TY - JOUR
T1 - 5,7,3′,4′,5′-pentamethoxyflavone (PMF) exhibits anti-obesity and neuroprotective effects in an obese zebrafish model
AU - Vohra, Muhammad Sufyan
AU - Ahmad, Bilal
AU - Taylor, Emerald R.
AU - Benchoula, Khaled
AU - Fong, Isabel Lim
AU - Parhar, Ishwar S.
AU - Ogawa, Satoshi
AU - Serpell, Christopher J.
AU - Wong, Eng Hwa
N1 - Publisher Copyright:
© 2025
PY - 2025/7/1
Y1 - 2025/7/1
N2 - Obesity is a multi-chronic illness characterized by superfluous fat accumulation, contributing to significant metabolic and neurological complications. Current therapeutic approaches have limited efficacy and notable side effects, underscoring an urgent demand for novel, safer alternatives. This study is the first to investigate the anti-obesity potential of 5,7,3′,4′,5′-pentamethoxyflavone (PMF) in vivo using a zebrafish model. Our findings demonstrate that PMF administration exerts pronounced anti-obesogenic effects, evidenced by reductions in blood glucose, plasma triglycerides, total cholesterol, hepatic low-density lipoproteins (LDL), and high-density lipoproteins (HDL). Mechanistically, PMF suppressed hepatic adipogenic and lipogenic gene expression while promoting lipid catabolism through activation of peroxisome proliferator-activated receptor-alpha (PPAR-α) and its downstream enzymes, including acyl-CoA oxidase 1 (ACOX1), medium-chain acyl-CoA dehydrogenase (ACADM), and carnitine palmitoyl transferase 1B (CPT-1β). Additionally, PMF markedly mitigated oxidative stress by lowering malondialdehyde (MDA) and nitric oxide (NO) levels, accompanied by increased antioxidant enzyme activities, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione S-transferase (GST). Notably, PMF effectively prevented obesity by suppressing food intake, downregulating orexigenic genes, and enhancing anorexigenic signals. Furthermore, PMF exhibited neuroprotective properties by elevating brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin receptor kinase B2 (TrkB2), revealing a novel link between metabolic and neurological regulation. This study provides pioneering, comprehensive in vivo evidence supporting PMF as a promising therapeutic candidate with dual beneficial roles in metabolic health and neuroprotection.
AB - Obesity is a multi-chronic illness characterized by superfluous fat accumulation, contributing to significant metabolic and neurological complications. Current therapeutic approaches have limited efficacy and notable side effects, underscoring an urgent demand for novel, safer alternatives. This study is the first to investigate the anti-obesity potential of 5,7,3′,4′,5′-pentamethoxyflavone (PMF) in vivo using a zebrafish model. Our findings demonstrate that PMF administration exerts pronounced anti-obesogenic effects, evidenced by reductions in blood glucose, plasma triglycerides, total cholesterol, hepatic low-density lipoproteins (LDL), and high-density lipoproteins (HDL). Mechanistically, PMF suppressed hepatic adipogenic and lipogenic gene expression while promoting lipid catabolism through activation of peroxisome proliferator-activated receptor-alpha (PPAR-α) and its downstream enzymes, including acyl-CoA oxidase 1 (ACOX1), medium-chain acyl-CoA dehydrogenase (ACADM), and carnitine palmitoyl transferase 1B (CPT-1β). Additionally, PMF markedly mitigated oxidative stress by lowering malondialdehyde (MDA) and nitric oxide (NO) levels, accompanied by increased antioxidant enzyme activities, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione S-transferase (GST). Notably, PMF effectively prevented obesity by suppressing food intake, downregulating orexigenic genes, and enhancing anorexigenic signals. Furthermore, PMF exhibited neuroprotective properties by elevating brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin receptor kinase B2 (TrkB2), revealing a novel link between metabolic and neurological regulation. This study provides pioneering, comprehensive in vivo evidence supporting PMF as a promising therapeutic candidate with dual beneficial roles in metabolic health and neuroprotection.
KW - Anti-adipogenic
KW - Anti-oxidative
KW - Flavones
KW - Neuroprotective effects
KW - Obesity
UR - http://www.scopus.com/inward/record.url?scp=105002784188&partnerID=8YFLogxK
U2 - 10.1016/j.mce.2025.112554
DO - 10.1016/j.mce.2025.112554
M3 - 学術論文
AN - SCOPUS:105002784188
SN - 0303-7207
VL - 604
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
M1 - 112554
ER -