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Naturally occurring homoisoflavonoids isolated from some Liliaceae plants have been reported to have diverse biological activities (e.g., antioxidant, anti-inflammatory, and anti-angiogenic effects). The exact mechanism by which homoisoflavonones exert anti-neuroinflammatory effects against activated microglia-induced inflammatory cascades has not been well studied. Here, we aimed to explore the mechanism of homoisoflavonoid SH66 having a potential anti-inflammatory effect in lipopolysaccharide (LPS)-primed BV2 murine microglial cells. Microglia cells were pre-treated with SH66 followed by LPS (100 ng/mL) activation. SH66 treatment attenuated the production of inflammatory mediators, including nitric oxide and proinflammatory cytokines, by down-regulating mitogen-activated protein kinase signaling in LPS-activated microglia. The SH66-mediated inhibition of the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome complex and the respective inflammatory biomarker-like active interleukin (IL)-1ß were noted to be one of the key pathways of the anti-inflammatory effect. In addition, SH66 increased the neurite length in the N2a neuronal cell and the level of nerve growth factor in the C6 astrocyte cell. Our results demonstrated the anti-neuroinflammatory effect of SH66 against LPS-activated microglia-mediated inflammatory events by down-regulating the NLRP3 inflammasome complex, with respect to its neuroprotective effect. SH66 could be an interesting candidate for further research and development regarding prophylactics and therapeutics for inflammation-mediated neurological complications.
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Antiinflamatorios , Lipopolisacáridos , Microglía , Microglía/efectos de los fármacos , Microglía/metabolismo , Lipopolisacáridos/farmacología , Animales , Ratones , Antiinflamatorios/farmacología , Antiinflamatorios/química , Línea Celular , Isoflavonas/farmacología , Isoflavonas/química , Citocinas/metabolismo , Óxido Nítrico/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Inflamasomas/metabolismoRESUMEN
BACKGROUND: It is well known that adequate water intake and moisturizer application improves skin barrier function. OBJECTIVE: This study was conducted to analyze the effects of daily water intake and moisturizer application on skin barrier function and the degree of response to barrier recovery. METHODS: Participants with daily water intake more than 1 L were classified as high daily water intake group (H) and those with less than 1 L as low daily water intake group (L). Each group was subcategorized into four groups according to intervention method: additional water intake (H1, L1), moisturizer (H2, L2), both (H3, L3), and control (H4, L4). Transepidermal water loss (TEWL) and stratum corneum hydration (SCH) were measured at baseline during the 2nd and 4th week. RESULTS: A total of 43 participants completed the study (H: 22, L: 21). At baseline, there was no significant difference in SCH and TEWL in any on the anatomical sites between the high daily water intake and low daily water intake groups. However, SCHs of left forearm (group H2, p=0.004; group H3, p=0.004), left hand dorsum (group H2, p=0.010; group H3, p=0.026), and left shin (group H2, p=0.016; group H3, p=0.001) in group H2 and H3 were significantly increased in the 4th week as compared to the baseline values. CONCLUSION: The results suggest that the degree of water intake may be related to improved skin barrier function. However, application of additional moisturizers had more favorable impact on skin hydration as compared to additional water intake.
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Probiotic fermentation of plant-based materials can lead to the generation of various bioactive substances via bacterial metabolites and the biotransformation of phenolic compounds. We compared the metabolic differences between fermentation by Limosilactobacillus fermentum KCTC15072BP (LFG) and fermentation by Lactiplantibacillus plantarum KGMB00831 (LPG) in guava leaf extract (0%, 0.5%, and 2% (w/v))-supplemented medium via non-targeted metabolite profiling. By performing multivariate statistical analysis and comparing the different guava leaf extract groups, 21 guava-derived and 30 bacterial metabolites were identified. The contents of guava-derived glucogallin, gallic acid, and sugar alcohols were significantly higher in LFG than they were in LPG. Similarly, significantly higher contents of guava-derived pyrogallol, vanillic acid, naringenin, phloretin, and aromatic amino acid catabolites were obtained with LPG than with LFG. LFG led to significantly higher antioxidant activities than LPG, while LPG led to significantly higher antiglycation activity than LFG. Interestingly, the fermentation-induced increase in the guava-leaf-extract-supplemented group was significantly higher than that in the control group. Thus, the increased bioactivity induced by guava fermentation with the Lactobacillaceae strain may be influenced by the synergistic effects between microbial metabolites and plant-derived compounds. Overall, examining the metabolic changes in plant-based food fermentation by differentiating the origin of metabolites provides a better understanding of food fermentation.
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Limosilactobacillus fermentum , Psidium , Antioxidantes/metabolismo , Psidium/química , Fenoles/análisis , Extractos Vegetales/farmacología , Extractos Vegetales/químicaRESUMEN
BACKGROUND: Analysis of hair microscopic morphology is a simple and less invasive method to differentiate alopecia areata (AA) from other alopecic diseases. However, there is limited information on the distribution of the microscopic characteristics. OBJECTIVE: This study evaluated the microscopic morphological characteristics of pulled-out hair and their correlation with disease course in AA. METHODS: Morphological characteristics of pulled-out hair were classified into 5 categories: the presence of typical clubbing, surface undulation, tapering, breakage, and depigmentation in proximal hair shaft. Clinical course of AA was investigated through assessment of Severity of Alopecia Tool (SALT) score (initial score, maximal score and difference of them [ΔSALT]). RESULTS: Among 1,272 pulled-out hairs (n=179) obtained at initial visit, depigmentation (59.5%) was the most common, followed by loss of typical clubbing (57.2%) and surface undulation (55.2%). The percentage of loss of typical clubbing and proximal tapering was significantly higher in severe type of AA, younger age of onset and shorter disease duration. The ratio of typical clubbing (<50% vs. ≥50%) was associated with difference in maximal score and ΔSALT (p<0.05). Strong activity group (pulled-out hair ≥10, n=33) showed difference in clinical course (maximal score, ΔSALT) as well as distribution of microscopic features (loss of typical clubbing) compared with those in non-strong activity group. The ratio of typical clubbing significantly increased at follow-up than initially in strong activity group (p<0.05). CONCLUSION: Microscopic hair morphology, especially loss of typical clubbing and proximal tapering, could be useful tool to predict the course of AA.
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New supplements with preventive effects against skin photodamage are receiving increasing attention. This study evaluated the anti-photoaging effects of salmon nasal cartilage proteoglycan (SPG), acting as a functional material for skin health. We administered SPG to in vitro and in vivo models exposed to ultraviolet B (UVB) radiation and assessed its moisturizing and anti-wrinkle effects on dorsal mouse skin and keratinocytes and dermal fibroblasts cell lines. These results showed that SPG restored the levels of filaggrin, involucrin, and AQP3 in the epidermis of UVB-irradiated dorsal skin and keratinocytes, thereby enhancing the keratinization process and water flow. Additionally, SPG treatment increased the levels of hyaluronan and skin ceramide, the major components of intercellular lipids in the epidermis. Furthermore, SPG treatment significantly increased the levels of collagen and procollagen type 1 by down-regulating matrix metalloproteinase 1, which play a crucial role in skin fibroblasts, in both in vitro and in vivo models. In addition, SPG strongly inhibited mitogen-activated protein kinase (MAPKs) signaling, the including extracellular signal-regulated kinase, c-Jun N-terminal kinase (JNK), and p38. These findings suggest that dietary SPG may be an attractive functional food for preventing UVB-induced photoaging. And this SPG product may provide its best benefit when treating several signs of skin photoaging.
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Advanced glycation end products (AGEs) have potential implications on several diseases including skin inflammation and aging. AGEs formation can be triggered by several factors such as UVB, glyoxal and methylglyoxal etc. However, little attention has been paid to glyoxal-derived AGEs (GO-AGEs) and UVB-induced skin inflammaging, with none have investigated together. This study aimed to investigate the possible role of GO-AGEs and UVB in skin inflammaging focusing on revealing its molecular mechanisms. The effects of GO-AGEs in the presence or absence of UVB were studied by using enzyme linked immunosorbent assay, western blotting, qPCR, flow cytometry and in silico approaches. In HaCaT cells, GO-AGEs in the presence of UVB irradiation (125 mJ/cm2) dramatically enhanced the release of different pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α) with further activation of RAGE signaling pathways (NF-κB, COX 2, and IL- 1ß) and increased oxidative stress also noticed in NHEK cells. In NHDF cells, extracellular matrix disruption noted via increasing matrix metalloproteinase release and decreasing collagen type 1 and SIRT1 expression. Besides that, the docking scores obtained from the molecular docking study support the above-mentioned results. This study strongly suggests the pivotal role of GO-AGEs in skin inflammaging and illuminates novel molecular pathways for searching most effective and updated anti-aging therapy.
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Dermatitis , Glioxal , Humanos , Simulación del Acoplamiento Molecular , Piel , Interleucina-1beta , Productos Finales de Glicación AvanzadaRESUMEN
Isoflavones and their derivatives possess neuroprotective activities against neurological disorders. Recently, the active compound SPA1413 (dehydroequol) derived from S-equol, an isoflavone-derived metabolite produced by human intestinal bacteria, was identified as a potent anti-amyloidogenic and neuroinflammatory candidate against Alzheimer's disease. However, its detailed modes of action, associated signaling pathways, and comparison with potential isoflavone derivatives have not yet been studied. Hence, the current study aimed to identify signaling pathways associated with SPA1413 using lipopolysaccharides (LPS)-stimulated BV2 cells as the experimental model via biological assays, Western blotting, and quantitative (q)RT-PCR. The results indicate that the SPA1413 anti-neuroinflammatory effect arises due to suppression of the nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and mitogen-activated protein kinase (MAPK) signaling networks, including those of p38 and c-Jun N-terminal kinase (JNK). Interestingly, SPA1413 inhibited IL-11 through the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway. In addition, SPA1413 inhibited neuronal cell death by reducing LPS-activated microglia in neuronal N2a cells. Our findings suggest that SPA1413 may act as a strong anti-neuroinflammatory candidate by suppressing the MAPK and JAK/STAT signaling pathways.
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Isoflavonas , Proteínas Quinasas Activadas por Mitógenos , Humanos , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antiinflamatorios/metabolismo , Lipopolisacáridos/farmacología , Quinasas Janus/metabolismo , Quinasas Janus/farmacología , FN-kappa B/metabolismo , Transducción de Señal , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Isoflavonas/farmacología , Isoflavonas/uso terapéutico , Isoflavonas/metabolismo , Óxido Nítrico/metabolismo , MicroglíaRESUMEN
After anaplastic large-cell lymphoma (ALCL) was first described by Stain in 1985, there have been several histological variants of ALCL reported. There are classified histological subtypes of ALCL, such as lymphohistiocytic, small cell, Hodgkin-like, composite pattern, and other less common variants including neutrophil-rich ALCL. A 63-year-old male patient presented with erythematous exophytic mass on the left lower leg. In the past, his condition had been diagnosed as abdominal primary cutaneous ALCL (pcALCL), which recurred as systemic ALCL (sALCL) in the left bronchus. After treatment, he achieved complete remission. Histopathologic examination showed large-sized pleomorphic, anaplastic mitotic tumor cells, several neutrophils, and a few lymphocytes. Neutrophil-rich ALCL is a rare histological variant of ALCL. It is characterized by the presence of CD30-positive anaplastic tumor cells with numerous neutrophil infiltrations. Neutrophil-rich ALCL responds well to treatment but tends to recur. There were four cases reported to have recurrent neutrophil-rich ALCL. All cases were diagnosed with neutrophil-rich pcALCL prior to recurrence. Three cases had local recurrence, and only one case relapsed as sALCL. Herein, we present the first case of neutrophil-rich ALCL recurring as sALCL twice.
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Armoracia rusticana P. G. Gaertner. belongs to the Brassicaceae family and has aroused scientific interest for its anti-inflammatory and anticancer activities. In a continuing investigation to discover bioactive constituents from A. rusticana, we isolated 19 phenolic glycosides including three undescribed flavonol glycosides and one undescribed neolignan glycoside from MeOH extract of this plant. Their structures were elucidated based on NMR spectroscopic analysis (1H, 13C, 1H-1H COSY, HSQC, and HMBC), HRESIMS, and chemical methods. The determination of their absolute configuration was accomplished by ECD and LC-MS analysis. All the compounds were assessed for their potential neurotrophic activity through induction of nerve growth factor in C6 glioma cell lines and for their anti-neuroinflammatory activity based on the measurement of inhibition levels of nitric oxide production and pro-inflammatory cytokines (i.e., IL-1ß, IL-6, and TNF-α) in lipopolysaccharide-activated microglia BV-2 cells.
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Armoracia , Glicósidos , Glicósidos/farmacología , Glicósidos/análisis , Armoracia/química , Armoracia/metabolismo , Antiinflamatorios/farmacología , Línea Celular , Macrófagos/metabolismo , Raíces de Plantas/química , Óxido NítricoRESUMEN
BACKGROUND: Severity of Alopecia Tool (SALT) is widely used to assess the severity of alopecia areata (AA). However, physician-related subjectivity exists in SALT scoring (S1-5), especially with initial inspection in the clinical practice. This study investigated two-dimensional planimetric method to calculate actual surface area of AA, validating SALT scoring. MATERIALS AND METHODS: SALT score was measured twice in each patient based on "initial" inspection in the clinic (SALT-I) and retrospective assessment of the "photograph" (SALT-P). Planimetric surface area was calculated by Image J program. Subgroup analysis was performed depending on the agreement between SALT-I and -P; score was described in the order of SALT-I and SALT-P. RESULTS: A total of 93 subjects were enrolled. Planimetric surface area (cm2 ) of SALT-I was 2.5-74.9 (S1), 48.8-100.6 (S2), 83.6-205.4 (S3), and 282-367.9 (S4), while SALT-P was 2.5-59.2 (S1), 41.6-205.4 (S2), 48.8-183.2 (S3), and 282-367.9 (S4). In subgroup analysis, SALT-I and SALT-P agreed group showed planimetric surface area (cm2 ) as 2.5-59.2 (S1-1), 64.2-100.6 (S2-2), 168.3-183 (S3-3), and 282.6-367.9 (S4-4). Disagreed group showed the value as 54.7 (S1-2), 41.6-74.9 (S2-1), 83.6-205.4 (S2-3), and 48.8-88.6 (S3-2). CONCLUSION: SALT-P was more clearly correlated with actual surface area than SALT-I. Planimetric surface area measurement could be used as a supplementary method especially in the S1 to S3, suggesting 60 cm2 , 100 cm2 , and 200 cm2 as objective cutoff values to differentiate S1, S2, and S3.
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Aspacochioside C (ACC) is a steroidal saponin isolated from Asparagus cochinchinensis. Steroidal saponins, such as pseudoprotodioscin and dioscin, are known to inhibit melanogenesis, but the role of ACC in melanogenesis remains unknown. Due to the toxic effect of the commonly used skin whitening agents like arbutin, kojic acid and α-lipoic acid alternative plant products are recentlybeen studied for their anti-hypergmentation effect. This study explores the role of ACC in melanogenesis in both in vivo and in vitro models. Here, we for the first time demonstrate that ACC attenuated α-MSH- and UVB-induced eumelanin production by inhibiting tyrosinase-related protein (TRP)-2 protein expression in both murine B16F10 and human melanoma MNT1 cells. However, ACC had no significant effect on pheomelanin concentration. ACC also decreased the pigmentation density in zebrafish embryos, which indicates that ACC targets TRP2 and inhibits eumelanin synthesis. Our results demonstrate that ACC inhibits TRP2, thereby attenuating eumelanin synthesis both in in vitro and in vivo zebrafish model. Therefore, ACC can potentially be used as an anti-melanogenic agent for both aesthetic and pharmaceutical purposes.
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Asparagus , Pez Cebra , Humanos , Animales , Ratones , Inhibición Psicológica , ArbutinaRESUMEN
Muscle atrophy is characterized by the loss of muscle function. Many efforts are being made to prevent muscle atrophy, and exercise is an important alternative. Methylglyoxal is a well-known causative agent of metabolic diseases and diabetic complications. This study aimed to evaluate whether methylglyoxal induces muscle atrophy and to evaluate the ameliorative effect of moderate-intensity aerobic exercise in a methylglyoxal-induced muscle atrophy animal model. Each mouse was randomly divided into three groups: control, methylglyoxal-treated, and methylglyoxal-treated within aerobic exercise. In the exercise group, each mouse was trained on a treadmill for 2 weeks. On the last day, all groups were evaluated for several atrophic behaviors and skeletal muscles, including the soleus, plantaris, gastrocnemius, and extensor digitorum longus were analyzed. In the exercise group, muscle mass was restored, causing in attenuation of muscle atrophy. The gastrocnemius and extensor digitorum longus muscles showed improved fiber cross-sectional area and reduced myofibrils. Further, they produced regulated atrophy-related proteins (i.e., muscle atrophy F-box, muscle RING-finger protein-1, and myosin heavy chain), indicating that aerobic exercise stimulated their muscle sensitivity to reverse skeletal muscle atrophy. In conclusion, shortness of the gastrocnemius caused by methylglyoxal may induce the dynamic imbalance of skeletal muscle atrophy, thus methylglyoxal may be a key target for treating skeletal muscle atrophy. To this end, aerobic exercise may be a powerful tool for regulating methylglyoxal-induced skeletal muscle atrophy.
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Four undescribed neolignan analogs, together with eight known compounds, were isolated from the twigs of Pinus koraiensis (Korean pine). The chemical structure of the isolated compounds was determined through extensive spectroscopic analysis and chemical method. Their relative and absolute configurations were assigned through a well-established empirical rule and electronic circular dichroism (ECD) analysis, respectively. Four compounds (3 and 9-11) at 20 µM concentration showed significant neurotrophic effect by inducing nerve growth factor (NGF) secretion in C6 cells with the stimulation levels a range of 140.82 ± 4.62% to 160.04 ± 11.04%. Additionally, the result indicated that the glycosylation of neolignan led to an improvement in neurotrophic activity compared to their aglycone form. A compound (7) inhibited nitric oxide production with an IC50 value of 31.74 µM in LPS-activated BV2 cells.
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Lignanos , Pinus , Lignanos/farmacología , Lignanos/química , Estructura Molecular , Dicroismo Circular , Óxido NítricoRESUMEN
Two new ecdysteroids, spectasterone A (1) and spectasterone B (2), together with four known ecdysteroids, breviflorasterone (3), ajugalactone (4), 20-hydroxyecdysone (5), and polypodine B (6) were isolated from the Korean endemic plant Ajuga spectabilis using feature-based molecular networking analysis. The chemical structures of 1 and 2 were determined based on the interpretation of NMR and mass spectrometric data. Their absolute configurations were established using 3JH, H coupling constants, NOESY interactions, Mosher's method, and ECD and DP4+ calculations. To identify their biological target, a machine learning-based prediction system was applied, and the results indicated that ecdysteroids may have 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1)-related activity, which was further supported by molecular docking results of ecdysteroids with 11ß-HSD1. Following this result, all the isolated ecdysteroids were tested for their ability to affect the expression of 11ß-hydroxysteroid dehydrogenase type 1 and glucocorticoid receptors (GRs) in HaCaT cells irradiated with UVB. Compounds 2-5 exhibited inhibition of 11ß-HSD1 expression and increases in GR activity.
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BACKGROUND: Alopecia areata (AA) is common non-scarring hair loss disease. Sleep distrubance has been regarded as a triggering or aggravating factor for AA. However, objective evaluation of sleep disturbance and its clinical effect on AA has not been clearly demonstrated. OBJECTIVE: This study investigated objective sleep evaluation tool for AA patients and their clinical correlation. METHODS: Patients presenting with new-onset AA or recurrences of pre-existing AA were included, and those who reported sleep disturbance in the preliminary survey were designated as the sleep disturbance group (SD group). Sleep quality was investigated for them using three self-administered questionnaires: Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), and Epworth Sleep Scale (ESS). Demographic information and clinical features of AA were analyzed according to sleep quality. RESULTS: A total of 400 participants were enrolled, and 53 were categorized into the SD group. The incidence of stressful events was significantly higher in the SD group (54.7%) than in the non-SD group (25.1%) (p<0.001). Based on the PSQI, 77.3% of participants were objective poor sleepers (score of 5 or more), and they showed a significantly higher incidence of stressful events compared to good sleepers (p=0.019). The proportion of poor sleepers was significantly lower in patients with mild AA (S1) than in those with moderate to severe AA (S2~S5) (p=0.045). CONCLUSION: This study demonstrated a positive correlation among stress, SD, and AA. The degree of SD was objectively represented by the PSQI score, showing different scores according to AA severity.
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Oxylipins are important biological molecules with diverse roles in human and plants such as pro-/anti-inflammatory, antimicrobial, and regulatory activity. Although there is an increasing number of plant-derived oxylipins, most of their physiological roles in humans remain unclear. Here, we describe the isolation, identification, and biological activities of four new oxylipins, chaenomesters A-D (1-4), along with a known compound (5), obtained from Chaenomeles sinensis twigs. Their chemical structures were determined by spectroscopic (i.e., NMR) and spectrometric (i.e., HRMS) data analysis including 1H NMR-based empirical rules and homonuclear-decoupled 1H NMR experiments. Chaenomester D (4), an omega-3 oxylipin, showed a potent inhibitory effect on nitric oxide (NO) production in lipopolysaccharide (LPS)-activated BV-2 cells (NO production, 8.46 ± 0.68 µM), neurotrophic activity in C6 cells through the induction of the secretion of nerve growth factor (NGF, 157.7 ± 2.4%), and cytotoxicity in A549 human cancer cell lines (IC50 = 27.4 µM).
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Seven undescribed triterpenoids, abikoranes A-G, along with three known triterpenoids were isolated from the leaves of Abies koreana E. H. Wilson. The structures of compounds were elucidated by 1D and 2D NMR, HRMS, ECD, specific rotation, and DP4+ analysis. Abikorane A represents the second example of nor-3,4-seco-17,14-friedo-lanostane triterpenoid. Among the isolates, some compounds showed strong cytotoxic activities against some of four tested cancer cell lines (A549, SK-OV-3, SK-MEL-2, and HCT-116) with the values of IC50 0.89-9.62 µM, inhibited lipopolysaccharide-stimulated nitric oxide production with IC50 values of 11.57-15.16 µM, and exhibited significant nerve growth factor release effect (192.54 ± 12.33%) from C6 glioma cells.