Translation of hydroethanolic extract of leaves of Psidium guajava Linn
for pediatric non-alcoholic fatty liver disease
Abstract
To develop hydroethanolic extract of leaves of Psidium guajava L.
(Myrtaceae), identify novel target and lead compound for pediatric non
alcoholic fatty liver disease (ped-NAFLD). Hydroethanolic extract
(PG-HM) and sequential fractions of locally collected leaves of
P.guajava were prepared and standardized for quercetin content using
LC-MS/MS. The effect of PG-HM on markers of ped-NAFLD in weaned rats
with unrestricted access to liquid fructose (15%) till puberty and
early adulthood, was evaluated. The PG-HM was investigated using 1)
HepG2 cells grown in fructose containing medium for intercellular
signalling, 2) isolated murine hepatocytes for mitochondrial effects, 3)
jejunum isolated from fructose drinking rats for effect on ex vivo
fructose transport, 4) molecular dynamics for in silico binding of
quercetin with GLUT5, 5) normal rats for oral pharmacokinetics. The
quercetin content in PG-HM was 3630.66 ± 17.61 ng ml-1 and the Cmax and
Tmax were 140.527 ± 5.718 ng ml-1 and 0.75 ± 0.079 h, respectively. The
PG-HM mitigated ped-NAFLD through hepatic signalling pathways of 1)
leptin-insulin (Akt/FOX-O1/SREBP-1c), 2) hypoxia-inflammation
(HIF-1ɑ/VEGF, TNF-ɑ), 3) mitochondrial function (complexes I-V), 4)
oxidative stress (MDA, GSH, SOD) and 5) glycolysis/gluconeogenesis/de
novo lipogenesis (hexokinase, phosphofructokinase, ketohexokinase,
aldehyde dehydrogenase). For the first time, the PG-HM is reported to
reduce and delay the fructose transport across jejunum that may be
implicated to the binding of quercetin with GLUT5. For prevention and
treatment of ped-NAFLD, the PG-HM, GLUT5 and quercetin are evidenced as
dietary supplement, drug target and lead compound, respectively.