Effects Of Triterpenoids From Psidium Guajava Leaves And Its Possible Mechanism On Improving Insulin Resistance In3T3-L1Adipocyte

Objective:To investigate influences of Triterpenoids from Psidium Guajava Leaves (PGs)on the differentiation, proliferation, glucose uptake, FFA production, adiponectinsecretion of3T3-L1pre-adipocyte and its possible mechanism.Methods:3T3-L1pre-adipocyte was cultured in vitro. After adding Triterpenoids fromPsidium Guajava Leaves (PGs) PG-1, PG-3, PG-5, PG-7(1μM,3μM,10μM,30μM,100μM) and positive drug Rosiglitazone10μM and Sodium orthovanadate10μM tothe culture medium for48h, the cell viability was tested by MTT assay. Induced for6days, the lipid accumulation of adipocyte was measured by Oil Red O staining. Theinsulin resistant cell model was established with Dexamethasone. Cellular glucoseuptake was determined with GOD-POD assays and FFA concentration wasdetermined at the time of48h. Secreted adiponectin were measured by ELISA. Theprotein levels of PPARγ and PTP1B in insulin resistant-adipocyte were measured byWestern Blotting.Results:1. Compared to the medium control group,100μM PG-1, PG-5could increaseits proliferation (P<0.05), in which PG-7shows no effect(P>0.05). In contrast, PG-3at30μM,100μM may inhibit its proliferation(P<0.05,or P<0.01).2. Compared to the medium control group,100μM PG-1，PG-3，PG-7couldincrease its differentiation significantly(P<0.05,or P<0.01). In contrast, PG-5at30μM,100μM may inhibit its differentiation (P<0.05, or P<0.01).3. Compared to the model group, Triterpenoids from Psidium GuajavaLeavesPG-1，PG-3，PG-5，PG-7at100μM could enhance cellular glucose uptake ofinsulin resistant adipocyte significantly both in basic and insulin stimulationstate(P<0.05, or P<0.01), while PG-1,PG-7at30μM could already enhance its glucoseuptake significantly(P<0.05).4. Compared to the model group, PG-1，PG-7at30μM could already decrease its FFA production significantly(P<0.05, or P<0.01), in which PG-3shows noeffect(P>0.05),whiel PG-5at100μM could inhibit its production significantly(P<0.05).5. Compared to the model group, PG-1at30μM,100μM could increase thesecretion of adiponectin on insulin resistant adipocyte significantly (P<0.05, orP<0.01), up-regulate the expression of PPARγ protein (P<0.05, or P<0.01), but showsno effect to the PTP1B protein expression, while PG-5shows no effect to thesecretion of adiponectin and PPARγ protein expression at30μM,100μM, but maydown-regulate the expression of PTP1B protein(P<0.05, or P<0.01).Conclusions:1.Triterpenoids from Psidium Guajava Leaves PG-1,PG-3,PG-5,PG-7couldenhance glucose uptake of insulin resistant adipocyte, which indicate that they maycan improve insulin resistance.2. PG-1can increase the proliferation and differentiation of3T3-L1pre-adipocyte, inhibit the FFA production but enhance the secretion of adiponectin ofinsulin resistant adipocyte via up-regulating the expression of protein PPARγ, all ofwhich play the roles of increasing insulin sensitivity and improving insulin resistance3. PG-5can enhace glucose uptake of insulin resistant adipocyte, inhibit FFAproduction via down-regulating the expression of protein PTP1B, all of which playthe roles of increasing insulin signaling, sensitivity to improve insulin resistance.4. In conclusion, PG-1,PG-5show better effect on improving insulin resistance,while PG-7shows the less effect. Since PG-3have no significant effect on FFAproduction, its shows the worst effect.