neutrophil elastase inhibitor used to treat patients with ARDS (Iwata et al, 2010) and recently Sivelestat has been proposed to treat acute lung injury in COVID patients (Sahebnasagh et al, 2020). The creation of innovative medications to prevent and treat disorders brought on by the overactive elastase or the pathological breakdown of Frontiers in Pharmacology frontiersin.org elastin could be greatly impacted by the identification of new elastase inhibitors from natural sources, including plants, animals, fungus, bacteria, and sponges (Marinaccio et al, 2022). A naturally occurring macrocyclic peptide called Cyclotheonellazole A (CTL-A) has been described as a powerful elastase inhibitor (Cui et al, 2022).…”

Neutrophil serine proteases

“…Bacteria, plants, fungi or venomous animals are known as potential sources of new HNE inhibitors. Many of these compounds have been described in the literature; unfortunately, most of them have shown low potency of action, selectivity and stability in physiological conditions [47,48] .…”

Depsipeptides Targeting Tumor Cells: Milestones from In Vitro to Clinical Trials

“…Elastases are a group of proteases that degrade and lyse elastin, one of the main components of the extracellular matrix [ 96 ]. These enzymes are also involved in tumor cell migration [ 97 ].…”