Search

Boswellic acids, triterpenoids derived from the genus Boswellia (Burseraceae), are known for their anti-inflammatory and anti-tumor efficacy. Atopic dermatitis is a chronic, non-infectious inflammatory skin disease. However, the effects of α-boswellic acid on atopic dermatitis have not been studied. Therefore, in this study we examined the expression level of pro-inflammatory cytokines, histopathological analysis, and physiological data from BALB/c mice with atopic-like dermatitis induced by 2,4-dinitrochlorobenzene and TNF-α/IFN-γ-stimulated HaCaT cells to better understand the agent’s anti-atopic dermatitis efficacy. First, we found that α-boswellic reduced the epidermal thickening, mast cell numbers, and dermal infiltration of 2,4-dinitrochlorobenzene-induced atopic-like dermatitis in BALB/c mice. Furthermore, we also found that α-boswellic acid can restore transepidermal water loss and skin reddening in mice. In human keratinocytes inflamed by TNF-α/IFN-γ, α-boswellic acid inhibited MAP kinase activation and showed a reduction in NF-κB nuclear translocation. Finally, α-boswellic acid can reduce the expression level of cytokines (IL-1β, IL-6, and IL-8) following the stimulation of TNF-α/IFN-γ in HaCaT cells. Taken together, our study suggests that α-boswellic acids are a potential component for the development of anti-atopic dermatitis drugs.

Cytokine-induced endothelial dysfunction leads to inflammation and vascular adhesion molecule production in retinal pigment epithelium (RPE) cells. Inflammation is a critical mediator in retinal degeneration (RD) diseases, including age-related macular degeneration (AMD), and RD progression may be prevented through anti-inflammatory activity in RPE cells. The flavonoid polyphenol luteolin (LU) has anti-inflammatory and antidiabetes activities, but its effects regarding retinal protection remain unknown. Here, we examined the ability of luteolin to alleviate markers of inflammation related to RD in cytokine-primed APPE-19 cells. We found that luteolin decreased the levels of interleukin- (IL-) 6, IL-8, soluble intercellular adhesion molecule-1 (sICAM-1), and monocyte chemoattractant protein-1 (MCP-1) and attenuated adherence of the human monocytic leukemia cell line THP-1 to IL-1β-stimulated ARPE-19 cells. Luteolin also increased anti-inflammatory protein heme oxygenase-1 (HO-1) levels. Interestingly, luteolin induced protein kinase B (AKT) phosphorylation, thus inhibiting nuclear factor- (NF-) κB transfer from cytoplasm into the nucleus and suppressing mitogen-activated protein kinase (MAPK) inflammatory pathways. Furthermore, cotreatment with MAPK inhibitors and luteolin decreased inflammatory cytokine and chemokine levels, and further suppressed THP-1 adhesion. Overall, these results provide evidence that luteolin protects ARPE-19 cells from IL-1β-stimulated increases of IL-6, IL-8, sICAM-1, and MCP-1 production by blocking the activation of MAPK and NF-κB signaling pathways, thus ameliorating the inflammatory response.

Background: In a previous study, we evaluated the potential beneficial effect of nano-bubble curcumin extract (NCE) in reducing exercise-related injuries and improving performance. Methods: In this study, we seek to investigate changes in the gut microbiota composition upon NCE supplementation in relation to health and exercise performance. Male ICR mice were divided into 3 groups (n = 8 per group) and orally administered NCE once daily for six weeks at 0 (vehicle), 3.075 (NCE-1X) and 15.375 g kg−1 day−1 (NCE-5X). The gut microbiota from the mice was analyzed using 16S rRNA gene sequencing. Results: NCE-5X did not appear to obviously cluster with the vehicle group, although NCE-5X groups showed an increased Firmicutes/Bacteroidetes ratio compared with the vehicle group. In addition, anti-fatigue activity and exercise performance were evaluated by investigating the exhaustive swimming time, forelimb grip strength and serum levels of lactate, ammonia, glucose, blood urea nitrogen (BUN), creatine kinase (CK) and lactate dehydrogenase (LDH) after swimming. The NCE-1X and NCE-5X groups showed a significantly longer exhaustive swimming time and higher relative forelimb grip strength than the vehicle group. Tissue glycogen content, an important energy source for exercise, increased significantly with NCE supplementation. Conclusion: Taken together, our results indicate that NCE supplementation alters the gut microbiota composition and aids in overcoming physical fatigue. Curcumin may be acting on the gut microbiome to modulate the gut system towards improving exercise performance.

Introduction: The ablative laser can be used as an effective approach for enhancing drug permeation via the skin. The enhancement mechanisms of laser-assisted drug permeation are the direct ablation of the superficial skin, optical breakdown by a photomechanical wave, and a photothermal effect. Areas covered: This review describes the development of laser-assisted drug delivery in the recent 5 years. This review systematically introduces the concepts and enhancement mechanisms of the technique, highlighting the potential of the laser approach for increasing drug absorption via the skin. A recent advance of this approach is the use of fractional laser offering limited skin damage and short recovery time. Another sign of progress regarding laser-assisted drug delivery in the recent 5 years is the clinical trials for treating various dermatological disorders. Expert opinion: The potential use of the laser-assisted approach affords a novel treatment for topical drug application with significant efficacy. Although many clinical studies have been performed, further studies using a large group for patients are needed to confirm and clarify the findings in the in vitro or animal experiments. The laser-assisted delivery should be optimized to achieve skin targeting without the risk of diffusion into circulation.

Fractional CO2 laser treatment has been used in some clinical trials to promote topical drug delivery. Currently, there is no standard for laser settings to achieve a feasible therapy. The cutaneous recovery following laser treatment and its influence on drug absorption have not been well explored. This study evaluated the kinetics of laser-treated skin-barrier restoration and drug permeation in nude mice. The skin recovery and observation of the process were characterized by transdermal water loss (TEWL), erythema measurement, gross appearance, optical microscopy, and scanning electron microscopy (SEM). The skin absorption of a lipophilic small permeant (tretinoin), a hydrophilic small permeant (acyclovir), and a large molecule (fluorescein isothiocyanate dextran 4 kDa, FD4) was examined in vitro using Franz cell. TEWL suggested that the laser-treated skin restored its barrier function at 16 h after irradiation. The fractional laser produced microchannels of about 150 μm in diameter and 25 μm in depth that were surrounded with thermal coagulation. The bright-field imaging indicated that the micropores were progressively closed during the recovery period but had not completely closed even after a 16-h recovery. The laser treatment led to a rapid tretinoin penetration across the skin immediately after irradiation, with a 5-fold enhancement compared to intact skin. This enhancement was gradually reduced following the increase of recovery time. Conversely, the acyclovir and FD4 permeation peaked at 1–2 h post-irradiation. The FD4 flux was even elevated as the recovery time increased. The reasons for this could have been the subsequent inflammation after laser exposure and the deficient tight junction (TJ) barrier. The confocal imaging demonstrated the perpendicular diffusion of rhodamine B and FD4 through microchannels immediately after laser exposure. The lateral diffusion from the microchannels was observed at 2 h post-irradiation. Our results revealed a time-dependent recovery of skin permeation. The time frame for applying the drugs after laser irradiation was dependent upon the permeants and their various physicochemical properties.

Ludwigia octovalvis extract (LOE) is a widely used traditional Chinese herbal medicine. To date, few studies have demonstrated the effect of LOE supplementation on exercise performance, physical fatigue and biochemical profile. The purpose of this study is to evaluate the potential beneficial effects of LOE extract on fatigue and ergogenic functions following physiological challenge. Male ICR mice from 3 groups (n=8 per group) were orally administered LOE for 4 weeks at 0 (vehicle), 61.5 (LOE-1X) or 307.5 (LOE-5X) mg/kg/day. LOE supplementation was able to dose-dependently increase endurance swimming time (P

Psoriasis is a common non-contagious chronic inflammatory skin lesion, with frequent recurrence. It mainly occurs due to aberrant regulation of the immune system leading to abnormal proliferation of skin cells. However, the pathogenic mechanisms of psoriasis are not fully understood. Although most of the current therapies are mostly efficient, the side effects can result in therapy stop, which makes the effectiveness of treatment strategies limited. Therefore, it is urgent and necessary to develop novel therapeutics. Here, we investigated the efficacy of chrysin, a plant flavonoid, which we previously reported to possess strong antioxidant and anti-inflammatory effects, against psoriasis-like inflammation. Our results revealed that chrysin significantly attenuated imiquimod-induced psoriasis-like skin lesions in mice, and improved imiquimod-induced disruption of skin barrier. Moreover, the TNF-α, IL-17A, and IL-22-induced phosphorylation of MAPK and JAK-STAT pathways, and activation of the NF-κB pathway were also attenuated by chrysin pretreatment of epidermal keratinocytes. Most importantly, chrysin reduced TNF-α-, IL-17A-, and IL-22-induced CCL20 and antimicrobial peptide release from epidermal keratinocytes. Thus, our findings indicate that chrysin may have therapeutic potential against inflammatory skin diseases. Our study provides a basis for further investigating chrysin as a novel pharmacologic agent and contributes to the academic advancement in the field of Chinese herbal medicine.

Background The extracts from wild bitter gourd fruit (WBGE) were reported to possess numerous pharmacological activities. However, the anti-inflammatory effects of WBGE on human lung epithelial cells and the underlying mechanisms have not been determined. Purpose To evaluate the molecular basis of the effects of WBGE on intercellular adhesion molecule-1 (ICAM-1) expression in alveolar epithelial (A549) cells, C57BL/6 wild-type (WT) mice and microRNA (miR)-221/-222 knockout (KO) mice with or without tumor necrosis factor (TNF-α; 3 ng/ml) treatment. Study design/methods WT mice and miR-221/-222 KO mice were fed a control diet and divided into four groups (C: control mice; T: treated with TNF-α alone; WBGE/T: pretreated with WBGE and then stimulated with TNF-α; WBGE: treated with WBGE alone). The effects of WBGE on ICAM-1 expression and the related signals in A549 cells and mice with or without TNF-α treatment were examined by Western blot and immunofluorescent staining. Results WBGE significantly decreased the TNF-α-induced ICAM-1 expression in A549 cells through the inhibition of phosphoinositide 3-kinase (PI3K)/ protein kinase B (AKT)/ nuclear factor- kappa B (NF-κB)/ inhibitor of NF-κB (IκB) phosphorylation and decreased leukocyte adhesion. In addition, WBGE reduced endogenous ICAM-1 expression and upregulated miR-221/-222 expression. The overexpression of miR-222 decreased PI3K/AKT/NF-κB/IκB and ICAM-1 expression, which resulted in reducing monocyte adhesion. Moreover, WBGE reduced ICAM-1 expression in lung tissues of WT mice with or without TNF-α treatment and upregulated miR-221/222. WBGE did not affect the miR-221/-222 level and had little effect on ICAM-1 expression in miR-221/-222 KO mice. Conclusions These results suggest that WBGE reduced ICAM-1 expression both under in vitro and in vivo conditions. The protective effects were mediated partly through the miR-221/-222/PI3K/AKT/NF-κB pathway.

Antrodia camphorata and Panax ginseng are well-known medicinal plants in Taiwan folk and traditional Chinese medicine, which have been reported for multifunctional bioactivities. However, there is limited evidence that a fixed combination formula of these two plant extracts is effective for the exercise improvement or anti-fatigue. We aimed to evaluate the potential beneficial effects of the mix formulation of these two herbal medicines (AG formulation) on fatigue and ergogenic functions following physiological challenge. Male Institute of Cancer Research (ICR) mice from four groups (n=10 per group) were orally administered AG formulation for 4 weeks at 0.984, 2.952 and 5.904 g/kg/day, which were designated the Vehicle, AG-1X, AG-3X and AG-6X groups, respectively. The anti-fatigue activity and exercise performance were evaluated using exhaustive swimming time, forelimb grip strength, and levels of serum lactate, ammonia, glucose, blood urea nitrogen (BUN) and creatine kinase (CK) after a swimming exercise. The exhaustive swimming time of the 1X, 3X or 6X AG group was significantly longer than that of the Vehicle group, and the forelimb grip strength of the 1X, 3X or 6X AG group was also significantly higher than that of the Vehicle group. AG supplementation also produced decreases in serum lactate, ammonia, BUN and CK activity after the swimming test, as well as increases in glucose. Therefore, the AG complex could be a potential formulation with an anti-fatigue pharmacological effect.

Hualian No. 4 wild bitter gourd (WBG) is a specific vegetable cultivated by the Hualien District Agricultural Research and Extension Station in Taiwan. WBG is commonly consumed as a vegetable and used as a popular folk medicine. However, few studies have demonstrated the effects of WBG supplementation on exercise performance, physical fatigue and the biochemical profile. The purpose of this study was to evaluate the potential beneficial effects of WBG extract on fatigue and ergogenic functions following physiological challenge. Three groups of male ICR mice (n=8 per group) were orally administered 0, 1 or 2.5 g/kg/day of WBG for 4 weeks. They were respectively designated the vehicle, WBG-1X and WBG-2.5X groups. WBG significantly decreased body weight (BW) and epididymal fat pad (EFP) weight. Concerning physical performance, WBG supplementation dose-dependently increased grip strength and endurance swimming time. Concerning anti-fatigue activity, WBG decreased levels of serum lactate, ammonia, creatine kinase and blood urea nitrogen, and economized glucose metabolism after acute exercise challenge. Glycogen in the liver and gastrocnemius muscle dose-dependently increased with WBG treatment. Concerning the biochemical profile, WBG treatment significantly decreased alanine aminotransferase (ALT), blood urea nitrogen (BUN) and urea acid (UA), and increased total protein (TP). Therefore, 4-week supplementation with WBG may decrease white adipose weight, enhance energy economy, increase glycogen storage to enhance exercise performance and reduce fatigue.

Background: Vascular endothelial growth factor (VEGF) is upregulated by hypoxia and is a crucial stimulator for choroidal neovascularization (CNV) in age-related macular degeneration and pathologic myopia, as well as retinal neovascularization in proliferative diabetic retinopathy. Retinal and choroidal endothelial cells play key roles in the development of retinal and CNV, and subsequent fibrosis. At present, the effects of gold nanoparticles (AuNPs) on the VEGF-induced choroid-retina endothelial (RF/6A) cells are still unknown. In our study, we investigated the effects of AuNPs on RF/6A cell viabilities and cell adhesion to fibronectin, a major ECM protein of fibrovascular membrane. Furthermore, the inhibitory effects of AuNPs on RF/6A cell migration induced by VEGF and its signaling were studied. Methods: The cell viability assay was used to determine the viability of cells treated with AuNPs. The migration of RF/6A cells was assessed by the Transwell migration assay. The cell adhesion to fibronectin was examined by an adhesion assay. The VEGF-induced signaling pathways were determined by western blotting. Results: The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) viability assay revealed no cytotoxicity of AuNPs on RF/6A cells. AuNPs inhibited VEGF-induced RF/6A cell migration in a concentration-dependent manner but showed no significant effects on RF/6A cell adhesion to fibronectin. Inhibitory effects of AuNPs on VEGF-induced Akt/eNOS were found. Conclusions: These results suggest that AuNPs are an effective inhibitor of VEGF-induced RF/6A cell migration through the Akt/eNOS pathways, but they have no effects on their cell viabilities and cell adhesion to fibronectin.

Electronic cigarette(s) (EC) becoming a preferred replacement for nicotine delivery among many smokers in recent years. However, the effect of EC on human health is inconclusive due to a lack of empirical research investigating EC-induced health hazard or benefit. In this study, we examine the effect of vapor produced by EC on exercise performance and health-related profiles in a mouse model. Female ICR mice were divided into five groups (n = 6 per group) and exposed for 14 days. Our results indicate that EC exposure leads to dose-dependent decrease in the grip strength and swimming time of the mice. The EC-treated groups also showed a dose-dependent decrease in liver and muscle glycogen storage. In addition, EC treatment had no negative effect on levels of biochemical indices. We also did not detect any adverse effect or gross abnormalities on the morphology of the major organs.

Purpose. To verify the beneficial effects of Nanobubbles water curcumin extract (NCE) supplementation on health promotion and to demonstrate the application of NCE in reducing the risk of musculoskeletal injury. Methods. In the current study, 12 females were randomly assigned to NCE (15g/day) and maltodextrin groups. Performance and related body composition were evaluated at 2 time points—presupplementation (pre-) and after 4 weeks of postsupplementation (post-). The posttest consists of a set of biochemical parameters for antifatigue activity and injury status evaluation. Results. NCE group exhibited significantly lower levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), triglycerides (TG), and higher high-density lipoprotein (HDL) after a 4-week supplementation, compared with the placebo group. After a 15-minute session on the spinning bike, serum lactate and ammonia levels were decreased and glucose was economized in the NEC group. 4-week-NCE supplementation was also able to reduce the peak vertical ground reaction force (PVGRF) during drop jump. Therefore, the risk of musculoskeletal system in lower extremity could be reduced. Conclusion. We demonstrate that 4-week-NCE supplementation can also be used in explosiveness exercise for better physiological adaptation. Thus, NCE has potential for use with nutrient supplements toward a variety of benefits for athletics.

Platelet-rich plasma (PRP) is rich in cytokines and growth factors and is a novel approach for tissue regeneration. It can be used for skin rejuvenation but the large molecular size of the actives limits its topical application. In this study, low-fluence laser-facilitated PRP was delivered to evaluate its effect on absorption through the skin, infection-induced wound, and photoaging. The PRP permeation enhancement was compared for two ablative lasers: fractional (CO2) laser and fully-ablative (Er:YAG) laser. In the Franz cell experiment, pig skin was treated with lasers with superficial ablation followed by the application of recombinant cytokines, growth factors, or PRP. The transport of interferon (IFN)-γ and tumor necrosis factor (TNF)-α was negligible in intact skin and stratum corneum (SC)-stripped skin. Both lasers significantly elevated skin deposition of IFN-γ and TNF-α from PRP, and fully-ablative laser showed a higher penetration enhancement. A similar tendency was found for vascular endothelial growth factor and epidermal growth factor. Er:YAG laser-exposed skin displayed 1.8- and 3.9-fold higher skin deposition of platelet-derived growth factor (PDGF)-BB and transforming growth factor (TGF)-β1 from PRP, respectively. According to the confocal images, both laser interventions led to an extensive and deep distribution of IFN-γ and PDGF-BB in the skin. In the in vivo methicillin-resistant Staphylococcus aureus (MRSA) infection model, CO2 laser- and Er:YAG laser-assisted PRP delivery reduced bacterial load from 1.8 × 106 to 5.9 × 105 and 1.4 × 104 colony-forming units, respectively. The open wound induced by MRSA was closed by the laser-assisted PRP penetration. In the mouse photoaging model, elastin and collagen deposition were fully restored by combined PRP and full-ablative laser but not by PRP alone and PRP combined with fractional laser. Laser-facilitated PRP delivery even with a low fluence setting can be considered a promising strategy for treating some dermatological disorders.

Ethnopharmacological relevance Numerous epidemiological and clinical studies have demonstrated the protective role of dietary isoflavones against development of several chronic diseases. ISO-1, one fraction of isoflavone powders derived from soybean cake, is reported to attenuate inflammation and photodamage. Aim of the study Contact dermatitis is a common inflammatory skin disease, which accounts for most occupational skin disorders. Instead of oral administration, we aimed to explore the effects of topical ISO-1 application on contact dermatitis by using 2,4-dinitrochlorobenzene (DNCB)-stimulated HaCaT keratinocytes and DNCB-induced mouse dermatitis as models. Materials and methods In the in vitro study, we first evaluated the biologic effects of DNCB on HaCaT keratinocytes. HaCaT keratinocytes were treated with 2,4-dinitrochlorobenzene (DNCB), and cell viability was measured by MTT assay. Then, we detect the prominent induction of IL-8 mRNA expression after DNCB and ISO-1 treatment by reverse transcription polymerase chain reaction (RT-PCR), and release of IL-8 from HaCaT keratinocytes was measured by ELISA assay. HaCaT keratinocytes were pretreated with ISO-1 and then treated with DNCB, phosphorylation of JNK, p38, ERK and IκBα was analyzed by western blot. In the in vivo study, the hairless mice were used for an induced contact dermatitis model. The surface changes in the dorsal skin after DNCB and ISO-1 treatment were recorded using photography, and TEWL, erythema were measured using an MPA-580 cutometer. Blood was also collected from mice for measurement of white blood cell counts. Results Results showed ISO-1 inhibited DNCB-induced IL-8 production and also suppressed DNCB-induced phosphorylation of JNK and p38, and IκBα in HaCaT. In the animal model of DNCB-induced contact dermatitis, topical ISO-1 treatment significantly decreased DNCB-induced erythema and transepidermal water loss (TEWL) in mouse skin. ISO-1 also reduced DNCB-induced skin thickening and increase of white blood cell count. Conclusions ISO-1 is promising for improvement of DNCB-induced inflammation and skin barrier impairment, suggesting the potential application of topical ISO-1 for inflammatory dermatoses.

Flavonoids inhibit skin inflammation. Previous study suggests that the flavonoids with flavanone backbone were beneficial to penetrate into the skin. We aimed to investigate the possibility of psoriasis treatment by topically applied flavanone and its derivatives including naringenin, hesperetin, 6-hydroxyflavanone, flavanone, and 6-bromoflavone. The skin absorption of the compounds was determined by Franz cells. Molecular modeling was used to compute the physicochemical and molecular parameters of the penetrants in order to elucidate the correlation between structure and permeation. Among the compounds tested, flavanone showed the greatest skin absorption. The in vitro skin absorption predicted efficient skin targeting of 6-bromoflavone with minimal risk of circulation absorption. The permeation of naringenin was remarkably enhanced 13-fold in the barrier-defective skin mimicking inflamed skin. The penetrants with fewer hydrogen bond number, total polarity surface, and molecular volume were advantageous for facile skin absorption. In the cell-based study, IL-1β inhibition in imiquimod (IMQ)-stimulated keratinocytes was increased following the increase in compound lipophilicity. Naringenin, a flavanone analog with three hydroxyl moieties, could suppress IL-6 overexpression to baseline control. We assessed the anti-inflammatory potency of the chemicals in comparison with tacrolimus as reference in a psoriasis-like mouse model. Flavanone was found to mitigate scaling and epidermal hyperplasia at a higher level than naringenin. Flavanone lessened IL-6 overexpression by 80% in the psoriasiform plaque. The skin barrier function recorded by transepidermal water loss (TEWL) was recovered by naringenin but not flavanone. The experimental data indicate that naringenin and flavanone are potential candidates for anti-psoriatic therapy.

Spilanthol has been reported to possess antioxidant, anti‑inflammatory, antimicrobial and antinociceptive properties. At present, the literature has reported the beneficial role of spilanthol on tumor necrosis factor‑α (TNF‑α)‑stimulated HaCaT cells. The present study investigated the effects of spilanthol on the expression of TNF‑α‑induced intercellular adhesion molecule 1 (ICAM‑1) and cyclooxygenase (COX)‑2 in the human keratinocyte cell line HaCaT. Cells were pretreated with various concentrations of spilanthol (10‑150 µM) followed by TNF‑α to induce inflammation. Pretreatment with spilanthol decreased TNF‑α‑induced COX‑2 expression by western blotting and suppressed the expression of pro‑inflammatory mediators, including interleukin (IL)‑6, IL‑8 and monocyte chemotactic protein 1 using ELISA. Spilanthol also decreased the expression of TNF‑α‑induced ICAM‑1 protein and mRNA assay by western blotting and RT‑qPCR, respectively, in addition to the monocyte adhesiveness of HaCaT cells. Furthermore, spilanthol significantly suppressed the phosphorylation of c‑Jun N‑terminal kinase (JNK), while pretreatment with spilanthol enhanced heme oxygenase (HO)‑1 protein expression by western blotting. These results demonstrated that spilanthol may exert its anti‑inflammatory activity by suppressing the TNF‑α‑induced expression of ICAM‑1, COX‑2 and pro‑inflammatory mediators by enhancing that of HO‑1, and inhibiting the activation of the phosphorylated JNK signaling pathway. It is hypothesized that spilanthol may be a natural anti‑inflammatory drug to attenuate skin inflammatory disease.

Background: Topical tranexamic acid has been used to treat melasma and as a skin whitener. Objective: The aim of this study was to compare the skin histology and permeation of tranexamic acid after fractional and conventional CO2 laser pretreatment. Methods: The effect of treatment with different strengths of fractional and conventional CO2 laser treatment was examined by scanning and transmission electron microscopy. Permeation of tranexamic acid through porcine skin was tested in vitro using a Franz diffusion chamber. Results: Four passes of fractional laser treatment caused less skin damage than conventional laser treatment at the same fluency. Fractional laser treatment caused at least 85% of the cumulative tranexamic aid permeation at the same fluency, and as fluency increased, the number of passes needed to achieve this goal decreased. Conclusion: Fractional laser treatment is as effective as conventional laser treatment in enhancing tranexamic acid delivery and causes less skin damage.

Antrodia camphorata and Panax ginseng are well-known medicinal plants in Taiwan folk and traditional Chinese medicine, which have been reported for multifunctional bioactivities. However, there is limited evidence that a fixed combination formula of these two plant extracts is effective for the exercise improvement or anti-fatigue. We aimed to evaluate the potential beneficial effects of the mix formulation of these two herbal medicines (AG formulation) on fatigue and ergogenic functions following physiological challenge. Male Institute of Cancer Research (ICR) mice from four groups (n=10 per group) were orally administered AG formulation for 4 weeks at 0.984, 2.952 and 5.904 g/kg/day, which were designated the Vehicle, AG-1X, AG-3X and AG-6X groups, respectively. The anti-fatigue activity and exercise performance were evaluated using exhaustive swimming time, forelimb grip strength, and levels of serum lactate, ammonia, glucose, blood urea nitrogen (BUN) and creatine kinase (CK) after a swimming exercise. The exhaustive swimming time of the 1X, 3X or 6X AG group was significantly longer than that of the Vehicle group, and the forelimb grip strength of the 1X, 3X or 6X AG group was also significantly higher than that of the Vehicle group. AG supplementation also produced decreases in serum lactate, ammonia, BUN and CK activity after the swimming test, as well as increases in glucose. Therefore, the AG complex could be a potential formulation with an anti-fatigue pharmacological effect.

Lutein is a carotenoid with anti-oxidant properties. Autophagy, an evolutionarily conserved catabolic cellular pathway for coping with stress conditions, is responsive to reactive oxygen species (ROS) and degrades damaged organelles. We previously demonstrated that lutein can induce anti-oxidant enzymes to relieve methotrexate-induced ROS stress. We therefore hypothesized that lutein, which activates ROS-scavenging enzymes, can also induce autophagy for cell survival. In this study, we demonstrated that lutein treatment attenuated the reduction in cell viability caused by H2O2. Lutein dose-dependently induced the processing of microtubule-associated protein light chain 3 (LC3)-II, an autophagy marker protein, and accumulation of LC3-positive puncta in rat intestinal IEC-6 cells. Furthermore, (a) direct observation of autophagosome formation through transmission electron microscopy, (b) upregulation of autophagy-related genes including ATG4A, ATG5, ATG7, ATG12, and beclin-1 (BENC1), and (c) increased BECN1/Bcl-2 ratio confirmed the induction of autophagy by lutein. The results revealed that bafilomycin-A1-induced inhibition of autophagy reduced cell viability and increased apoptosis in lutein-treated cells, indicating a protective role of lutein-induced autophagy. Lutein treatment also activated adenosine monophosphate–activated protein kinase (AMPK), c-Jun N-terminal kinase (JNK), and p-38, but had no effects on the induction of extracellular signal-related kinase or inhibition of mTOR; however, the inhibition of activated AMPK, JNK, or p-38 did not attenuate lutein-induced autophagy. Finally, increased BECN1 expression levels were detected in lutein-treated cells, and BECN1 knockdown abolished autophagy induction. These results suggest that lutein-induced autophagy was mediated by the upregulation of BECN1 in IEC-6 cells. We are the first to demonstrate that lutein induces autophagy. Elevated autophagy in lutein-treated IEC-6 cells may have a protective role against various stresses, and this warrants further investigation.

Hualian No. 4 wild bitter gourd (WBG) is a specific vegetable cultivated by the Hualien District Agricultural Research and Extension Station in Taiwan. WBG is commonly consumed as a vegetable and used as a popular folk medicine. However, few studies have demonstrated the effects of WBG supplementation on exercise performance, physical fatigue and the biochemical profile. The purpose of this study was to evaluate the potential beneficial effects of WBG extract on fatigue and ergogenic functions following physiological challenge. Three groups of male ICR mice (n=8 per group) were orally administered 0, 1 or 2.5 g/kg/day of WBG for 4 weeks. They were respectively designated the vehicle, WBG-1X and WBG-2.5X groups. WBG significantly decreased body weight (BW) and epididymal fat pad (EFP) weight. Concerning physical performance, WBG supplementation dose-dependently increased grip strength and endurance swimming time. Concerning anti-fatigue activity, WBG decreased levels of serum lactate, ammonia, creatine kinase and blood urea nitrogen, and economized glucose metabolism after acute exercise challenge. Glycogen in the liver and gastrocnemius muscle dose-dependently increased with WBG treatment. Concerning the biochemical profile, WBG treatment significantly decreased alanine aminotransferase (ALT), blood urea nitrogen (BUN) and urea acid (UA), and increased total protein (TP). Therefore, 4-week supplementation with WBG may decrease white adipose weight, enhance energy economy, increase glycogen storage to enhance exercise performance and reduce fatigue.

Background: Topical vitamin C derivatives have been used to treat melasma and used as a skin whitener. The aim of this study was to compare skin histology and permeation of l-ascorbic acid 2-phosphate sesquimagnesium salt (MAP-1) and magnesium l-ascorbic acid-2-phosphate (MAP-2) after fractional CO2 laser pretreatment. Methods: The effect of fractional laser treatment on porcine skin was examined by scanning electron microscopy and confocal laser scanning electron microscopy. The effect of fractional CO2 laser treatment of different fluencies and pass numbers on transdermal flux of the two vitamin C derivatives through porcine skin was examined in vitro using a Franz diffusion chamber. Results: Fluxes of MAP-1 and MAP-2 across fractional CO2 laser-treated (5 W) skin were eight- to 13-fold, and 20- to 22-fold higher, respectively, than the fluxes of these compounds across intact skin. Fluxes of MAP-1 and MAP-2 across fractional CO2 laser-treated (9 W) skin were 14- to 19-fold, and 30- to 42-fold higher, respectively, than their fluxes across intact skin. Conclusion: Fractional CO2 laser treatment is an effective way of delivering vitamin C derivatives into the skin.

Ultraviolet (UV) radiation, particularly ultraviolet A (UVA), is known to play a major role in photoaging of the human skin. Many studies have demonstrated that UV exposure causes the skin cells to generate reactive oxygen species and activates the mitogen-activated protein kinase (MAPK) pathway. Previous studies have also demonstrated that cycloheterophyllin has an antioxidant effect and can effectively scavenge free radicals. Extending the aforementioned investigations, in this study, human dermal fibroblasts were used to investigate the protective effect of cycloheterophyllin against UV-induced damage. We found that cycloheterophyllin not only significantly increased cell viability, but also attenuated the phosphorylation of MAPK after UVA exposure. Furthermore, cycloheterophyllin could reduce hydrogen peroxide (H2O2) generation and down-regulate H2O2-induced MAPK phosphorylation. In the in vivo studies, the topical application of cycloheterophyllin before UVA irradiation significantly decreased trans-epidermal water loss (TEWL), erythema, and blood flow rate. These results indicate that cycloheterophyllin is a photoprotective agent that inhibits UVA-induced oxidative stress and damage, and could be used in the research on and prevention of skin photoaging.

BACKGROUND Laser pretreatment of skin can be used to enable drugs used in dermatology to penetrate the skin to the depth necessary for their effect to take place. OBJECTIVE To compare the permeation of tranexamic acid after conventional non-fractionated ablative Er:YAG and CO2 laser pretreatment in a laser-aided transdermal delivery system. MATERIALS AND METHODS An erbium-doped yttrium aluminium garnet (Er:YAG) and a CO2 laser were used to pretreat dorsal porcine skin. Scanning electron microscopy was used to examine disruption of the skin surface. Confocal laser scanning microscopy was used to determine the depth of penetration of a reporter molecule (fluorescein isothiocyanate) into the skin. A Franz diffusion assembly was used to examine fluency-related increases in transdermal delivery of transexamic acid. RESULTS Transdermal delivery of tranexamic acid increased as Er:YAG laser fluency increased. Transdermal delivery was higher when CO2 laser pretreatment was used than when Er:YAG laser pretreatment was used, but a "ceiling effect" was present and increasing the wattage did not cause a further increase in delivery. CO2 laser pretreatment also caused more extensive and deeper skin disruption than Er:YAG laser pretreatment. CONCLUSION For conventional, non-fractionated ablative laser pretreatment, the Er:YAG laser would be an optimal choice to enhance transdermal penetration of transexamic acid.

Topical treatment with vitamin C has been used to treat photoaged skin and as a skin whitener, but no standard procedure exists for percutaneous delivery.To compare skin histology and the permeation of ascorbic acid 2-glucoside (AA2G) after fractional and conventional carbon dioxide (CO(2) ) laser pretreatment.The effect on porcine skin of treatment with different strengths of fractional and conventional CO(2) laser treatment was examined using scanning electron microscopy and transmission electron microscopy. Permeation of AA2G through porcine skin was tested in vitro using a Franz diffusion chamber. In vivo changes in fluorescein thiocyanate permeability in nude mice were examined using confocal laser scanning microscopy.Fractional CO(2) laser treatment with four or fewer passes caused less disruption than conventional laser treatment at the same fluence. AA2G permeation using four passes of fractional laser treatment was similar to that seen with conventional CO(2) laser treatment of the same fluence. Changes in permeability and in depth of permeation were higher with conventional than fractional laser treatment.Fractional CO(2) laser treatment can cause similar transdermal delivery of AA2G to conventional laser treatment with less skin disruption and a different pattern of histologic change.

Ethnopharmacological relevance Eupafolin, a major bioactive compound found in Phyla nodiflora, has the anti-inflammatory property. Upregulation of cell adhesion molecules in the lung airway epithelium is associated with the epithelium–leukocyte interaction and plays a critical role in the pathogenesis of lung airway inflammatory disorders. To investigate the effects of eupafolin on tumor necrosis factor-α (TNF-α)-induced intercellular cell adhesion molecule-1 (ICAM-1) expression in A549 human lung airway epithelial cells and the underlying mechanisms. Materials and methods The effect of eupafolin on ICAM-1 expression in A549 cells were examined by Western blotting and immunofluorescent staining. The mice were injected intraperitoneally with or without eupafolin and then were left untreated or were injected intratracheally with TNF-α. To detect the effect of eupafolin on ICAM-1 expression, the lung tissues were also examined by Western blotting and immunohistochemical staining. Results Eupafolin pretreatment reduced the TNF-α-induced ICAM-1 expression and also the ERK1/2, JNK, p38, and AKT/PI3K phosphorylation. However, the increase in ICAM-1 expression with TNF-α treatment was unaffected by p38 and PI3K inhibitors. Eupafolin decreased the TNF-α-induced NF-κB p65 activation and its nuclear translocation. Furthermore, eupafolin reduced ICAM-1 expression in the lung tissues of TNF-α-treated mice. Conclusions Eupafolin exerts its anti-inflammatory activity by suppressing the TNF-α-induced ICAM-1 expression and subsequent monocyte adhesion via AKT/ERK1/2/JNK phosphorylation and nuclear translocation of NF-κB p65. These results suggest that eupafolin may represent a novel therapeutic agent targeting epithelial activation in lung inflammation.

Licorice (Glycyrrhiza) species have been widely used as a traditional medicine and a natural sweetener in foods. The 18β-glycyrrhetinic acid (18β-GA) is a bioactive compound in licorice that exhibits potential anti-cancer, anti-inflammatory, and anti-microbial activities. Many synthesized derivatives of 18β-GA have been reported to be cytotoxic and suggested for the treatment of malignant diseases. In this study, we explored the possible pharmacological roles of an 18β-GA derivative in skin biology using primary human dermal fibroblasts and HaCaT keratinocytes as cell models. We found that this 18β-GA derivative did not cause cell death, but significantly enhanced the proliferation of dermal fibroblasts and HaCaT keratinocytes. A scratch wound healing assay revealed that the 18β-GA derivative promoted the migration of fibroblasts. Due to the important role of aquaporin-3 in cell migration and proliferation, we also investigated the expression of aquaporin-3 and found this compound up-regulated the expression of aquaporin-3 in dermal fibroblasts and HaCaT keratinocytes. In dermal fibroblasts, the 18β-GA derivative induced the phosphorylation of Akt, ERK, and p38. The inhibitor of Akt predominantly suppressed the 18β-GA derivative-induced expression of aquaporin-3. Collectively, this compound had a positive effect on the proliferation, migration, and aquaporin-3 expression of skin cells, implying its potential role in the treatment of skin diseases characterized by impaired wound healing or dermal defects.

Topical tranexamic acid has been used to treat melasma and as a skin whitener.The aim of this study was to compare the skin histology and permeation of tranexamic acid after fractional and conventional CO2 laser pretreatment.The effect of treatment with different strengths of fractional and conventional CO2 laser treatment was examined by scanning and transmission electron microscopy. Permeation of tranexamic acid through porcine skin was tested in vitro using a Franz diffusion chamber.Four passes of fractional laser treatment caused less skin damage than conventional laser treatment at the same fluency. Fractional laser treatment caused at least 85% of the cumulative tranexamic aid permeation at the same fluency, and as fluency increased, the number of passes needed to achieve this goal decreased.Fractional laser treatment is as effective as conventional laser treatment in enhancing tranexamic acid delivery and causes less skin damage.

We prepare an elastic macroporous gelatin/chondoitin-6-sulfate/hyaluronan (GCH) cryogel scaffold mimic the composition of cartilage extracellular matrix for cartilage tissue engineering. By incorporating chitosan in the cryogel to replace 20% gelatin, a GCH-chitosan cryogel was also synthesized and compared with GCH cryogel for scaffold mechanical properties and chondrocytes response. The GCH-chitosan cryogel has larger pores, higher ultimate strain (stress) and elastic modulus, and lower stress relaxation percentage than the GCH cryogel. Both cryogels show a highly elastic property with a loss tangent around 0.1, but chitosan incorporation increases the storage modulus (elasticity). Chondrocytes proliferate and redifferentiate in cryogels; chitosan diminishes cell proliferation but up-regulates glycosaminoglycans (GAGs) and type II collagen (COL II) secretion. Implantation of a chondrocytes/GCH-chitosan cryogel construct in a full-thickness articular cartilage defect regenerates cartilage with positive stainings for GAGs and COL II and an elastic modulus similar to the native cartilage.

During the course of proliferative vitreoretinopathy (PVR), the retinal pigment epithelium (RPE) cells will de-differentiate, proliferate, and migrate onto the surfaces of the sensory retina. Several studies have shown that platelet-derived growth factor (PDGF) can induce migration of RPE cells via an Akt-related pathway. In this study, the effect of lutein on PDGF-BB-induced RPE cells migration was examined using transwell migration assays and Western blot analyses. We found that both phosphorylation of Akt and mitochondrial translocation of Akt in RPE cells induced by PDGF-BB stimulation were suppressed by lutein. Furthermore, the increased migration observed in RPE cells with overexpressed mitochondrial Akt could also be suppressed by lutein. Our results demonstrate that lutein can inhibit PDGF-BB induced RPE cells migration through the inhibition of both cytoplasmic and mitochondrial Akt activation.

The objective of this study was to investigate the effects of two lasers (Er:YAG and CO2) in enhancing skin permeation of three vitamin C derivatives, L-ascorbic acid 2-phosphate sesquimagnesium salt (MAP-1), magnesium L-ascorbic acid-2-phosphate (MAP-2), and 2-phospho-L-ascorbic acid trisodium salt (SAP). Dorsal skin of 1-week-old pathogen-free pigs was used for this in vitro study. Changes in permeation in laser-treated skin treated by the lasers were examined by confocal scanning electron microscopy. Transdermal flux of vitamin C derivatives was examined with a Franz diffusion cell. Fluxes of MAP-1, MAP-2, and SAP across Er:YAG laser-treated skin were 15-27-fold, 48-123-fold, and 22-56-fold higher, respectively, than their fluxes across intact skin. The fluxes of MAP-1, MAP-2, and SAP across CO2 laser-treated skin were 28-36-fold, 116-156-fold, and 79-102-fold higher, respectively, than their fluxes across intact skin. Optimal fluency for the Er:YAG laser was 3.8 J/cm(2) for MAP-1 and 5 J/cm(2) for MAP-2 and SAP. Optimal fluency for the CO2 laser was 5 W for all three derivatives. In conclusion, optimal fluency for all derivatives was 5 W for the CO2 laser and 3.8 to 5 J/cm(2) for the Er:YAG laser.

The objective of this study is to investigate the effects of two lasers (erbium:YAG and CO(2)) on the ability to enhance skin permeation of two vitamin C derivatives, 3-O-ethyl ascorbic acid (EAC) and ascorbic acid 2-glucoside (AA2G). The study was taken in the skin of a female nude mouse (Balb/c-nu strain, 8 weeks old) in vitro. The histologic and ultrastructural changes of the nude mouse skin treated by the lasers were examined under light microscopy and transmission electron microscopy, respectively. The in vitro permeation of vitamin C derivatives was performed in Franz cell. The stratum corneum (SC) layer in the skin was partly ablated by erbium:YAG laser treatment, resulting in greater permeation of both vitamin C derivatives. The flux of EAC and AA2G across erbium:YAG laser-treated skin was 105 to 189-fold and 35 to 78-fold higher, respectively, than their flux across intact skin. The increase in enhancement ratio with increase in fluency decreases markedly for both compounds at the last dose escalation (from 5.0 to 6.3 J/cm(2)). Both SC ablation and a thermal effect may contribute to the effect of the CO(2) laser on skin structure. The flux of EAC and AA2G across CO(2) laser-treated skin was 181 to 277-fold and 82 to 117-fold higher, respectively, than their flux across intact skin. We concluded that both erbium:YAG and CO(2) laser pretreatment increased the transdermal flux of two stable vitamin C derivatives, EAC and AA2G. The optimal fluency for the Er:YAG laser was 5 J/cm(2).