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Synergistic stimulatory effect of 12-O-tetradecanoylphorbol-13-acetate and capsaicin on macrophage differentiation in HL-60 and HL-525 human myeloid leukemia cells.

Our previous studies demonstrated that 12-O-tetradecanoylphorbol-13-acetate (TPA) had pharmacological activity for the treatment of myeloid leukemia patients. In the present study, we investigated the effects of TPA alone or in combination with capsaicin (8-methyl-N-vanillyl-6-nonenamide) on growth and differentiation in myeloid leukemia HL-60 cells and in a TPA-resistant HL-60 variant cell line termed HL-525. Treatment of HL-60 cells with TPA (0.16-1.6 nM) for 48 h resulted in concentration-dependent growth inhibition and cell differentiation (via the macrophage pathway). Capsaicin (5-50 microM) inhibited the growth of HL-60 cells in a concentration-dependent manner. Treatment of HL-60 cells with capsaicin alone only resulted in a small increase in the number of differentiated cells but treatment of the cells with TPA in combination with capsaicin synergistically increased differentiation. Moreover, inhibitors of protein kinase C (PKC), 7-hydroxystaurosporin (UCN-01; 100 nM) and chelerythrine (0.5 microM), significantly decreased HL-60 cell differentiation induced by the combination of TPA and capsaicin. These results suggest that PKC may be involved in HL-60 cell differentiation induced by TPA in combination with capsaicin. Capsaicin alone caused a very small increase in differentiation in the TPA-resistant HL-525 cells. However, treatment of HL-525 cells with combinations of TPA (0.16 nM) and capsaicin (10-50 microM) caused a strong synergistic increase in differentiation. Results from the present study suggest that a combination of TPA and capsaicin may improve the therapeutic efficacy of TPA and overcome resistance to TPA in some myeloid leukemia patients.

Alkaloids↗

[Studies on the alkaloids from the herb of Corydalis adunca].

OBJECTIVE: To study the alkaloid constituents of Corydalis adunca. METHOD: The constituents were isolated on silica gel column and their structures were elucidated by IR, NMR, MS data. RESULT: Eight alkaloid compounds were isolated from alcohol extracts of the herb of C. adunca, and identified as dihydrosanguinarine (I), tetrahydrocolumbamine (II), 1,2,3,4-tetrahydro-7-methoxy-1-[(4-methoxy)phenyl]methyl-8-quinolinol (III), protopine (IV) and 6-acetonyl-5,6-dihydrosanguinarine (V). CONCLUSION: Five compounds were isolated from C. adunca for the first time.

Alkaloids↗

Effects of protopine on intracellular calcium and the PKC activity of rat aorta smooth muscle.

We have previously shown that the vasodilator effect of protopine (Pro) on rabbit aorta is related to the elevations of cAMP and cGMP. In the present study, the vasodilator mechanisms of Pro were further explored by recording the isotonic contraction of the rat aortic strips, detecting directly the intracellular free Ca(2+) concentration ([Ca(2+)](i)) with Fura-2/AM loaded vascular smooth muscle cells (VSMCs) of rat aorta, and determining the activity of protein kinase C (PKC) in rat aortic tissue with radioactive isotope gamma-32P -ATP-catalyzing assay. By recording the aortic strips contraction induced by noradrenaline (NA) and high potassium (K(+)), Pro shifted nonparallelly the concentration-response curves of NA and high K(+) to right, in which the maximal response was depressed in the presence of Pro (30 and 100 micromol/L), and the values of pD'(2) were 3.70-/+0.25 and 3.97-/+0.15 for NA and high K(+), respectively. In the Fura-2/AM loaded VSMCs, Pro (50 and 100 micromol/L) could not produce any significant change on the resting [Ca(2+)](i), but significantly decreased the [Ca(2+)](i) elevated by NA and high K(+). Pro (30 and 100 micromol/L) had no significant effect on the activity of the cytosolic and membrane PKC in the aortic strips inpretreated by NA. However, in the aortic strips pretreated by NA, the activity of membrane PKC was significantly increased and the activity of cytosolic PKC tended to be decreased by Pro, while the activity of total PKC did not change. These results suggest that Pro seems to promote the translocation of PKC from the cytosol to the membrane in the presence of NA, its vasodilator effect may be the comprehensive result of its decreasing effect on the [Ca(2+)](i) and the increasing effect on cAMP and cGMP, as well as its influence on the PKC.

Animals↗

Toothpastes.

It is well known that plaque is the main cause of caries and parodontopathies, which puts the role of toothpastes as an important means of prevention of odontopathies to the foreground. Toothpastes can be more or less oriented towards having a particular effect, such as cleaning, anticaries effect, antimicrobial effect or inhibition of the formation of tartar. Toothpastes contain substances which promote dental health, such as abrasives (silicium dioxide, brushite, calcite, calcite and aragonite, gibbsite etc.), active components (fluorides, triclosan, metal ions, sanguinarine and surface-active substances), substances which motivate the use of toothpaste (sweetening agents, aromatic oil, colours) and components which are necessary for technical reasons, such as moisturizing agents, binders and opacifiers.

Alkaloids↗

Hepatic injury in rats with obstructive jaundice: roles of the protein kinase C signal pathway and cytoprotection of fructose.

BACKGROUND: Fructose is cytoprotective during bile salt-induced apoptosis of hepatocytes by regulating protein kinase C (PKC). This study was undertaken to explore the regulating mechanism of hepatic injury in rats with obstructive jaundice, and to detect the PKC signal pathway. METHODS: Rat hepatocytes were isolated by in situ collagenase perfusion and primary culture, and pretreated with various concentrations of PKC agonist phorbol myristate acetale (PMA) and inhibitor chelerythrine for 20 minutes. After pretreatment, 50 mumol/L glycochenodeoxycholate (GCDC) was added for additional 24 hours. Subsequently, the cells were detected by FCM and TUNEL. After adding with different concentrations of fructose and 100 mumol GCDC, the hepatocytes were evaluated by FCM and TUNEL. Experimental obstructive jaundice was induced with fructose and without fructose via double ligation of the bile duct for 3, 7, 14, and 21 days. Apoptotic status in the liver of all rats was detected with TUNEL, and PKC protein in the liver of obstructive jaundice (OJ) with the immunohistochemistry method. RESULTS: PMA increased GCDC-induced apoptosis and chelerythrine decreased GCDC-induced apoptosis in a concentration-dependent manner. Adding with different concentration of fructose and 100 mumol GCDC, the decreased apoptotic rate was related to the concentration of fructose. The apoptotic rate of the liver was related to times of OJ. PKC and apoptosis index (AI) were the highest after a 14-day ligation of the bile duct without use of fructose. AI and PKC were decreasing from a 14-day ligation of the bile duct with fructose. CONCLUSIONS: PKC takes part in the regulation, occurrence, and progression of hepatic injury in OJ. Fructose is cytoprotective during bile salt-induced apoptosis of hepatocytes by regulating PKC.

Alkaloids↗

[Effect of alkaloid sanguinarine and a pharmaceutical preparation ukrain on modulation of vesicular membrane fusion and actin cytoskeleton of macrophages].

A study was made of modulations of lysosome-phagosome fusion process and of fibrillar actin content in mouse peritoneal macrophages by an antitumor alkaloid sanguinarine and a derivative drug Ukrain. In addition, effects of these substances on in vitro polymerization of monomeric globular actin from rabbit muscle were investigated. Sanguinarine and Ukrain stimulated lysosome-phagosome fusion and increased the content of polymerized fibrillar form of actin in mouse macrophages. Effects of these substances were enhanced at their higher concentrations. Both sanguinarine and Ukrain induced in vitro polymerization of globular actin from rabbit muscle. A possible role of sanguinarine and Ukrain in changing vesicular membrane states during intracellular membrane interaction in lysosome-phagosome fusion process was discussed. The influence of these substances on actin polymerization and actin cytoskeleton rearrangement was evaluated. It could be supposed that sanguinarine and Ukrain may alter intracellular membrane transport.

Actins↗

[Relaxant effects of protopine on smooth muscles].

The relaxant effects of protopine (Pro) on smooth muscles were studied by recording isotonic contraction and radioimmunoassay. Pro relaxed the contraction of rabbit thoracic aorta, mesenteric artery, portal vein and guinea pig ileum and taenia colon induced by high K+ (70 mmol.L-1). Pro also inhibited the contraction of rabbit thoracic aorta, mesenteric artery, portal vein induced by NE (0.3 mumol.L-1) and guinea pig taenia colon induced by BaCl2 (1 mmol.L-1). Pro inhibited the intracellular Ca2+ release, but did not inhibit Ca2+ influx induced by NE. These results suggested that the smooth muscle relaxant mechanism of action of Pro may be the inhibition of intracellular Ca2+ release.

Alkaloids↗

[Experimental study of the inhibitory effects of Chelidonium majus L. extractive on Streptococcus mutans in vitro].

PURPOSE: To study the inhibitory effects of Chelidonium majus L. extractive on the growth of Streptococcus mutans in vitro, and to explore its mechanism in caries prevention. METHODS: Streptococcus mutans 25175 was chosen as the experimental bacterium. The Chelidonium majus L. extractives chelidonine and chelerythrine were double diluted to different concentrations by two-fold dilution. The inhibitory effect of Streptococcus mutans was measured by slip diffusion method. The minimal inhibitory concentration(MIC) was also determined. 0.16% liquor hibitane was used as positive control. Spearman correlation was used for statistical analysis. RESULTS: Inhibition zone of Streptococcus mutans appeared in some concentration of chelerythrine, but no inhibition zone in each concentration of chelidonine. The MIC of chelerythrine was 0.78 mg/ml which determined by liquid culture medium. The concentration of chelerythrine was highly related to the inhibitory zone of Streptococcus mutans (r=0.99, P<0.01). CONCLUSION: The antibacterial activity of Chelidonium majus L. extractive chelerythrine on Streptococcus mutans was significant,and the antibacterial activity of the concentration 100 mg/ml was higher than that of 0.16% liquor hibitane (19.4 mm), indicating that chelerythrine can be used as an agent for prevention of dental caries.

Anti-Bacterial Agents↗

[Protective effect of protein kinase C and mitogen-activated protein kinases and its mechanism in liver ischemic preconditioning].

OBJECTIVE: To investigate the protective effects of protein kinase C (PKC) and mitogen-activated protein kinases (MAPKs) their and mechanisms in liver ischemic preconditioning. METHODS: In rat models of liver ischemia-reperfusion (IR) and ischemic preconditioning (IP), the liver function was evaluated by examining serum alanine aminotransferase and aspartate aminotransferase levels, and the morphological changes of the liver cells were observed under microscope. PKC activator phorbol 12-myristate 13-acetate(PMA) and inhibitor chelerythrine(CHE), as well as MEK inhibitor PD98059, were utilized to analyze the phosphorylation of PKC and P44/42 MAPKs. RESULTS: Compared with the control rats, the liver function was best protected in rats of IP group, but not in those of IP group with PD98059 or CHE treatment. The rats in IR group showed improved liver function after PMA treatment. Similarly, the phosphorylation of PKC and P44/42 MAPKs was correlated with the liver function, and highly enhanced PKC and P44/42 MAPKs activity was observed in IP and IR+PMA groups, but decreased activity in IR and IP+CHE groups. CONCLUSION: Phosphorylation of PKC and MAPKs plays a pivotal role in the preservation of the hepatocytes during IP.

Alanine Transaminase↗

Comparative study of four over-the-counter mouthrinses claiming antiplaque and/or antigingivitis benefits.

The efficacy of over-the-counter mouthrinses claiming to have antiplaque/antigingivitis benefits was compared using the modified Löe-Silness Gingival Index and the Quigley-Hein Plaque Index. The double-blind in vivo study involved 122 subjects. Each subject was randomly assigned to one of five groups. Gingival inflammation and plaque were evaluated at 0, 2, 4 and 6 weeks of product use. Results revealed that plaque scores for some of the products were statistically significant from the control at the 4-week and 6-week visits. Changes in the gingival scores were negligible.

Adolescent↗

Epidemic dropsy in Andhra Pradesh due to contaminated ghee.

An outbreak of epidemic dropsy in Andhra Pradesh was studied during August to September 1987. Thirty cases from 6 families were identified and examined. Ghee and one oil sample were found to be contaminated with the toxic compound sanguinarine. The affected families had purchased ghee from one vendor. The epidemic ended after alerting the villagers of the contaminated ghee, and stopping its further use.

Alkaloids↗

[Effects of dequalinium chloride and sanguinarine on the ultrastructure of early supragingival plaque].

The influence of antimicrobial mouthrinses containing dequalinium chloride or sanguinarine on early plaque formation was assessed in vivo in a clinical-experimental study. Rinses with water served as controls. After 24 and 72 hours, plastic films, which were applied to the buccal surfaces of six upper front teeth at the start of experiment, were removed and processed for transmission electron microscopic study. Dequalinium chloride or sanguinarine applied on plaque resulted in an increased and higher structured surface coating. Degenerated microorganisms were observed and the variety of bacteria seemed to be reduced. Both mouthrinses effected the early supragingival plaque formation. The effect of sanguinarine was more intensive than that of dequalinium chloride.

Adult↗

Antimicrobials and oral health.

Effective control of plaque and gingivitis are among our most important treatment goals. Several antimicrobial products have demonstrated safety and various degrees of effectiveness as adjuncts to mechanical plaque control. Our clinical decisions relating to antimicrobial products should be based on the expanding body of research that documents product safety and effectiveness in reducing both plaque and gingivitis. Antimicrobials present exciting prospects for in-office and home use, but they do not replace thorough root debridement and traditional plaque control. However, when selected based on individual patient needs and used in recommended regimens, antimicrobials can be important additions to both professional treatment and oral hygiene practices.

Alkaloids↗

[Chemical control of plaque: comparative review].

Plaque control can be achieved by mechanical means. Since plaque removal can be laborious and difficult, chemical agents became important adjuncts to traditional oral hygiene procedures. Chlorhexidine is one of the synthetic antiseptics that has a unique antiplaque effect and 0.2% chlorhexidine can achieve a practically complete plaque control. It has one negative effect namely an extrinsic brown-yellow staining. Listerine has proven its ability to reduce plaque and gingivitis in a moderate way. Hexetidine has a greater antiplaque effect in combination with zinc and can be compared with a 0.1% chlorhexidine. Povidone-iodine can not be used to keep plaque at low levels. Sanguinarine can reduce plaque accumulation when the toothpaste and mouthrinse are used together. H2O2 is an antiplaque agent but has some negative effects such as ulcerations... One can conclude that the use of a chemical agent cannot replace a good mechanical plaque control but is rather an adjunct to oral hygiene under certain conditions.

Alkaloids↗