Supakit Wongwiwatthananukit

Anti-inflammatory sesquiterpene lactones from the flower of Vernonia cinerea

Bioassay-guided fractionation of the hexane extract from the flowers of Vernonia cinerea (Asteraceae) led to the isolation of a new sesquiterpene lactone, 8α-hydroxyhirsutinolide (2), and a new naturally occurring derivative, 8α-hydroxyl-1-O-methylhirsutinolide (3), along with seven known compounds (1 and 4-9). The structures of the new compounds were determined by 1D and 2D NMR experiments and by comparison with the structure of compound 1, whose relative stereochemistry was determined by X-ray analysis. The isolated compounds were evaluated for their cancer chemopreventive potential based on their ability to inhibit nitric oxide (NO) production and tumor necrosis factor alpha (TNF-α)-induced NF-κB activity. Compounds 1, 2, 4, 5, and 9 inhibited TNF-α-induced NF-κB activity with IC(50) values of 3.1, 1.9, 0.6, 5.2, and 1.6 μM, respectively; compounds 4 and 6-9 exhibited significant NO inhibitory activity with IC(50) values of 2.0, 1.5, 1.2, 2.7, and 2.4 μM, respectively.

Comparative Efficacy and Safety of Low-Dose Pitavastatin Versus Atorvastatin in Patients with Hypercholesterolemia

Background: Previous studies have shown conflicting results on low-density lipoprotein cholesterol (LDL-C) reduction for comparable doses of pitsvastatin and atorvastatin. Objective: To compare the efficacy of pitavastatin 1 mg once daily with that of atorvastatin 10 mg once daily on lipoprotein change, safety, and cost per percent LDL-C reduction. Methods: An 8-week, randomized, open-label, parallel trial was conducted in patients with hypercholesterolemia. One hundred patients were equally randomized to receive pitavastatin 1 mg once daily or atorvastatin 10 mg once daily; 98 completed the study. Outcomes were assessed at baseline and at the end of the study. Results: Pitavastatin lowered LDL-C levels from baseline by 37% compared with 46% in the atorvastatin group (p < 0.001). The reduction of total cholesterol (TC) levels from baseline was significantly different between the pitavastatin (28%) and atorvastatin (32%) groups (p = 0.005). There was no significant difference in the percentage of changes in triglyceride and high-density lipoprotein cholesterol levels between groups. The percentage of patients who achieved LDL-C goals according to National Cholesterol Education Program–Adult Treatment Panel III guidelines was not significantly different between the pitavastatin (74%) and atorvastatin (84%) groups (p = 0.220). In addition, both regimens were well tolerated, with no patient developing an elevation of more than 3 times the upper normal limit of alanine aminotransferase or 10 times that of creatine kinase. The monthly cost per percent LDL-C reduction in the pitavastatin group (

Effects of vitamin D 2 supplementation on insulin sensitivity and metabolic parameters in metabolic syndrome patients

0.77) was about 50% lower than the cost in the atorvastatin (

A Training Program for Pharmacy Students on Providing Diabetes Care

1.56) group. Conclusions: Although pitavastatin 1 mg daily was not as effective at lowering LDL-C and TC levels as atorvastatin 10 mg daily, the number of patients achieving their LDL-C goals with pitavastatin was comparable with the number using atorvastatin. Pitavastatin 1 mg once daily may be an alternative regimen with cost-saving benefits but without a significant decrease in therapeutic benefit or increase in adverse events in patients with hypercholesterolemia.

Sesquiterpene Lactones from Vernonia cinerea

Background: Vitamin D deficiency has been linked to many of the characteristics of metabolic syndrome, but whether supplementation with vitamin D2 would improve insulin sensitivity or metabolic risk factors is not known. Aim: To investigate effects of vitamin D2 supplementation on insulin sensitivity and metabolic parameters in metabolic syndrome patients. Subjects and methods: An 8-week, prospective randomized, double-blind, double-dummy, parallel trial was conducted in patients with metabolic syndrome. Ninety patients were equally randomized to receive vitamin D2 40,000 IU per week, vitamin D2 20,000 IU per week, or placebo. Outcomes were assessed at baseline and at the end of the study. Results: At week 8, serum 25(OH)D concentrations were increased significantly in both vitamin D2 groups (i.e., 20,000 IU and 40,000 IU) when compared with placebo group (11.72 ng/ml vs 2.80 ng/ml; p<0.001 and 15.74 ng/ml vs 2.80 ng/ml; p<0.001, respectively). Serum 25(OH)D concentrations in both vitamin D2 treatment groups were also significantly different (p=0.04). Insulin sensitivity assessed by homeostasis model assessment of insulin resistance (HOMA-IR) at week 8 in the three groups was not significantly different (p=0.36). Conclusions: Vitamin D2 20,000 IU per week and 40,000 IU per week givn for 8 weeks, were able to increase serum 25(OH)D concentrations significantly more than placebo group. However, HOMA-IR was not significantly different in the three groups. Our results do not support a positive effect of vitamin D2 on metabolic risk factors.

Abstract 4847: Discovery, semisynthesis, and structure-activity relationship studies of hirsutinolide derivatives as new STAT3 inhibitors and anti-glioma agents

Objective. To compare second- and third-year pharmacy students’ competence, attitudes, and self-confidence in providing diabetes care before and after completing a hand-on diabetes training program and to determine if the program had an impact on students’ attitude and self-confidence based on their year in the curriculum. Design. The program included classroom lectures and hands-on learning sessions in 5 facets of diabetes care. Pre- and post-test instruments measured students’ competence, attitudes, and confidence in diabetes care. Assessment. Students’ competence and the mean overall confidence score significantly improved after completing the program, while mean overall attitude score did not. Third-year students had significantly higher confidence scores than did second-year students on both pre- and post-program tests. No significant difference was found for attitude scores between second- and third-year students. Conclusion. The hands-on learning program was an effective approach to training pharmacy students in diabetes care, improving both their competence and confidence.

Bioactive sesquiterpene lactones and other compounds isolated from Vernonia cinerea.

A new hirsutinolide-type sesquiterpene lactone, 8α-(2′Z-tigloyloxy)-1α-methoxyhirsutinolide (1), and a new naturally occurring 8α-(2′-hydroxymethylacryloyloxy)-1α-methoxyhirsutinolide-13-O-acetate (2) were isolated from the CHCl3 extract of the aerial parts of Vernonia cinerea (Asteraceae). The structures of the new compounds were determined by 1D and 2D NMR and MS experiments, as well as by comparison of their data with the published values.

Modified Mallampati test and thyromental distance as a predictor of difficult laryngoscopy in Thai patients.

Clinically, natural product has played a pivotal role in anticancer drug discovery and development. Cancer chemotherapy and/or radiotherapy due to glioma treatment are not ideal, frequently cause unwanted adverse effects, and justify further research and development of alternative, novel, safe, and effective agents. In our continued efforts to identify new signal transducer and activator of transcription 3 (STAT3) and antiglioma agents with enhanced efficacy and specificity, we have initiated a collaborative and multidisciplinary natural product drug discovery project and the goal was to isolate, semisynthesize, and evaluate the potential of Vernonia cinerea-derived phytochemicals as STAT3 inhibitors with therapeutic remedy of human glioma and may be even more effective than the existing ones. To date, our preliminary studies have been conducted and resulted in the discovery of a class of sesquiterpene lactone hirsutinolide series with an a,â-unsaturated-a-lactone ring as new STAT3 inhibitors. Specifically, on the basis of encouraging biological data and to expand the existing structure activity relationship (SAR) of isolated natural hirsutinolide analogues, chemical modifications were performed using conventional Steglich esterification protocol to produce a series of semisynthetic hirsutinolide derivatives in moderate to high yields. Thus far, biological evaluation revealed that several semisynthetic analogues showed low micromolar inhibitory activities against constitutively-active STAT3 and malignant glioma phenotype. SAR showed that a bulky and lipophilic ester functionality at position 13 is essential for STAT3 inhibition as well as whole cell based anticancer activity. A lipophilic side chain at position 8 also plays an important role in anticancer activity and may contribute a detrimental effect on specificity. In addition, the methoxy group at position 1 enhances the cell-type specificity and selectivity. Finally, selected promising lead candidates also demonstrated in vivo efficacy following oral gavage delivery, inhibiting human glioma tumor growth in subcutaneous mouse xenografts. Together, natural and chemically modified hirsutinolide-type sesquiterpene lactones represent a promising natural product class of new anticancer agents for the treatment of malignant human glioma. Citation Format: Mingming Zhang, Ui Joung Youn, Gabriella Miklossy, Supakit Wongwiwatthananukit, James Turkson, Leng Chee Chang, Dianqing Sun. Discovery, semisynthesis, and structure-activity relationship studies of hirsutinolide derivatives as new STAT3 inhibitors and anti-glioma agents. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4847.