South East Asian Nutrition Surveys II (SEANUTS II) Thailand: Triple burden of malnutrition among Thai children aged 6 months to 12 years.

OBJECTIVE: This study assessed nutritional status among Thai children using anthropometry, dietary intakes, and micronutrient status. DESIGN: Cross-sectional survey with multi-stage cluster sampling. Body weight and height were measured in all children. Dietary intakes were assessed using 24-hour dietary recall. Biochemical assessment was performed in one-third of the children. SETTING: The study was conducted in Thailand's four geographical regions and Bangkok. PARTICIPANTS: 3478 Thai children aged 0.5-12.9 years. RESULTS: Stunting showed a downward trend by age group and was most prevalent among infants and toddlers. Overweight and obesity showed a significant upward trend by age group, location, and sex, and was highest among children aged 7-12.9 years. Risks of inadequate micronutrient intakes (calcium, iron, zinc, vitamins A, C, and D) were high (53.2-93.6%). Prevalence of zinc and mild vitamin A deficiencies were low; vitamin D and B12 deficiencies were nil. Vitamin D insufficiency was significantly higher in the urban area and among girls aged 7-12.9 years. Anemia was very high in infants and toddlers (56.6 and 35.2%), but showed a significant downward trend by age group. There was an overall high prevalence of iron deficiency without anemia (25%) versus iron deficiency anemia (4.2%) among children aged 4-12.9 years old. CONCLUSIONS: The high prevalence of stunting and anemia among children aged 1-3.9 years and overweight and obesity among children aged 7-12.9 years requires continued attention. While prevalence of biochemical micronutrient deficiencies was not high (except for iron), high prevalence of dietary inadequacies for several micronutrients warrants further in-depth investigations.

Anti-Inflammatory Activity and Mechanism of Sweet Corn Extract on Il-1ß-Induced Inflammation in a Human Retinal Pigment Epithelial Cell Line (ARPE-19).

Age-related macular degeneration (AMD) is an eye disease associated with aging. Development of AMD is related to degeneration and dysfunction of the retinal pigment epithelium (RPE) caused by low-grade chronic inflammation in aged RPE cells leading to visual loss and blindness. Sweet corn is a good source of lutein and zeaxanthin, which were reported to exert various biological activities, including anti-inflammatory activity. The present study aims to investigate the anti-inflammatory activity and mechanisms of SCE to inhibit the production of inflammatory biomarkers related to AMD development. Cells were pretreated with SCE for 1 h followed by stimulation with IL-1ß for another 24 h. The results demonstrated that SCE attenuated IL-1ß-induced production of IL-6, IL-8, and MCP-1 and the expression of ICAM-1 and iNOS in a dose-dependent manner. In addition, SCE suppressed the phosphorylation of ERK1/2, SAPK/JNK, p38, and NF-κB (p65) in IL-1ß-stimulated ARPE-19 cells. These results proved that SCE protected ARPE-19 cells from IL-1ß-induced inflammation by inhibiting inflammatory markers partly via suppressing the activation of MAPK and NF-κB signaling pathways. Overall, SCE is a potential agent for the prevention of AMD development, which should be further evaluated in animals.

An Integrative Approach to Investigate the Mode of Action of (-)-Dendroparishiol in Bacterial Meningitis: Computer-Aided Estimation of Biological Activity and Network Pharmacology.

Bacterial meningitis remains one of the most prevalent infectious diseases worldwide. Although advances in medical care have improved mortality and morbidity, neurological complications remain high. Therefore, aside from antibiotics, therapeutic adjuvants targeting neuroinflammation are essential to combat the long-term neuronal sequelae of bacterial meningitis. In the present study, we propose (-)-dendroparishiol as a potential add-on therapy to improve neuroinflammation associated with bacterial meningitis. The biological activity of (-)-dendroparishiol was first predicted by computational analysis and further confirmed in vitro using a cell-based assay with LPS-induced BV-2 microglial cells. Biological pathways involved with (-)-dendroparishiol were identified by applying network pharmacology. Computational predictions of biological activity indicated possible attenuation of several inflammatory processes by (-)-dendroparishiol. In LPS-induced BV-2 microglial cells, (-)-dendroparishiol significantly reduced the expression of inflammatory mediators: iNOS, NO, COX-2, IL-6, and TNF-α. Molecular docking results demonstrated the potential iNOS and COX-2 inhibitory activity of (-)-dendroparishiol. Network pharmacological analysis indicated the plausible role of (-)-dendroparishiol in biological processes involved in oxidative stress and neuroinflammation with enrichment in neuroinflammatory pathways. Overall, this study provides scientific evidence for the potential application of (-)-dendroparishiol in the management of bacterial meningitis-associated neuroinflammation.

Metabolomic Analysis of Phytochemical Compounds from Ethanolic Extract of Lime (Citrus aurantifolia) Peel and Its Anti-Cancer Effects against Human Hepatocellular Carcinoma Cells.

Lime peels are food waste from lime product manufacturing. We previously developed and optimized a green extraction method for hesperidin-limonin-rich lime peel extract. This study aimed to identify the metabolomics profile of phytochemicals and the anti-cancer effects of ethanolic extract of lime (Citrus aurantifolia) peel against liver cancer cells PLC/PRF/5. The extract's metabolomics profile was analyzed by using LC-qTOF/MS and GC-HRMS. The anti-cancer effects were studied by using MTT assay, Annexin-PI assay, and Transwell-invasion assay. Results show that the average IC50(s) of hesperidin, limonin, and the extract on cancer cells' viability were 165.615, 188.073, and 503.004 µg/mL, respectively. At the IC50 levels, the extract induced more apoptosis than those of pure compounds when incubating for 24 and 48 h (p < 0.0001). A combination of limonin and hesperidin showed a synergistic effect on apoptosis induction (p < 0.001), but the effect of the combination was still less than that of the extract at 48 h. Furthermore, the extract significantly inhibited cancer cell invasion better than limonin but equal to hesperidin. At the IC50 level, the extract contains many folds lower amounts of hesperidin and limonin than the IC50 doses of the pure compounds. Besides limonin and hesperidin, there were another 60 and 22 compounds detected from the LCMS and GCMS analyses, respectively. Taken altogether, the superior effect of the ethanolic extract against liver cancer cells compared to pure compound likely results from the combinatorial effects of limonin, hesperidin, and other phytochemical components in the extract.

A Green Extraction Method to Achieve the Highest Yield of Limonin and Hesperidin from Lime Peel Powder (Citrus aurantifolia).

Green extraction is aimed at reducing energy consumption by using renewable plant sources and environmentally friendly bio-solvents. Lime (Citrus aurantifolia) is a rich source of flavonoids (e.g., hesperidin) and limonoids (e.g., limonin). Manufacturing of lime products (e.g., lime juice) yields a considerable amount of lime peel as food waste that should be comprehensively exploited. The aim of this study was to develop a green and simple extraction method to acquire the highest yield of both limonin and hesperidin from the lime peel. The study method included ethanolic-aqueous extraction and variable factors, i.e., ethanol concentrations, pH values of solvent, and extraction temperature. The response surface methodology was used to optimize extraction conditions. The concentrations of limonin and hesperidin were determined by using UHPLC-MS/MS. Results showed that the yields of limonin and hesperidin significantly depended on ethanol concentrations and extraction temperature, while pH value had the least effect. The optimal extraction condition with the highest amounts of limonin and hesperidin was 80% ethanol at pH 7, 50 °C, which yields 2.072 and 3.353 mg/g of limonin and hesperidin, respectively. This study illustrates a green extraction process using food waste, e.g., lime peel, as an energy-saving source and ethanol as a bio-solvent to achieve the highest amount of double bioactive compounds.

Anti-Inflammatory Activity of Oxyresveratrol Tetraacetate, an Ester Prodrug of Oxyresveratrol, on Lipopolysaccharide-Stimulated RAW264.7 Macrophage Cells.

Oxyresveratrol (OXY) has been reported for its anti-inflammatory activity; however, the pharmaceutical applications of this compound are limited by its physicochemical properties and poor pharmacokinetic profiles. The use of an ester prodrug is a promising strategy to overcome these obstacles. In previous researches, several carboxylate esters of OXY were synthesized and oxyresveratrol tetraacetate (OXY-TAc) was reported to possess anti-melanogenic and anti-skin-aging properties. In this study, in addition to OXY-TAc, two novel ester prodrugs of OXY, oxyresveratrol tetrapropionate (OXY-TPr), and oxyresveratrol tetrabutyrate (OXY-TBu), were synthesized. Results from the Caco-2-permeation assay suggested that synthesized ester prodrugs can improve the membrane-permeation ability of OXY. The OXY-TAc exhibited the most significant profile, then this prodrug was chosen to observe anti-inflammatory activities with lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Our results showed that OXY-Tac significantly alleviated secretion of several pro-inflammatory mediators (nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α)), mitigated expression of enzyme-regulated inflammation (inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2)), and suppressed the MAPK cascades. Interestingly, the observed anti-inflammatory activities of OXY-TAc were more remarkable than those of its parent compound OXY. Taken together, we demonstrated that OXY-TAc improved physicochemical and pharmacokinetic profiles and enhanced the pharmacological effects of OXY. Hence, the results in the present study would strongly support the clinical utilities of OXY-TAc for the treatment of inflammation-related disorders.

Protective Effects of a Lutein Ester Prodrug, Lutein Diglutaric Acid, against H2O2-Induced Oxidative Stress in Human Retinal Pigment Epithelial Cells.

Oxidative stress-induced cell damage and death of the retinal pigmented epithelium (RPE), a polarized monolayer that maintains retinal health and homeostasis, lead to the development of age-related macular degeneration (AMD). Several studies show that the naturally occurring antioxidant Lutein (Lut) can protect RPE cells from oxidative stress. However, the poor solubility and low oral bioavailability limit the potential of Lut as a therapeutic agent. In this study, lutein diglutaric acid (Lut-DG), a prodrug of Lut, was synthesized and its ability to protect human ARPE-19 cells from oxidative stress was tested compared to Lut. Both Lut and Lut-DG significantly decreased H2O2-induced reactive oxygen species (ROS) production and protected RPE cells from oxidative stress-induced death. Moreover, the immunoblotting analysis indicated that both drugs exerted their protective effects by modulating phosphorylated MAPKs (p38, ERK1/2 and SAPK/JNK) and downstream molecules Bax, Bcl-2 and Cytochrome c. In addition, the enzymatic antioxidants glutathione peroxidase (GPx) and catalase (CAT) and non-enzymatic antioxidant glutathione (GSH) were enhanced in cells treated with Lut and Lut-DG. In all cases, Lut-DG was more effective than its parent drug against oxidative stress-induced damage to RPE cells. These findings highlight Lut-DG as a more potent compound than Lut with the protective effects against oxidative stress in RPE cells through the modulation of key MAPKs, apoptotic and antioxidant molecular pathways.

Molecular Insight into the Anti-Inflammatory Effects of the Curcumin Ester Prodrug Curcumin Diglutaric Acid In Vitro and In Vivo.

Curcumin diglutaric acid (CurDG), an ester prodrug of curcumin, has the potential to be developed as an anti-inflammatory agent due to its improved solubility and stability. In this study, the anti-inflammatory effects of CurDG were evaluated. The effects of CurDG on inflammatory mediators were evaluated in LPS-stimulated RAW 264.7 macrophage cells. CurDG reduced the increased levels of NO, IL-6, and TNF- α, as well as iNOS and COX-2 expression in cells to a greater extent than those of curcumin, along with the potent inhibition of MAPK (ERK1/2, JNK, and p38) activity. The anti-inflammatory effects were assessed in vivo by employing a carrageenan-induced mouse paw edema model. Oral administration of CurDG demonstrated significant anti-inflammatory effects in a dose-dependent manner in mice. The effects were significantly higher compared to those of curcumin at the corresponding doses (p < 0.05). Moreover, 25 mg/kg curcumin did not exert a significant anti-inflammatory effect for the overall time course as indicated by the area under the curve data, while the equimolar dose of CurDG produced significant anti-inflammatory effects comparable with 50, 100, and 200 mg/kg curcumin (p < 0.05). Similarly, CurDG significantly reduced the proinflammatory cytokine expression in paw edema tissues compared to curcumin (p < 0.05). These results provide the first experimental evidence for CurDG as a promising anti-inflammatory agent.

Exploring Novel Cocrystalline Forms of Oxyresveratrol to Enhance Aqueous Solubility and Permeability across a Cell Monolayer.

Oxyresveratrol (ORV) is a naturally extracted compound with many pharmacological activities. However, information about the crystalline form is not known when considering the development of a form for oral dosage. Cocrystal engineering offers drug molecular understanding and drug solubility improvements. Thus, we attempted cocrystallization of ORV using 10 carboxylic acids as a coformer at a 1:1 M ratio. Each combination was processed with liquid-assisted grinding, solvent evaporation and a slurry method, then characterized by powder X-ray powder diffraction (PXRD), conventional and low-frequency Raman spectroscopy and thermal analysis. The solubility, dissolution and permeation studies across Caco-2 cell monolayers were conducted to evaluate the ORV samples. A screening study revealed that an ORV and citric acid (CTA) cocrystal formed by ethyl acetate-assisted grinding had characteristic PXRD peaks (14.0 and 16.5°) compared to those of ORV dihydrate used as a starting material. Low-frequency Raman measurements, with peaks at 100 cm-1, distinguished potential cocrystals among three processing methods while conventional Raman could not. An endothermic melt (142.2°C) confirmed the formation of the novel crystalline complex. The solubility of the cocrystal in the dissolution media of pH 1.2 and 6.8 was approximately 1000 µg/mL, a 1.3-fold increase compared to ORV alone. In vitro cytotoxicity studies showed that the cocrystal and physical blend were not toxic at concentrations of 25 and 12.5 µM ORV, respectively. The ORV-CTA cocrystal enhanced the cellular transport of ORV across Caco-2 monolayers. Therefore, cocrystallization could be used to improve aqueous solubility and permeability, leading to better oral bioavailability of ORV.

A new phenanthrene dimer from Dendrobium palpebrae.

A new phenanthrene dimer, namely dendropalpebrone (1), was isolated from the whole plant of Dendrobium palpebre, along with nine known compounds (2-10). All of the isolates were evaluated for their hydroxyl radical scavenging effects using a deoxyribose assay. Dendroflorin (10) showed an appreciable activity, and therefore was selected for further studied in RAW264.7 cells. Compound 10 significantly decreased ROS in H2O2-stimulated RAW264.7 cells in a dose-dependent manner, and improved activity of SOD, GPx, and CAT enzymes.

Protective Effects of Curcumin Ester Prodrug, Curcumin Diethyl Disuccinate against H2O2-Induced Oxidative Stress in Human Retinal Pigment Epithelial Cells: Potential Therapeutic Avenues for Age-Related Macular Degeneration.

Oxidative stress-induced damage to the retinal pigmented epithelium (RPE), a specialised post-mitotic monolayer that maintains retinal homeostasis, contributes to the development of age-related macular degeneration (AMD). Curcumin (Cur), a naturally occurring antioxidant, was previously shown to have the ability to protect RPE cells from oxidative stress. However, poor solubility and bioavailability makes Cur a poor therapeutic agent. As prodrug approaches can mitigate these limitations, we compared the protective properties of the Cur prodrug curcumin diethyl disuccinate (CurDD) against Cur in relation to oxidative stress induced in human ARPE-19 cells. Both CurDD and Cur significantly decreased H2O2-induced reactive oxygen species (ROS) production and protected RPE cells from oxidative stress-induced death. Both drugs exerted their protective effects through the modulation of p44/42 (ERK) and the involvement of downstream molecules Bax and Bcl-2. Additionally, the expression of antioxidant enzymes HO-1 and NQO1 was also enhanced in cells treated with CurDD and Cur. In all cases, CurDD was more effective than its parent drug against oxidative stress-induced damage to ARPE-19 cells. These findings highlight CurDD as a more potent drug compared to Cur against oxidative stress and indicate that its protective effects are exerted through modulation of key apoptotic and antioxidant molecular pathways.

Synergistic Effects of Photo-Irradiation and Curcumin-Chitosan/Alginate Nanoparticles on Tumor Necrosis Factor-Alpha-Induced Psoriasis-Like Proliferation of Keratinocytes.

Psoriasis is a chronic inflammatory skin disease characterized by hyperproliferation of the epidermal cells and is clinically presented as thick, bright red to pink plaques with a silvery scale. Photodynamic therapy (PDT) using visible light has become of increasing interest in the treatment of inflammatory skin diseases. In this study, we demonstrate that a combination of curcumin-loaded chitosan/alginate nanoparticles (Cur-CS/Alg NPs) and blue light emitting diodes (LED) light irradiation effectively suppressed the hyperproliferation of tumor necrosis factor-alpha (TNF-α)-induced cultured human kerlatinocyte (HaCaT) cells. The Cur-CS/Alg NPs were fabricated by emulsification of curcumin in aqueous sodium alginate solution and ionotropic gelation with calcium chloride and chitosan using an optimized formulation derived from a Box-Behnken design. The fabricated Cur-CS/Alg NPs were characterized for their particle size, zeta potential, encapsulation efficiency, and loading capacity. The surrogate 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, to measure the relative number of viable cells, showed that the CS/Alg NPs were nontoxic to normal HaCaT cells, while 0.05 µg/mL and 0.1 µg/mL of free curcumin and Cur-CS/Alg NPs inhibited the hyperproliferation of HaCaT cells induced by TNF-α. However, the Cur-CS/Alg NPs demonstrated a stronger effect than the free curcumin, especially when combined with blue light irradiation (10 J/cm²) from an LED-based illumination device. Therefore, the Cur-CS/Alg NPs with blue LED light could be potentially developed into an effective PDT system for the treatment of psoriasis.

A curcumin-diglutaric acid conjugated prodrug with improved water solubility and antinociceptive properties compared to curcumin.

In this work, a curcumin-diglutaric acid (CurDG) prodrug was synthesized by conjugation of curcumin with glutaric acid via an ester linkage. The water solubility, partition coefficient, release characteristics, and antinociceptive activity of CurDG were compared to those of curcumin. The aqueous solubility of CurDG (7.48 µg/mL) is significantly greater than that of curcumin (0.068 µg/mL). A study in human plasma showed that the CurDG completely releases curcumin within 2 h, suggesting the ability of CurDG to serve as a prodrug of curcumin. A hot plate test in mice showed the highest antinociceptive effect dose of curcumin at 200 mg/kg p.o., whereas CurDG showed the same effect at an effective dose of 100 mg/kg p.o., indicating that CurDG significantly enhanced the antinociceptive effect compared to curcumin. The enhanced antinociceptive effect of CurDG may be due to improved water solubility and increased oral bioavailability compared to curcumin.

Stability and biological activity enhancement of fucoxanthin through encapsulation in alginate/chitosan nanoparticles.

A response surface methodology based on the Box-Behnken design was employed to develop fucoxanthin (FX) delivery nanocarrier from alginate (ALG) and chitosan (CS). The FX-loaded ALG/CS nanoparticles (FX-ALG/CS-NPs) were fabricated using oil-in-water emulsification and ionic gelation. The optimal formulation consisted of an ALG:CS mass ratio of 0.015:1, 0.71 % w/v Tween™ 80, and 5 mg/mL FX concentrations. The resulting FX-ALG/CS-NPs had a size of 227 ± 23 nm, a zeta potential of 35.3 ± 1.7 mV, and an encapsulation efficiency of 81.2 ± 2.8 %. These nanoparticles exhibited enhanced stability under simulated environmental conditions and controlled FX release in simulated gastrointestinal fluids. Furthermore, FX-ALG/CS-NPs showed increased in vitro oral bioaccessibility, gastrointestinal stability, antioxidant activity, anti-inflammatory effect, and cytotoxicity against various cancer cells. The findings suggest that ALG/CS-NPs are effective nanocarriers for the delivery of FX in nutraceuticals, functional foods, and pharmaceuticals.

Efficacy of a dietary supplement derived from five edible plants on telomere length in Thai adults: A randomized, double-blind, placebo-controlled trial.

Mylife/Mylife100® is a dietary supplement consisting of black sesame seed, guava fruit, mangosteen aril, pennywort leaves, and soy protein. These edible plants contain multiple high-potential bioactive compounds exerting various vital biological functions including antioxidants which contribute to delaying the rate of telomere shortening. Telomere length is associated with cellular aging and age-related diseases. This study aimed to assess the efficacy of Mylife/Mylife100® on telomere length through a randomized, double-blind placebo-controlled trial. The trial assessed the alteration of leukocyte telomere length after 32 adults aged 50-65 years received either Mylife/Mylife100® or placebo (five capsules/day) for 8-week supplementation. The results demonstrated a significant increase in mean telomere length from baseline (6313 bp) to the 8-week supplementation period (6655 bp; p < 0.05) in the group receiving the product, whereas no significant change was observed in the placebo group. Additionally, the product group exhibited a significant improvement in plasma total antioxidant capacity levels compared to the placebo group (mean change, +35 vs -38; p = 0.006). This study also showed a significant correlation between telomere length and % CD4 + T cells (r = +0.325; p = 0.00003), % CD8 + T cells (r = +0.156; p = 0.048), and visceral fat (r = - 0.349; p = 0.000006). The findings suggest that consuming this dietary supplement (Mylife/Mylife100®) for 8 weeks has a positive effect on cellular aging by lengthening telomeres possible through their antioxidant capacities. Oxidative stress and cellular aging are underlying predisease mechanisms that might be alleviated by supplementing with this product.

Cleistocalyx nervosum var. paniala berry extract and cyanidin-3-glucoside inhibit hepatotoxicity and apoptosis.

Excessive oxidative toxicity in liver cells is a significant risk factor that can cause cellular injury, leading to the development of chronic liver disease (CLD). Natural anthocyanins have been shown to prevent the harmful effects of oxidative toxicity in mammalian cells. Ripe Cleistocalyx nervosum var. paniala berry fruits are rich in anthocyanins, which have been reported to possess many health benefits. Therefore, this study examined the protective effect of ethanolic fruit extract of C. nervosum var. paniala (CNPE) against hydrogen peroxide (H2O2)-induced oxidative damage and cell death in human hepatoma HepG2 cells. Results showed that CNPE had strong antioxidant capabilities and high amounts of total phenolics and anthocyanins. HPLC analysis showed that CNPE consists of cyanidin-3-glucoside (C3G). Our investigations found that HepG2 cells pretreated with CNPE or anthocyanin C3G inhibited H2O2-induced cellular damage and apoptosis by increasing the viability of cells, the expression of antiapoptotic Bcl-2 protein, and the activities of cellular antioxidant enzymes, namely SOD, CAT, and GPx. Moreover, both CNPE and C3G significantly suppressed expression of apoptotic proteins (Bax and cytochrome c) and the activities of cleaved caspase-9 and caspase-3 caused by H2O2. Our results indicate that CNPE and C3G can suppress H2O2-induced hepatotoxicity and cell death through stimulation of endogenous antioxidant enzyme activities and inhibition of apoptosis pathway in HepG2 cells. These findings might support development of CNPE as an alternative natural product for preventing CLD.

Potential Health Benefits of Fermented Vegetables with Additions of Lacticaseibacillus rhamnosus GG and Polyphenol Vitexin Based on Their Antioxidant Properties and Prohealth Profiles.

Fermented vegetables are increasingly being recognized as an important dietary component, particularly of plant-based diets, to achieve a sustainable healthy gut because of their microbial diversity and antioxidant properties. However, the functional relevance of fermented vegetables varies based on the raw ingredients used and nutrient supplementation. Therefore, in the present study, we investigated the microbial diversity and antioxidant activity of three formulas of fermented vegetables (standard, supplemented with Lacticaseibacillus rhamnosus GG, and supplemented with polyphenol vitexin) at days 0 and 15. The bacterial community profiles were determined through 16S rRNA sequencing analysis, and antioxidant activity was analyzed using 2,2-diphenyl-1-picrylhydrazyl and by measuring the oxygen radical absorbance capacity, the ferric reducing ability of plasma, and the total phenolic content. The results confirm microbial diversity in the taxonomic composition of the different formulas of fermented vegetables, with different bacteria predominating, particularly lactic acid bacteria including the genera Weissella, Pedicocccus, Leuconostoc, and Lactobacillus. Spearman's correlation analysis showed significant differences in the specific bacteria present in the different formulas of fermented vegetables that conferred antioxidant capacity. Our findings show that supplementation with L. rhamnosus GG and polyphenol vitexin may effectively enhance the functional relevance of foods by promoting cellular protection against oxidative stress.

Untargeted metabolomics reveal pathways associated with neuroprotective effect of oxyresveratrol in SH-SY5Y cells.

Oxyresveratrol has been documented benefits for neurodegenerative disease. However, the specific molecular mechanisms and pathways involved is currently limited. This study aimed to investigate the potential neuroprotective mechanisms of oxyresveratrol using rotenone-induced human neuroblastoma SH-SY5Y cytotoxicity. Cells were divided into the following groups: control, rotenone, and oxyresveratrol pre-treated before being exposed to rotenone. Cellular assays were performed to investigate neuroprotective effects of oxyresveratrol. The results showed that 20 µM oxyresveratrol was effective in preventing rotenone-induced cell death and decreasing ROS levels in the cells. The alteration of metabolites and pathways involved in the neuroprotective activities of oxyresveratrol were further investigated using LC-QTOF-MS/MS untargeted metabolomics approach. We hypothesized that oxyresveratrol's neuroprotective effects would be associated with neurodegenerative pathways. A total of 294 metabolites were identified. 7,8-dihydrobiopterin exhibited the highest VIP scores (VIP > 3.0; p < 0.05), thus considered a biomarker in this study. Our results demonstrated that pretreatment with oxyresveratrol upregulated the level of 7,8-dihydrobiopterin compared to the positive control. Pathway analysis verified that 7,8-dihydrobiopterin was primarily associated with phenylalanine, tyrosine, and tryptophan metabolism (impact = 1, p < 0.001), serving as essential cofactors for enzymatic function in the dopamine biosynthesis pathway. In conclusion, oxyresveratrol may be benefit for the prevention of neurodegenerative diseases by increasing 7,8-dihydrobiopterin concentration.

Potential Oral Anticancer Therapeutic Agents of Hexahydrocurcumin-Encapsulated Chitosan Nanoparticles against MDA-MB-231 Breast Cancer Cells.

Hexahydrocurcumin-encapsulated chitosan nanoparticles (HHC-CS-NPs) were formulated by oil-in-water emulsification and ionotropic gelation and optimized using the Box-Behnken design. The particle size, zeta potential, and encapsulation efficiency of the optimized HHC-CS-NPs were 256 ± 14 nm, 27.3 ± 0.7 mV, and 90.6 ± 1.7%, respectively. The TEM analysis showed a spherical shape and a dense structure with a narrow size distribution. The FT-IR analysis indicated no chemical interaction between the excipients and the drugs in the nanoparticles, but the existence of the drugs was molecularly dispersed in the nanoparticle matrices. The drug release profile showed a preliminary burst release followed by a sustained release under simulated gastrointestinal (GI) and physiological conditions. A stability study suggested that the HHC-CS-NPs were stable under UV light, simulated GI, and body fluids. The in vitro bioaccessibility and bioavailability of the HHC-CS-NPs were 2.2 and 6.1 times higher than those of the HHC solution, respectively. The in vitro evaluation of the antioxidant, anti-inflammatory, and cytotoxic effects of the optimized HHC-CS-NPs demonstrated that the CS-NPs significantly improved the biological activities of HHC in radical scavenging, hemolysis protection activity, anti-protein denaturation, and cytotoxicity against MDA-MB-231 breast cancer cells. Western blot analysis showed that the apoptotic protein expression of Bax, cytochrome C, caspase-3, and caspase-9, were significantly up-regulated, whereas the anti-apoptotic protein Bcl-2 expression was down-regulated in the HHC-CS-NP-treated cells. Our findings suggest that the optimized HHC-CS-NPs can be further developed as an efficient oral treatment for breast cancer.

Neuroprotective Effects of Albizia lebbeck (L.) Benth. Leaf Extract against Glutamate-Induced Endoplasmic Reticulum Stress and Apoptosis in Human Microglial Cells.

Endoplasmic reticulum (ER) stress caused by excessive glutamate in the central nervous system leads to neurodegeneration. Albizia lebbeck (L.) Benth. has been reported to possess neuroprotective properties. We aimed to investigate the effect and mechanism of A. lebbeck leaf extracts on glutamate-induced neurotoxicity and apoptosis linked to ER stress using human microglial HMC3 cells. A. lebbeck leaves were extracted using hexane (AHE), mixed solvents, and ethanol. Each different extract was evaluated for cytotoxic effects on HMC3 cells, and then non-cytotoxic concentrations of the extracts were pretreated with the cells, followed by glutamate. Our results showed that AHE treatment exhibited the highest protective effect and was thus selected for finding the mechanistic approach. AHE inhibited the specific ER stress proteins (calpain1 and caspase-12). AHE also suppressed the apoptotic proteins (Bax, cytochrome c, cleaved caspase-9, and cleaved caspase-3); however, it also increased the antiapoptotic Bcl-2 protein. Remarkably, AHE increased cellular antioxidant activities (SOD, CAT, and GPx). To support the activation of antioxidant defense and inhibition of apoptosis in our HMC3 cell model, the bioactive phytochemicals within AHE were identified by HPLC analysis. We found that AHE had high levels of carotenoids (α-carotene, ß-carotene, and lutein) and flavonoids (quercetin, luteolin, and kaempferol). Our novel findings indicate that AHE can inhibit glutamate-induced neurotoxicity via ER stress and apoptosis signaling pathways by activating cellular antioxidant enzymes in HMC3 cells, suggesting a potential mechanism for neuroprotection. As such, A. lebbeck leaf might potentially represent a promising source and novel alternative approach for preventing neurodegenerative diseases.