Suppressive effects of methoxyflavonoids isolated from Kaempferia parviflora on inducible nitric oxide synthase (iNOS) expression in RAW 264.7 cells

Ethnopharmacological relevance

The rhizomes of Kaempferia parviflora Wall. ex Baker have been traditionally used in Thailand to treat abscesses, gout, and peptic ulcers.

Aim

Previously, we reported that the chloroform fraction of a Kaempferia parviflora extract had an inhibitory effect on rat paw-edema. In the present study, we isolated the constituents of this fraction and investigated the anti-inflammatory mechanism against nitric oxide (NO) production, tumor necrosis factor-α (TNF-α) and the expression of inducible nitric oxide synthase (iNOS) as well as phosphorylated extracellular signal-regulated kinase (p-ERK), and phosphorylated c-Jun N-terminal kinase (p-JNK). In addition, effects of trimethylapigenin (4) on the enzyme activities of protein kinases possibly leading to iNOS expression were examined to clarify the targets.

Materials and methods

The chloroform fraction was isolated using silica gel column chromatography and HPLC. Isolated compounds were tested against NO and TNF-α using RAW264.7 cells. Cytotoxicity and iNOS, p-ERK and p-JNK expression were also examined.

Results

Three active components, 5,7-dimethoxyflavone (2), trimethylapigenin (4), and tetramethylluteolin (5), markedly inhibited the production of NO in lipopolysaccharide (LPS)-activated RAW264.7 cells. Compounds 2, 4, and 5 moderately inhibited production of TNF-α. Compounds 2, 4, and 5 strongly inhibited expression of iNOS mRNA and iNOS protein in a dose-dependent manner, but did not inhibit p-ERK or p-JNK protein expression. The most active compound, 4, did not inhibit the enzyme activity of inhibitor of κB kinases or mitogen-activated protein kinases, but inhibited that of spleen tyrosine kinase (SYK).

Conclusion

The mechanism responsible for the anti-inflammatory activity of methoxyflavonoids from the chloroform fraction of the rhizomes of Kaempferia parviflora is mainly the inhibition of iNOS expression, and the inhibition of SYK by 4 may be involved in the suppression of LPS-induced signaling in macrophages.     

Effects of an n-butanol extract from the stem of Tinospora crispa on blood pressure and heart rate in anesthetized rats

Ethnopharmacological relevance

Tinospora crispa has been used in folkloric medicine for control of blood pressure, as an antipyretic, for cooling down the body temperature and for maintaining good health.

Aim of the study

To investigate the effects and mechanisms of action of an n-butanol extract from the stems of Tinospora crispa (T. crispa extract) on blood pressure and heart rate in anesthetized rats.

Materials and methods

Air-dried stems of T. crispa were extracted with water, followed by partitioned extract with chloroform, ethyl acetate, and finally by n-butanol. The n-butanol soluble part was evaporated under reduced pressure and lyophilization to obtain a crude dried powder (T. crispa extract). The effects and mechanisms of the T. crispa extract on blood pressure and heart rate were studied in anesthetized normal and reserpinized rats in vivo in the presence of different antagonists.

Results

T. crispa extract (1-100 mg/kg, i.v.) caused a decrease in mean arterial blood pressure (MAP) and this effect was inhibited by propranolol, phentolamine, atenolol and/or the β₂-antagonist ICI-118,551, but not by atropine or hexamethonium. In reserpinized rats, the T. crispa extract had a dual effect: reduction in hypotensive activity, followed by a small increase in blood pressure. The decrease in MAP in reserpinized rat was slightly potentiated by phentolamine, but inhibited by propranolol or ICI-118,551 only if atenolol and phentolamine were also present. The increase in MAP was potentiated by propranolol and ICI-118,551, but was inhibited by phentolamine. The T. crispa extract had a dual effect on heart rate in the normal rat: a small transient decrease, followed by an increase in heart rate. The positive chronotropic effect of T. crispa extract was inhibited by propranolol, phentolamine and atenolol, but not by ICI-118,551, atropine or hexamethonium. Reserpine potentiated the positive chronotropic effect of the T. crispa extract and this effect was inhibited by propranolol, atenolol and ICI-118,551, but not by phentolamine.

Conclusions

From these results we suggest that T. crispa extract possesses at least three different cardiovascular-active components that act directly via (1) β₂-adrenergic receptors to cause a decrease in blood pressure, and β₁- and β₂-adrenergic receptors to cause an increase in heart rate, (2) α-adrenergic receptors to cause an increase in blood pressure and heart rate, and (3) a non-adrenergic and non-cholinergic pathway to cause a decrease in MAP and heart rate. These findings provide scientific support for the tradition of using this plant to modify the actions of the human cardiovascular system.     

Antiinflammatory Constituents from Eclipta prostrata using RAW264.7 Macrophage Cells

The whole plant extract of Eclipta prostrata and its isolated compounds were tested for their antiinflammatory effects against lipopolysaccharide (LPS)‐induced nitric oxide (NO), prostaglandin E₂ (PGE₂) and tumor necrosis factor‐alpha (TNF‐α) release in RAW264.7 cells, as well as for the antiinflammatory mechanism of the active compound on mRNA expression. Among the isolated compounds, orobol (5) exhibited the highest activity against NO release with an IC₅₀ value of 4.6 μm , followed by compounds 1, 2 and 4 with IC₅₀ values of 12.7, 14.9 and 19.1 μm , respectively. The IC₅₀ value of compound 5 against PGE₂ release was found to be 49.6 μm , whereas it was inactive towards TNF‐α (IC₅₀ > 100 μm ). The mechanism of orobol (5) was found to down‐regulate iNOS and COX‐2 mRNA expression in a concentration‐dependent manner. The present study may support the traditional use of Eclipta prostrata for the treatment of inflammatory‐related diseases. Copyright © 2011 John Wiley & Sons, Ltd.     

Dexamethasone and perioperative blood glucose in patients undergoing total joint arthroplasty: A retrospective study

Study objectivePerioperative dexamethasone is commonly used to prevent nausea. It can also increase blood glucose levels, and recent concern about its blood glucose-elevating effect in humans has been raised. This study aimed to demonstrate relationships between dexamethasone administration and elevated perioperative blood glucose in patients undergoing total joint arthroplasty.DesignRetrospective study.SettingAcademic, orthopedic hospital.PatientsA total of 625 patients (18–99 years) who underwent total hip or total knee arthroplasty with an ASA ≤ 3 were included in the study.InterventionsPatients who received dexamethasone perioperatively were compared to those who did not receive dexamethasone.MeasurementsThe primary outcome, which was any postoperative glucose > 200 mg/dl, was compared between groups using multiple logistic regression. Demographic information, intraoperative information, incidence of postoperative nausea and vomiting, white blood cell count, medication use, and length of stay were also collected.Main resultsPerioperative dexamethasone (median [1st quartile, 3rd quartile] dose = 4 [4, 8] mg) was administered to 76% of patients. Only 5.6% (95% CI: 3.8–7.5) of patients had postoperative glucose levels > 200 mg/dl. After covariate adjustment, there was no evidence of a difference in odds of experiencing postoperative glucose levels > 200 mg/dl (odds ratio [95% CI]: 0.76 [0.28–2.07]; P = 0.594) and maximum glucose levels (P = 0.518) between groups. Dexamethasone-treated patients had greater changes in white blood cell count between baseline and postoperative days 0–1. There was no evidence of a difference in wound healing and length of stay between groups.ConclusionsThere was no evidence of an association between perioperative dexamethasone administration and the odds of having postoperative glucose levels > 200 mg/dl or higher maximum glucose levels. However, these findings may not be generalizable to patients having different baseline characteristics or procedures.     

Renal abscess in healthy children: report of three cases

We report three cases of renal abscess in otherwise healthy boys. One had a history of blunt trauma and two of antecedent skin infection. All presented with flank pain and fever. Urine and blood cultures were sterile. The diagnosis was made using ultrasound and computerized axial tomography. The first patient had recurrent renal abscess, following surgery and a short course of antibiotics. Eventually all responded well to long-term antibiotics only.     

Solitary rectal ulcer

Two cases of solitary rectal ulcer syndrome occurred in an 18-year-old woman and a 24-year-old man. Each had a history of bleeding on defecation, together with constipation alternating with diarrhea. In each case, a solitary rectal ulcer was noted by sigmoidoscopy and confirmed by both light and electron microscopic evaluations of biopsy material. Both clinical and pathologic features of these cases are compatible with classic rectal ulcer syndrome, which has been suggested to result from trauma followed by an ischemic event leading to fibrosis of the mucosa. Fibrosis in these two cases was confirmed by electron microscopy.     

Effects of Rhodomyrtus tomentosa extract on virulence factors of Candida albicans and human neutrophil function

ObjectiveCandida albicans has become a major problem of oral candidiasis due to increase in antibiotic resistance. Rhodomyrtus tomentosa, a medicinal plant possessing several phytochemical constituents, has been considered as a potential source of antimicrobial and immunomodulatory agents. The aim of this study was to investigate anti-virulence and immunostimulatory activity of R. tomentosa ethanolic leaf extract against C. albicans.MethodsThe effects of the extract on C. albicans were assessed on germ tube production, adherence of the organisms to surfaces, and biofilm. In addition, the effects of the extract on phagocytosis and killing activity of neutrophils against the pathogen were investigated.ResultsSuppression of germ tube production following 30 min exposure to the extract at 256 μg/mL was significantly increased in comparison with that of the unexposed cells (p < 0.05). The pathogens demonstrated a significant reduction in adherence ability to surfaces in a dose dependent manner, compared with the control (p < 0.05). At 48 h, the extract at 512–1024 μg/mL significantly reduced biofilm forming ability of the organisms up to 42.31–64.58% (p < 0.05). Compared with the control group, a significant inhibition of mature biofilm after treated with the extract at 256 μg/mL was observed (p < 0.05). The extract at 50 μg/mL significantly enhanced phagocytosis and killing activity of neutrophils against the organism, compared with the control (p < 0.05).ConclusionsThe findings suggest that R. tomentosa extract displayed a dual mode of action, inhibiting virulence factors of C. albicans and enhancing neutrophil functions. Further pharmaceutical development of the extract might be useful as an alternative therapeutic agent against oral candidiasis.     

Determinants of hospital loss in Thailand: experience from the first year of a universal coverage health insurance program

The objective of this study was to examine determinants of hospital loss in Thailand. Administration national data for 640 public hospitals of fiscal year 2002 from Ministry of Public Health were analyzed. Results showed that various managerial, service mix, and market variables were significantly associated with the likelihood of the hospital being unprofitable. Hospital characteristics were associated with the amount of loss. The results also suggested that managing the number of hospital employees, inventory, and patient hospitalization could control the amount of loss. In conclusion, most of identified factors associated with hospital loss were manageable. The ramification of this study was to help policy makers understand the hospital loss situation in Thailand after implementing the UC scheme and design policy to resolve the hospital loss problems.     

Dammarane triterpenes from the hypocotyls and fruits of Ceriops tagal

Three new dammarane triterpenes, cereotagaloperoxide, cereotagalol A, and cereotagalol B, together with four known dammarane triterpenes, an oleanane triterpene, and 13 known lupane triterpenes were isolated from the hypocotyls and fruits of Ceriops tagal. The structures of 1-3 were characterized on the basis of their spectroscopic data.