Ethanolic Fenugreek Extract: Its Molecular Mechanisms against Skin Aging and the Enhanced Functions by Nanoencapsulation.

Fenugreek, or L. (family Leguminosae) seeds, are typically used as food supplements to increase postnatal lactation. Fenugreek extract displays antioxidative and anti-inflammatory properties, but its mechanisms against skin aging have not been exploited.

Flavonoids kaempferide and 4,2'-dihydroxy-4',5',6'-trimethoxychalcone inhibit mitotic clonal expansion and induce apoptosis during the early phase of adipogenesis in 3T3-L1 cells.

Objective: Kaempferide and 4,2'-dihydroxy-4',5',6'-trimethoxychalcone (DTMC) are two major flavonoids found in Chromolaena odorata Linn. leaf extract. The aim of this study was to elucidate the mechanism by which these two flavonoids exerted their effect on adipogenesis.

Anti-adipogenic effect of flavonoids from Chromolaena odorata leaves in 3T3-L1 adipocytes.

Objective: The leaves of Chromolaena odorata, a highly invasive shrub found growing wild worldwide, are traditionally used for wound healing. Due to its high flavonoid contents, we aimed to find a new application for this plant. Preliminary tests using its ethanolic leaf extract showed that it could suppress the accumulation of lipids in adipocytes.

A Comparative of Ginger Extract in Nanostructure Lipid Carrier (NLC) and 1% Diclofenac Gel for Treatment of Knee Osteoarthritis (OA).

Objective: To compare and evaluate the efficacy of ginger (Zingiber officinale Roscoe) extracts in NLC for treatment of osteoarthritis of knee compared to 1% diclofenac gel as an active control.

Material And Method: One hundred twenty patients age 50 to 75 years with OA knee, based on the American College of Rheumatology (ACR) criteria were randomized into two groups receiving ginger extracts in NLC and control 1% diclofenac gel for 12 weeks. The efficacy of treatment was monitored at 4, 8, and 12 weeks by using the WOMAC composite index and the Patient Global Assessment (PGA).

Improving of Knee Osteoarthritic Symptom by the Local Application of Ginger Extract Nanoparticles: A Preliminary Report with Short Term Follow-Up.

Objective: An evaluation ofthe efficacy and safety of Ginger (Zingiber officinale Roscoe) extract nanoparticlefor treatment of osteoarthritis (OA) of the knee.

Material And Method: Sixty patients at the age range of 50 to 75 years old who were diagnosed with OA knee based on the American College of Rheumatology (ACR) diagnosis criteria were included in the present study. Participants received ginger extract in Nanostructure Lipid Carrier (NLC) rubbed three times a day for 12 weeks.

The interaction mechanism between lipopeptide (daptomycin) and polyamidoamine (PAMAM) dendrimers.

The interaction mechanism of lipopeptide antibiotic daptomycin and polyamidoamine (PAMAM) dendrimers was studied using fluorescence spectroscopy. The fluorescence changes observed are associated with daptomycin-dendrimer interactions. The binding isotherms were constructed by plotting the fluorescence difference at 460 nm from kynurenine (Kyn-13) of daptomycin in the presence and absence of dendrimer.

Carbon nanotubes induce apoptosis resistance of human lung epithelial cells through FLICE-inhibitory protein.

Chronic exposure to single-walled carbon nanotubes (SWCNT) has been reported to induce apoptosis resistance of human lung epithelial cells. As resistance to apoptosis is a foundation of neoplastic transformation and cancer development, we evaluated the apoptosis resistance characteristic of the exposed lung cells to understand the pathogenesis mechanism. Passage control and SWCNT-transformed human lung epithelial cells were treated with known inducers of apoptosis via the intrinsic (antimycin A and CDDP) or extrinsic (FasL and TNF-α) pathway and analyzed for apoptosis by DNA fragmentation, annexin-V expression, and caspase activation assays.

Molecular signalings in keloid disease and current therapeutic approaches from natural based compounds.

Context: Keloid is an excessive dermal scar occurring in response to skin injuries. Several therapeutic strategies have been proposed to ease the aggressiveness of keloid scarring. Even though the principle mechanism underlying the disease propagation still remains unidentified, several signaling pathways were highly focused as plausible pathways involving keloid formation, including transforming growth factor-beta 1 (TGF-β1), mitogen-activated protein kinase (MAPK), insulin-like growth factor-I (IGF-I), and integrin pathways.

Mitochondrial superoxide mediates doxorubicin-induced keratinocyte apoptosis through oxidative modification of ERK and Bcl-2 ubiquitination.

Massive apoptosis of keratinocytes has been implicated in the pathogenesis of chemotherapy-induced skin toxicities, but the underlying mechanisms of action are not well understood. The present study investigated the apoptotic effect of doxorubicin (DOX) on HaCaT keratinocytes and determined the underlying mechanisms. Treatment of the cells with DOX induced reactive oxygen species (ROS) generation and a concomitant increase in apoptotic cell death through the mitochondrial death pathway independent of p53.

Effects of different carboxylic ester spacers on chemical stability, release characteristics, and anticancer activity of mono-PEGylated curcumin conjugates.

We investigated the effects of different carboxylic ester spacers of mono-PEGylated curcumin conjugates on chemical stability, release characteristics, and anticancer activity. Three novel conjugates were synthesized with succinic acid, glutaric acid, and methylcarboxylic acid as the respective spacers between curcumin and monomethoxy polyethylene glycol of molecular weight 2000 (mPEG(2000) ): mPEG(2000) -succinyl-curcumin (PSC), mPEG(2000) -glutaryl-curcumin (PGC), and mPEG(2000) -methylcarboxyl-curcumin (PMC), respectively. Hydrolysis of all conjugates in buffer and human plasma followed pseudo first-order kinetics.

Hydroxyl radical mediates cisplatin-induced apoptosis in human hair follicle dermal papilla cells and keratinocytes through Bcl-2-dependent mechanism.

Induction of massive apoptosis of hair follicle cells by chemotherapy has been implicated in the pathogenesis of chemotherapy-induced alopecia (CIA), but the underlying mechanisms of regulation are not well understood. The present study investigated the apoptotic effect of cisplatin in human hair follicle dermal papilla cells and HaCaT keratinocytes, and determined the identity and role of specific reactive oxygen species (ROS) involved in the process. Treatment of the cells with cisplatin induced ROS generation and a parallel increase in caspase activation and apoptotic cell death.

Synthesis, characterization and biological evaluation of succinate prodrugs of curcuminoids for colon cancer treatment.

A novel series of succinyl derivatives of three curcuminoids were synthesized as potential prodrugs. Symmetrical (curcumin and bisdesmethoxycurcumin) and unsymmetrical (desmethoxycurcumin) curcuminoids were prepared through aldol condensation of 2,4-pentanedione with different benzaldehydes. Esterification of these compounds with a methyl or ethyl ester of succinyl chloride gave the corresponding succinate prodrugs in excellent yields.

Hydrogen peroxide inhibits non-small cell lung cancer cell anoikis through the inhibition of caveolin-1 degradation.

Anoikis or detachment-induced apoptosis plays an essential role in the regulation of cancer cell metastasis. Caveolin-1 (Cav-1) is a key protein involved in tumor metastasis, but its role in anoikis and its regulation during cell detachment are unclear. We report here that Cav-1 plays a key role as a negative regulator of anoikis through a reactive oxygen species (ROS)-dependent mechanism in human lung carcinoma H460 cells.

Regulation of lung cancer cell migration and invasion by reactive oxygen species and caveolin-1.

The acquired capability of tumor cells to migrate and invade neighboring tissues is associated with high metastatic potential and advanced stage of cancers. Recently, signaling molecules such as reactive oxygen species (ROS) and caveolin-1 (Cav-1) have been implicated in the aggressive behavior of cancer cells. However, the roles of specific ROS in cancer cell migration and Cav-1 regulation are unclear.

Protection of HT22 neuronal cells against glutamate toxicity mediated by the antioxidant activity of Pueraria candollei var. mirifica extracts.

Neuronal degeneration is known to be due to oxidative stress acting through a pathway involving the excessive activation of glutamate receptors. We studied the neuroprotection potential of an ethyl acetate-ethanol extract of Pueraria mirifica (P. candollei var.

Curcumin sensitizes non-small cell lung cancer cell anoikis through reactive oxygen species-mediated Bcl-2 downregulation.

Anoikis, an apoptosis triggered by loss of cell anchorage, has been shown to be a principal mechanism of inhibition of tumor metastasis. Recently, anti-apoptotic Bcl-2 and Cav-1 proteins have been demonstrated to be highly associated with tumor metastasis and apoptosis resistance. Curcumin, a major active component of turmeric, Curcuma longa, has been shown to inhibit neoplastic evolution and tumor progression; however, the underlying mechanisms are unclear.

Nitric oxide regulates lung carcinoma cell anoikis through inhibition of ubiquitin-proteasomal degradation of caveolin-1.

Anoikis, a detachment-induced apoptosis, is a principal mechanism of inhibition of tumor cell metastasis. Tumor cells can acquire anoikis resistance which is frequently observed in metastatic lung cancer. This phenomenon becomes an important obstacle of efficient cancer therapy.

Type I pro-collagen promoting and anti-collagenase activities of Phyllanthus emblica extract in mouse fibroblasts.

As part of an ongoing search for the novel pharmacological activities of Phyllanthus emblica, the present study has shown its type I collagen promoting and anti-collagenase effects on primary mouse fibroblast cells. At a concentration of 0.1 mg/ml, emblica extract significantly increased the type I pro-collagen level up to 1.

An evaluation of a fluorometric method for determining binding parameters of drug-carrier complexes using mathematical models based on total drug concentration.

A fluorescence method for determining the mode of binding and estimating binding parameters in a model drug-carrier complex was developed using the lipopeptide antibiotic daptomycin and polyamidoamine (PAMAM) dendrimer. Mathematical simulations of model equations describing fluorescence changes induced by antibiotic-carrier binding in terms of total drug concentration were used to evaluate the sensitivity of parameter variation on binding isotherms for both one- and two-site binding models. Nonlinear regression analysis was used to estimate binding parameters and to identify pH-dependent binding models.

Curcumin sensitizes lung cancer cells to cisplatin-induced apoptosis through superoxide anion-mediated Bcl-2 degradation.

The purpose of this study was to investigate the sensitizing effect of curcumin on cisplatin-induced apoptosis in non-small cell lung cancer (NSCLC) H460 cells. Curcumin was shown to induce superoxide anion generation, down-regulate anti-apoptotic Bcl-2 protein, and subsequently sensitize cells to cisplatin-induced apoptosis. Co-treatment of the cells with curcumin and cisplatin resulted in increased apoptosis and reversal of Bcl-2-mediated cisplatin resistance.

A novel anti-HIV dextrin-zidovudine conjugate improving the pharmacokinetics of zidovudine in rats.

The aim of this study was to investigate a newly synthesized dextrin-zidovudine (AZT) conjugate designed as a sustained release prodrug of AZT for parenteral administration. AZT was first reacted with succinic anhydride to form a succinoylated AZT which was subsequently coupled with dextrin to yield the dextrin-AZT conjugate. The structure of the conjugate was characterized by FT-IR and (1)H-NMR spectroscopy.

Microemulsions as topical delivery vehicles for the anti-melanoma prodrug, temozolomide hexyl ester (TMZA-HE).

A prodrug, temozolomide acid hexyl ester (TMZA-HE), was identified as a skin-deliverable congener for temozolomide (TMZ) to treat skin cancers. Poor solubility and instability of TMZA-HE rendered a serious challenge for formulation of a topical preparation. Microemulsions (ME) were chosen as a potential vehicle for TMZA-HE topical preparations.

Reactive oxygen species mediate caspase activation and apoptosis induced by lipoic acid in human lung epithelial cancer cells through Bcl-2 down-regulation.

The antioxidant alpha-lipoic acid (LA) is a naturally occurring compound that has been shown to possess promising anticancer activity because of its ability to preferentially induce apoptosis and inhibit proliferation of cancer cells relative to normal cells. However, the molecular mechanisms underlying the apoptotic effect of LA are not well understood. We report here that LA induced reactive oxygen species (ROS) generation and a concomitant increase in apoptosis of human lung epithelial cancer H460 cells.

Nitric oxide regulates cell sensitivity to cisplatin-induced apoptosis through S-nitrosylation and inhibition of Bcl-2 ubiquitination.

Cisplatin is a potent cytotoxic agent commonly used for the treatment of solid tumors. However, tumor cell-acquired resistance to cisplatin-induced apoptosis is a major limitation for efficient therapy, as frequently observed in human lung cancer. Nitric oxide (NO) is a key regulator of apoptosis, but its role in cisplatin-induced cell death and the underlying mechanism are largely unknown.

Nitric oxide negatively regulates Fas CD95-induced apoptosis through inhibition of ubiquitin-proteasome-mediated degradation of FLICE inhibitory protein.

Stimulation of cell surface Fas (CD95) results in recruitment of cytoplasmic proteins and activation of caspase-8, which in turn activates downstream effector caspases leading to programmed cell death. Nitric oxide (NO) plays a key role in the regulation of apoptosis, but its role in Fas-induced cell death and the underlying mechanism are largely unknown. Here we show that stimulation of the Fas receptor by its ligand (FasL) results in rapid generation of NO and concomitant decrease in cellular FLICE inhibitory protein (FLIP) expression without significant effect on Fas and Fas-associated death domain (FADD) adapter protein levels.