Anticancer effects of 6-shogaol via the AKT signaling pathway in oral squamous cell carcinoma

Abstract Objective Oral squamous cell carcinoma (OSCC) is one of the common type of cancer that leads to death; and is becoming a global concern. Due to the lack of efficient chemotherapeutic agents for patients with oral cancer, the prognosis remains poor. 6-shogaol, a bioactive compound of ginger, has a broad spectrum of bioactivities and has been widely used to relieve many diseases. However, its effects on human oral cancer have not yet been fully evaluated. In our study, we investigated the anticancer effects of 6-shogaol on the proliferation, migration, invasion, apoptosis, and underlying mechanisms within human OSCC cell lines. Methodology We investigated the effect of 6-shogaol on the growth of OSCC cells by cell viability and soft agar colony formation assay. Migration and invasion assays were conducted to confirm the effect 6-shogaol on OSCC cell metastasis. Apoptosis was detected by flow cytometry and the underlying mechanism on the antigrowth effect of 6-shogaol in OSCC cells was assessed using western blotting. Results In our results, 6-shogaol not only suppressed proliferation and anchorage-independent cell growth in OSCC cells, but also induced apoptosis by regulating the apoptosis-associated factors such as p53, Bax, Bcl-2, and cleaved caspase-3. Migration and invasion of OSCC cells were inhibited following the regulation of E-cadherin and N-cadherin by 6-shogaol. Additionally, 6-shogaol treatment significantly inhibited the PI3K/AKT signaling pathway. Conclusion Therefore, our results may provide critical evidence that 6-shogaol can be a potential new therapeutic candidate for oral cancer.

6-Gingerol inhibits hair cycle via induction of MMP2 and MMP9 expression

ABSTRACT 6-Gingerol is the major active constituent of ginger. In the current study, we aimed to investigate the mechanisms underlying the effects of 6-Gingerol on hair growth. Mice were randomly divided into five groups; after hair depilation (day 0), mice were treated with saline, or different concentrations of 6-Gingerol for 11 days. The histomorphological characteristics of the growing hair follicles were examined after hematoxylin and eosin staining. The results indicated that 6-Gingerol significantly suppressed hair growth compared with that in the control group. And choose the concentration of 6-Gingerol at 1 mg/mL to treated with mice. Moreover, 6-Gingerol (1 mg/mL) significantly reduced hair re-growth ratio, hair follicle number, and hair follicle length, which were associated with increased expression of MMP2 and MMP9. Furthermore, the growth factors, such as EGF, KGF, VEGF, IGF-1 and TGF-β participate in the hair follicle cycle regulation and regulate hair growth. We then measured the concentrations of them using ELISA assays, and the results showed that 6-Gingerol decreased EGF, KGF, VEGF, and IGF-1 concentrations, and increased TGF-β concentration. Thus, this study showed that 6-Gingerol might act as a hair growth suppressive drug via induction of MMP2 and MMP9 expression, which could interfere with the hair cycle.

Homologous human milk supplement for very low birth weight preterm infant feeding / Aditivo homólogo para a alimentação do recém-nascido pré-termo de muito baixo peso

OBJECTIVE: To develop a homologous human milk supplement for very low-birth weight infant feeding, using an original and simplified methodology, to know the nutritional composition of human milk fortified with this supplement and to evaluate its suitability for feeding these infants. METHODS: For the production and analysis of human milk with the homologous additive, 25 human milk samples of 45mL underwent a lactose removal process, lyophilization and then were diluted in 50mL of human milk. Measurements of lactose, proteins, lipids, energy, sodium, potassium, calcium, phosphorus and osmolality were performed. RESULTS: The composition of the supplemented milk was: lactose 9.22±1.00g/dL; proteins 2.20±0.36g/dL; lipids 2.91±0.57g/dL; calories 71.93±8.69kcal/dL; osmolality 389.6±32.4mOsmol/kgH2O; sodium 2.04±0.45mEq/dL; potassium 1.42±0.15mEq/dL; calcium 43.44±2.98mg/dL; and phosphorus 23.69±1.24mg/dL. CONCLUSIONS: According to the nutritional contents analyzed, except for calcium and phosphorus, human milk with the proposed supplement can meet the nutritional needs of the very low-birth weight preterm infant. .

OBJETIVO: Elaborar com metodologia original e simplificada um aditivo homólogo do leite humano para a alimentação do recém-nascido de muito baixo peso, conhecer a composição nutricional do leite humano fortificado com esse aditivo e avaliar sua adequação para a alimentação desses recém-nascidos. MÉTODOS: Para a produção e análise do leite humano com o aditivo homólogo, 25 amostras de 45 mL de leite humano passaram por processos de retirada de lactose, liofilização e foram diluídas em 50 mL de leite humano. Foram feitas dosagens de lactose, proteínas, lipídios, energia, sódio, potássio, cálcio, fósforo e osmolalidade. RESULTADOS: A composição do leite aditivado foi lactose 9,22 ± 1 g/dL; proteínas 2,20 ± 0,36 g/dL; lípides 2,91 ± 0,57 g/dL; calorias 71,93 ± 8,69 kcal/dL; osmolalidade 389,6 ± 32,4mOsmol/kgH2O; sódio 2,04 ± 0,45mEq/dL; potássio 1,42 ± 0,15mEq/dL; cálcio 43,44 ± 2,98 mg/dL; e fósforo 23,69 ± 1,24 mg/dL. CONCLUSÕES: De acordo com os teores nutricionais analisados, com exceção do cálcio e do fósforo, o leite humano com o aditivo proposto pode atender às necessidades nutricionais do recém-nascido pré-termo de muito baixo peso. .

Antioxidant effect of 4-nerolidylcatechol and -tocopherol in erythrocyte ghost membranes and phospholipid bilayers

4-Nerolidylcatechol (4-NC) is found in Pothomorphe umbellata root extracts and is reported to have a topical protective effect against UVB radiation-induced skin damage, toxicity in melanoma cell lines, and antimalarial activity. We report a comparative study of the antioxidant activity of 4-NC and α-tocopherol against lipid peroxidation initiated by two free radical-generating systems: 2,2′-azobis(2-aminopropane) hydrochloride (AAPH) and FeSO4/H2O2, in red blood cell ghost membranes and in egg phosphatidylcholine (PC) vesicles. Lipid peroxidation was monitored by membrane fluidity changes assessed by electron paramagnetic resonance spectroscopy of a spin-labeled lipid and by the formation of thiobarbituric acid-reactive substances. When lipoperoxidation was initiated by the hydroxyl radical in erythrocyte ghost membranes, both 4-NC and α-tocopherol acted in a very efficient manner. However, lower activities were observed when lipoperoxidation was initiated by the peroxyl radical; and, in this case, the protective effect of α-tocopherol was lower than that of 4-NC. In egg PC vesicles, malondialdehyde formation indicated that 4-NC was effective against lipoperoxidation initiated by both AAPH and FeSO4/H2O2, whereas α-tocopherol was less efficient in protecting against lipoperoxidation by AAPH, and behaved as a pro-oxidant for FeSO4/H2O2. The DPPH (2,2-diphenyl-1-picrylhydrazyl) free-radical assay indicated that two free radicals were scavenged per 4-NC molecule, and one free radical was scavenged per α-tocopherol molecule. These data provide new insights into the antioxidant capacity of 4-NC, which may have therapeutic applications for formulations designed to protect the skin from sunlight irradiation.

Six-shogaol inhibits production of tumour necrosis factor alpha, interleukin-1 beta and nitric oxide from lipopolysaccharide-stimulated RAW 264.7 macrophages / El 6-shogaol inhibe la producción del factor de necrosis tumoral alfa, la interleuquina-1 beta, y el óxido Nítrico de los macrófagos 264.7 RAW estimulados por lipopolisacáridos

OBJECTIVE: We previously reported that 6-shogaol, a phenolic compound from ginger, has anti-inflammatory properties in a Complete Freund's Adjuvant (CFA) model of mono-arthritic rats. In the present study, we investigated the effects of 6-shogaol on the production of inflammatory mediators from lipopolysaccharide (LPS) activated RAW 264.7 macrophages. These mediators (TNF-α, IL-1-and NO) and their output from macrophages are involved in various pathophysiological events of chronic inflammation and arthritis. METHODS: Effects of 6-shogaol were investigated on the production of the mediators TNF-α, IL-1-and NO (measured as nitrate) from macrophages. Lipopolysaccharide activated RAW 264.7 macrophages were cultured in the presence and absence of 6-shogaol (2 M, 10 M and 20 µM) and ELISA was used to quantify the output of the mediators. RESULTS: 6-shogoal (2 M, 10 M and 20 M) significantly inhibited the production of nitric oxide (NO), IL-1 and TNF-α from the LPS activated RAW264.7 macrophages. CONCLUSION: The results suggest that macrophages are targets for the anti-inflammatory effects of 6 shogaol. Also, the inhibitory effects against TNF-α, IL-1 and NO production from LPS activated macrophages are cellular mechanisms by which 6-shogaol produced its anti-inflammatory effects. These mechanisms provide an explanation of the protection by 6-shogaol against development of joint inflammation and cartilage degradation in CFA induced mono-arthritis that we previously demonstrated (1). Based on these results with 6-shogaol, there is evidence that it exhibits exploitable anti-inflammatory properties.

OBJETIVO: Con anterioridad reportamos que el 6-shogaol - un compuesto fenólico del jengibre - posee propiedades anti-inflamatorias en un modelo CFA de ratas monoartríticas. En el presente estudio, investigamos los efectos del 6-shogaol sobre la producción de mediadores inflamatorios de macrófagos 264.7 RAW estimulados por lipopolisacáridos. Estos mediadores (TNF-α, IL-1-y NO) y su producción de macrófagos están involucrados en varios eventos patofisiológicos de inflamación crónica y artritis. MÉTODOS: Se investigaron los efectos del 6-shogaol sobre la producción de los mediadores TNF-α, IL-1-y NO (medidos como nitratos) de los macrófagos. Macrófagos 264.7 RAW estimulados por lipopolisacáridos fueron cultivados en presencia y ausencia de 6-shogaol (2 M, 10 M y 20 M) y se usó la técnica de ensayo por inmunoabsorción ligado a enzimas (ELISA) a fin de cuantificar la producción de mediadores. RESULTADOS: El 6-shogaol (2 M, 10 M y 20 M) inhibieron significativamente la producción de óxido nítrico (NO), IL-1 βy TNF-α de los macrófagos RAW 264.7 activados mediante LPS. CONCLUSIÓN: Los resultados sugieren que los macrófagos son blancos de los efectos anti-inflamatorios del 6-shogaol. Por otro lado, los efectos inhibitorios contra la producción de TNF-α, IL-1 y NO a partir de macrófagos activados por LPS, son mecanismos celulares mediante los cuales 6-shogaol produjo sus efectos anti-inflamatorios. Estos mecanismos ofrecen una explicación de la protección mediante 6-shogaol contra el desarrollo de inflamación en las articulaciones y la degradación de los cartílagos en la monoartritis inducida mediante CFA que demostramos con anterioridad (1). Sobre la base de estos resultados con 6-shogaol, hay evidencia de que posee propiedades anti-inflamatorias explotables.

Role of adenosine in drug-induced catatonia in mice.

Parkinson's disease is one of the most common neurodegenerative disorders affecting large majority of population who are older than age of 65. Apart from dopamine, acetylcholine and glutamate, adenosinc has also been identified in the basal ganglia. Adenosine modulates the release of a variety of neurotransmitters including dopamine. In order to establish adenosine-dopamine interactions in drug-induced catatonia we studied the effect of adenosine in drug-induced catatonia in mice. In the present study adenosine dose dependently produced catatonia when assessed on rota-rod and bar tests in mice. Adenosine also potentiated the catatonic effect of perphenazine. L-dopa plus carbidopa or OR-486 (a potent centrally acting COMT inhibitor) completely reversed adenosine-induced catatonia. Since reversal by scopolamine of adenosine-induced catatonia was not to the same extent as with l-dopa and OR-486 it appears that catecholamines particularly dopamine rather than cholinergic modulation is more important in adenosine induced catatonia. The motor dysfunction (catatonia) could be easily assessed using rota-rod test apparatus in mice.

Some aspects of pharmacological profile of sodium curcuminate.

Rapid i.v. injection of sodium curcuminate (NaC) produced transient hypotension and bradycardia in anaesthetized dogs and cats which were not blocked by bilateral vagotomy, atropine, mepyramine or propranolol. In open-chest anaesthetized cats, decrease in blood pressure and heart rate was accompanied by simultaneous transient reductions in left ventricular systolic pressure, maximal rate of rise of left ventricular pressure and a concomitant increase in left ventricular end-diastolic pressure. It was concluded that the transient hypotensive effect of NaC is due to its myocardial depressant action. NaC exhibited negative inotropic and chronotropic effect on isolated perfused rabbit heart, an antispasmodic effect on smooth muscle of dog s intestine in vivo and of vas deferens of guinea-pig in vitro but no effect on the rectus abdominis muscle of frog or its response to cholinergic stimulation.