salvianolic-acid-B and Neuroblastoma

Alzheimer's disease (AD) is a neurodegenerative disease with subtle onset, early diagnosis remains challenging. Accumulating evidence suggests that the emergence of retinal damage in AD precedes cognitive impairment, and may serve as a critical indicator for early diagnosis and disease progression. Salvianolic acid B (Sal B), a bioactive compound isolated from the traditional Chinese medicinal herb Salvia miltiorrhiza, has been shown promise in treating neurodegenerative diseases, such as AD and Parkinson's disease. In this study we investigated the therapeutic effects of Sal B on retinopathy in early-stage AD. One-month-old transgenic mice carrying five familial AD mutations (5×FAD) were treated with Sal B (20 mg·kg

Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Amyloid Precursor Protein Secretases; Animals; Aspartic Acid Endopeptidases; Disease Models, Animal; Humans; Mice; Mice, Transgenic; Neuroblastoma; Neurodegenerative Diseases; Retina

Parkinson's disease (PD) is associated with mitochondrial dysfunction, oxidative stress, and activation of the apoptotic cascade. In the study, we investigated the effects of salvianolic acid B (Sal B) on 1-methyl-4-phenylpyridinium (MPP(+))-treated SH-SY5Y cells, a classic in vitro model for PD. We found Sal B inhibited the loss of cell viability by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The underlying mechanisms of Sal B action were further studied. Treatment of SH-SY5Y cells with MPP(+) caused a loss of cell viability and mitochondrial membrane potential, condensation of nuclei, elevation in the level of reactive oxygen species (which was associated with cytochrome c release), an increase in the Bax/Bcl-2 mRNA ratio, and activation of caspase-3. Sal B ameliorated the MPP(+)-altered phenotypes. These results indicate that the Sal B protected SH-SY5Y cells against MPP(+)-induced apoptosis by relieving oxidative stress and modulating the apoptotic process. Our findings suggest that salvianolic acid B may be a promising agent to prevent PD.

Topics: 1-Methyl-4-phenylpyridinium; Antiparkinson Agents; Apoptosis; bcl-2-Associated X Protein; Benzofurans; Biological Assay; Caspase 3; Cell Culture Techniques; Cell Line, Tumor; Cell Survival; Humans; Membrane Potential, Mitochondrial; Molecular Structure; Neuroblastoma; Parkinson Disease; Proto-Oncogene Proteins c-bcl-6; Reactive Oxygen Species; Reverse Transcriptase Polymerase Chain Reaction

Oxidative stress caused by dopamine may play an important role in the pathogenesis of Parkinson's disease. Salvianolic acid B is an antioxidant derived from the Chinese herb, Salvia miltiorrhiza. In this study, we investigated the neuroprotective effect of salvianolic acid B against 6-hydroxydopamine-induced cell death in human neuroblastoma SH-SY5Y cells. Pretreatment of SH-SY5Y cells with salvianolic acid B significantly reduced 6-hydroxydopamine-induced generation of reactive oxygen species, and prevented 6-hydroxydopamine-induced increases in intracellular calcium. Our data demonstrated that 6-hydroxydopamine-induced apoptosis was reversed by salvianolic acid B treatment. Salvianolic acid B reduced the 6-hydroxydopamine-induced increase of caspase-3 activity, and reduced cytochrome C translocation into the cytosol from mitochondria. The 6-hydroxydopamine-induced decrease in the Bcl-x/Bax ratio was prevented by salvianolic acid B. Additionally, salvianolic acid B decreased the activation of extracellular signal-regulated kinase and induced the activation of 6-hydroxydopamine-suppressed protein kinase C. These results indicate that the protective function of salvianolic acid B is dependent upon its antioxidative potential. Our results strongly suggest that salvianolic acid B may be effective in treating neurodegenerative diseases associated with oxidative stress.

Topics: Adrenergic Agents; Antioxidants; Apoptosis; Apoptosis Regulatory Proteins; Benzofurans; Calcium; Caspase 3; Cell Line, Tumor; Cytochromes c; Drugs, Chinese Herbal; Humans; Neuroblastoma; Neuroprotective Agents; Oxidative Stress; Oxidopamine; Protein Kinase C; Reactive Oxygen Species; Salvia miltiorrhiza; Sympatholytics

To investigate and compare the antioxidant activities of salvianolic acid B (SalB) and Ginkgo biloba extract (EGb 761) in aqueous solution, rat microsomes and the cellular system.. Superoxide anion (O2-.) was generated using xanthine/xanthine oxidase system and phenazine methosulate/NADH system, and the effects of SalB and EGb 761 on the generation of O2-.were achieved by spectrophotometric measurement of the product formed on reduction of nitro blue tetrazolium. Two different methods were used to assess the scavenging effects of the extracts on hydroxyl radical (. OH): HPLC method was used for quantitation of . OH by oxy-radical trapping of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) to form DMPO-OH adducts in Fe2+-EDTA-H2O2 system. To confirm the HPLC data, .OH was also measured by spectrophotometry using a commercial detection kit. The anti-lipid peroxidation effects of the extracts in microsomes of rat brain, liver and kidney induced by ascorbate-NADPH were determined by thiobarbituric acid (TBA) method. The protective effects of the extracts on peroxide hydrogen (H2O2)-induced oxidative damage in SH-SY5Y cells were investigated by assessing cell viability assay, the level of lipid peroxidation, and the lactate dehydrogenase(LDH) release.. Both SalB and EGb 761 were able to scavenge O2-. and . OH, inhibit lipid peroxidation of microsomes, and protect SH-SY5Y cells against H2O2-induced oxidative damage. However, the concentration of SalB was far lower than that of EGb 761 when a similar effect was obtained.. The antioxidant efficiency of SalB was greater than that of EGb 761. These results suggest that SalB, like EGb 761, has promising potential in treating oxidative damage-derived neurodegenerative disorders.

Topics: Animals; Antioxidants; Benzofurans; Brain; Cell Line, Tumor; Drugs, Chinese Herbal; Ginkgo biloba; Humans; Male; Neuroblastoma; Plant Extracts; Plants, Medicinal; Rats; Rats, Wistar; Salvia miltiorrhiza