Treatment with bromelain-containing enzyme preparation for 3-4 weeks is effective for treatment of knee osteoarthritis (OA). Here, we aimed to assess 16-week treatment with bromelain in mild-to-moderate knee OA patients. We performed a randomized, single-blind, active-controlled pilot study. Forty knee OA patients were randomized to receive oral bromelain (500 mg/day) or diclofenac (100 mg/day). Primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) analyzed by Wilcoxon signed rank test. Secondary outcome was the short-form 36 (SF-36). Plasma malondialdehyde (MDA) and nitrite were measured as oxidative stress markers. There was no difference in WOMAC and SF-36 scores compared between bromelain and diclofenac groups after 4 weeks. At week 4, the improvement of total WOMAC and pain subscales from baseline was observed in both groups; however, two patients given diclofenac had adverse effects leading to discontinuation of diclofenac. However, observed treatment difference was inconclusive. At week 16 of bromelain treatment, the patients had improved total WOMAC scores (12.2 versus 25.5), pain subscales (2.4 versus 5.6), stiffness subscales (0.8 versus 2.0), and function subscales (9.1 versus 17.9), and physical component of SF-36 (73.3 versus 65.4) as compared with baseline values. OA patients had higher plasma MDA, nitrite, and prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-stimulated whole blood but lower plasma α-tocopherol than control subjects. Plasma MDA and LPS-stimulated PGE2 production were decreased at week 16 of bromelain treatment. Bromelain has no difference in reducing symptoms of mild-to-moderate knee OA after 4 weeks when compared with diclofenac.
BackgroundThe purpose of this study is to investigate cardiovascular benefits of juices obtained from two commonly consumed fruits in Thailand, Pachyrhizus erosus, L. (yam bean) and Psidium guajava, L. (guava), by examining their acute cardiovascular effects in healthy volunteers. Possible involvements of the dietary nitrate on their effects were investigated as well.MethodThirty healthy volunteers were randomly divided into three groups of 10 subjects per group and each group was allocated to drink 500 ml of freshly prepared yam bean root juice, guava fruit juice, or water. Systemic nitrate and nitrite concentrations, heart rate, systolic and diastolic blood pressure, serum K+ concentrations, ex vivo platelet aggregation, and plasma cGMP concentrations were monitored at the baseline and at various time points after the intake of juices or water. Data were compared by repeated measures ANOVA.ResultsFollowing the ingestion of both yam bean root juice and guava fruit juice, collagen-induced but not ADP-induced platelet aggregation was attenuated. Ingestion of yam bean root juice increased systemic nitrate and nitrite concentrations whereby elevated nitrite concentrations correlated with the extent of inhibiting collagen-induced platelet aggregation. In addition, positive correlation between systemic nitrite and plasma cGMP concentrations and negative correlation between plasma cGMP concentrations and the extent of collagen-induced platelet aggregation were revealed. Nevertheless, yam bean root juice reduced only diastolic blood pressure while guava fruit juice reduced heart rate, systolic and diastolic blood pressure.ConclusionThe present study has illustrated, for the first time, acute inhibitory effects of yam bean root juice and guava fruit juice on ex vivo collagen-induced platelet aggregation in healthy subjects. Dietary nitrate was shown to underlie the effect of yam bean root juice but not that of guava fruit juice. Following yam bean root juice ingestion, systemic nitrate apparently converts to nitrite and further to NO which may attenuate platelet responses to collagen stimulation. Cardiovascular benefits of juices from yam bean root and guava fruit are noteworthy in term of the cardiovascular health-promoting approach.Trial registrationRandomized controlled trial TCTR20150228001.
Cadmium (Cd) is accumulated in human astrocytes and induces the production of interleukin (IL)-6 and IL-8. Astrocytes are one of the major sources of chemokine CC motif ligand 2 (CCL2; known as monocyte chemoattractant protein-1 [MCP-1]), in the brain. Elevated CCL2 levels are associated with cognitive impairment as well as the migration and invasion of glioblastoma cells. The present study hypothesized that non-toxic concentrations of Cd (as cadmium chloride [CdCl 2 ]) could up-regulate CCL2 production in U-87 MG human glio-blastoma cells. The results showed that after exposure of the U-87 MG cells to CdCl 2 at 1 and 10 mM, there was an up-regulation of CCL2 mRNA expression after 3 h of exposure and increased CCL2 secretion after 6 and 24 h. The study also found that inhibition of MAPK pathways, including ERK1/ 2, p38, and JNK by U0126, SB203580 and SP600125, respectively, reduced Cd-induced CCL2 secretion by the cells. Moreover, when cells were pretreated with Ro 32-0432 (an inhibitor of calcium-dependent PKC) and LY294002 (a PI3K inhibitor), this also resulted in a down-regulation of any Cd-induced CCL2 expression. Taken together, the results of this study allow for the conclusion to be made that CCL2 up-regulation in U-87 MG cells induced by Cd is mediated, in part, by an activation of MAPK, PI3K/Akt, and PKC pathways.
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