METHODS: We established an in vitro OA culture model by exposing human chondrocytes to proinflammatory cytokine and interleukin (IL)-1β for 36 hours prior to treatment with the herbals: C. quadrangularis, W. somnifera, and the combination of the two herbals. Cell viability, toxicity, and gene expression of OA modifying agents were examined. In addition, expression of survivin, which is crucial for cell growth, was analyzed. In vivo work on osteotomized rats studied the bone and cartilage regenerative effects of C. quadrangularis, W. somnifera, and the combination therapy.
RESULTS: Exposure of chondrocytes to IL-1β induced significant toxicity and cell death. However, herbal treatment alleviated IL-1β induced cell toxicity and upregulated cell growth and proliferation. C. quadrangularis inhibited gene expression of cytokines and matrix metalloproteinases, known to aggravate cartilage and bone destruction, and augmented expression of survivin by inhibiting p38 MAPK. Interestingly, osteotomized rats treated with C. quadrangularis drastically enhanced alkaline phosphatase and cartilage tissue formation as compared to untreated, W. somnifera only, or the combination of both herbals.
CONCLUSION: Our findings demonstrate for the first time the signaling mechanisms regulated by C. quadrangularis and W. somnifera in OA and osteogenesis. We suggest that the chondroprotective effects and regenerative ability of these herbals are via the upregulation of survivin that exerts inhibitory effects on the p38 MAPK signaling pathway. These findings thus validate C. quadrangularis as a potential therapeutic for rheumatic disorders.
METHODS: The distribution of polymorphic variants in the SLCO1B1 gene at eight loci that spanned approximately 48 kb was investigated in the three different Asian ethnic groups and in 32 non-cancerous liver tissues from Chinese patients.
RESULTS: Of the 26 polymorphisms screened, we found eight polymorphic variants that differed in genotypic and allelic frequencies between the Chinese, Malay and Indian populations. Significant interethnic differences were observed in the genotype frequency distributions across the promoter SNP [g.-11187G>A (P = 0.030)] as well as three coding region SNPs [c.388G>A (P < 0.001); c.571T>C (P < 0.001); c.597C>T (P < 0.001)] in the healthy subjects. Haplotype analysis revealed 12 different haplotypes in both the Chinese and Malay populations and 18 haplotypes in the Indian population. In both the Malay and Indian populations, the htSNPs were c.388A>G, c.571T>C and c.597C>T, whereas in the Chinese population they were g.-11187G>A, c.388A>G and c.597C>T. The c.388A>G and c.597C>T htSNPs accounted for more than 70% of the variations between the three major haplotypes in each Asian ethnic group. In terms of the c.388A>G htSNPs, genotypic-phenotypic association analyses revealed that there was no effect on SLCO1B1 expression in hepatic tissues; in addition, no genotypic-phenotypic associations were evident with regards to the c.597C>T htSNP.
CONCLUSION: Future studies should investigate the phenotypic effects of the c.388A>G htSNP on the disposition of OATP1B1 substrates in Asian populations.