Validation of Active Compound of Terminalia catappa L. Extract and Its Anti-Inflammatory and Antioxidant Properties by Regulating Mitochondrial Dysfunction and Cellular Signaling Pathways.

As chronic inflammation and oxidative stress cause various diseases in the human body, this study aimed to develop functional materials to prevent inflammation and oxidative stress. This study investigated the biological function and components of Terminalia catappa L. extract prepared using its leaves and branches (TCE). TCE was determined using ultraperformance liquid chromatography-quadrupole-time-of-flight mass spectrometry. Using RAW 264.7 mouse macrophages, inhibitory effects of the identified compounds on nitric oxide (NO) and reactive oxygen species (ROS) generation were analyzed. Therefore, α-punicalagin was selected as an active compound with the highest content (986.6 ± 68.4 µg/g) and physiological activity. TCE exhibited an inhibitory effect on lipopolysaccharide (LPS)-induced inflammatory markers, including NO, inducible nitric oxide synthase, and inflammatory cytokines without exerting cytotoxicity. Moreover, TCE prevented excessive ROS production mediated by LPS and upregulated hemeoxygenase-1 expression via the nuclear translocation of nuclear factor erythroid 2-related factor 2. Interestingly, TCE prevented LPS-induced mitochondrial membrane potential loss, mitochondrial ROS production, and dynamin-related protein 1 phosphorylation (serine 616), a marker of abnormal mitochondrial fission. Furthermore, TCE considerably repressed the activation of LPS-induced mitogen-activated protein kinase pathway. Thus, TCE is a promising anti-inflammatory and antioxidant pharmaceutical or nutraceutical, as demonstrated via mitochondrial dysfunction and cellular signaling pathway regulation.

In Vitro and In Vivo Models for the Development of Hair Growth Materials By Regulating the ß-Catenin Signaling Pathways.

Although hair loss contributes to various social and economic, research methods for material development are currently limited. In this study, we established a research model for developing materials for hair growth through the regulation of ß-catenin. We confirmed that 100 nM tegatrabetan (TG), a ß-catenin inhibitor, decreased the proliferation of human hair follicle dermal papilla cells (HFDPCs) at 72 h. In addition, TG-induced apoptosis suppressed the phosphorylation of GSK-3ß and Akt, translocation of ß-catenin from the cytosol to the nucleus, and the expression of cyclin D1. Interestingly, TG significantly increased the G2/M arrest in HFDPCs. Subcutaneous injection of TG suppressed hair growth and the number of hair follicles in C57BL/6 mice. Moreover, TG inhibited the expression of cyclin D1, ß-catenin, keratin 14, and Ki67. These results suggest that TG-induced inhibition of hair growth can be a promising model for developing new materials for enhancing ß-catenin-mediated hair growth.

Recovery Effects of Nephelium lappaceum var. pallens (Hiern) Leenh. Extract on Testosterone-Induced Inhibition of Hair Growth in C57BL/6 Mice and Human Follicular Dermal Papilla Cells.

Although various hair health medicines have been developed and are used today, additional safe and effective natural hair growth therapies still need to be developed. Nephelium lappaceum var. pallens (Hiern) Leenh. extract (NLE) reportedly exhibits anticancer, antidiabetic, and antioxidant effects, which could be linked to androgenic processes; however, there are no reports of its effects on testosterone (TS)-inhibited hair growth. The present study investigated the effects of NLE on TS-induced inhibition of hair growth in C57BL/6 mice and human follicular dermal papilla cells. Oral administration of NLE restored hair growth that was suppressed following subcutaneous injection of TS more effectively than finasteride, a drug used for treating hair loss. Histological analysis demonstrated that oral NLE administration increased the number and diameter of hair follicles in the dorsal skin of C57BL/6 mice. In addition, western blot and immunofluorescence assays showed that the oral NLE administration restored TS-induced suppression of cyclin D1, proliferating cell nuclear antigen, and loricrin expression in the skin cells of the mice. Finally, TS suppression of cell proliferation in human follicular dermal papilla cells was significantly reversed by NLE pretreatment. The results suggest that NLE is a promising nutraceutical for hair growth because it promotes hair growth in androgenetic alopecia-like models.

Innate Immune-Enhancing Effect of Pinus densiflora Pollen Extract via NF-κB Pathway Activation.

Considering the emergence of various infectious diseases, including the coronavirus disease 2019 (COVID-19), people's attention has shifted towards immune health. Consequently, immune-enhancing functional foods have been increasingly consumed. Hence, developing new immune-enhancing functional food products is needed. Pinus densiflora pollen can be collected from the male red pine tree, which is commonly found in Korea. P. densiflora pollen extract (PDE), obtained by water extraction, contained polyphenols (216.29 ± 0.22 mg GAE/100 g) and flavonoids (35.14 ± 0.04 mg CE/100 g). PDE significantly increased the production of nitric oxide (NO) and reactive oxygen species (ROS) but, did not exhibit cytotoxicity in RAW 264.7 cells. Western blot results indicated that PDE induced the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2. PDE also significantly increased the mRNA and protein levels of cytokines and the phosphorylation of IKKα/ß and p65, as well as the activation and degradation of IκBα. Additionally, western blot analysis of cytosolic and nuclear fractions and immunofluorescence assay confirmed that the translocation of p65 to the nucleus after PDE treatment. These results confirmed that PDE increases the production of cytokines, NO, and ROS by activating NF-κB. Therefore, PDE is a promising nutraceutical candidate for immune-enhancing functional foods.

Sinapic acid alleviates inflammatory bowel disease (IBD) through localization of tight junction proteins by direct binding to TAK1 and improves intestinal microbiota.

Introduction: Although sinapic acid is found in various edible plants and has been shown to have anti-inflammatory properties including colitis, its underlying mechanism and effects on the composition of the gut microbiota are largely unknown. We aimed to identify an early response kinase that regulates the localization of tight junction proteins, act at the onset of the inflammatory response, and is regulated by sinapic acid. Additionally, we analyzed the effects of sinapic acid on the homeostasis of the intestinal microbiome. Methods: We examined the aberrant alterations of early response genes such as nuclear factor-kappa B (NF-κB) and activating transcription factor (ATF)-2 within 2 h of sinapic acid treatment in fully differentiated Caco-2 cells with or without lipopolysaccharide and tumor necrosis factor (TNF)-α stimulation. To confirm the effect of sinapic acid on stimulus-induced delocalization of tight junction proteins, including zonula occludens (ZO)-1, occludin, and claudin-2, all tight junction proteins were investigated by analyzing a fraction of membrane and cytosol proteins extracted from Caco-2 cells and mice intestines. Colitis was induced in C57BL/6 mice using 2% dextran sulfate sodium and sinapic acid (2 or 10 mg/kg/day) was administrated for 15 days. Furthermore, the nutraceutical and pharmaceutical activities of sinapic acid for treating inflammatory bowel disease (IBD) evaluated. Results: We confirmed that sinapic acid significantly suppressed the stimulus-induced delocalization of tight junction proteins from the intestinal cell membrane and abnormal intestinal permeability as well as the expression of inflammatory cytokines such as interleukin (IL)-1ß and TNF-α in vitro and in vivo. Sinapic acid was found to bind directly to transforming growth factor beta-activated kinase 1 (TAK1) and inhibit the stimulus-induced activation of NF-κB as well as MAPK/ATF-2 pathways, which in turn regulated the expression of mitogen-activated protein kinase (MLCK). Dietary sinapic acid also alleviated the imbalanced of gut microbiota and symptoms of IBD, evidenced by improvements in the length and morphology of the intestine in mice with colitis. Discussion: These findings indicate that sinapic acid may be an effective nutraceutical and pharmaceutical agent for IBD treatment as it targets TAK1 and inhibits subsequent NF-κB and ATF-2 signaling.

Dietary protocatechuic acid redistributes tight junction proteins by targeting Rho-associated protein kinase to improve intestinal barrier function.

Inflammatory bowel disease (IBD) is continuously increasing globally and caused by intestinal barrier dysfunction. Although protocatechuic acid (PCA) has a protective effect on colitis, the molecular mechanisms underlying its contribution to intestinal barrier function remain unknown. Transepithelial electrical resistance (TEER) and FITC-dextran permeability measurements reveled that PCA suppresses lipopolysaccharide (LPS) and tumor necrosis factor (TNF)-α-induced increase in intestinal permeability; zonula occludens (ZO)-1 and claudin-2 redistribution was also suppressed in the epithelial cell membranes of differentiated Caco-2 cells. PCA was found to directly bind Rho-associated coiled-coil containing protein kinase (ROCK), subsequently suppressing myosin light chain (MLC) phosphorylation. Notably, PCA binds ROCK to a similar degree as Y27632, a selective ROCK inhibitor. Orally administering PCA (5 or 25 mg per kg per day) to C57BL/6 mice alleviated the 3% dextran sulfate sodium (DSS)-induced colitis symptoms including reduced colon length, disrupted intestinal barrier structure, and increased proinflammatory cytokines expressions, such as interleukin (IL)-1ß, TNF-α, and IL-6. Furthermore, orally administering PCA suppressed DSS-induced ZO-1 and claudin-2/4 redistribution in mice colon membrane fractions. Therefore, PCA may serve as a promising nutraceutical to improve gut health and alleviate IBD by maintaining intestinal barrier function in vitro and in vivo.

Preventive Effect of Pharmaceutical Phytochemicals Targeting the Src Family of Protein Tyrosine Kinases and Aryl Hydrocarbon Receptor on Environmental Stress-Induced Skin Disease.

The skin protects our body; however, it is directly exposed to the environment and is stimulated by various external factors. Among the various environmental factors that can threaten skin health, the effects of ultraviolet (UV) and particulate matter (PM) are considered the most notable. Repetitive exposure to ultraviolet and particulate matter can cause chronic skin diseases such as skin inflammation, photoaging, and skin cancer. The abnormal activation of the Src family of protein tyrosine kinases (SFKs) and the aryl hydrocarbon receptor (AhR) in response to UV and/or PM exposure are involved in the development and aggravation of skin diseases. Phytochemicals, chemical compounds of natural plants, exert preventive effects on skin diseases through the regulation of various signaling pathways. Therefore, this review aims to highlight the efficacy of phytochemicals as potential nutraceuticals and pharmaceutical materials for the treatment of skin diseases, primarily by targeting SFK and AhR, and to explore the underlying mechanisms of action. Future studies are essential to validate the clinical potential for the prevention and treatment of skin diseases.

Effect of Methyl Gallate on 1-Nitropyrene-Induced Keratinocyte Toxicity in a Human and Canine Skin Model.

The skin, which is the largest organ of the human body, is in direct contact with pollutants in the surrounding atmosphere. Meanwhile, 1-nitropyrene (1-NP), the most abundant nitro-polycyclic aromatic hydrocarbon found in particulate matter, is known to have carcinogenic effects; however, studies on its toxicity in human and canine skin are still needed. In this study, we investigated 1-NP-induced apoptosis and inflammatory pathways in HaCaT cells. In addition, we also measured the cytoprotective effect of methyl gallate (MG), which is widely distributed in medicinal and edible plants and is well known for its anti-inflammatory and antioxidant properties. MG inhibited 1-NP-induced cell death and apoptosis pathways, including the cleavage of PARP and activation of caspase-3, -7, and -9. MG also suppressed 1-NP-induced COX-2 expression and phosphorylation of mitogen-activated protein kinases (MAPKs) and MAPK kinases (MAPKKs). Our findings suggest that 1-NP induces skin toxicity in human and canine through apoptosis and inflammatory responses, and moreover, that this can be prevented by treatment with MG.

4-phenylpyridine suppresses UVB-induced skin inflammation by targeting c-Src in vitro and in vivo.

Acute or repetitive exposure to ultraviolet (UV) cause disruptions to the skin barrier and subsequent inflammatory skin disease. 4-phenylpyridine (4-PP) is a constituent of Brassica campestris L. ssp. Pekinensis and its effect on skin inflammation and molecular target remain unclear. The purpose of this study is to confirm the anti-inflammatory efficacy of 4-PP on UVB-induced skin inflammation in human keratinocytes HaCaT and mouse skin and validation of its molecular target. 4-PP also attenuated UVB-induced phosphorylation of p38/mitogen-activated protein kinase kinase (MKK) 3/6, c-Jun N-terminal kinase 1/2, MKK 4/7, extracellular-signal-regulated kinase 1/2, mitogen-activated protein kinase 1/2. Additionally, 4-PP inhibited UVB-induced phosphorylation of epidermal growth factor receptor (EGFR) Y1068, Y1045 and 854 residues but not the proto-oncogene tyrosine-protein kinase c-Src. Drug affinity responsive target stability assay revealed that 4-PP directly binds to c-Src and inhibits pronase c-proteolysis. Knockdown of c-Src inhibited UVB-induced COX-2 expression and phosphorylation of MAPKs and EGFR in HaCaT cells. Dorsal treatment of 4-PP prevented UVB (0.5 J/cm2 )-induced skin thickness, phosphorylation of EGFR and COX-2 expression in mouse skin. Our findings suggest that 4-PP can be used as anti-inflammatory agent with an effect of skin inflammation by inhibiting the COX-2 expression via suppressing the c-Src/EGFR/MAPKs signalling pathway.

NADPH Oxidase and Epidermal Growth Factor Receptor Are Promising Targets of Phytochemicals for Ultraviolet-Induced Skin Carcinogenesis.

The skin acts as the primary defense organ that protects the body from the external environment. Skin cancer is one of the most common cancers in the world. Skin carcinogenesis is usually caused by cell degeneration due to exposure to ultraviolet (UV) radiation, which causes changes in various signaling networks, disrupting the homeostasis of single skin cells. In this review, we summarize the roles of nicotinamide adenine dinucleotide phosphate oxidase (NOX) and epidermal growth factor receptor (EGFR) in UV-induced skin carcinogenesis. Furthermore, we describe the crosstalk that exists between NOX, EGFR, and protein tyrosine phosphatase κ and its oncogenic downstream signaling pathways. Chemoprevention is the use of chemical compounds to recover the healthy status of the skin or delay cancer development. Current evidence from in vitro and in vivo studies on chemopreventive phytochemicals that target NOX, EGFR, or both, as major regulators of skin carcinogenesis will also be discussed.

Paeonia lactiflora Root Extract and Its Components Reduce Biomarkers of Early Atherosclerosis via Anti-Inflammatory and Antioxidant Effects In Vitro and In Vivo.

Although various physiological activities of compounds obtained from Paeonia lactiflora have been reported, the effects of P. lactiflora extract (PLE) on early atherosclerosis remain unclear. Therefore, in this study, we investigated the in vitro and in vivo antiatherosclerosis and in vitro antioxidant effects of PLE and its compounds. PLE suppresses the tumor necrosis factor (TNF)-α-induced capacity of THP-1 cells to adhere to human umbilical vein endothelial cells (HUVECs), vascular cell adhesion molecule (VCAM)-1 expression, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling in HUVECs. PLE also suppresses TNF-α-induced nuclear translocation of NF-κB p65 from cytosol as well as the enhanced TNFA and C-C motif chemokine ligand 2 (CCL2) mRNA expression in HUVECs. We identified and quantified the following PLE compounds using high-performance liquid chromatography with diode array detection: methyl gallate, oxypaeoniflorin, catechin, albiflorin, paeoniflorin, benzoic acid, benzoylpaeoniflorin, and paeonol. Among these, methyl gallate had the strongest inhibitory effect on monocyte adherence to TNF-α-induced HUVECs and the VCAM-1 expression. Reverse transcriptase real-time quantitative polymerase chain reaction showed that PLE compounds had a dissimilar inhibition effect on TNF-α-induced mRNA expression levels of CCL2, TNFA, and IL6 in HUVECs. Except for paeonol, the compounds inhibited lipopolysaccharide (LPS)-induced reactive oxygen species production in RAW264.7 cells. In vivo, oral administration of PLE improved TNF-α-induced macrophage infiltration to the vascular endothelium and expression of VCAM-1, as well as IL6 and TNFA gene expression in the main artery of mice. PLE could be useful as a nutraceutical material against early atherosclerosis via the combined effects of its components.

Kmeria duperreana (Pierre) Dandy Extract Suppresses LPS-Induced iNOS and NO via Regulation of NF-κB Pathways and p38 in Murin Macrophage RAW 264.7 Cells.

Development of anti-inflammatory products remains in high demand due to the incidence of inflammatory diseases, including diabetes, cardiovascular disease, and neurodegenerative diseases. In this study, we examined the potential anti-inflammatory activity of the nutraceutical, Kmeria duperreana (Pierre) Dandy extract (KDE). We evaluated the ability of KDE to inhibit lipopolysaccharide (LPS)-induced inflammatory markers, including nitric oxide (NO), nuclear factor kappa-B, and mitogen-activated protein kinases, in RAW 264.7 cells. KDE suppressed LPS-induced nitrite production and inducible NO synthase (iNOS) expression in RAW 264.7 cells, but has no effect on cyclooxygenase-2 expression. KDE also suppressed LPS-induced phosphorylation of p65, IκB kinase, and p38 in RAW 264.7 cells. Through Western blot assays and immunofluorescence results, we showed that KDE suppresses LPS-induced p65 translocation from cytosol to the nucleus in RAW 264.7 cells. Moreover, KDE suppressed mRNA expression of LPS-induced interleukin (IL)-1ß in RAW 264.7 cells, but had no effect on mRNA expression of IL-6 or tumor necrosis factor-a. These results demonstrate that KDE may be a promising anti-inflammatory nutraceutical. KDE may act by suppressing iNOS expression and subsequent NO production by inhibiting phosphorylation of p65 and p38 and suppressing translocation of p65 from the cytosol to the nucleus.

Smilax guianensis Vitman Extract Prevents LPS-Induced Inflammation by Inhibiting the NF-κB Pathway in RAW 264.7 Cells.

Nutraceutical treatments can reduce inflammation and prevent the development of inflammatory diseases. In this study, the anti-inflammatory effects of Smilax guianensis Vitman extract (SGE) were examined. SGE suppressed lipopolysaccharide (LPS)-mediated nitrite production in RAW 264.7 cells. SGE also prevented the LPS-induced expression of inducible nitric oxide synthase (iNOS) but not cyclooxygenase (COX)-2. Western blot analysis showed that SGE attenuated LPS-induced phosphorylation of IκB kinase (IKK), inhibitor of kappa B (IκB), and p65. Additionally, SGE inhibited LPS-induced IκB degradation in RAW 264.7 cells. Western blot analysis of the cytosolic and nuclear fractions, as well as immunofluorescence assay results, revealed that SGE suppressed LPS-induced p65 nuclear translocation in RAW 264.7 cells. Moreover, SGE reduced LPS-induced interleukin (IL)- 1ß, IL-6, and tumor necrosis factor-α (TNF-α) mRNA expression and IL-1ß and IL-6 protein expression in RAW 264.7 cells. Collectively, these results indicate that SGE suppresses the NF-κB signaling pathway and thereby inhibits the production of NO, IL-1ß, and IL-6.

Nutraceuticals for prevention of atherosclerosis: Targeting monocyte infiltration to the vascular endothelium.

Cardiovascular disease (CVD) is the leading cause of death, globally, and is a serious problem in developing countries. Preventing atherosclerosis is key to reducing the risk of developing CVD. Similar to carcinogenesis, atherogenesis can be divided into four stages: initiation, promotion, progression, and acute events. The current study focuses on the promotion stage, which is characterized by circular monocyte penetration into vascular endothelial cells, monocyte differentiation into macrophages, and the formation of foam cells. This early stage of atherogenesis is a major target for nutraceuticals. We discuss nutraceuticals that can potentially inhibit monocyte adhesion to the vascular endothelium, thereby preventing the promotional stage of atherosclerosis. The mechanisms through which these nutraceuticals prevent monocyte adhesion are classified according to the following targets: NF-κB, ROS, MAPKs, and AP-1. Additionally, we discuss promising targets for nutraceuticals that can regulate monocyte adhesion to the endothelium. PRACTICAL APPLICATIONS: Introduction of atherogenesis with initiation, promotion, progression, and acute events provide specific information and factors for each step in the development of atherosclerosis. Functional food or pharmaceutical researchers can set target stages and use them to develop materials that control atherosclerosis. In particular, because it focuses on vascular inflammation via interaction between monocytes and vascular endothelial cells, it provides specific information to researchers developing functional foods that regulate this process. Therefore, this manuscript, unlike previous papers, will provide material information and potential mechanisms of action to researchers who want to develop functional foods that control vascular inflammation rather than vascular lipids.

Croton hirtus L'Hér Extract Prevents Inflammation in RAW264.7 Macrophages Via Inhibition of NF-κB Signaling Pathway.

Consumption of anti-inflammatory nutraceuticals may help treat or prevent inflammation-related illnesses such as diabetes, cardiovascular disease, and cancer. This study evaluated the effect of Croton hirtus L'Hér extract (CHE) on lipopolysaccharide (LPS)-induced nitric oxide (NO) production and nuclear factor kappa-B (NF-κB) signaling cascades. CHE significantly suppressed LPS-induced NO production and inducible nitric oxide synthase (iNOS) expression in RAW264.7 macrophages, although cyclooxygenase (COX)-2 expression was not affected. CHE also suppressed LPS-induced IκB kinase (IKK), IκB, and p65 phosphorylation in RAW264.7 cells. Western blot and immunofluorescence assays of cytosol and nuclear p65 and the catalytic subunit of NF-κB showed that CHE suppressed LPS-induced p65 translocation from the cytosol to the nucleus. CHE also suppressed LPS-induced Interleukin (IL)-6 and tumor necrosis factor (TNF)-α production in RAW264.7 cells. These results suggest that CHE prevents NO-mediated inflammation by suppressing NF-κB and inflammatory cytokines.

Anticancer activity of paroxetine in human colon cancer cells: Involvement of MET and ERBB3.

The concept of drug repositioning has recently received considerable attention in the field of oncology. In the present study, we propose that paroxetine can be used as a potent anticancer drug. Paroxetine, one of the selective serotonin reuptake inhibitors (SSRIs), has been widely prescribed for the treatment of depression and anxiety disorders. Recently, SSRIs have been reported to have anticancer activity in various types of cancer cells; however, the underlying mechanisms of their action are not yet known. In this study, we investigated the potential anticancer effect of paroxetine in human colorectal cancer cells, HCT116 and HT-29. Treatment with paroxetine reduced cell viability, which was associated with marked increase in apoptosis, in both the cell lines. Also, paroxetine effectively inhibited colony formation and 3D spheroid formation. We speculated that the mode of action of paroxetine might be through the inhibition of two major receptor tyrosine kinases - MET and ERBB3 - leading to the suppression of AKT, ERK and p38 activation and induction of JNK and caspase-3 pathways. Moreover, in vivo experiments revealed that treatment of athymic nude mice bearing HT-29 cells with paroxetine remarkably suppressed tumour growth. In conclusion, paroxetine is a potential therapeutic option for patients with colorectal cancer.

Syringic acid prevents skin carcinogenesis via regulation of NoX and EGFR signaling.

Validation of nutraceutical and pharmaceutical targets is essential for the prediction of physiological and side effects. Epidemiologic evidence and molecular studies suggest that non-melanoma skin cancer is directly associated with excessive exposure to ultraviolet (UV) radiation. The aim of the present study was to evaluate the inhibitory effects of syringic acid on UVB-induced signaling and skin carcinogenesis, and determine the molecular targets. Treatment of human epidermal keratinocytes (HaCaT) cells with syringic acid resulted in the suppression of UVB-induced cyclooxygenase-2, matrix metalloproteinase-1, and prostaglandin E2 expression as well as activator protein-1 activity. Moreover, syringic acid inhibited the UVB-induced phosphorylation of mitogen-activated protein kinases and Akt signaling pathways as well as epidermal growth factor receptor (EGFR). Syringic acid treatment further inhibited intracellular reactive oxygen species and protein-tyrosine phosphatase-κ activity, a regulator of EGFR activation. Syringic acid and the antioxidant N-acetyl-l-cysteine inhibited UVB-induced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. In vivo, pretreatment of mouse skin with syringic acid significantly suppressed UVB-induced skin tumor incidence in a dose-dependent manner. Overall, these results indicate that syringic acid exerts potent chemopreventive activity in skin carcinogenesis mainly by inhibition of the Nox/PTP-κ/EGFR axis. Syringic acid might serve as an effective chemopreventive and therapeutic agent against UVB-mediated skin cancer.

Silkworm dropping extract ameliorate trimellitic anhydride-induced allergic contact dermatitis by regulating Th1/Th2 immune response.

Allergic contact dermatitis (ACD) is an inflammatory skin disease caused by hapten-specific immune response. Silkworm droppings are known to exert beneficial effects during the treatment of inflammatory diseases. Here, we studied whether topical treatment and oral administration of silkworm dropping extract (SDE) ameliorate trimellitic anhydride (TMA)-induced ACD. In ACD mice model, SDE treatment significantly suppressed the increase in both ear thickness and serum IgE levels. Furthermore, IL-1ß and TNF-α levels were reduced by SDE. In allergic responses, SDE treatment significantly attenuated the production of the Th2-associated cytokine IL-4 in both ear tissue and draining lymph nodes. However, it increased the production of the Th1-mediated cytokine IL-12. Thus, these results showed that SDE attenuated TMA-induced ACD symptoms through regulation of Th1/Th2 immune response. Taken together, we suggest that SDE treatment might be a potential agent in the prevention or therapy of Th2-mediated inflammatory skin diseases such as ACD and atopic dermatitis. ABBREVIATIONS: ACD: allergic contact dermatitis; AD: atopic dermatitis; APC: antigen presenting cells; CCL: chemokine (C-C motif) ligand; CCR: C-C chemokine receptor; Dex: dexamethasone; ELISA: enzyme-linked immunosorbent assay; IFN: interferon; Ig: immunoglobulin; IL: interleukin; OVA: ovalbumin; PS: prednisolone; SDE: silkworm dropping extract; Th: T helper; TMA: trimellitic anhydride; TNF: tumor necrosis factor.

Ultrasonicated Lespedeza cuneata extract prevents TNF-α-induced early atherosclerosis in vitro and in vivo.

This study evaluated the use of ultrasonication to extract Lespedeza cuneata as a potential nutraceutical for preventing vascular inflammation. Ultrasonicated L. cuneata extract (ULCE) was prepared using 20% ethanol and 2 h of ultrasonication at room temperature, and its effects were investigated using relevant in vitro and in vivo models. ULCE suppressed tumor necrosis factor-alpha (TNF-α)-induced adhesion capacity, vascular cell adhesion protein 1 (VCAM-1) expression, and nuclear factor kappa-B (NF-κB) activity in human umbilical vein endothelial cells (HUVECs). ULCE also suppressed TNF-α-induced NF-κB signaling pathways and p65 translocation from the cytosol to the nucleus, as well as the mRNA expression of IL-1ß, IL-6, and TNF-α in HUVECs. Oral administration of ULCE suppressed TNF-α-induced monocyte infiltration into the intima and VCAM-1 expression, as well as the IL-1ß, IL-6, TNF-α, and monocyte chemoattractant protein-1 (MCP-1) mRNA expression in the main artery in mice. Among the compounds identified in the hydrolyzed ULCE, quercetin exhibited the strongest inhibitory effect against TNF-α-induced cell adhesion capacity. These results demonstrate that ULCE contains potent preventive factors against early atherosclerosis, which act by suppressing the NF-κB and VCAM-1 signaling axis.

Synthesis, characterization, and functional properties of chlorophylls, pheophytins, and Zn-pheophytins.

The aims of this study were to synthesize chlorophyll derivatives, pheophytins and Zn-pheophytins, from chlorophylls extracted from spinach, characterize them, and evaluate their antioxidant and anti-inflammatory activities. The chlorophylls isolated from spinach were identified by means of FT-IR and NMR spectroscopies. The synthesis of pheophytins and Zn-pheophytins was confirmed by UV-Vis spectral analyses. The antioxidant activity of chlorophylls, pheophytins, and Zn-pheophytins was studied. The results revealed that the Zn-pheophytins showed the highest 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and ß-carotene bleaching activities, followed by chlorophylls and pheophytins. Additionally, Zn-pheophytins showed substantial inhibitory activity against lipopolysaccharide (LPS)-induced NO production in RAW 264.7 cells. Furthermore, Zn-pheophytins remarkably suppressed LPS-induced expression of inducible nitric oxide synthase (iNOS) in RAW 264.7 cells and showed no cytotoxicity. Our findings indicated that Zn-pheophytins have strong antioxidant and anti-inflammatory properties and can therefore be a potential source of bioactive compounds for nutraceutical, cosmetic, and pharmaceutical applications.