49 research outputs found
Protection from UVB Toxicity in Human Keratinocytes by Thailand Native Herbs Extracts.
No full textThai traditional medicine employs a wide range of indigenous herbs in the forms of tincture or tea for the cure of skin and systemic inflammatory diseases. The protection by Thai plants extracts against UVB DNA damage and cytotoxicity was investigated in human keratinocytes. Petroleum ether, dichloromethane and ethanol extracts were prepared from 15 Thai herb species, and the total phenolic and flavonoid contents, the antioxidant and UV-absorbing properties were assessed by standard procedures. Cytoprotective effects were evaluated on the basis of cell survival, caspase-3 activity and pyrimidine dimers determination. High total phenolic and flavonoid contents were found in the ethanol and dichloromethane fractions. Dichloromethane extract of turmeric was shown to possess the highest antioxidant activity. The maximum UV absorptions were found in the ethanol extract of turmeric and in the dichloromethane extract of ginger. These extracts stimulated the synthesis of Thioredoxin 1, an antioxidant protein, and could protect human HaCaT keratinocytes from UV-induced DNA damage and cytotoxicity. The present data support the utilization of turmeric and ginger extracts in anti-UV cosmetic pharmaceuticals
Mucuna pruriens Seed Extract Promotes Neurite Outgrowth via Ten-4 Dependent and Independent Mechanisms in Neuro2a Cells
No full textNeurological diseases are one of the serious health hazards faced by mankind for decades. Neurite outgrowth is a key factor responsible for proper neuronal development. Any misplacement in the process could lead to neurological diseases like Alzheimer’s and Parkinson’s. Treatment with the available synthetic drugs imparts many difficulties to the patients due to the side effects. Compounds from natural sources can be considered as an effective replacement for this. Mucuna pruriens, used in traditional ayurvedic medicine, contains L-3,4-dihydroxy phenylalanine (L-DOPA) in its seeds, which possesses medicinal effects against neurological diseases. In this regard, seed extracts of M. pruriens originated from Thailand and India, were analyzed for their neuroprotective effects in Neuro2a cells. Hexane, ethyl acetate and ethanol extracts were found to be non-toxic to the viability of the cells. Ethanol extracts of M. pruriens of Thai origin (MTE), hexane extracts of M. pruriens of Indian origin (MIH) and ethyl acetate extracts of M. pruriens of Indian origin (MIEA) were able to induce neurite outgrowth in Neuro2a cells. Interestingly, both MTE and MIH induced neurite outgrowth dependent on Teneurin-4 (Ten-4) transmembrane protein whereas MIEA did the same independent of Ten-4, which was confirmed by real time PCR and gene silencing approach. The present study suggested that M. pruriens can be used as a potential drug in the treatment of neurological diseases as it can induce neurite outgrowth by multiple mechanisms, which will be of great use in the field of medicine
Dipentylammonium Binds to the Sigma-1 Receptor and Protects Against Glutamate Toxicity, Attenuates Dopamine Toxicity and Potentiates Neurite Outgrowth in Various Cultured Cell Lines
No full textAlzheimer’s disease is a neurodegenerative disease that affects 44 million people worldwide, costing the world $605 billion to care for those affected not taking into account the physical and psychological costs for those who care for Alzheimer’s patients. Dipentylammonium is a simple amine, which is structurally similar to a number of other identified sigma-1 receptor ligands with high affinities such as (2R-trans)-2butyl-5-heptylpyrrolidine, stearylamine and dodecylamine. This study investigates whether dipentylammonium is able to provide neuroprotective effects similar to those of sigma-1 receptor agonists such as PRE-084. Here we identify dipentylammonium as a sigma-1 receptor ligand with nanomolar affinity. We have found that micromolar concentrations of dipentylammonium protect from glutamate toxicity and prevent NFκB activation in HT-22 cells. Micromolar concentrations of dipentylammonium also protect stably expressing amyloid precursor protein Swedish mutant (APP/Swe) Neuro2A cells from toxicity induced by 150 μM dopamine, suggesting that dipentylammonium may be useful for the treatment of Parkinsonian symptoms in Alzheimer’s patients which are often associated with a more rapid deterioration of cognitive and physical ability. Finally, we found that low micromolar concentrations of dipentylammonium could out preform known sigma-1 receptor agonist PRE-084 in potentiating neurite outgrowth in Neuro2A cells, further suggesting that dipentylammonium has a potential use in the treatment of neurodegenerative diseases and could be acting through the sigma-1 receptor
Caesalpinia mimosoides leaf extract promotes neurite outgrowth and inhibits bace1 activity in mutant app-overexpressing neuronal neuro2a cells
No full textAlzheimer’s disease (AD) is implicated in the imbalance of several proteins, including Amyloid-β (Aβ), amyloid precursor protein (APP), and BACE1. APP overexpression interferes with neurite outgrowth, while BACE1 plays a role in Aβ generation. Medicinal herbs with effects on neurite outgrowth stimulation and BACE1 inhibition may benefit AD. This study aimed to investi-gate the neurite outgrowth stimulatory effect, along with BACE1 inhibition of Caesalpinia mimosoides (CM), using wild-type (Neuro2a) and APP (Swedish mutant)-overexpressing (Neuro2a/APPSwe) neurons. The methanol extract of CM leaves stimulated neurite outgrowth in wild-type and APP-overexpressing cells. After exposure to the extract, the mRNA expression of the neurite outgrowth activation genes growth-associated protein-43 (GAP-43) and teneurin-4 (Ten-4) was increased in both Neuro2a and Neuro2a/APPSwe cells, while the mRNA expression of neurite outgrowth negative regulators Nogo receptor (NgR) and Lingo-1 was reduced. Additionally, the extract suppressed BACE1 activity in the APP-overexpressing neurons. Virtual screening demonstrated that quercetin-3′-glucuronide, quercetin-3-O-glucoside, clausarinol, and theogallin were possible inhibitors of BACE1. ADMET was analyzed to predict drug-likeness properties of CM-constituents. These results suggest that CM extract promotes neurite outgrowth and inhibits BACE1 activity in APP-over-expressing neurons. Thus, CM may serve as a source of drugs for AD treatment. Additional studies for full identification of bioactive constituents and to confirm the neuritogenesis in vivo are needed for translation into clinic of the present findings
Turmeric Toxicity in A431 Epidermoid Cancer Cells Associates with Autophagy Degradation of Anti-apoptotic and Anti-autophagic p53 Mutant
No full textThe keratinocyte-derived A431 Squamous Cell Carcinoma cells express the p53R273H mutant, which has been reported to inhibit apoptosis and autophagy. Here, we show that the crude extract of turmeric (Curcuma longa), similarly to its bioactive component Curcumin, could induce both apoptosis and autophagy in A431 cells, and these effects were concomitant with degradation of p53. Turmeric and curcumin also stimulated the activity of mTOR, which notoriously promotes cell growth and acts negatively on basal autophagy. Rapamycin-mediated inhibition of mTOR synergized with turmeric and curcumin in causing p53 degradation, increased the production of autophagosomes and exacerbated cell toxicity leading to cell necrosis. Small-interference mediated silencing of the autophagy proteins BECLIN 1 or ATG7 abrogated the induction of autophagy and largely rescued p53 stability in Turmeric-treated or Curcumin-treated cells, indicating that macroautophagy was mainly responsible for mutant p53 degradation. These data uncover a novel mechanism of turmeric and curcumin toxicity in chemoresistant cancer cells bearing mutant p53
The Potential for Plant Derivatives against Acrylamide Neurotoxicity
No full textCertain industrial chemicals and food contaminants have been demonstrated to possess neurotoxic activity and have been suspected to cause brain-related disorders in humans. Acrylamide (ACR), a confirmed neurotoxicant, can be found in trace amount in commonly consumed human aliments as a result of food processing or cooking. This discovery aroused a great concern in the public, and increasing efforts are continuously geared towards the resolution of this serious threat. The broad chemical diversity of plants may offer the resources for novel antidotes against neurotoxicants. With the goal of attenuating neurotoxicity of ACR, several plants extracts or derivatives have been employed. This review presents the plants and their derivatives that have been shown most active against ACR-induced neurotoxicity, with a focus on their origin, pharmacological activity, and antidote effects
Psoriasis: A review of the role of serotonergic system
No full textPsoriasis, a chronic inflammatory skin disease, is not yet curable, and its precise causes remain unclear. Nevertheless, several lines of evidence support that psoriasis is a multifactorial disease. Because psoriasis occurs in connection with stress and mood disorders, the genes in serotonergic system may be involved in psoriasis with regard to etiology and pathogenesis. Such molecular impacts supported by scientific evidence on serotonergic gene expression changes and genetic polymorphisms have been increasingly highlighted. The serotonergic system has also received considerable attention as a potential target for the therapy of psoriasis. Here, we summarize the current knowledge about role of genes in serotonergic system in psoriasis and point out possible directions of future studies
An investigation of the relationship between serotonin transporter gene promoter polymorphism and psoriasis susceptibility in a Thai population
No full textModulatory effects of Thai medicinal plant extract on proinflammatory cytokines-induced apoptosis in human keratinocyte HaCaT cells
No full textIt has been experimentally proven that proinflammatory cytokines, interferon (IFN)-y and tumor necrosis factor (TNF)-a are able to synergistically induce apoptosis in HaCaT keratinocyte cells. The present study aimed to elucidate modulatory effects of ethanolic extracts derived from Thai traditional medicinal plants on IFN-y/TNF-a-caused HaCaT apoptosis and correlate with their natural phenolic content. Using 3-(4-5 dimethylthiozol-2-yl) 2-5 diphenyl-tetrazolium bromide (MTT) assay, we found that herbal extracts derived from members of the Acanthaceae family, Rhinacanthus nasutus (L.) Kurz (0.1, 1 and 10 μg/ml) and Clinacanthus nutans (Burm.f.) Lindau (1 and 100 μg/ml), significantly inhibited the IFN-y/TNF-a- induced HaCaT apoptosis, while members of the Zingiberaceae family, Curcuma longa L. and Alpinia galanga (L.) Willd, significantly enhanced apoptosis when a concentration of 100 μg/ml was used. Furthermore, the ethanolic plant extracts were found to possess different amounts of total phenolics ranging from 1.64 to 10.04 mg GAE/g as determined using Folin-Ciocalteu assay. The richest phenolic sources were R. nasutus (10.04 ± 1.12 mg GAE/g) and C. longa (7.49 ± 0.50 mg GAE/g), whereas the least phenolic source was Centella asiatica (1.64 ± 0.84 mg GAE/g). Taken together, we found certain modulatory effects of Thai medicinal extracts on IFN-y/TNF-a-induced apoptosis in HaCaT cells, but these findings might not be directly correlated with their natural phenolic content. Therefore, further investigations on different types of natural phenolic contents in these Thai medicinal extracts and their relevant molecular mechanisms in keratinocytes, should be carried out in the near future.Key words: Interferon, tumor necrosis factor, Thai medicinal herbs, apoptosis, phenolics, human keratinocytes
Acceleration of gene transfection efficiency in neuroblastoma cells through polyethyleneimine/poly(methyl methacrylate) core-shell magnetic nanoparticles
No full textTewin Tencomnao,1,* Kewalin Klangthong,2,* Nuttaporn Pimpha,3 Saowaluk Chaleawlert-umpon,3 Somsak Saesoo,3 Noppawan Woramongkolchai,3 Nattika Saengkrit,31Center for Excellence in Omics-Nano Medical Technology Development Project, 2Graduate Program in Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, 3National Nanotechnology Center, National Science and Technology Development Agency, Pathumthani, Thailand*Both authors contributed equally to this workBackground: The purpose of this study was to demonstrate the potential of magnetic poly(methyl methacrylate) (PMMA) core/polyethyleneimine (PEI) shell (mag-PEI) nanoparticles, which possess high saturation magnetization for gene delivery. By using mag-PEI nanoparticles as a gene carrier, this study focused on evaluation of transfection efficiency under magnetic induction. The potential role of this newly synthesized nanosphere for therapeutic delivery of the tryptophan hydroxylase-2 (TPH-2) gene was also investigated in cultured neuronal LAN-5 cells.Methods: The mag-PEI nanoparticles were prepared by one-step emulsifier-free emulsion polymerization, generating highly loaded and monodispersed magnetic polymeric nanoparticles bearing an amine group. The physicochemical properties of the mag-PEI nanoparticles and DNA-bound mag-PEI nanoparticles were investigated using the gel retardation assay, atomic force microscopy, and zeta size measurements. The gene transfection efficiencies of mag-PEI nanoparticles were evaluated at different transfection times. Confocal laser scanning microscopy confirmed intracellular uptake of the magnetoplex. The optimal conditions for transfection of TPH-2 were selected for therapeutic gene transfection. We isolated the TPH-2 gene from the total RNA of the human medulla oblongata and cloned it into an expression vector. The plasmid containing TPH-2 was subsequently bound onto the surfaces of the mag-PEI nanoparticles via electrostatic interaction. Finally, the mag-PEI nanoparticle magnetoplex was delivered into LAN-5 cells. Reverse-transcriptase polymerase chain reaction was performed to evaluate TPH-2 expression in a quantitative manner.Results: The study demonstrated the role of newly synthesized high-magnetization mag-PEI nanoparticles for gene transfection in vitro. The expression signals of a model gene, luciferase, and a therapeutic gene, TPH-2, were enhanced under magnetic-assisted transfection. An in vitro study in neuronal cells confirmed that using mag-PEI nanoparticles as a DNA carrier for gene delivery provided high transfection efficiency with low cytotoxicity.Conclusion: The mag-PEI nanoparticle is a promising alternative gene transfection reagent due to its ease of use, effectiveness, and low cellular toxicity. The mag-PEI nanoparticle is not only practical for gene transfection in cultured neuronal cells but may also be suitable for transfection in other cells as well.Keywords: magnetic nanoparticle, non-viral vector, gene delivery, tryptophan hydroxylase-2, LAN-5, neuronal cell
