Uncovering Novel Capsaicin Inhibitory Activity towards Human Carbonic Anhydrase Isoforms IX and XII by Combining In Silico and In Vitro Studies

Abstract

Hot pepper (Capsicum annuum) represents one of the most widespread functional foods of the Mediterranean diet, and is associated with a reduced risk of developing cardiovascular disease, cancer, and mental disorders. In particular, its bioactive spicy molecules, named Capsaicinoids, exhibit polypharmacological properties. Among them, Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is the most studied and reported in variegated scientific contributions for its beneficial effects, often linked to mechanisms of action unrelated to the activation of Transient Receptor Potential Vanilloid 1 (TRPV1). In this study, we present the application of in silico methods to Capsaicin for evaluating its inhibitory activity against the tumor-associated human (h) expressed CA IX and XII. In vitro assays confirmed Capsaicin inhibitory activity towards the most relevant tumor-related hCA isoforms. In particular, the hCAs IX and XII showed an experimental KI value of 0.28 μM and 0.064 μM, respectively. Then, an A549 model of non-small cell lung cancer, typically characterized by an elevated expression of hCA IX and XII, was employed to test the inhibitory effects of Capsaicin in vitro under both normoxic and hypoxic conditions. Finally, the migration assay revealed that Capsaicin [10 µM] inhibits cells from moving in the A549 cells model.

Capsaicin pretreatment attenuates salt-sensitive hypertension by alleviating AMPK/Akt/Nrf2 pathway in hypothalamic paraventricular nucleus

“…Capsaicin and related compounds form a naturally occurring chemical group called capsaicin, which give chili peppers a unique spicy taste, and are believed to constitute a natural defense of plants against herbivores and fungi ( Cheng et al, 2023 ). Interest to study their role in cardiovascular diseases is increasing among scholars ( Gualtieri et al, 2023 ; Zaleski et al, 2023 ). On the other hand, the role the PVN, in the occurrence, development, and prognosis of hypertension is largely acknowledged ( Souza et al, 2019 ; Li et al, 2021 ; Gao et al, 2023 ), however, whether capsaicin influence the course of salt-induced hypertension through the PVN remains unclear.…”

Capsaicin: A chili pepper bioactive phytocompound with a potential role in suppressing cancer development and progression

“…Capsaicin were decreased (Liu et al, 2022). Recently, it has been reported that capsaicin (1-100 μM) inhibited A549 lung cancer cell growth by reducing cell viability associated with decreased MMP-9 expression (Gualtieri et al, 2023). Therefore, capsaicin exhibited significant in vitro anticancer activity against various lung cancer cell lines.…”