TY - JOUR
T1 - Ecliptal, a promising natural lead isolated from Eclipta alba modulates adipocyte function and ameliorates metabolic syndrome
AU - Gupta, Abhishek
AU - Kumar, Ashok
AU - Kumar, Durgesh
AU - Singh, Rohit
AU - Shankar, Kripa
AU - Varshney, Salil
AU - Rajan, Sujith
AU - Srivastava, Ankita
AU - Gupta, Sanchita
AU - Narender, T.
AU - Gaikwad, Anil Nilkanth
N1 - Publisher Copyright:
© 2017
PY - 2018/1/1
Y1 - 2018/1/1
N2 - A swift increase has been observed in the number of individuals with metabolic syndrome worldwide. A number of natural compounds have been identified towards combating metabolic syndrome. Adding to this premise, here we report the pleiotropic activities of Ecliptal (EC); a natural compound isolated from the herb Eclipta alba. Administration of EC was shown to have prominent anti-adipogenic effects in 3T3-L1 and hMSC derived adipocytes. It was shown to activate Wnt-pathway and alter AKT signaling. Additionally, it caused cell cycle arrest and inhibited mitotic clonal expansion. EC treatment augmented mitochondrial biogenesis as well as function as estimated by expression of PGC1α, UCP-1, mitochondrial complexes and estimation of oxygen consumption rate. EC also reduced LPS-induced inflammation and tunicamycin induced ER stress. Further, EC enhanced insulin sensitivity by increasing AKT phosphorylation, inhibiting PKCα/βII phosphorylation and reducing leptin/adiponectin ratio. Finally, EC administration in Syrian golden hamsters was shown to have potent anti-dyslipidemic effects. Cumulatively, encompassing pleiotropic activities of EC, it could prove to be a potential drug candidate against obesity, insulin resistance and related metabolic syndrome.
AB - A swift increase has been observed in the number of individuals with metabolic syndrome worldwide. A number of natural compounds have been identified towards combating metabolic syndrome. Adding to this premise, here we report the pleiotropic activities of Ecliptal (EC); a natural compound isolated from the herb Eclipta alba. Administration of EC was shown to have prominent anti-adipogenic effects in 3T3-L1 and hMSC derived adipocytes. It was shown to activate Wnt-pathway and alter AKT signaling. Additionally, it caused cell cycle arrest and inhibited mitotic clonal expansion. EC treatment augmented mitochondrial biogenesis as well as function as estimated by expression of PGC1α, UCP-1, mitochondrial complexes and estimation of oxygen consumption rate. EC also reduced LPS-induced inflammation and tunicamycin induced ER stress. Further, EC enhanced insulin sensitivity by increasing AKT phosphorylation, inhibiting PKCα/βII phosphorylation and reducing leptin/adiponectin ratio. Finally, EC administration in Syrian golden hamsters was shown to have potent anti-dyslipidemic effects. Cumulatively, encompassing pleiotropic activities of EC, it could prove to be a potential drug candidate against obesity, insulin resistance and related metabolic syndrome.
KW - 3T3-L1 adipocyte
KW - Anti-adipogenic
KW - Dyslipidemia
KW - Insulin sensitivity
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U2 - 10.1016/j.taap.2017.11.016
DO - 10.1016/j.taap.2017.11.016
M3 - Article
C2 - 29175456
AN - SCOPUS:85034997220
SN - 0041-008X
VL - 338
SP - 134
EP - 147
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
ER -