Inhibition of SARS-CoV-2-Induced NLRP3 Inflammasome-Mediated Lung Cell Inflammation by Triphala-Loaded Nanoparticle Targeting Spike Glycoprotein S1.

The COVID-19 pandemic, caused by SARS-CoV-2, poses a significant global health threat. The spike glycoprotein S1 of the SARS-CoV-2 virus is known to induce the production of pro-inflammatory mediators, contributing to hyperinflammation in COVID-19 patients. Triphala, an ancient Ayurvedic remedy composed of dried fruits from three plant species-Emblica officinalis (Family Euphorbiaceae), Terminalia bellerica (Family Combretaceae), and Terminalia chebula (Family Combretaceae)-shows promise in addressing inflammation. However, the limited water solubility of its ethanolic extract impedes its bioavailability. In this study, we aimed to develop nanoparticles loaded with Triphala extract, termed "nanotriphala", as a drug delivery system. Additionally, we investigated the in vitro anti-inflammatory properties of nanotriphala and its major compounds, namely gallic acid, chebulagic acid, and chebulinic acid, in lung epithelial cells (A549) induced by CoV2-SP. The nanotriphala formulation was prepared using the solvent displacement method. The encapsulation efficiency of Triphala in nanotriphala was determined to be 87.96 ± 2.60% based on total phenolic content. In terms of in vitro release, nanotriphala exhibited a biphasic release profile with zero-order kinetics over 0-8 h. A549 cells were treated with nanotriphala or its active compounds and then induced with 100 ng/mL of spike S1 subunit (CoV2-SP). The results demonstrate that chebulagic acid and chebulinic acid are the active compounds in nanotriphala, which significantly reduced cytokine release (IL-6, IL-1ß, and IL-18) and suppressed the expression of inflammatory genes (IL-6, IL-1ß, IL-18, and NLRP3) (p < 0.05). Mechanistically, nanotriphala and its active compounds notably attenuated the expression of inflammasome machinery proteins (NLRP3, ASC, and Caspase-1) (p < 0.05). In conclusion, the nanoparticle formulation of Triphala enhances its stability and exhibits anti-inflammatory properties against CoV2-SP-induction. This was achieved by suppressing inflammatory mediators and the NLRP3 inflammasome machinery. Thus, nanotriphala holds promise as a supportive preventive anti-inflammatory therapy for COVID-19-related chronic inflammation.

Modification of Polyethylene Glycol-Hydroxypropyl Methacrylate Polymeric Micelles Loaded with Curcumin for Cellular Internalization and Cytotoxicity to Wilms Tumor 1-Expressing Myeloblastic Leukemia K562 Cells.

Curcumin loaded in micelles of block copolymers of ω-methoxypoly(ethylene glycol) and N-(2-hydroxypropyl) methacrylamide modified with aliphatic dilactate (CD) or aromatic benzoyl group (CN) were previously reported to inhibit human ovarian carcinoma (OVCAR-3), human colorectal adenocarcinoma (Caco-2), and human lymphoblastic leukemia (Molt-4) cells. Myeloblastic leukemia cells (K562) are prone to drug resistance and differ in both cancer genotype and phenotype from the three mentioned cancer cells. In the present study, CD and CN micelles were prepared and their effects on K562 and normal cells were explored. The obtained CD and CN showed a narrow size distribution with diameters of 63 ± 3 and 50 ± 1 nm, respectively. The curcumin entrapment efficiency of CD and CN was similarly high, above 80% (84 ± 8% and 91 ± 3%). Both CD and CN showed suppression on WT1-expressing K562 and high cell-cycle arrest at the G2/M phase. However, CD showed significantly higher cytotoxicity to K562, with faster cellular uptake and internalization than CN. In addition, CD showed better compatibility with normal red blood cells and peripheral blood mononuclear cells than CN. The promising CD will be further investigated in rodents and possibly in clinical studies for leukemia treatment.

Lipid-Based Nanoparticles in Delivering Bioactive Compounds for Improving Therapeutic Efficacy.

In recent years, due to their distinctive and adaptable therapeutic effects, many natural bioactive compounds have been commonly used to treat diseases. Their limited solubility, low bioavailability, inadequate gastrointestinal tract stability, high metabolic rate, and shorter duration of action limited their pharmaceutical applications. However, those can be improved using nanotechnology to create various drug delivery systems, including lipid-based nanoparticles, to adjust the compounds' physicochemical properties and pharmacokinetic profile. Because of the enormous technical advancements made in the fundamental sciences and the physical and chemical manipulation of individual atoms and molecules, the subject of nanotechnology has experienced revolutionary growth. By fabricating certain functionalized particles, nanotechnology opens an innovative horizon in research and development for overcoming restrictions, including traditional medication administration systems. Nanotechnology-driven bioactive compounds are certain to have a high impact and clinical value for current and future uses. Lipid-based nanotechnologies were shown to deliver a range of naturally occurring bioactive compounds with decent entrapment potential and stability, a successfully controlled release, increased bioavailability, and intriguing therapeutic activity. This review outlines bioactive compounds such as paclitaxel, curcumin, rhodomyrtone, quercetin, kaempferol, resveratrol, epigallocatechin-3-gallate, silymarin, and oridonin, fortified within either a natural or synthetic lipid-based drug delivery system based on nanotechnology and their evaluation and clinical considerations.

Clerodendrum chinense Stem Extract and Nanoparticles: Effects on Proliferation, Colony Formation, Apoptosis Induction, Cell Cycle Arrest, and Mitochondrial Membrane Potential in Human Breast Adenocarcinoma Breast Cancer Cells.

Breast cancer stands out as the most widespread form of cancer globally. In this study, the anticancer activities of Clerodendrum chinense (C. chinense) stem ethanolic extract were investigated. High-performance liquid chromatography (HPLC) analysis identified verbascoside and isoverbascoside as the major bioactive compounds in the C. chinense stem extract. Successfully developed nanoparticles exhibited favorable hydrodynamic diameter, polydispersity index, and surface charge, thus ensuring stability after four months of storage. The total phenolic content and total flavonoid contents in the nanoparticles were reported as 88.62% and 95.26%, respectively. The C. chinense stem extract demonstrated a dose-dependent inhibitory effect on MCF-7, HeLa, A549, and SKOV-3 cancer cell lines, with IC50 values of 109.2, 155.6, 206.9, and 423 µg/mL, respectively. C. chinense extract and NPs exhibited dose-dependent cytotoxicity and the highest selectivity index values against MCF-7 cells. A dose-dependent reduction in the colony formation of MCF-7 cells was observed following treatment with the extract and nanoparticles. The extract induced cytotoxicity in MCF-7 cells through apoptosis and necrosis. C. chinense stem extract and nanoparticles decreased mitochondrial membrane potential (MMP) and induced G0/G1 phase arrest in MCF-7 cells. In conclusion, use of C. chinense stem extract and nanoparticles may serve as a potential therapeutic approach for breast cancer, thus warranting further exploration.

Poly (vinyl alcohol)-gelatin-sericin copolymerized film fortified with vesicle-entrapped demethoxycurcumin/bisdemethoxycurcumin for improved stability, antibacterial, anti-inflammatory, and skin tissue regeneration.

Vesicle delivery carriers, used to stabilize hydrophobic drugs, are characterized by the propensity to aggregate, and fuse, limiting its applications. Fortifying vesicle-entrapped drugs within a biodegradable polymeric film constitutes a promising solution. In this study, biodegradable poly (vinyl alcohol) copolymerized with gelatin-sericin film and integrated alongside vesicle-entrapped demethoxycurcumin (DMC) or bisdemethoxycurcumin (BDMC) was developed, extensively characterized for improve efficacy, and compared. Vesicle-entrapped DMC or BDMC was spherical in shape with no changes in size, zeta-potential, and morphology after storing at 4 °C for 30 days. Antibacterial activity of vesicle-entrapped DMC formulations against Acinetobacter baumannii and Staphylococcus epidermidis was more effective than that of its free form. DMC and BDMC demonstrated dose dependent reduction in lipopolysaccharides (LPS)-induced nitric oxide (NO) levels either in free or in entrapped form. Moreover, vesicle-entrapped DMC/BDMC suppressed NO production at lower concentrations, compared with that of their free form and significantly improved the viability of RAW264.7 and HaCaT cells. Furthermore, functionalized film with vesicle-entrapped DMC/BDMC demonstrated excellent radical scavenging, biocompatibility, and cell migration efficacy. Thus, incorporating vesicle, entrapped DMC/BDMC within biodegradable polymeric film may comprised a promising strategy for improving stability, wound healing, and inflammation attenuation efficacy.

Utilization of the sugar fraction from Arabica coffee pulp as a carbon source for bacteria producing cellulose and cytotoxicity with human keratinocyte.

Coffee pulp (CP), a by-product of coffee production, is an underutilized resource with significant potential value. CP contains monosaccharides that can serve as an ideal carbon source for bacterial cultivation, enabling the production of value-added components such as medical-grade cellulose. Herein, we extracted the sugar fraction from Arabica CP and used it as a supplement in a growing media of a bacteria cellulose (BC), Komagataeibacter nataicola. The BC was then characterized and tested for cytotoxicity. The CP sugar fraction yielded approximately 7% (w/w) and contained glucose at 4.52 mg/g extract and fructose at 7.34 mg/g extract. Supplementing the sugar fraction at different concentrations (0.1, 0.3, 0.5, 0.7, and 1 g/10 mL) in sterilized glucose yeast extract broth, the highest yield of cellulose (0.0020 g) occurred at 0.3 g/10 mL. It possessed similar physicochemical attributes to the BC using glucose, with some notable improvements in fine structure and arrangement of the functional groups. In cytotoxicity assessments on HaCaT keratinocyte cells, bacterial cellulose concentrations of 2-1000 µg/mL exhibited viability of ≥ 80%. However, higher concentrations were toxic. This research innovatively uses coffee pulp for bacterial cellulose, aligning with the principles of a bio-circular economy that focuses on sustainable biomass utilization.

The sugar fraction of Arabica CP (6.64 g/100 g sample) contained glucose and fructose of 4.52 and 7.34 mg/g extract respectively.Different sugar fraction concentrations (0.1, 0.3, 0.5, 0.7, and 1 g/10 mL) were tested in sterilized glucose yeast extract broth. Optimal BC yield (0.0020 g) was achieved at 0.3 g/10 mL.The BC exhibited comparable physicochemical characteristics to cellulose obtained from glucose.The cytotoxicity indicate that HaCaT cells exposed to 2­1000 µg/mL of BC had a percentage cell viability of ≥80%, but it was toxic at higher concentrations.CP represents a cheap and readily-available source for BC production, contributing to the bio-circular economic goal.

KLVFF Conjugated Curcumin Microemulsion-Based Hydrogel for Transnasal Route: Formulation Development, Optimization, Physicochemical Characterization, and Ex Vivo Evaluation.

Curcumin is a potent natural compound used to treat Alzheimer's disease (AD). However, the clinical usefulness of curcumin to treat AD is restricted by its low oral bioavailability and difficulty permeating the blood-brain barrier. To overcome such drawbacks, various alternative strategies have been explored, including the transnasal route. However, rapid mucociliary clearance in the nasal cavity is a major hindrance to drug delivery. Thus, designing a delivery system for curcumin to lengthen the contact period between the drug and nasal mucosa must be employed. This study describes the optimization of KLVFF conjugated curcumin microemulsion-base hydrogel (KCMEG) to formulate a prototype transnasal preparation using the response surface method to improve a mucoadhesive property. A central composite design was employed to optimize and evaluate two influencing factors: the concentration of carbopol 940 and the percentage of KLVFF conjugated curcumin microemulsion (KCME). The physicochemical properties, anti-cholinesterase activity, and anti-aggregation activities of KCME were investigated in this study. The studied factors, in terms of main and interaction effects, significantly (p < 0.05) influenced hardness and adhesiveness. The optimized KCMEG was evaluated for pH, spreadability, and mucoadhesive properties. Ex vivo nasal ciliotoxicity to optimize KCMEG was performed through the porcine nasal mucosa. KCME was transparent, with a mean globule size of 70.8 ± 3.4 nm and a pH of 5.80 ± 0.02. The optimized KCMEG containing 2% carbopol 940 showed higher in vitro mucoadhesive potential (9.67 ± 0.13 min) compared with microemulsion and was also found to be free from nasal ciliotoxicity during histopathologic evaluation of the porcine nasal mucosa. The result revealed that both the concentration of carbopol 940 and the percentage of KCME play a crucial role in mucoadhesive properties. In conclusion, incorporating a mucoadhesive agent in a microemulsion can increase the retention time of the formulation, leading to enhanced brain delivery of the drug. Findings from the investigation revealed that KCMEG has the potential to constitute a promising approach to treating AD via transnasal administration.

Targeting Spike Glycoprotein S1 Mediated by NLRP3 Inflammasome Machinery and the Cytokine Releases in A549 Lung Epithelial Cells by Nanocurcumin.

Chronic inflammation and tissue damage can result from uncontrolled inflammation during SARS-CoV-2 or COVID-19 infections, leading to post-acute COVID conditions or long COVID. Curcumin, found in turmeric, has potent anti-inflammatory properties but limited effectiveness. This study developed nanocurcumin, a curcumin nanoparticle, to enhance its physical and chemical stability and investigate its in vitro anti-inflammatory properties upon CoV2-SP induction in lung epithelial cells. Nanocurcumin was prepared by encapsulating curcumin extract in phospholipids. The particle size, polydispersity index, and zeta potential of nanocurcumin were measured using dynamic light scattering. The encapsulated curcumin content was determined using HPLC analysis. The encapsulation efficiency of curcumin was 90.74 ± 5.35% as determined by HPLC. Regarding the in vitro release of curcumin, nanocurcumin displayed a higher release content than non-nanoparticle curcumin. Nanocurcumin was further investigated for its anti-inflammatory properties using A549 lung epithelial cell line. As determined by ELISA, nanocurcumin showed inhibitory effects on inflammatory cytokine releases in CoV2-SP-stimulated conditions, as evidenced by a significant decrease in IL-6, IL-1ß and IL-18 cytokine secretions compared with the spike-stimulated control group (p < 0.05). Additionally, as determined by RT-PCR, nanocurcumin significantly inhibited the CoV2-SP-stimulated expression of inflammatory genes (IL-6, IL-1ß, IL-18, and NLRP3) compared with the spike-stimulated control group (p < 0.05). Regarding the inhibition of NLRP3 inflammasome machinery proteins by Western blot, nanocurcumin decreased the expressions of inflammasome machinery proteins including NLRP3, ASC, pro-caspase-1, and the active form of caspase-1 in CoV2-SP-stimulated A549 cells compared with the spike-stimulated control group (p < 0.05). Overall, the nanoparticle formulation of curcumin improved its solubility and bioavailability, demonstrating anti-inflammatory effects in a CoV2-SP-induced scenario by inhibiting inflammatory mediators and the NLRP3 inflammasome machinery. Nanocurcumin shows promise as an anti-inflammatory product for preventing COVID-19-related airway inflammation.

Smart Polymeric Nanoparticles in Cancer Immunotherapy.

Cancer develops with unexpected mutations and causes death in many patients. Among the different cancer treatment strategies, immunotherapy is promising with the benefits of high specificity and accuracy, as well as modulating immune responses. Nanomaterials can be used to formulate drug delivery carriers for targeted cancer therapy. Polymeric nanoparticles used in the clinic are biocompatible and have excellent stability. They have the potential to improve therapeutic effects while significantly reducing off-target toxicity. This review classifies smart drug delivery systems based on their components. Synthetic smart polymers used in the pharmaceutical industry, including enzyme-responsive, pH-responsive, and redox-responsive polymers, are discussed. Natural polymers derived from plants, animals, microbes, and marine organisms can also be used to construct stimuli-responsive delivery systems with excellent biocompatibility, low toxicity, and biodegradability. The applications of smart or stimuli-responsive polymers in cancer immunotherapies are discussed in this systemic review. We summarize different delivery strategies and mechanisms that can be used in cancer immunotherapy and give examples of each case.

Phenylethanoid Glycoside-Enriched Extract Prepared from Clerodendrum chinense Leaf Inhibits A549 Lung Cancer Cell Migration and Apoptosis Induction through Enhancing ROS Production.

This study aims to investigate the antioxidant and anti-cancer activities of Clerodendrum chinense leaf ethanolic extract. The phenylethanoid glycoside-enriched extract, namely verbascoside and isoverbascoside, was determined in the ethanolic C. chinense leaf extract using the validated HPLC method. The ethanolic extract showed DPPH and ABTS free radical scavenging activities with the IC50 values of 334.2 ± 45.48 µg/mL and 1012.77 ± 61.86 µg/mL, respectively, and a FRAP value of 88.73 ± 4.59 to 2480.81 ± 0.00 µM. C. chinense leaf extract exhibited anti-proliferative activity against A549 lung cancer cells in a dose- and time-dependent manner, with the IC50 value of 340.63 ± 89.43, 210.60 ± 81.74, and 107.08 ± 28.90 µg/mL after treatment for 24, 48, and 72 h, respectively. The IC50 values of verbascoside, isoverbascoside, and hispidulin were 248.40 ± 15.82, 393.10 ± 15.27, and 3.86 ± 0.87 µg/mL, respectively, indicating that the anti-proliferative effects of the C. chinense leaf extract mainly resulted from hispidulin and verbascoside. The selectivity index (SI) of C. chinense leaf extract against A549 lung cancer cells vs. normal keratinocytes were 2.4 and 2.8 after incubation for 24 and 48 h, respectively, suggesting the cytotoxic selectivity of the extract toward the cancer cell line. Additionally, the C. chinense leaf extract at 250 µg/mL induced late apoptotic cells up to 21.67% with enhancing reactive oxygen species (ROS) induction. Furthermore, the lung cancer cell colony formation was significantly inhibited after being treated with C. chinense leaf extract in a dose-dependent manner. The C. chinense leaf extract at 250 µg/mL has also shown to significantly inhibit cancer cell migration compared with the untreated group. The obtained results provide evidence of the anti-lung cancer potentials of the C. chinense leaf ethanolic extract.

Natural Melanogenesis Inhibitor, Antioxidant, and Collagen Biosynthesis Stimulator of Phytochemicals in Rice Bran and Husk Extracts from Purple Glutinous Rice (Oryza sativa L. cv. Pieisu 1 CMU) for Cosmetic Application.

Oryza sativa L. cv. Pieisu 1 CMU (PES1CMU) has a high anthocyanin content in the colored bran and high phenolic content in the husk. Biologically active compounds in plants are available as dietary supplements and cosmetics. To expand the utilization of natural resources, PES1CMU will be a natural remedy for skin hyperpigmentation and aging. Cell-free tyrosinase inhibition and scavenging assays were used to screen all extracts, including PES1CMU-rice bran oil (RBO), PES1CMU-defatted rice bran (DFRB), and PES1CMU-husk (H). PES1CMU extracts were first examined in IBMX-stimulated B16 cells and H2O2-induced fibroblasts. The results exhibited that PES1CMU-DFRB was the most effective inhibitor of mushroom tyrosinase, intracellular melanin production (fold change of 1.11 ± 0.01), and tyrosinase activity (fold change of 1.22 ± 0.10) in IBMX-stimulated B16 cells. Particularly, PES1CMU-DFRB showed a comparable whitening effect to the standard arbutin with no significant difference (p > 0.05). Moreover, PES1CMU-DFRB and PES1CMU-H demonstrated strong scavenging activities. After accelerated cell aging caused by H2O2 exposure in fibroblasts, the levels of malondialdehyde production in all PES1CMU-treated fibroblasts were comparable with those of standard l-ascorbic acid (p > 0.05). Besides, PES1CMU-DFRB and PES1CMU-H treatment significantly inhibited collagen degradation against MMP-2 compared to l-ascorbic acid-treated cells (p > 0.05). PES1CMU rice-processing wastes (DFRB and H) could become potential natural sources for dermatocosmetic constituents in skin anti-aging and whitening products.

Antioxidant, Anti-Inflammatory and Attenuating Intracellular Reactive Oxygen Species Activities of Nicotiana tabacum var. Virginia Leaf Extract Phytosomes and Shape Memory Gel Formulation.

Oxidative stress is one of the major causes of skin aging. In this study, the shape memory gels containing phytosomes were developed as a delivery system for Nicotiana tabacum var. Virginia fresh (VFL) and dry (VDL) leaf extracts. The extracts were loaded in the phytosomes by a solvent displacement method. The physical and chemical characteristics and stability of phytosomes were evaluated by dynamic light scattering and phytochemistry, respectively. The in vitro antioxidant activity and intracellular reactive oxygen species reduction of phytosomes and/or extracts were investigated by the DPPH and ABTS radical scavenging assays, FRAP assay, and DCFH-DA fluorescent probe. The cytotoxicity and anti-inflammatory activity of VDL and VFL phytosomes were studied by an MTT and a nitric oxide assay, respectively. Here, we first reported the total phenolic content in the dry leaf extract of N. tabacum var. Virginia was significantly greater than that of the fresh leaf extract. The HPLC analysis results revealed that VDL and VFL extracts contained 4.94 ± 0.04 and 3.13 ± 0.01 µg/mL of chlorogenic acid and 0.89 ± 0.00 and 0.24 ± 0.00 µg/mL of rutin, respectively. The phytosomes of the VDL and VFL extracts displayed stable size, polydispersity index, zeta potential values, and good chemical stability. VDL and VDL phytosomes showed higher phenolic and flavonoid contents which showed stronger DPPH and ABTS radical scavenging effects and reduced the intracellular ROS. The results suggested that the phenolic compounds are the main factor in their antioxidant activity. Both VDL and VFL phytosomes inhibited nitric oxide production induced by LPS, suggesting the anti-inflammatory activity of the phytosomes. The shape memory gel containing VDL and VFL phytosomes had good physical stability in terms of pH and viscosity. The VDL and VFL phytosomes dispersed in the shape memory gels can be considered as a promising therapeutic delivery system for protecting the skin from oxidation and reactive oxygen species.

Electron Beam Irradiation Cross-Linked Hydrogel Patches Loaded with Red Onion Peel Extract for Transdermal Drug Delivery: Formulation, Characterization, Cytocompatibility, and Skin Permeation.

The use of bioactive molecules derived from medicinal plants in wound healing has recently attracted considerable attention in both research and public interest. In this work, we demonstrated the first attempt to incorporate the extract from Thai red onion skins in hydrogel patches intended for transdermal delivery. The red onion skin extract (ROSE) was first prepared and evaluated for cytotoxicity by MTT assay with both L929 and human dermal fibroblast cells. Hydrogel patches with porous microstructure and high water content were fabricated from polyvinyl alcohol (PVA) by electron beam irradiation and characterized for their physical, mechanical, morphological, and cytocompatible properties prior to the loading of ROSE. After decontamination by electron beam irradiation, the in vitro release profile exhibited the burst release of extract from ROSE-coated hydrogel patches within 5 h, followed by the sustained release up to 48 h. Finally, evaluation of skin permeation using Franz cell setup with a newborn pig skin model showed that the permeation of ROSE from the hydrogel patch increased with time and reached the maximum of 262 µg/cm2, which was well below the cytotoxicity threshold, at 24 h. These results demonstrated that our ROSE-coated hydrogel patches could potentially be used in transdermal delivery.

The Identification and Cytotoxic Evaluation of Nutmeg (Myristica fragrans Houtt.) and Its Substituents.

The aril and seed of nutmeg, Myristica fragrans Houtt. (Myristicaceae), hold significant value in various industries globally. Our preliminary research found two morphological variations: a globose shape and an oval shape. Due to these different characteristics, the safety of consumers is of primary concern. Thus, authentication and comparative pharmacological and toxicity analyses are necessary. In this study, pharmacognostic and advanced phytochemical analyses, DNA barcoding, cytotoxicity, and the anti-nitric oxide production of commercial Thai nutmeg were examined. Via morphologic examinations and TLC fingerprinting, all the sampled aril and seed were categorized into globose and oval-shaped groups. The results of HPLC, GC-MS, and LC-MS/MS experiments revealed distinct differences between these groups. The DNA barcoding of the trnH-psbA region using the BLAST method and neighbor-joining tree analyses confirmed the globose nutmeg as M. fragrans and the oval-shaped variant as M. argentea. A comparison was then carried out between the potential toxicity and anti-inflammatory capabilities of M. fragrans and M. argentea. Cytotoxicity tests on HaCaT, 3T3-L1, Caco-2, HEK293, and RAW264.7 were performed using both methanolic extracts and volatile oil from the arils and seeds of both species. This study concludes that blending or substituting these two species maintains their therapeutic integrity without posing safety concerns.

Comparison of Biological Activities and Protective Effects on PAH-Induced Oxidative Damage of Different Coffee Cherry Pulp Extracts.

Polycyclic aromatic hydrocarbons (PAHs) are the main toxic components of ambient air particulate matter (PM), causing oxidative damage to the skin and ultimately resulting in skin aging. This study was conducted to determine the anti-oxidant, anti-aging properties and protective effects of the extracts of coffee cherry pulp (Coffea arabica L.), which is a by-product of the coffee industry, against the oxidative damage induced by PAH exposure in human epidermal keratinocytes (HaCaT). Three different techniques were used to extract the coffee cherry pulp: maceration, Soxhlet and ultrasonication to obtain CCM, CCS and CCU extract, respectively, which were then compared to investigate the total phenolic content (TPC) and total flavonoid content (TFC). The chemical compositions were identified and quantified using high-performance liquid chromatography (HPLC). The results demonstrated that Soxhlet could extract the highest content of chlorogenic acid, caffeine and theophylline. CCS showed the significantly highest TPC (324.6 ± 1.2 mg GAE/g extract), TFC (296.8 ± 1.2 mg QE/g extract), anti-radical activity against DPPH free radicals (98.2 ± 0.8 µM Trolox/g extract) and lipid peroxidation inhibition (136.6 ± 6.2 µM Trolox/g extract). CCS also showed the strongest anti-aging effects based on collagenase, elastase, hyaluronidase and tyrosinase inhibitory enzymes. In addition, CCS can protect human keratinocyte cells from PAH toxicity by increasing the cellular anti-oxidant capacity. This study suggests that CCS has the potential to be used as a cosmetic material that helps alleviate skin damage caused by air pollution.

Guava (Psidium guajava L.) Leaf Extract as Bioactive Substances for Anti-Androgen and Antioxidant Activities.

Leaves of guava (Psidium guajava L.) have been used in Thai folk medicine without any supporting evidence as a traditional herbal remedy for hair loss. Androgenetic alopecia (AGA) is chronic hair loss caused by effects of androgens in those with a genetic predisposition, resulting in hair follicle miniaturization. Our objectives were to provide the mechanistic assessment of guava leaf extract on gene expressions related to the androgen pathway in well-known in vitro models, hair follicle dermal papilla cells (HFDPC), and human prostate cancer cells (DU-145), and to determine its bioactive constituents and antioxidant activities. LC-MS analysis demonstrated that the main components of the ethanolic extract of guava leaves are phenolic substances, specifically catechin, gallic acid, and quercetin, which contribute to its scavenging and metal chelating abilities. The guava leaf extract substantially downregulated SRD5A1, SRD5A2, and SRD5A3 genes in the DU-145 model, suggesting that the extract could minimize hair loss by inhibiting the synthesis of a potent androgen (dihydrotestosterone). SRD5A suppression by gallic acid and quercetin was verified. Our study reveals new perspectives on guava leaf extract's anti-androgen properties. This extract could be developed as alternative products or therapeutic adjuvants for the treatment of AGA and other androgen-related disorders.

Fabrication and Evaluation of Water Hyacinth Cellulose-Composited Hydrogel Containing Quercetin for Topical Antibacterial Applications.

Water hyacinth is an aquatic weed species that grows rapidly. In particular, it causes negative impacts on the aquatic environment and ecological system. However, water hyacinth is rich in cellulose, which is a biodegradable material. This study isolated cellulose from the water hyacinth petiole. It was then used to fabricate composite hydrogels made with water hyacinth cellulose (C), alginate (A), and pectin (P) at different mass ratios. The selected water hyacinth cellulose-based hydrogel was incorporated with quercetin, and its properties were evaluated. The FTIR and XRD of extracted water hyacinth cellulose indicated specific characteristics of cellulose. The hydrogel which consisted of the water hyacinth cellulose alginate characterized pectin: pectin had a mass ratio of 2.5:0.5:0.5 (C2.5A0.5P0.5), showed good puncture strength (2.16 ± 0.14 N/mm2), the highest swelling index (173.28 ± 4.94%), and gel content (39.35 ± 0.53%). The FTIR showed an interaction between water hyacinth cellulose and quercetin with hydrogen bonding. The C2.5A0.5P0.5 hydrogel containing quercetin possessed 92.07 ± 5.77% of quercetin-loaded efficiency. It also exhibited good antibacterial activity against S. aureus and P. aeruginosa due to hydrogel properties, and no toxicity to human cells. This study indicated that water hyacinth cellulose-composited hydrogel is suitable for topical antibacterial applications.

Potential of Alpha-Mangostin-Loaded PLGA Nanoparticles for Cholangiocarcinoma Treatment.

Alpha-mangostin (AM), a significant component isolated from the pericarp of mangosteen (Garcinia mangostana L.), has been demonstrated as a potential compound for the treatment of cholangiocarcinoma (CCA). Due to its hydrophobic nature, however, its clinical uses may be limited by its low aqueous solubility, poor stability, and low bioavailability. The present study aimed to formulate and characterize the AM-loaded PLGA nanoparticles (AM-PLGA-NPs) and further evaluate the antiproliferative and proapoptotic activities, including the inhibitory activities on CCA cell (CL-6 and HuCCT-1) invasion and migration. The AM-PLGA-NPs were prepared using PLGA MW 7000-17,000 and 38,000-54,000 by the solvent displacement method. The methods used to evaluate these activities included a MTT assay, flow-cytometry, QCM ECMatrix cell migration, and cell invasion assays, respectively. The optimized AM-PLGA-NPs were characterized for physical (particle size and morphology, polydispersity index, and zeta potential) and pharmaceutical (encapsulation efficiency, loading efficiency, and drug release profile) parameters. AM-PLGA-NPs showed relatively potent and selective antiproliferative and proapoptotic activities in both CCA cell lines in a concentration- and time-dependent manner. The results revealed that the PLGA nanoparticles could be a suitable nanocarrier to encapsulate AM for its delivery to the CCA cells.