OBJECTIVE: To investigate the effects of total
flavonoids from
Psidium guajava leaves (GLTF) on the related factors for
estrogen -associated receptor γ(ERRγ)/cyclic
adenosine monophosphate responsive
element binding protein H(CREBH)pathway in
liver of
type 2 diabetes mellitus (T2DM)model
mice , and to investigate the specific mechanism of its
hypoglycemic effect .
METHODS : Healthy
male ICR mice were collected. T2DM models were established by high-
sugar and
high-fat diet feeding combined with repeated
intraperitoneal injection of low
dose streptozotocin . According to the
blood glucose value, model
mice were randomly divided into model group,
metformin group(positive control, 0.17 g/kg),Xiaoke jiangtang
capsule group(positive control, 0.75 g/kg),GLTF low-
dose and high-
dose groups(0.047, 0.094 g/kg), with 12
mice in each group. Another 12 normal
mice were included in normal group. Except that normal group and model group were given constant volume of
water intragastrically, other groups were given relevant
solution 10 mL/kg intragastrically, qd, for consecutive 21 d. After
administration ,
fasting blood glucose and
serum insulin levels of
mice were measured and
insulin sensitivity index (ISI) was calculated. Histopathological changes of
liver and
pancreas were observed by HE
staining . The
protein expressions of ERRγ and CREBH in
liver tissues were detected by
immunoblotting . The
mRNA expression of
peroxisome proliferator-activated receptor -γ coactivator-1α(PGC1α)and
CREB protein co-activator 2(
TORC2 )in
liver tissue of
mice were measured by RT-PCR. RESULTS: Compared with normal group, the levels of
fasting blood glucose and
serum insulin in T2DM
mice were significantly increased in model group, while ISI was decreased significantly (P<0.01). The pathological changes of
liver tissue were obvious and a large number of
vacuoles could be seen. The number and volume of islets in pancreatic
tissue decreased, and
islet cells showed mild vacuolar lesions. The
protein expression of ERRγ and CREBH,
mRNA expression of PGC1α and
TORC2 in
liver tissue were increased significantly (P<0.01). Compared with model group, above
blood glucose ,
insulin indexes and pathological changes were improved significantly in GLTF groups.
Protein expression of ERRγ and CREBH,
mRNA expression of PGC1α and
TORC2 in
liver tissue were decreased significantly (P<0.05 or P<0.01). CONCLUSIONS: GLTF showed obvious
hypoglycemic effect on T2DM model
mice ; its mechanism might be related to inhibiting ERRγ/CREBH signaling pathway.