Pomegranate leaf(PGL)has a definite role in regulating lipid metabolism.However,pharmacokinetic results show the main active ingredient,ellagic acid,in PGL has lower oral bioavailability,suggesting that the lipid-lowering effect of PGL may act through inhibiting lipid absorption in the small intestine.Our results demonstrated that pomegranate leaf and its main active ingredients(i.e.,ellagic acid,gallic acid,pyrogallic acid and tannic acid)were capable of inhibiting pancreatic lipase activity in vitro.In computational molecular docking,the four ingredients had good affinity for pancreatic lipase.Acute lipid overload experiments showed that a large dosage of PGL significantly reduced serum total cholesterol(TG)and triglycerides(TC)levels in addition to inhibiting intestinal lipase activity,which demonstrated that PGL could inhibit lipase activity and reduce the absorption of lipids.We also found that PGL could reverse the reduced tight-junction protein expression due to intestinal lipid overload,promote Occludin and Claudin4 expression in the small intestine,and enhance the intestinal mucosal barrier.In conclusion,we demonstrated that PGL can inhibit lipid absorption and reduce blood TG and TC by targeting pancreatic lipase,promoting tight-junction protein expression and thereby preventing intestinal mucosa damage from an overload of lipids in the intestine.
A simple, reliable, economical method was developed using HPLC with a diode-array detector for determination of total flavonoids in plasma after introvenous administration of ginkgo biloba extract. The method simultaneously detects quercetin, kaempferol, and isorhamnetin after acid hydrolysis and recalcula-tion. The hydrolysis and extraction conditions were optimized in an orthogonal test. The specificity was tested by comparing the retention time, UV spectra, and peak purity indices with standards. The detection limits were 20 ng/mL for quercetin, 20 ng/mL for kaempferol, and 50 ng/mL for isorhamnetin. The calibration curve ranges were 75-2400, 71-2280, and 70-2240 ng/mL. The pharmacokinetic characteristics of ginkgo biloba flavonoids after venous administration of 50 mg/kg ginkgo biloba extract to rats were analyzed using a two-compartment model. The initial plasma concentration was 171.22 μg/mL. The half-life of flavonoids in the first compartment (distribution) was 0.07 h and at the second compartment (elimination) was 4.51 h, while the AUC(0-∞) was 1711.06 μg·min/mL. The apparent volume of distribution was 0.11 L/kg. The total body clearance is 10.52 mL/(min·kg). The result shows the method is suitable for pharmacokinetic studies.
A series of animal models are used to investigate the anti-depression mechanism of flavonoids in scutellariae radix (SR) in vivo. Depression-like behavior in mice was studied after intraperitoneal administra-tion of SR. The results showed that SR administered to mice by the intraperitoneal route obviously short-ened the duration in the tail suspension test and the forced swimming test, aggravated the symptoms of eyelid ptosis, akinesia, and mortality caused by reserpine, prolonged climbing times, affected the condi-tioned place preference, and increased sugar consumption in mice. However the SR did not affect the head twitches induced by 5-HTP, locomotor activity in mice, the toxicity of yohimbine, and the body temperature decrease caused by high dosage of apomorphine. The tests show that SR has some anti-depression effect related to the dopamine system. Furthermore another anti-depression mechanism was possible that could affect the mechanism of brain reward, bring positive reinforcement, and increase the sensitivity to euphoria in mice.
