Biological effects of essential oils - A review

Curcumin as “Curecumin”: From kitchen to clinic

Epidemiological studies have revealed that a diet rich in plant-derived foods has a protective effect on human health. Identifying bioactive dietary constituents is an active area of scientific investigation that may lead to new drug discovery. Kaempferol (3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) is a flavonoid found in many edible plants (e.g. tea, broccoli, cabbage, kale, beans, endive, leek, tomato, strawberries and grapes) and in plants or botanical products commonly used in traditional medicine (e.g. Ginkgo biloba, Tilia spp, Equisetum spp, Moringa oleifera, Sophora japonica and propolis). Some epidemiological studies have found a positive association between the consumption of foods containing kaempferol and a reduced risk of developing several disorders such as cancer and cardiovascular diseases. Numerous preclinical studies have shown that kaempferol and some glycosides of kaempferol have a wide range of pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial, anticancer, cardioprotective, neuroprotective, antidiabetic, anti-osteoporotic, estrogenic/antiestrogenic, anxiolytic, analgesic and antiallergic activities. In this article, the distribution of kaempferol in the plant kingdom and its pharmacological properties are reviewed. The pharmacokinetics (e.g. oral bioavailability, metabolism, plasma levels) and safety of kaempferol are also analyzed. This information may help understand the health benefits of kaempferol-containing plants and may contribute to develop this flavonoid as a possible agent for the prevention and treatment of some diseases.

A review on the dietary flavonoid kaempferol.

New therapeutic aspects of flavones: the anticancer properties of Scutellaria and its main active constituents Wogonin, Baicalein and Baicalin.

Reactive oxygen species and cancer paradox: To promote or to suppress?

Induction of inducible nitric oxide synthase (iNOS) gene expression, nitric oxide (NO) production and migration of RAW264.7 macrophages by coculture with breast cancer MDA-MB-231 cells or the addition of conditioned medium derived from MDA-MB-231 cells (MDA-CM) was identified. Increased iNOS/NO induction and migration of macrophages by MDA-CM were significantly blocked by adding the c-Jun-N-terminal protein kinase (JNK) inhibitor, SP600125, the nuclear factor-kappa B (NF-κB) inhibitor, BAY117082 and pyrrolidine dithiocarbamic acid and a dominant-negative JNK. The addition of an NO donor, Diethylenetriamine-NONOate, significantly activated expressions of MMP-9 and VEGF-A genes in breast carcinoma MDA-MD-231 cells and invasion of MDA-MB-231 cells in coculture with RAW264.7 macrophages as determined using Transwell systems, but that was inhibited by adding SP600125, BAY117082 and the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester. Induction of heme oxygenase-1 in macrophages reduced MDA-CM-induced iNOS/NO, JNK and NF-κB activations in accordance with inhibiting VEGF-A and MMP-9 gene expressions by MDA-MB-231 cells via Transwell assays. Furthermore, VEGF, sRANKL, TNF-α, IL-1α, TGF-β, CSF-1 and MCP-1 were applied, and CSF-1 showed the most potent stimulation of iNOS/NO production and migration of macrophages. MCF-7 cells with lower CSF-1 expression than MDA-MB-231 cells showed a poor stimulatory effect on iNOS/NO production and migration of macrophages. Neutralization of CSF-1 in MDA-CM using CSF-1 antibody inhibited MDA-CM-induced iNOS protein expression and migration of macrophages, and CSF-1-induced iNOS protein and migration was blocked by adding JNK inhibitor SP and NF-κB inhibitor BAY. The reciprocal activation of breast cancer and macrophages via NO-CSF-1 is first elucidated herein.

Reciprocal activation of macrophages and breast carcinoma cells by nitric oxide and colony-stimulating factor-1

In the present study, we found that baicalein (BE), but not its glycoside baicalin (BI), induced apoptosis in human leukemia HL-60 and Jurkat cells, but not in primary murine peritoneal macrophages (PMs) or human polymorphonuclear (PMN) cells, by the MTT assay, LDH release assay, and flow cytometric analysis. Activation of the caspase 3, but not caspase 1, enzyme via inducing protein processing was detected in BE-induced apoptosis. The ROS-scavenging activity of BE was identified by the anti-DPPH radical, DCHF-DA, and in vitro plasmid digestion assay, and none of chemical antioxidants including allpurinol (ALL), N-acetyl-cystein (NAC), and diphenylene iodonium (DPI) affected BE-induced apoptosis in HL-60 cells. This suggests that apoptosis induced by BE is independent of the production of ROS in HL-60 cells. Interestingly, the apoptotic events such as DNA ladders formation and activation of the caspase 3 cascade were significantly blocked by TPA addition in the presence of membrane translocation of PKCα, and TPA-induced protection was reduced by adding the PKC inhibitors, GF-109203X and staurosporin. TPA addition induces the phosphorylation of JNKs and ERKs, but not p38, protein in HL-60 cells, and incubation of HL-60 cells with JNKs inhibitor SP600125, but not ERKs inhibitor, PD98059 or the p38 inhibitor SB203580, suppressed the protective effect of TPA against BE-induced apoptotic events including DNA ladders, apoptotic bodies, caspase 3 and D4-GDI protein cleavage in according with blocking JNKs protein phosphorylation. In addition, PKC inhibitor GF-109203X treatment blocks TPA-induced ERKs and JNKs protein phosphorylation, which indicates that activation of PKC locates at upstream of MAPKs activation in TPA-treated HL-60 cells. Additionally, a loss in mitochondrial membrane potential with a reduction in Bcl-2 protein expression, the induction of Bad protein phosphorylation, and translocation of cytochrome c from mitochondria to the cytosol were observed in BE-treated HL-60 cells, and these events were prevented by the addition of TPA. GF-109203X and SP600125 suppression of TPA against cytochrome c release induced by BE was identified. This suggests that activation of PKC and JNKs participate in TPA's prevention of BE-induced apoptosis via suppressing mitochondrial dysfunction in HL-60 cells.

12-o-Tetradecanoylphorbol 13-acetate prevents baicalein-induced apoptosis via activation of protein kinase C and JNKs in human leukemia cells.

Cytotoxic effects of metal protoporphyrins in glioblastoma cells: roles of albumin, reactive oxygen species, and heme oxygenase-1.

BACKGROUND There is compelling evidence that children of mothers with postnatal depression (PD) experience poor developmental outcomes. However, no studies have specifically ascertained the risk of mortality for offspring during preschool years, the most catastrophic outcome in the vulnerable period. This nationwide population-based study aimed to investigate whether maternal depression in the first year after giving birth was associated with increased mortality risk among their preschool children aged up to 5 years. METHOD Three nationwide population-based datasets [the National Health Insurance Research Database (NHIRD), birth certificate registry and death certificate registry] were linked in this study. A total of 10 236 offspring of mothers with PD were recruited, together with a comparison cohort of 81 888 births matched with the affected women in terms of maternal age and year of delivery. Each child was traced for 5 years from delivery between 2001 and 2003 until the end of 2008 to determine mortality during preschool years. RESULTS During preschool years, 98 (0.96%) deaths were identified among the offspring of mothers with PD and 470 (0.57%) children in the comparison cohort died. For children up to 5 years old, exposure to maternal PD was independently associated with a 1.47-fold [95% confidence interval (CI) 1.16-1.87] increased mortality risk, after adjusting for family income, urbanization level and the characteristics of mother, father and infant. The risk of death by unnatural causes was even higher (about 2.23 times the risk, 95% CI 1.34-3.70) among exposed offspring. CONCLUSIONS PD places preschool children at significantly increased risk of mortality, especially from unnatural causes of death.

Increased mortality risk among offspring of mothers with postnatal depression: a nationwide population-based study in Taiwan

Although apoptosis induced by amyloid β (Aβ) has been identified, the effect of Aβ on telomerase activity in relation to apoptosis induction remains unclear. In the present study, Aβ(1-40) and Aβ(25-35), but not Aβ(1-16) and Aβ(35-25), reduce the viability of primary cerebral endothelial cells (CECs) in accordance with apoptosis induction. Increases in caspase 3 and PARP protein cleavage with reductions of the Bcl-2/Bax protein ratio accompanied by a loss in the mitochondria membrane potential were identified in Aβ(1-40) and Aβ(25-35)-treated CECs. A significant decrease in intracellular telomerase activity by Aβ(1-40) and Aβ(25-35) was detected; meanwhile, reduced telomerase activity by telomerase reverse transcriptase (TERT) siRNA enhanced the cytotoxic effect of Aβ. The addition of serum might block the Aβ(25-35)-induced cytotoxic effect via elevated telomerase activity in according with stimulating phospho-AKT protein expression, which was blocked by adding AKT inhibitor LY294002. Decreases in heat shock protein 90 (HSP90) and its client proteins including TERT, AKT, p53, CDK4 were observed in Aβ(1-40) and Aβ(25-35), but not Aβ(1-16) and Aβ(35-25), -treated CECs. The knockdown of HSP90 gene expression by HSP90 siRNA significantly inhibits telomerase activity with decreasing TERT protein expression. The application of HSP90 activity inhibitor geldanamycin (GA) and radicicol (RD) potentiates the telomerase inhibition and apoptosis induction of Aβ in CECs. An increase in protein ubiquitination by Aβ(25-35), but not Aβ(35-25), treatment was examined, and Aβ-inhibited HSP90 and TERT protein expression and telomerase activity was reversed by adding proteasome inhibitor, MG132. Additionally, increased TERT protein ubiquitination by Aβ(25-35) was detected in CECs via immunoprecipitation/Western blotting analysis. The data of the present study firstly demonstrates that telomerase inhibition contributes to the apoptosis induction of Aβ in CECs.

Yen-Chou Chen

Papers

Reciprocal activation of macrophages and breast carcinoma cells by nitric oxide and colony-stimulating factor-1

12-o-Tetradecanoylphorbol 13-acetate prevents baicalein-induced apoptosis via activation of protein kinase C and JNKs in human leukemia cells.

Cytotoxic effects of metal protoporphyrins in glioblastoma cells: roles of albumin, reactive oxygen species, and heme oxygenase-1.

Increased mortality risk among offspring of mothers with postnatal depression: a nationwide population-based study in Taiwan

Inhibition of HSP90‐dependent telomerase activity in amyloid β‐induced apoptosis of cerebral endothelial cells