Structural modification of olibergin A,an isoflavonoid,from Dalbergia stipulacea Roxb. and its cytotoxicity

Fifteen derivatives were synthesized from olibergin A, a major isoflavonoid isolated from the stems of Dalbergia stipulacea Roxb. All compounds were evaluated for cytotoxicity against HCT-116, HT-29, MCF-7 and vero cell lines using MTT assay. Cytotoxicity results showed 5-hydroxy-7,2′,4′,5′-tetramethoxyisoflavone (5) was the most active with IC₅₀ values of 19.03 ± 0.70, 10.83 ± 1.65, 12.53 ± 0.70 and 13.53 ± 0.84 μM against HCT-116, HT-29, MCF-7 and vero cell lines, respectively. It should be noted that 5-hydroxy-7,2′,4′,5′-tetramethoxyisoflavone (5) showed two times less toxicity against vero cells than the cisplatin standard (IC₅₀ = 6.55 ± 0.81 μM) while 5 and cisplatin exhibited nearly equal cytotoxicity against the MCF-7 cell line. 5,7,2′,4′,5′-Pentamethoxyisoflavanone (10) showed an IC₅₀ value of 30.34 ± 1.15 μM against the HCT-116 cell line and exhibited weak cytotoxicity against normal cells, the vero cell line. In addition, 5,7,4′-trihydroxy-2′,5′-dimethoxyisoflavan oxime (13) demonstrated cytotoxicity against HT-29 cells with an IC₅₀ value of 31.41 ± 1.38 μM and displayed weak activity toward the vero cell line. The information revealed that these compounds were suitable for development to anticancer agents against HCT-116, HT-29 and MCF-7 cell lines.

Fifteen derivatives were synthesized from olibergin A, a major isoflavonoid isolated from the stems of Dalbergia stipulacea Roxb.     

Adiponectin/ACP30, a collagen-like plasma protein in relation to anthropometric measurement in Thai overweight and obese subjects

Adiponectin, anthropometric parameters including weight, height, body mass index (BMI), arm circumference, triceps skinfold, subscapular skinfold, waist, hip circumferences and waist/hip ratio were recorded in 48 male and 166 female overweight and obese Thai volunteers (BMI?≥?25.0 kg/m²), and in 26 male and 81 female normal subjects (BMI?=?18.5???24.9 kg/m²). Thai volunteers were investigated. Statistically significantly lower adiponectin concentrations in overweight and obese subjects were found when compared with control subjects of both sexes. Anthropometric parameters, including weight, height, BMI, arm circumference, triceps skinfold, subscapular skinfold, waist, hip circumferences and waist/hip ratio, except arm span, were statistically significantly higher in overweight and obese subjects than in control subjects. The overweight and obese subjects had higher glucose concentrations than the control subjects. The BMI and glucose concentrations were found to be significantly related, under these conditions, to adiponectin.     

The Effects of Crocodile Blood Supplementation on Delayed-Onset Muscle Soreness

Delayed-onset muscle soreness (DOMS) is associated with increases in acute inflammatory and biochemical markers, muscle swelling, pain, and reduced functional performance. This study aimed to investigate the preventative effects of crocodile blood supplementation on DOMS induced by eccentric exercise. Sixteen healthy males were randomly allocated to either a crocodile blood (CB, n = 8) or a placebo (PL, n = 8) treatment. Participants receiving the CB treatment consumed four capsules of freeze–dried CB powder (1 g day⁻¹) over 18 days. Participants receiving the other treatment were administered a placebo over the same period. An eccentric exercise protocol was performed, and functional performance, visual analogue scale (VAS)-measured pain, knee range of movement (ROM), thigh circumference (swelling), and cytokines, enzymes, and biochemical parameters were assessed immediately after exercise as well as after 24 h, 48 h, and 72 h. CB supplementation could significantly maintain maximum voluntary isometric contraction (MVIC) at 24 h (p = 0.001) and 48 h after exercise (p = 0.001) when comparing values at different times for the CB group. In the CB group, thigh circumference decreased only immediately after eccentric exercise (p = 0.031) in comparison with pre-eccentric exercise values. An 18-day supplementation (1 g day⁻¹) of crocodile blood does aid in the maintenance of functional performance and muscle swelling after eccentric exercise. Our data indicate that 1 g day⁻¹ of crocodile blood supplementation should be safe for human consumption.     

Leukemia inhibitory factor can mediate Ras/Raf/MEK/ERK-induced growth inhibitory signaling in medullary thyroid cancer cells

Medullary thyroid carcinoma (MTC) is a multiple endocrine neoplasia type 2 syndrome caused by mutations in extracellular receptor or intracellular kinase domains of the RET proto-oncogene. Activation of the Ras/Raf/MEK/ERK pathway can lead to growth arrest by secreting leukemia inhibitory factor (LIF) in MTC cells harboring a RET receptor domain mutation. Here, we report that Ras/Raf/MEK/ERK can also mediate, via LIF, growth inhibition in MTC cells harboring a RET kinase domain mutation. Ras/Raf/MEK/ERK activation was sufficient to induce growth inhibition and LIF expression in the human MTC line MZ-CRC-1. Presence of LIF-mediated signaling was determined by blocking the activity of culture medium conditioned by Raf-activated cells using anti-LIF neutralizing antibody. In addition, recombinant LIF effectively suppressed cell proliferation via cell cycle arrest in G0/G1 phase. Expression of dominant negative STAT3 abrogated LIF effects, indicating that LIF mediates its signaling through the JAK/STAT3 pathway. These results suggest that growth inhibition and activation of the autocrine/paracrine signaling through LIF/JAK/STAT may be a common response to Ras/Raf activation in different MTC types, and justify further evaluation of LIF as a potential anticancer agent for MTC.     

Adiponectin/ACP30, a collagen-like plasma protein in relation to anthropometric measurement in Thai overweight and obese subjects

Adiponectin, anthropometric parameters including weight, height, body mass index (BMI), arm circumference, triceps skinfold, subscapular skinfold, waist, hip circumferences and waist/hip ratio were recorded in 48 male and 166 female overweight and obese Thai volunteers (BMI=25.0 kg/m(2)), and in 26 male and 81 female normal subjects (BMI=18.5-24.9 kg/m(2)). Thai volunteers were investigated. Statistically significantly lower adiponectin concentrations in overweight and obese subjects were found when compared with control subjects of both sexes. Anthropometric parameters, including weight, height, BMI, arm circumference, triceps skinfold, subscapular skinfold, waist, hip circumferences and waist/hip ratio, except arm span, were statistically significantly higher in overweight and obese subjects than in control subjects. The overweight and obese subjects had higher glucose concentrations than the control subjects. The BMI and glucose concentrations were found to be significantly related, under these conditions, to adiponectin.     

Inhibitory effects of Thai plants β-glycosides on <Emphasis Type="Italic">Trichomonas vaginalis</Emphasis>

Trichomoniasis is now an important health problem in developing countries. Although metronidazole has so far been widely used to treat this disease, the prevalence of metronidazole-resistant protozoa and unpleasant adverse effects have been found. In this study, natural products purified from Thai plants were, therefore, investigated for their effectiveness against Trichomonas vaginalis. The minimal inhibitory concentrations for all beta-glycosides against Trichomonas vaginalis at 24 h were in a range of 6.25-12.5 microM. In addition, torvoside A and H were found to be more potent than their corresponding aglycones, deglucosylated torvoside A and H, while other beta-glycosides were generally as active as their corresponding aglycones. The cytotoxicity of these compounds was also determined. Except for dalcochinin, none of the tested compounds showed cytotoxicity against Vero and cancer cell lines (KB and MCF-7), having IC(50) values greater than 50 microg/ml. In conclusion, beta-glycosides and several aglycones showed selective inhibition against Trichomonas vaginalis without harmful effect to mammalian cells.