RESUMO
Parkinson's disease(PD)is the second most common neurodegenerative disease in the world;however,it lacks effective and safe treatments.Ginkgo biloba dropping pill(GBDP),a unique Chinese G.biloba leaf extract preparation,exhibits antioxidant and neuroprotective effects and has a potential as an alternative therapy for PD.Thus,the aims of this study were to evaluate the effects of GBDP in in vitro and in vivo PD models and to compare the chemical constituents and pharmacological activities of GBDP and the G.biloba extract EGb 761.Using liquid chromatography tandem-mass spectrometry,46 GBDP constitu-ents were identified.Principal component analysis identified differences in the chemical profiles of GBDP and EGb 761.A quantitative analysis of 12 constituents showed that GBDP had higher levels of several flavonoids and terpene trilactones than EGb 761,whereas EGb 761 had higher levels of organic acids.Moreover,we found that GBDP prevented 6-hydroxydopamine-induced dopaminergic neuron loss in zebrafish and improved cognitive impairment and neuronal damage in methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD mice.Although similar effects were observed after EGb 761 treatment,the neuroprotective effects were greater after GBDP treatment on several endpoints.In addition,in vitro results suggested that the Akt/GSK3β pathway may be involved in the neuroprotective effects of GBDP.These findings demonstrated that GBDP have potential neuroprotective effects in the treatment of PD.
RESUMO
Objective To observe the effect of intra-articular injection of berberine on the expression of matrix metalloproteinase (MMP)-13,ADAMTS-5,Aggrecan and Collagen Ⅱ in the cartilage of rabbits with osteoarthritis.Methods Thirty male New Zealand White rabbits underwent bilateral anterior cruciate ligament transection (ACLT).On the basis of randomization one knee of each rabbit was treated with 0.3 ml 100 μmol/L berberine resolved in the normal saline (NS) (the experimental group) and the other knee was treated under the same schedule using NS (the placebo group) 4 weeks after transection,once a week for five weeks.Nine weeks after ACLT,all rabbits were killed and the knee joints were evaluated by histology and biochemistry.The mRNA expression of MMP-13,ADAMTS-5,Aggrecan and Collagen Ⅱ in the cartilage was analyzed using reverse transcription polymerase chain reaction (RT-PCR).All data were analyzed using Student's t test.Results Mankin histological evaluation showed that the extent and grade of cartilage damage in the experimental group (6.9±1.9) were less severe than the placebo group (9.3±1.2)(t=3.394,P＜0.01).The mRNA expression of MMP-13 and ADAMTS-5 decreased (160±54;166±47) (t=3.311,P＜0.01;t=2.651,P＜0.05) while that of Aggrecan (261±50) and Collagen Ⅱ (335±64) increased in cartilage compared to the placebo group (233±45;234±67;186±64;254±69),the differences were significant (t=2.941,P＜0.01;t=2.743,P＜0.05).The content of hydroxyproline (Hyp) and glycosaminoglycan (GAG) in cartilage [(23.5±2.8) μg/mg;(30±3) μg/mg] increased significantly in the experimental group (t=2.941,P＜0.01;t=2.743,P＜0.05) compared to the placebo group [(19.9±2.8) μg/mg;(27.4±2.9) μg/mg].Conclusion Berberine protects against cartilage degradation and inhibits the progression of osteoarthritis by suppressing MMP-13 and ADAMTS-5 expression.