Growth Regulated Oncogene-α Upregulates TNF-α and COX-2 and Activates NOD1/RIPK2 mediated-MAPK Pathway in Head and Neck Squamous Cell Carcinoma.

Purpose: The long-term prognosis and survival rate of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) are poor, although the identification of specific biomarkers that reveal its nature and aggressiveness has improved it. Growth-related oncogene alpha (Groα) and NOD1 (nucleotide-binding oligomerization domain 1) can be used as prognosis markers to identify subgroups of HNSCC patients with low survival rates and as potential therapeutic targets for HNSCC patients. However, the mechanism associated with the Groα-mediated NOD pathway in HNSCC progression remains unclear. Method: Overall survival analysis and multiple-gene comparison were analyzed using Gene Expression Profiling Interactive Analysis (GEPIA). qRT-PCR and RT-PCR were used to analyze mRNA expression. Microarray, immunofluorescence staining or western blot analyses were carried out to detect protein expression. Results: Groα was significantly higher in the grade 4 HNSCC tumor tissues compared with that in grade 1-3 and healthy subjects. High expression of Groα, NOD1 and RIPK2 (receptor-interacting serine-threonine kinase 2) is correlated with survival rate in HNSCC patients. Treatment of SCC25 and OECM-1 cells with Groα increased the expression of NOD1 and RIPK2 in a concentration-dependent manner. The findings herein reveal the association of Groα, NOD1 and RIPK2 biomarkers with HNSCC carcinogenesis. Moreover, Groα is the major stimulus of inflammatory mediation and promotes TNF-α (tumor necrosis factor-α) and COX-2 (cyclooxygenase-2) expression in HNSCC. Groα induces TNF-α and COX-2 expression through regulation involving ERK (extracellular signal-regulated kinase)-, JNK (C-Jun N-terminal kinase)- and p38 MAPK (mitogen-activated protein kinase)-dependent signaling pathways. Conclusions: Our findings herein constitute the first evidence that Groα is important in HNSCC progression and metastasis via the NOD1-mediated MAPK pathway, suggesting a role for Groα and NOD1 in mediating metastasis and its potential as a therapeutic target.

Ameliorating Effect of Crassocephalum rabens (Asteraceae) Extract on Skin Aging: A Randomized, Parallel, Double-Blind, and Placebo-Controlled Study.

Crassocephalum rabens (Asteraceae) is a common herb used in Taiwanese folk medicine to treat inflammation-related syndromes. Pharmacological studies have revealed that galactolipids exhibit anti-oxidative, anti-inflammatory, and anti-hyaluronidase activities and improve skin wrinkles, moisture, and elasticity in healthy subjects. However, the anti-aging effects of C. rabens and its primary active compound, 1,2-di-O-linolenoyl-3-O-ß-galactopyranosyl-sn-glycerol (dLGG), remain elusive. Here, we investigated whether C. rabens can improve skin conditions in healthy individuals using a double-blind approach. Forty enrolled volunteers were randomly and equally assigned to the control or treatment group and were required to take either a placebo or a C. rabens extract capsule daily for one month. Skin parameters were measured before and after the study. The results showed significant differences in skin elasticity, wrinkles, collagen content, brightness, and hydration between the baseline and week 4 in the treatment group. Particularly, compared with those in the placebo group, skin wrinkles (p < 0.05), brightness (p < 0.001), collagen content (p < 0.01), and UV spots (p < 0.05) were notably improved after treatment with the C. rabens extract. Our study successfully demonstrated the application of C. rabens in preventing skin aging. Further investigations will be conducted to study the underlying anti-aging mechanism of dLGG.

Growth regulated oncogene-α contribute to EMT/MMPs pathway by binding its receptors in head and neck squamous cell carcinoma.

Squamous cell carcinoma (SCC) is the most common malignant tumor of the head and neck and generally detected in the late stages when the cancer has advanced, and therefore has a poor prognosis and survival rate. A high expression of growth-related oncogene alpha (Groα) is associated with tumor metastasis and invasion and the poor survival rate of patients. Microarray reveals that Groα exhibits a cancer-specific response in HNSCC. Quantitative real-time PCR (qRT-PCR) results concerning the mRNA expression of Groα in HNSCC tissues; indicate that Groα was more highly expressed in HNSCC than in non-cancerous matched tissue (NCMT). The serum of HNSCC patients and healthy subjects demonstrates that the expression of Groα in the HNSCC patients significantly exceeded than in healthy subjects. Furthermore, exposure Groα to stimulated the proliferation, clonogenicity and migration with HNSCC cells (SCC4, SCC9, SCC25 and OECM-1), yielding a stronger response than in non-malignant HaCaT and DOK cells. A high expression of Groα and its receptors CXCR1/2 (chemokine (C-X-C motif) receptor) in HNSCC tissues are highly correlated with tumor progression stage and metastasis. Following the treatment of SCC25 and OECM-1 cells with Groα, ß-catenin, matrix metalloproteinases (MMP)-2, MMP-7 and MMP-9 expressions significantly increased but E-cadherin expression was slightly decreased, suggesting that the EMT and metastasis processes were activated by Groα. These findings constitute the first evidence that Groα promotes epithelial mesenchymal transition (EMT) and MMPs expressions in HNSCC via activating CXCR1/2, suggesting a role for Groα in mediating metastasis and its potential as a therapeutic target.

Novel application of a Co-Fermented postbiotics of TYCA06/AP-32/CP-9/collagen in the improvement of acne vulgaris-A randomized clinical study of efficacy evaluation.

BACKGROUND: Acne vulgaris is a chronic inflammatory skin disease. If skin lesions are not treated well in time, they can leave a permanent impact on the appearance and a negative influence on personal confidence. The common therapy for acne symptom includes antibiotics, benzoyl peroxide, and azeleic acid. However, those medications have side effects, and the long-term use should be cautious. Therefore, it is necessary to develop a safe and effective material, which is more suitable for daily use. OBJECTIVE: Collagen was selected to co-ferment with three probiotic strains TYCA06/AP-32/CP-9 (TAC) due to its excellent feature on wound healing. The fermented material was added into cosmetic gel and applied on subjects' acne lesions. The antimicrobial activity against Propionibacterium acnes and anti-inflammation effect around lesion area were investigated in a 4-week clinical study. MATERIAL AND METHODS: An anti-P. acnes assay, a keratinocytes HaCaT cell-based wound healing assay, and a cytokine assay on thymic stromal lymphopoietin (TSLP) and interleukin (IL)-33 were used to evaluate the function of the fermented material in vitro. The TAC/Collagen formula was further incorporated into a cosmetic gel, and the human clinical trial was carried out by applying this gel on 20 volunteers' face with acne vulgaris. The moisture score, sebum content, inflammation, porphyrins numbers, and brown spot number of whole face were observed and recorded. RESULTS: The postbiotics of the TAC/Collagen displayed a good growth inhibition against P. acnes and reduced TSLP and IL-33 inflammation in vitro. This TAC/Collagen formula enhanced the wound healing in HaCaT cell culture. The result of the clinical trial showed the TAC/Collagen gel improved the moisture score and inflammation index of the skin in vivo. In addition, this TAC/Collagen gel also improved the wound healing of acne symptom in volunteers with acne vulgaris. Moreover, this TAC/Collagen gel reduced the number of the porphyrins and brown spots on facial skin. CONCLUSION: These postbiotics of TAC/Collagen have beneficial effects on skin health and are able to ameliorate the redness, inflammation, and acne symptom in acne vulgaris patients.

Fermented pomegranate extracts protect against oxidative stress and aging of skin.

BACKGROUND: Punica granatum (pomegranate) potentially ameliorates skin inflammation and pain, including herpetic stromal keratitis. Fermentation is a biotechnological technique that may naturally induce health benefits by producing antioxidants. However, the anti-aging effect of fermented pomegranate extracts (FPE) on the skin is still unclear. AIM: This investigation evaluates the effects of fermented pomegranate as a functional supplement (FPE drink, FPE-D) and a cosmetic ingredient (FPE serum, FPE-S) in vitro and in vivo. PATIENTS/METHODS: The effects of FPE products for anti-oxidation, anti-tyrosinase, anti-inflammation, and anti-aging were examined. Forty subjects were randomly allocated to FPE-D or placebo drink groups (50 ml of a FPE-D /placebo drink daily for 8 weeks for each subject), and another 40 subjects were recruited to FPE-S or placebo serum groups (about 3 ml of a FPE-S /placebo serum daily and nightly/daily for 4 weeks for each subject) in a double-blind study. RESULTS: The effects of FPE products on the DPPH, ABTS+ , and NO· free radical scavenging activities, their inhibiting of tyrosinase activity and their enhancement of the skin health of healthy subjects, were investigated. FPE-D improved the moisture, brightness, elasticity, and collagen density of the skin of most subjects at 8 weeks relative to the baseline without treatment (p < 0.05). After 4 weeks of FPE-S serum consumption, the moisture, brightness, elasticity, spots, UV spots, and collagen density of skin were slightly better than those at week 0 (p < 0.05). CONCLUSIONS: The daily consumption of fermented pomegranate extracts can protect the skin against oxidative stress and slow skin aging.

The potential of Streptococcus thermophiles (TCI633) in the anti-aging.

BACKGROUND: Streptococcus thermophilus (TCI633) is a probiotic that has been newly isolated from human breast milk, and it can produce hyaluronic acid (HA) when colonizing the gastrointestinal (GI) tract of rodents and humans. A recent study has the established that TCI633 can alleviate synovial tissue inflammation and has potential to mitigate the progression of osteoarthritis. OBJECTIVE: TCI633 has not been available for use in skincare and this preliminary clinical study will assess its improvement of the skin. METHODS: In this study, DNA protection, Hyaluronidase assay, cell viability, and collagen synthesis on human fibroblasts of TCI633 were assessed. Subjects were enrolled in this clinical study and randomly assigned to the TCI633 or placebo group. Each subject was informed to intake two tablets daily for 8 weeks. Each subject was required to undergo skin condition inspection at weeks 0, 4, and 8 and hematology tests to monitor HA, superoxide dismutase (SOD) and catalase levels, and kidney and liver function at weeks 0 and 8. RESULTS: The effects of TCI633 supplementation, including the promotion of skin cell proliferation, the increase of their collagen content, their protection against DNA damage, and the inhibition of hyaluronidase activities, are investigated. Subjects were recruited for an 8-week long clinical trial to confirm the efficacy of TCI633 in improving the serum biochemical HA, SOD and catalase levels, and anti-skin age markers. CONCLUSIONS: This work provides an alternative approach to improving health, indicating the potential of TCI633 supplementation to delay the aging of skin and improve its condition.

Djulis supplementation against oxidative stress and ultraviolet radiation-induced cell damage: The influence of antioxidant status and aging of skin in healthy subjects.

BACKGROUND: Djulis (Chenopodium formosanum Koidz.) is a cereal food and its antioxidant and pigment constituents may protect skin from photoaging, but conclusive experiments have not been carried out. OBJECTIVE: This investigation evaluates the effects of djulis extract as a functional supplement. PATIENTS/METHODS: In this study, the effects of djulis functional drinks on the free radical scavenging activities, promotion of collagen synthesis and protection against oxidative stress and the effects of ultraviolet B (UVB)-irradiated of pUC119 DNA were explored. Thirty healthy subjects (aged 35-55 years old) were randomly allocated to djulis or placebo drinks groups (50 ml of a djulis/placebo drink daily for 8 weeks for each subject) in a double-blind crossover study. RESULTS: The regular consumption of the djulis functional drinks significantly increased levels of the serum biochemical superoxide dismutase (SOD) and catalase (+9.5% and +124.8%) after 8 weeks, relative to baseline controls. The improvements in skin moisture, brightness, elasticity, crow's feet, texture, wrinkles, pores, and collagen content after 8 weeks in the djulis group were +13.3%, +3.8%, +13.2%, -21.8%, -12.1%, -11.0%, -1.4%, and +33.7%, respectively, relative to the baseline without treatment. CONCLUSIONS: These work findings suggest the daily consumption of djulis drinks can protect the skin against oxidative stress-induced damage, delay skin aging and improve skin conditions.

Coffee pulp supplement affects antioxidant status and favors anti-aging of skin in healthy subjects.

BACKGROUND: Coffee and coffee products are known potentially to reduce levels of oxidative stress biomarkers in humans. OBJECTIVE: This investigation evaluates the effects of coffee pulp extract as a functional supplement (in coffee pulp drink, CPD) and a cosmetic ingredient (coffee pulp serum, CPS). PATIENTS/METHODS: The effects of CPD and CPS for anti-oxidation and anti-aging were investigated. Forty subjects were randomly allocated to CPD or placebo drink groups (50 ml of a CPD/placebo drink daily for 8 weeks for each subject), and another 40 subjects were recruited to CPS or placebo serum groups (about 3 ml of a CPS/placebo serum day and night/daily for 4 weeks for each subject) in a double-blind study. RESULTS: The CPD and CPS (20%) can increase free radical scavenging activities by 93.3% and 85% (p < 0.001) for DPPH, 94.5% and 61.3% (p < 0.01) for ABTS·+ , 43.8% and 15.3% (p < 0.05) for NO· than placebo. The inhibition of tyrosinase activity was increased by 91.6% and 51.0% (p < 0.05) after CPD and CPS application. The CPD comprehensively improved the moisture, brightness, elasticity, spotting, texture, and collagen content of skin for most subjects after 8 weeks, relative to the baseline without treatment (p < 0.05). After 4 weeks of CPS serum consumption, the brightness, elasticity, spotting, UV spots, and collagen content of skin were slightly better than those at week 0 (p < 0.05). CONCLUSIONS: The daily consumption of coffee pulp extract products can slow the skin aging process and improve skin health.

Encapsulation and Characterization of Nanoemulsions Based on an Anti-oxidative Polymeric Amphiphile for Topical Apigenin Delivery.

Apigenin (Apig) is used as a model drug due to its many beneficial bio-activities and therapeutic potentials. Nevertheless, its poor water solubility and low storage stability have limited its application feasibility on the pharmaceutical field. To address this issue, this study developed nanoemulsions (NEs) using an anti-oxidative polymeric amphiphile, d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), hydrogenated soy lecithin (HL), black soldier fly larvae (BSFL) oil, and avocado (AV) oil through pre-homogenization and ultrasonication method. Addition of TPGS (weight ratios 100 and 50% as compared to HL) into NEs effectively reduced particle size and phase transition region area of NEs with pure HL. Incorporation of Apig into NEs made particle size increase and provided a disorder effect on intraparticle molecular packing. Nevertheless, the encapsulation efficiency of NEs for Apig approached to about 99%. The chemical stability of Apig was significantly improved and its antioxidant ability was elevated by incorporation with BSFL oil and AV oil NEs, especially for NEs with single TPGS. NEs with single TPGS also exhibited the best Apig skin deposition. For future application of topical Apig delivery, NEs-gel was formed by the addition of hyaluronic acid (HA) into NEs. Their rheological characteristics were dominated by the surfactant ratios of HL to TPGS.

Collagen formula with Djulis for improvement of skin hydration, brightness, texture, crow's feet, and collagen content: A double-blind, randomized, placebo-controlled trial.

BACKGROUND: The efficacy of Djulis for skin care is currently based on cellular or animal models, and the clinical aspect is not in place. AIM: This clinical study is to investigate the synergistic effect of fish collagen and Djulis (Chenopodium formosanum Koidz.) for improvement of skin parameters. We used the combination of hydrolyzed collagen and Djulis to develop a new functional formula for skin improvement. PATIENTS/METHODS: Fifty volunteers were randomly allocated (in a 1:1 ratio) to the placebo or collagen drink group. Volunteers were required to consume a 50 mL of a collagen drink or placebo drink daily for 8 weeks. For measurements, the indexes of skin conditions were measured at the baseline and 4 and 8 weeks. RESULTS: The improvements of skin hydration, brightness, crow's feet, texture, wrinkles, pores, spots, and collagen content after 8 weeks in collagen group were 17.8%, 5.4%, 14.9%, 9.9%, 29.3%, 10.4%, 9.9%, and 22.3%, respectively. Noticeably, over 68% of subjects got improved for their skin parameters after 8-week intake of collagen drink. The improvement levels indicated competitive skin improvement effects in comparison with previous studies. CONCLUSION: This clinical study demonstrates the synergistic effect of fish collagen and Djulis (the main components) for the substantial improvements in hydration, brightness, crow's feet, texture, wrinkles, pores, surface spots, and collagen content in skin. The collagen drink comprehensively improved skin parameters for most subjects after 4-week intake and manifested competitive efficiency in comparison with other similar studies. We convince that the collagen drink may delay skin aging process and improve skin aging parameters.

Tris(8-Hydroxyquinoline)iron induces apoptotic cell death via oxidative stress and by activating death receptor signaling pathway in human head and neck carcinoma cells.

BACKGROUND: 8-Hydroxyquinoline derivatives have highly sensitive fluorescent chemosensors for metal ions, which are associated with anti-oxidant, anti-tumor and anti-HIV-1 properties. Head and neck squamous cell carcinoma (HNSCC) is associated with a high rate of mortality and novel anti-HNSCC drugs must be developed. Therefore, effective chemotherapy agents are required to address this public health issue. HYPOTHESIS/PURPOSE: The aim of this study was to investigate the inhibitory effect of tris(8-hydroxyquinoline)iron (Feq3) on the HNSCC and the underlying mechanism. STUDY DESIGN/METHODS: A novel 8-hydroxyquinoline derivative, Feq3, was synthesized. The cell viabilities were analyzed using MTT reagent. Apoptosis and the cell cycle distributions were determined by flow cytometer. Reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence, western blot, MitoSOX and CellROX stain assay were used to study the mechanism of Feq3. Feq3 combined with antioxidants NAC (N-acetylcysteine) and BSO (buthionine sulfoximine) measured the cell viability and intracellular ROS. RESULTS: Feq3 induced the death of HNSCC cells and caused them to exhibit the morphological features of apoptosis. Feq3 also induced apoptosis of SCC9 cells by cell cycle arrest during the G2/M phase and the induced arrest of SCC25 cells in the G0/G1 and G2/M phases, which was associated with decreased cyclin B1/cdc2 and cyclin D/cdk4 expressions. Feq3 increases reactive oxygen species (ROS) and reduces glutathione (GSH) levels, and responds to increased p53 and p21 expressions. Feq3 induced apoptosis by mitochondria-mediated Bax and cytochrome c up-expression and down-expression Bcl-2. Feq3 also up-regulated tBid, which interacts with the mitochondrial pathway and tumor necrosis factor-α (TNF-α)/TNF-Rs, FasL/Fas, and TNF-related apoptosis inducing ligand receptors (TRAIL-Rs)/TRAIL-dependent caspases apoptotic signaling pathway in HNSCC cells. However, Feq3 activates Fas but not FasL in SCC25 cells. Feq3 arrests the growth of HNSCC cells and is involved in the mitochondria- and death receptor (DR)-mediated caspases apoptotic pathway. CONCLUSION: This study is the first to suggest that apoptosis mediates the anti-HNSCC of Feq3. Feq3 has potential as a cancer therapeutic agent against HNSCC.

Antioxidant and anti-inflammatory capacities of collagen peptides from milkfish (Chanos chanos) scales.

Milkfish (Chanos chanos), which is resistant to water quality changes is the fourth largest aquaculture commodity. Abandoned wastes of fish scale and bones aggravate environmental pollution. In this study, the effect of collagen peptides isolated from milkfish scales (MSCP) by pepsin-soluble collagen method on cell viability was investigated. The antioxidant, anti-inflammatory, and DNA-protective activities of MSCP were also evaluated. Results revealed that more than 95% of viable cells were retained in human keratinocytes after addition of 100 mg/mL MSCP. Measurement of DPPH· and ABTS· + radical scavenging activities and cellular reactive oxygen species revealed the high antioxidant activities of MSCP. MSCP demonstrated anti-inflammatory activities by reducing lipoxygenase activity and nitric oxide (NO·) radicals. Moreover, DNA electrophoresis assay indicated that MSCP treatment can directly protect against cyclobutane di-pyrimidine production and DNA single-strand breaks, which are harmful effects of UV radiation and H2O2. Given its antioxidant, anti-inflammatory, and DNA-protective activities, MSCP has potential applications in cosmeceuticals and supplementary health food.

IL-8 promotes inflammatory mediators and stimulates activation of p38 MAPK/ERK-NF-κB pathway and reduction of JNK in HNSCC.

This investigation identifies interleukin 8 (IL-8) as the main inflammatory mediator in head and neck squamous cell carcinoma (HNSCC). The expressions of chemokines of IL-8, IL-1ß and IL-6 and the cytokines of tumor necrosis factor-α (TNF-α) were higher in HNSCC patient tissues than in non-cancerous matched tissues (NCMT) whereas the expression of IL-10 was lower. IL-8 is most highly expressed in the tissues of patients with HNSCC. Treatment of HNSCC cells with IL-8 increased the secretion of IL-1ß, IL-6 and TNF-α and reduced IL-10 expression; the increase in the expression of IL-1ß was particularly considerable. IL-8 silencing by siRNA reduced IL-1ß expression in HNSCC cells, suggesting that IL-8 as a main inflammatory mediator improved IL-1ß expression in HNSCC. The expressions of p-p38 mitogen-activated protein kinases (MAPK) and p-extracellular signal regulated kinase (p-ERK) were higher and that of p-c-Jun-NH2-terminal kinase (p-JNK) was lower in HNSCC patient tissues than in NCMT. IL-8 treatment induced p-p38 MAPK and p-ERK expression, but reduced p-JNK expressions in HNSCC cells. IL-8 siRNA suppressed p38 MAPK and ERK but increased JNK expression in HNSCC cells. Exposure of SCC25 cells to IL-8, increased the expressions of p-IκB-α and nuclear factor (NF)-κB, suggesting that IL-8 regulates inflammatory response by modulating the MAPK and NF-κB pathway in HNSCC cells. IL-8 promotes the migration of SCC25 cells and increases matrix metalloproteinase-2 (MMP-2) and MMP-9 expressions. These results reveal that IL-8 is the major stimulus of inflammatory mediation in HNSCC progression and migration by activating the p38 MAPK/ERK-NF-κB pathway and reducing JNK.

IL-8 promotes HNSCC progression on CXCR1/2-meidated NOD1/RIP2 signaling pathway.

NOD1 (nucleotide-binding oligomerization domain 1) is overexpressed in head and neck squamous cell carcinoma (HNSCC) cells, as is IL-8 in cancer cells. However, the mechanism of the IL-8-mediated overexpression of NOD in HNSCC not been identified. This study determines whether IL-8 promotes tumor progression via the NOD signaling pathway in HNSCC. Higher IL-8, NOD1 and receptor-interacting protein kinase (RIP2) expressions were observed in HNSCC tissue than in non-cancerous matched tissue (NCMT), whereas NOD2 was weakly expressed. Furthermore, IL-8 stimulated the proliferation of HNSCC cells (SCC4, SCC9 and SCC25) but not dysplastic oral mucosa DOK cells. Exposure to IL-8 increased the clonogenicity of HNSCC cells. IL-8 siRNA inhibited cell proliferation and cell colony formation, suggesting that IL-8 is involved in HNSCC cancer progression. The expressions of CXCR1 and CXCR2 were higher in HNSCC tissue than in NCMT. HNSCC cells that were exposed to IL-8 exhibited higher expression of CXCR1/2 than did controls. The blocking of IL-8 by siRNA reduced CXCR1/2 expression in HNSCC cells, suggesting that the cancer progression of HNSCC cells that is induced by IL-8 depends on CXCR1/2. Additionally, IL-8 is associated with increased NOD1 and RIP2 expression and reduced NOD2 expression in three types of HNSCC cells. The blocking of IL-8 by siRNA reduces IL-8, NOD1 and RIP2 expressions in HNSCC cells, but not the level of NOD2. These results suggest that IL-8 has an important role in HNSCC progression via a CXCR1/2-meidated NOD1/RIP2 signaling pathway.

The Inhibitory Mechanisms Study of 5,6,4'-Trihydroxy-7,3'-Dimethoxyflavone against the LPS-Induced Macrophage Inflammatory Responses through the Antioxidant Ability.

The whole plant of Anisomeles ovata has been widely used in Taiwan for treating inflammation-related skin and liver diseases, however, the detailed pharmacology mechanisms have yet to be elucidated. In the present study, one of the major components, 5,6,4'-trihydroxy-7,3'-dimethoxyflavone (5-TDMF), was purified from a methanol extract of Anisomeles ovata. A pharmacological study of this compound suggests that 5-TDMF possesses potent free radical scavenging activity both in vitro and ex vivo. Furthermore, 5-TDMF reduces nitric oxide and pro-inflammatory cytokine production in LPC-treated RAW 264.7 cells through the attenuation of nitric oxide synthase and cyclooxygenase-2. Additional experiments suggest that of 5-TDMF interferes with nuclear factor-κB translocation and mitogen-activated protein kinase pathways. These results identify 5-TDMF as an anti-oxidant and anti-inflammatory compound, explain the pharmacologic function of Anisomeles ovata and suggest its great potential as a new anti-inflammatory remedy.

Characterization and in vitro biocompatibility of catanionic assemblies formed with oppositely charged dicetyl amphiphiles.

In this study, cationic dicetyldimethylammonium bromide (DCB) and anionic dicetyl phosphate (DCP) were mixed to form catanionic assemblies in water, and their colloidal morphology, size, charge characteristics, phase behavior, membrane fluidity, and in vitro biocompatibility are comprehensively investigated for the first time. Our results show that the catanionic DCB and DCP mixtures in water are capable of forming circular vesicles and this binary mixed system expresses the miscibility with deviation from the ideal mixing. Compared to the nanoscale DCB-rich vesicles, the DCP-rich vesicles have smaller size, higher negative zeta potential, higher main transition temperature, and better storage stability. The temperature and molecular cooperativity of the main transition phase for the DCP vesicles can be reduced by an addition of DCB. This work demonstrates that the head groups and the relative composition of the two considered dicetyl amphiphiles remarkably affect the phase behavior, membrane rigidity, encapsulation ability and in vitro biocompatibility of DCB/DCP vesicles. The iso-stoichiometric mixed DCB/DCP vesicle, showing low cytotoxicity, long storage time, and high drug loading, is a potential candidate for the drug delivery system.

Simple synthesis, self-assembly, and cytotoxicity of novel dimeric cholesterol derivatives.

A simple and economic methodology to synthesize three types of novel dimeric cholesterol derivatives (DCDs) was developed. Results obtained from dynamic light scattering and transmission electron microscopy show that spherical and/or angular nano-structural aggregates of DCDs are formed by self-assembly in aqueous solution. The size and morphology of DCD dispersions depend on the spatial arrangement of the substituents and polarity of the head group in the DCD structures. The cytoxicity of DCD dispersions to human keratinocytes (HaCaT) and squamous cell carcinomas (SCC25) cells was also evaluated by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The present novel DCD dispersions were not toxic to HaCaT and SCC25 cells at appropriate tested concentrations.

Effects of lipid composition on physicochemical characteristics and cytotoxicity of vesicles composed of cationic and anionic dialkyl lipids.

The behaviors of cat-anionic vesicles composed of dioctadecyldimethylammonium bromide (DODAB) and dihexadecyl phosphate (DHP) with varying lipid composition were investigated through the measurements of size, zeta potential and fluorescence polarization, morphological observations, determination of thermotropic phase behavior, cell viability assay, and examination of entrapment efficiency and colloid stability. DODAB is miscible with DHP in the bilayer domain, which expresses a non-ideal mixing characteristic. The DODAB-rich vesicles show a smaller particle size, higher positive zeta potential, lower main transition temperature, less angular structure, better storage stability, and higher encapsulation efficiency than the DHP-rich ones. Introduction of DODAB into DHP vesicles enhances the membrane fluidity in the ripple and liquid crystalline phases. The membrane fluidity of mixed DODAB-DHP vesicles with the near charge might have a significant effect on the survival of nontransformed human skin fibroblast Hs68 cells. The degree of the cytotoxicity of Hs68 cells is dominated mainly by the charge nature of DODAB-DHP vesicles with varying lipid composition. The results gathered provide necessary information for future drug/gene delivery applications.

Antioxidant, anti-adipocyte differentiation, antitumor activity and anthelmintic activities against Anisakis simplex and Hymenolepis nana of yakuchinone A from Alpinia oxyphylla.

BACKGROUND: Alpinia oxyphylla is a common remedy in traditional Chinese medicine. Yakuchinone A is a major constituent of A. oxyphylla and exhibits anti-inflammatory, antitumor, antibacterial, and gastric protective activities. METHODS: Antioxidant and antitumor characteristics of yakuchinone A in skin cancer cells as well as novel mechanisms for the inhibition of adipocyte differentiation, cestocidal activities against Hymenolepis nana adults, and nematocidal activities against Anisakis simplex larvae are investigated. RESULTS: Yakuchinone A presents the ability of the removal of DPPH·and ABTS+ free radicals and inhibition of lipid peroxidation. Yakuchinone A suppresses intracellular lipid accumulation during adipocyte differentiation in 3 T3-L1 cells and the expressions of leptin and peroxisome proliferator-activated receptor γ (PPARγ). Yakuchinone A induces apoptosis and inhibits cell proliferation in skin cancer cells. The inhibition of cell growth by yakuchinone A is more significant for non-melanoma skin cancer (NMSC) cells than for melanoma (A375 and B16) and noncancerous (HaCaT and BNLCL2) cells. Treatment BCC cells with yakuchinone A shows down-regulation of Bcl-2, up-regulation of Bax, and an increase in cleavage poly (ADP-ribose) polymerase (PARP). This suggests that yakuchinone A induces BCC cells apoptosis through the Bcl-2-mediated signaling pathway. The anthelmintic activities of yakuchinone A for A. simplex are better than for H. nana. CONCLUSIONS: In this work, yakuchinone A exhibits antioxidative properties, anti-adipocyte differentiation, antitumor activity, and anthelmintic activities against A. simplex and H. nana.

Brazilein from Caesalpinia sappan L. Antioxidant Inhibits Adipocyte Differentiation and Induces Apoptosis through Caspase-3 Activity and Anthelmintic Activities against Hymenolepis nana and Anisakis simplex.

Brazilein, a natural, biologically active compound from Caesalpinia sappan L., has been shown to exhibit anti-inflammatory and antioxidant properties and to inhibit the growth of several cancer cells. This study verifies the antioxidant and antitumor characteristics of brazilein in skin cancer cells and is the first time to elucidate the inhibition mechanism of adipocyte differentiation, cestocidal activities against Hymenolepis nana, and reduction of spontaneous movement in Anisakis simplex. Brazilein exhibits an antioxidant capacity as well as the ability to scavenge DPPH(•) and ABTS(•+) free radicals and to inhibit lipid peroxidation. Brazilein inhibited intracellular lipid accumulation during adipocyte differentiation in 3T3-L1 cells and suppressed the induction of peroxisome proliferator-activated receptor γ (PPAR γ ), the master regulator of adipogenesis, suggesting that brazilein presents the antiobesity effects. The toxic effects of brazilein were evaluated in terms of cell viability, induction of apoptosis, and the activity of caspase-3 in BCC cells. The inhibition of the growth of skin cancer cells (A431, BCC, and SCC25) by brazilein is greater than that of human skin malignant melanoma (A375) cells, mouse leukemic monocyte macrophage (RAW 264.7 cells), and noncancerous cells (HaCaT and BNLCL2 cells). The anthelmintic activities of brazilein against Hymenolepis nana are better than those of Anisakis simplex.