METHODS: Pooled urine samples of patients with BTG (n=10), patients with PTC (n=9) and healthy controls (n=10) were subjected to iTRAQ analysis and immunoblotting.
RESULTS: The ITRAQ analysis of the urine samples detected 646 proteins, 18 of which showed significant altered levels (p<0.01; fold-change>1.5) between patients and controls. Whilst four urinary proteins were commonly altered in both BTG and PTC patients, 14 were unique to either BTG or PTC. Amongst these, four proteins were further chosen for validation using immunoblotting, and the enhanced levels of osteopontin in BTG patients and increased levels of a truncated gelsolin fragment in PTC patients, relative to controls, appeared to corroborate the findings of the iTRAQ analysis.
CONCLUSION: The data of the present study is suggestive of the potential application of urinary osteopontin and gelsolin to discriminate patients with BTG from those with PTC non-invasively. However, this needs to be further validated in studies of individual urine samples.
Aim: To evaluate the nephroprotective activity of CAE and its fractions in cisplatin-induced nephrotoxicity and to assess whether they compromise the anticancer efficacy of cisplatin.
Materials and methods: Cisplatin-induced renal damage was induced in Ehrlich Ascites Carcinoma (EAC) bearing mice during mild phase of tumor growth. CAE and its butanol (BF) and aqueous (AF) fractions were administered orally from the 5th day for five days. Nephroprotective potential (serum urea, creatinine, renal histology) and effect of VC on cisplatin anticancer efficacy (tumor volume, viable tumor cells, percentage increase in life span (% ILS)) were calculated.
Result: CAE and its fractions significantly reversed the cisplatin-induced renal damage. CAE and BF treated animals showed regeneration of 50%-75% of proximal tubular cells. Compared to EAC control mice, the % ILS of the cisplatin-treated group was 244% and it was further extended to 379% after CAE administration. The % ILS in the CAE treated group was 1.6 times higher than the cisplatin alone treated group. GC-MS study showed the presence of astaxanthin and betulin.
Conclusion: CAE of VC reverses cisplatin-induced kidney damage as well as regenerates proximal tubular epithelial cells, without compromising the anticancer effect of cisplatin. When CAE was further fractionated, the nephroprotective activity was retained, but the beneficial anticancer effect of cisplatin was compromised.
METHODS: The aqueous ethanolic leaf extracts of C. caudatus were characterized by NMR and LC-MS/MS. The total phenolic content and α-glucosidase inhibitory activity were evaluated by the Folin-Ciocalteu method and α-glucosidase inhibitory assay, respectively. The statistical significance of the results was evaluated using one-way ANOVA with Duncan's post hoc test, and correlation among the different activities was performed by Pearson's correlation test. NMR spectroscopy along with multivariate data analysis was used to identify the metabolites correlated with total phenolic content and α-glucosidase inhibitory activity of the C. caudatus leaf extracts.
RESULTS: It was found that the α-glucosidase inhibitory activity and total phenolic content of the optimized ethanol:water (80:20) leaf extract of the plant increased significantly as the plant matured, reaching a maximum at the 10th week. The IC50 value for α-glucosidase inhibitory activity (39.18 μg mL- 1) at the 10th week showed greater potency than the positive standard, quercetin (110.50 μg mL- 1). Through an 1H NMR-based metabolomics approach, the 10-week-old samples were shown to be correlated with a high total phenolic content and α-glucosidase inhibitory activity. From the partial least squares biplot, rutin and flavonoid glycosides, consisting of quercetin 3-O-arabinofuranoside, quercetin 3-O-rhamnoside, quercetin 3-O-glucoside, and quercetin 3-O-xyloside, were identified as the major bioactive metabolites. The metabolites were identified by NMR spectroscopy (J-resolve, HSQC and HMBC experiments) and further supported by dereplication via LC-MS/MS.
CONCLUSION: For high phytomedicinal quality, the 10th week is recommended as the best time to harvest C. caudatus leaves with respect to its glucose lowering potential.