23/12/2017 · Canadian Journal of Chemistry ..
MetaCyc berberine biosynthesis - BioCyc database …
FITC Annexin V and PI co-staining revealed thatberberine caused apoptosis in Huh7 HCC cells (). The Cide family is known as theinhibitory subunits of endonucleases, cleavage of which is inducedby downstream caspases (). Theresults support the notion that berberine induced the apoptosis ofcancer cells. shows thatBax, Bid, CIDEA, HRK and p21 were upregulated, while AKT and Bcl-2were downregulated in Huh7 cells following treatment withberberine. The change in the gene expression profile suggests thatberberine induced the apoptosis of Huh7 cells through theirintrinsic pro-apoptotic activity which was reported to beassociated with mitochondrial dysfunction in cell death (). The p21 protein is known to serve as aregulator of cell cycle progression at the G1 phase (). The increase in p21 gene expression() suggests that p21regulated the cell cycle progression following treatment withberberine. The AKT protein was reported to participate in theregulation of tumor cell survival and proliferation by stabilizingp21 protein (). Bcl-2 geneexpression was decreased in the present study. The results suggestthat berberine inhibited the gene expression of the Bcl-2 gene inthe HCC cells. An increased gene expression of Bid implies anincreased protein expression of Bid in the cytosol. It was reportedthat survivin is an anti-apoptosis gene expressed in cancer andlymphoma (,). The present results indicate thatsurvivin negatively regulated apoptosis by inhibiting caspaseactivation. The findings demonstrated that berberine may inhibitsurvivin gene expression in Huh7 cells. The real-time PCR resultsagreed with the PCR array analysis regarding the HRK gene, whichwas reported to be inhibited by Bcl-2 and Bcl-xL (). Previous studies have reported thatincreased Bcl-2 protein expression causes resistance tochemotherapeutic drugs and radiation therapy, while decreasingBcl-2 expression promotes apoptosis induced by anticancer drugs(). The results reflect the factthat an overexpression of Bcl-2 may cause accumulation of cells inthe G0 phase of the cell cycle distribution, resulting inchemoresistance (). The presentfindings provide experimental evidence that berberine modulated theprotein expression of Bcl-2 associated with caspase-3/7 activitiesin HCC cells. Higher caspase-3/7 activities were observed in Huh7cells. It has been reported that cytochrome interacts withApaf-1, which activates caspase-9 (). The effector caspases, caspase-7 andcaspase-3, are downstream targets of caspase-9. Poly(ADP-ribose)polymerase (PARP) is a well-known downstream target of activecaspase-3 (). PARP was reportedto produce poly(ADP-ribosyl)ation of nuclear proteins with NAD as asubstrate. PARP is inactivated by cleavage. The present findingsdemonstrated that the protein expression of full-length PARPdecreased while the cleaved form increased. Since berberinedecreased the protein expression of procaspase-9 and its downstreameffector caspases, procaspase-3 and procaspase-7, it is possiblethat berberine cleaves caspase-9, caspase-3 and caspase-7. Cleavedcaspases become active executioners of the intrinsic apoptoticpathway. The protein expression of proliferating cell nuclearantigen (PCNA) was found to be downregulated by berberine in Huh7cells. The experimental results indicate that as the expression ofPCNA was reduced by berberine, fewer cells were able to repairdamaged DNA.
Synthesis of berberine-baicalein ..
Since berberine activates phosphorylation of thePI3K/AKT, ERK, and GSK3β signaling pathways, we hypothesized thatLY 294002, a selective inhibitor of PI3K; PD 98059, a selectiveinhibitor of ERK; and BIO, a selective inhibitor of GSK3β, inhibitsthe suppressive effect of berberine on melanogenesis. B16F10melanoma cells were treated with berberine (10 g/ml) in thepresence or absence of LY 294002 (20 M/ml) or PD 98059 (10M/ml) or BIO (1 M/ml) for 3 days, and theextracellular melanin release was measured. As shown in , addition of the inhibitorsincreased the amount of melanin in the media. Berberine treatmentinhibited this melanin release ().