Fermented Brown Rice Extract Stimulates BDNF Gene Transcription in C6 Glioma Cells: Possible Connection with HO-1 Expression.

Fermented brown rice with Aspergillus oryzae, designated as FBRA, is known to be commercially available dietary fiber-rich food, which is appreciated as prebiotics to improve intestinal microflora, and also shown to contain various biologically active substances including polyphenolic compounds. On the other hand, polyphenolic compounds have been suggested to stimulate the expression of brain-derived neurotrophic factor (BDNF) gene in connection with the expression of heme oxidase-1 (HO-1) gene in glial cells, thus resulting in the augmentation of BDNF production in the brain, thereby being anticipated to have a putative effect on the brain function. Then, the effect of FBRA extract on HO-1 and BDNF messenger ribonucleic acid (mRNA) levels in C6 glioma cells was examined, and the extract was shown to stimulate both HO-1 and BDNF gene transcription in the glioma cells. Further studies showed that the stimulatory effect of FBRA extract on BDNF gene transcription was almost completely suppressed by silencing HO-1 gene expression with an HO-1 antisense oligodeoxynucleotide and also inhibiting HO-1 activity with an inhibitor zinc protoporphyrin, thus suggesting that FBRA might have a potential ability to induce BDNF gene expression through HO-1 activity in glial cells.

Fermented Brown Rice Extract Causes Apoptotic Death of Human Acute Lymphoblastic Leukemia Cells via Death Receptor Pathway.

Mixture of brown rice and rice bran fermented with Aspergillus oryzae, designated as FBRA, has been reported to reveal anti-carcinogenic and anti-inflammatory effects in rodents. Then, to test its potential anti-cancer activity, the aqueous extract was prepared from FBRA powder, and the effect of this extract on human acute lymphoblastic leukemia Jurkat cells was directly examined. The exposure to FBRA extract reduced the cell viability in a concentration- and time-dependent manner. The reduction of the cell viability was accompanied by the DNA fragmentation, and partially restored by treatment with pan-caspase inhibitor. Further studies showed that FBRA extract induced the cleavage of caspase-8, -9, and -3, and decreased Bcl-2 protein expression. Moreover, the expression of tBid, DR5, and Fas proteins was enhanced by FBRA extract, and the pretreatment with caspase-8 inhibitor, but not caspase-9 inhibitor, restored the reduction of the cell viability induced by FBRA extract. These findings suggested that FBRA extract could induce the apoptotic death of human acute lymphoblastic leukemia cells probably through mainly the death receptor-mediated pathway and supplementarily through the tBid-mediated mitochondrial pathway, proposing the possibility that FBRA was a potential functional food beneficial to patients with hematological cancer.