title: Deguelin and Its Role in Chronic Diseases.
abstract: Deguelin is one of four major naturally occurring rotenoids isolated from root extracts and is best recognized as a NADH: ubiquinone oxidoreductase (complex I) inhibitor, resulting in significant alterations in mitochondrial function. Deguelin has also been implicated as a regulator of apoptosis through signaling pathways, such as the (PI3K)/Akt pathway, as well as an initiator of cell cycle arrest. Consequently, this compound has accrued great interest as a potential chemopreventive and chemotherapeutic. Additionally, deguelin exposure has been linked to Parkinson's disease (PD). PD is a neurodegenerative disorder, characterized by a substantial loss of dopaminergic neurons in the substantia nigra, as well the manifestation of symptoms such as bradykinesia, rigidity, and rest tremor. While exploring the genetic impact of PD is imperative, environmental factors, such as exposure to pesticides, herbicides, and insecticides, have also been connected to the development of PD. The etiology and pathogenesis of PD are yet to be fully understood and elucidated, but mitochondrial dysfunction is gaining recognition as a molecular hallmark of PD. In fact, deguelin has been reported to elicit PD-like symptoms (degeneration of the dopaminergic pathway) in rats administered with deguelin (6 mg/kg/day for 6 days), possibly through the inhibition of mitochondrial complex I. Further research investigating the mechanisms by which deguelin inhibits central cellular processes is essential in order to advance any prospective research addressing potential applications and risks of deguelin.
authors: C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, West Virginia, USA. Jonathan.boyd@mail.wvu.edu.
authors: Jonathan
authors: J
authors: Boyd
authors: C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, West Virginia, USA.
authors: Alice
authors: A
authors: Han
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D000975:Antioxidants / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D002908:Chronic Disease / Q000188:drug therapy*; D004195:Disease Models, Animal; D055808:Drug Discovery / Q000379:methods*; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D015394:Molecular Structure; D010302:Parkinson Disease, Secondary / Q000139:chemically induced; D008517:Phytotherapy; D010946:Plants, Medicinal; D012307:Risk Factors; D012402:Rotenone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D004791:Enzyme Inhibitors; D012402:Rotenone; D042967:Electron Transport Complex I; C107676:deguelin
keywords: Apoptosis; Cell cycle arrest; Chemopreventive; Chemotherapeutic; Deguelin; Mitochondrial complex I inhibitor; Parkinson’s disease