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Bletilla formosana and Its Constituents as Promising Therapeutics via
Modulation of Redox Homeostasis
Po-Jen Chen* ,1,2
1 Department of Pharmacology, School of Medicine, College of Medicine, Kaohsiung Medical
University, Kaohsiung 807378, Taiwan
2 Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University,
Kaohsiung 807378, Taiwan
* E-mail: pjc@kmu.edu.tw
Abstract
Redox homeostasis tightly regulates a variety of physiological processes essential for human
health. Therefore, we are actively engaged in the development of drug candidates that target
redox homeostasis as a therapeutic strategy for disease treatment. Bletilla formosana (Hayata)
Schltr, a Taiwan native herbal medicine, exhibits anti-inflammatory and antioxidant activities.
To facilitate the development of B. formosana-derived therapeutics, we focused on neutrophilic
inflammatory disorders and cancers, which are closely associated with dysregulated oxidative
stress. Our research demonstrated for the first time that natural products, isolated from B.
formosana, function as novel inhibitors of Src family kinases (SFKs) and potent free radical
scavengers, effectively reducing neutrophilic oxidative stress-mediated lung and liver injury in
mouse models. Furthermore, cancer as the leading cause of mortality in Taiwan, we identified
benzyl and phenanthrene natural products from B. formosana as potent anticancer constituents
using chemical molecular networking analysis. Among these, a benzyl compound emerged as
a lead anticancer compound, exhibiting oxidative stress-dependent or microtubule-targeted
mechanisms in cancer cells and tumor-bearing mice. Together, our findings highlight B.
formosana and its constituents as promising lead candidates for therapeutic intervention against
neutrophilic inflammatory disorders and cancers. Therapeutically modulating neutrophilic
oxidative stress or inducing oxidative stress-dependent cytotoxicity in cancer cells offers
promising strategies for managing inflammatory conditions and cancers.
Keywords: Bletilla formosana; Oxidative stress; Neutrophilic inflammation; Anticancer;
natural products
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