Ultraviolet (UV) irradiation induces detrimental changes in human skin which result in photoaging. UV-induced intracellular changes cause degradation of extracellular matrix (ECM). UV-stimulated ...cleavage of collagen in ECM occurs via matrix metalloproteinases (MMPs). (±)-syringaresinol (SYR), a phytochemical which belongs to the lignan group of polyphenols, was investigated for its ability to reverse the UVA-induced changes in human HaCaT keratinocytes and dermal fibroblasts (HDFs) in vitro. Effect of SYR on UVA-induced changes was investigated by production and activation of MMPs and its transcriptional upstream effectors; mitogen-activated protein kinases (MAPKs) and pro-inflammatory mediators. Levels of expression were determined using ELISA, RT-PCR and immunoblotting. UVA irradiation stimulated the production of MMP-1 and inhibited collagen production. SYR treatment suppressed MMP-1 and enhanced collagen production in UVA-irradiated HaCaT keratinocytes and HDFs. SYR repressed the UV-induced phosphorylation of p38, ERK and JNK MAPKs in HaCaT keratinocytes while only suppressing JNK phosphorylation in HDFs. In addition, SYR was able to inhibit UVA-induced production of inflammatory cytokines; TNF-α, COX-2, IL-1β and IL-6. Moreover, SYR suppressed the activator protein-1 (AP-1), a heterodimer of phosphorylated transcription factors c-Jun and c-Fos. SYR-treatment decreased nuclear levels of activated c-Fos and c-Jun as a mechanism to inhibit UVA-induced transcriptional activities leading to MMP-1 production. In conclusion, current results demonstrated that SYR could inhibit UVA-induced upregulation of MMP-1 by suppressing MAPK/AP-1 signaling in HaCaT keratinocytes and HDFs. Therefore, SYR was suggested as a potential compound with antiphotoaging properties against UVA-induced skin aging.
A phenyl ethanoid, salidroside (SAL), and two secoiridoids, 8(
)-nuezhenide (NZD) and ligustroside (LIG), were isolated from fruits of
used as traditional folk medicine, and their chemical structures ...were elucidated by the comparison of spectral data with published literature. Matrix metalloproteinases (MMPs) are major enzymes that play crucial roles in the metastasis and invasive behavior of tumors. In particular, MMP-2 and MMP-9, regulated by the MAPK signaling pathways, including p38, ERK and JNK, are known to play a key role in the degradation of the basement membrane. In the present study, the effects of SAL, NZD and LIG on the expression of MMP-2 and -9 were examined in phorbol 12-myristate 13-acetate (PMA)-induced HT 1080 cells. All the compounds significantly lowered the amount of MMP-2 and MMP-9 released, as determined by gelatin zymography and ELISA. In addition, the mRNA and protein expression levels of MMP-2 and MMP-9 were significantly suppressed, as measured by RT-PCR and Western blotting. According to the Western blotting assay, SAL and LIG effectively reduced the expression of MMP-2 in a dose-dependent manner. NZD lowered the expression of MMP-9 in a similar way. The phosphorylation of p38, ERK and JNK was also significantly suppressed by these compounds. These findings suggest that all the compounds regulate the release and expression of MMP-2 and MMP-9 via MAPK signaling pathways.
Natural products, especially phenols, are promising therapeutic agents with beneficial effects against aging-related complications such as osteoporosis. This study aimed to investigate the effect of ...quercetin 3-
-β-D-galactopyranoside (Q3G), a glycoside of a common bioactive phytochemical quercetin, on osteogenic and adipogenic differentiation of human bone marrow-derived mesenchymal stromal cells (hBM-MSCs). hBM-MSCs were induced to differentiate into osteoblasts and adipocytes in the presence or absence of Q3G and the differentiation markers were analyzed to observe the effect. Q3G treatment stimulated the osteoblastogenesis markers: cell proliferation, alkaline phosphatase (ALP) activity and extracellular mineralization. In addition, it upregulated the expression of RUNX2 and osteocalcin protein as osteoblastogenesis regulating transcription factors. Moreover, Q3G treatment increased the activation of osteoblastogenesis-related Wnt and bone morphogenetic protein (BMP) signaling displayed as elevated levels of phosphorylated β-catenin and Smad1/5 in nuclear fractions of osteo-induced hBM-MSCs. The presence of quercetin in adipo-induced hBM-MSC culture inhibited the adipogenic differentiation depicted as suppressed lipid accumulation and expression of adipogenesis markers such as PPARγ, SREBP1c and C/EBPα. In conclusion, Q3G supplementation stimulated osteoblast differentiation and inhibited adipocyte differentiation in hBM-MSCs via Wnt/BMP and PPARγ pathways, respectively. This study provided useful information of the therapeutic potential of Q3G against osteoporosis mediated via regulation of MSC differentiation.
UV irradiation is one of the main causes of extrinsic skin aging. UV-mediated skin aging, also known as photoaging, causes excessive breakdown of extracellular matrix which leads skin to lose its ...elasticity and strength. Several phytochemicals are known to exert anti-photoaging effects via different mechanisms, partly due to their antioxidant properties. The current study has been carried out to determine the potential anti-photoaging properties of myricetin 3-O-β-d-galacto-pyranoside (M3G), a flavonol glycoside isolated from
, in UVA-irradiated in vitro models; HaCaT keratinocytes and human dermal fibroblasts (HDFs). UVA-induced changes in MMP-1 and collagen production have been observed in HaCaT keratinocytes and HDFs. Further, UVA-induced activation of MAPK signaling, and pro-inflammatory cytokine production have been investigated. TGFβ/Smad pathway has also been analyzed in UVA-irradiated HDFs. Treatment with M3G reversed the UVA-induced changes in MMP-1 and collagen production both in HaCaT keratinocytes and HDFs. UVA-mediated activation of p38, ERK and JNK MAPK activation was also inhibited by M3G treatment in HaCaT keratinocytes. In HDFs, M3G was able to upregulate the TGFβ/Smad pathway activation. In addition, M3G downregulated the UVA-induced pro-inflammatory cytokines in keratinocytes and HDFs. It has been suggested that the M3G has exerted potential antiphotoaging properties in vitro, by attenuating UVA-induced changes in MMP-1 and collagen production in keratinocytes and dermal fibroblasts.
Quercetin 3-
-galactoside (Q3G) is a common dietary flavanol that has been shown to possess several bioactivities, including anti-melanogenesis. However, how Q3G exerts its anti-melanogenic effect ...has not been studied. The current study, therefore aimed to investigate the anti-melanogenesis potential of Q3G and elucidate the underlying action mechanism in α-melanocyte-stimulating hormone (
-MSH)-induced hyperpigmentation model of B16F10 murine melanoma cells. Results showed that α-MSH stimulation significantly increased tyrosinase (TYR) and melanin production, which were significantly downregulated by Q3G treatment. The treatment with Q3G suppressed the transcriptional and protein expressions of melanogenesis-related enzymes TYR, tyrosinase related protein-1 (TRP-1), and TRP-2, along with the melanogenic transcription factor microphthalmia-associated transcription factor (MITF) in B16F10 cells. It was shown that Q3G downregulated MITF expression and suppressed its transcriptional activity by inhibiting the cAMP-dependent protein kinase A (PKA)-mediated activation of CREB and GSK3β. In addition, MAPK-regulated MITF activation signaling was also involved in the inhibition of melanin production by Q3G. The results suggest that the anti-melanogenic properties of Q3G rationalize further studies in vivo to confirm its action mechanism and consequent utilization as a cosmetic ingredient against hyperpigmentation.
Obesity and related complications are significant health issues in modern society, largely attributed to a sedentary lifestyle and a carbohydrate-rich diet. Since anti-obesity drugs often come with ...severe side effects, preventative measures are being sought globally, including dietary changes and functional foods that can counteract weight gain. In this context, plant-based metabolites are extensively studied for their advantageous biological effects against obesity. Several plants within the
genus have been reported to possess anti-adipogenic properties, preventing adipocytes from maturing and accumulating lipids. The present study investigated the anti-adipogenic potential of two sesquiterpenoids, reynosin and santamarine, isolated from
in adipose-induced 3T3-L1 preadipocytes. Differentiating 3T3-L1 adipocytes treated with these isolated compounds displayed fewer adipogenic characteristics compared to untreated mature adipocytes. The results indicated that cells treated with reynosin and santamarine accumulated 55.0% and 52.5% fewer intracellular lipids compared to untreated control adipocytes, respectively. Additionally, the mRNA expression of the key adipogenic marker, transcription factor PPARγ, was suppressed by 87.2% and 91.7% following 60 μM reynosin and santamarine treatment, respectively, in differentiated adipocytes. Protein expression was also suppressed in a similar manner, at 92.7% and 82.5% by 60 μM reynosin and santamarine treatment, respectively. Likewise, SERBP1c and C/EBPα were also downregulated at both gene and protein levels in adipocytes treated with samples during differentiation. Further analysis suggested that the anti-adipogenic effect of the compounds might be a result of AMPK activation and the subsequent suppression of MAPK phosphorylation. Overall, the present study suggested that sesquiterpenoids, reynosin, and santamarine were two potential bioactive compounds with anti-adipogenic properties. Further research is needed to explore other bioactive agents within
and elucidate the in vivo action mechanisms of reynosin and santamarine.
Aim
This study investigates the pattern of disease recurrence and identifies the clinicopathologic prognostic factors for patients with International Federation of Gynecology and Obstetrics (FIGO) ...stage IB and IIA cervical carcinoma treated with laparoscopic/robotic radical hysterectomy (LRH/RRH).
Methods
We conducted a retrospective analysis of 128 patients with FIGO stage IB and IIA cervical cancer. Preoperative examination did not uncover definitive evidence of parametrial invasion or lymph node metastasis in any of the patients; therefore, all patients underwent LRH/RRH with retroperitoneal lymphadenectomy between April 2006 and December 2013. Sites of disease recurrence and all possible clinicopathologic factors related to the risk of disease recurrence were determined.
Results
Multivariate analysis demonstrated that laparoscopic intracorporeal colpotomy (P < 0.041, odds ratio 7.038, 95% confidence interval 1.059–15.183) represented a strong prognostic factor related to disease recurrence. We categorized the minimally invasive surgery group into LRH through vaginal colpotomy (LRH‐VC; 79 patients) and LRH/RRH through intracorporeal colpotomy (LRH/RRH‐IC; 49 patients) according to the colpotomic approaches. Disease recurrence was higher in the LRH/RRH‐IC group than in the LRH‐VC group (16.3% vs 5.1%, P = 0.057), with five patients in the LRH/RRH‐IC group experiencing intraperitoneal spreads.
Conclusions
Total laparoscopic/robotic intracorporeal colpotomy under CO2 pneumoperitoneum may carry a risk of positive vaginal cuff margin, as well as intraperitoneal tumor spreads in patients with early‐stage cervical cancer treated with LRH/RRH.
Cutaneous aging is divided into intrinsic and exogenous aging correspondingly contributing to the complex biological phenomenon in skin. Intrinsic aging is also termed chronological aging, which is ...the accumulation of inevitable changes over time and is largely genetically determined. Superimposed on this intrinsic process, exogenous aging is associated with environmental exposure, mainly to ultraviolet (UV) radiation and more commonly termed as photoaging. UV-induced skin aging induces increased expression of matrix metalloproteinases (MMPs) which in turn causes the collagen degradation. Therefore, MMP inhibitors of natural origin are regarded as a primary approach to prevent or treat photoaging. This study investigated the effects of 3,5-dicaffeoyl-epi-quinic acid (DEQA) on photoaging and elucidated its molecular mechanisms in UVA-irradiated human dermal fibroblasts (HDFs). The results show that treatment with DEQA decreases MMP-1 production and increases type I collagen production in UVA-damaged HDFs. In addition, treatment of UVA-irradiated HDFs with DEQA downregulates MMP-1, MMP-3 and MMP-9 expression via blocking MAPK-cascade-regulated AP-1 transcriptional activity in UVA-irradiated HDFs. Furthermore, DEQA relieves the UVA-mediated suppression of type I procollagen and collagen expression through stimulating TGF-β/Smad signaling, leading to activation of the Smad 2/3 and Smad 4 nuclear translocation. These results suggest that DEQA could be a potential cosmetic agent for prevention and treatment of skin photoaging.
Background
Chronic exposure to ultraviolet (UV) radiation induces photo‐oxidation, which in turn causes the overproduction of matrix metalloproteinases (MMPs) and collagen degradation. These symptoms ...are referred to as photoaging, which is characterized by skin thickness, irregular pigmentation, elastosis and coarse wrinkles. In this study, the protective effects of oleracone C isolated from Portulaca olerace against UVB‐induced changes in MMPs and type I procollagen production were investigated in human keratinocytes.
Methods
Human immortalized keratinocytes have been used as an in vitro cell model to study the abnormal skin barrier development such as in photoaging. The effects of the compound on cell viability were determined by colorimetric MTT assay. This study also measured ROS production using DCFH‐DA assay. Releases of MMPs and type Iα1 procollagen were analysed by ELISA. RT‐PCR and Western blot were carried out to test the expressions of mRNA and proteins related to MMPs and type I procollagen biosynthesis.
Result
Effect of oleracone C against UVB‐mediated oxidative stress was evaluated measuring its ability to eliminate UVB‐induced activation of reactive oxygen species (ROS). Treatment of oleracone C hindered the production of intracellular ROS. UVB exposure increased MMPs (MMP‐1, MMP‐2 and MMP‐9) release from keratinocytes and decreased the release of type I procollagen. Treatment with oleracone C reversed these effects of UVB exposure. Oleracone C treatment also diminished the intracellular expression of MMP‐1, MMP‐2 and MMP‐9 and elevated the type I procollagen. Oleracone C suppressed the UVB irradiation‐dependent upregulation phosphorylation of p38 and ERK1/2 in the mitogen‐activated protein kinase (MAPK) pathway. Furthermore, oleracone C stimulated collagen production through the TGF‐β signalling pathway, which activates collagen synthesis in UVB‐irradiated keratinocytes.
Conclusion
These findings reasonably suggest ameliorating the potential of oleracone C against the UVB‐induced photoaging of the human keratinocytes.
Résumé
Contexte
L’exposition chronique aux rayons ultraviolets (UV) induit la photo‐oxydation, qui à son tour entraîne la surproduction de métalloprotéases matricielles (MMP) et la dégradation du collagène. Ces symptômes sont appelés photovieillissement, qui se caractérise par une épaisseur de la peau, une pigmentation irrégulière, une élastose et des rides grossières. Dans cette étude, les effets protecteurs de l’oléracone C isolée à partir du pourpier potager contre les changements induits par les UVB dans les MMP et la production de procollagène de type I ont été étudiés dans les kératinocytes humains.
Méthodes
Les kératinocytes humains immortalisés ont été utilisés comme modèle cellulaire in vitro pour étudier le développement anormal de la barrière cutanée, comme c’est le cas dans le photovieillissement. Les effets du composé sur la viabilité cellulaire ont été déterminés par test colorimétrique au MTT. Cette étude a également mesuré la production de DRO à l’aide du dosage DCFH‐DA. Les productions de MMP et de procollagène de type Iα1 ont été analysées par la méthode ELISA. La RT‐PCR et le Western blot ont été réalisés pour tester les expressions de l’ARNm, et des protéines liées aux MMP et à la biosynthèse du procollagène de type I.
Résultat
L’effet de l’oléracone C contre le stress oxydatif médié par les UVB a été évalué en mesurant sa capacité à éliminer l’activation induite par les UVB des dérivés réactifs de l’oxygène (DRO). Le traitement par oléracone C a empêché la production de DRO intracellulaires. L’exposition aux UVB a augmenté la production de MMP (MMP‐1, MMP‐2 et MMP‐9) par les kératinocytes et a diminué la production de procollagène de type I. Le traitement par oléracone C a inversé ces effets de l’exposition aux UVB. Le traitement par oléracone C a également diminué l’expression intracellulaire de MMP‐1, MMP‐2 et MMP‐9, et a augmenté le taux de procollagène de type I. L’oléracone C a supprimé la phosphorylation de régulation à la hausse dépendante de l’exposition aux UVB de p38 et ERK1/2 dans la voie de la protéine kinase activée par des agents mitogènes (Mitogen‐Activated Protein Kinase, MAPK). En outre, l’oléracone C a stimulé la production de collagène par la voie de signalisation de TGF‐β, qui active la synthèse du collagène dans les kératinocytes exposés aux UVB.
Conclusion
Ces résultats indiquent raisonnablement une amélioration du potentiel de l’oléracone C contre le photovieillissement induit par les UVB des kératinocytes humains.
Bone marrow adiposity has been associated with several metabolic syndromes such as diabetes and osteoporosis. Imbalance in adipogenic and osteoblastogenic differentiation of human bone marrow ...mesenchymal stromal cells (hBM-MSCs) was suggested to be the cause of elevated bone marrow adiposity. There are several drugs, of both natural and synthetic origin, to treat bone loss. In this study, as a part of a recent trend to discover natural products with more biocompatibility and fewer side effects to treat bone loss, the effect of hyunganol II (HNG), a coumarin isolated from Corydalis heterocarpa, on hBM-MSC adipogenesis was investigated. Cells treated with HNG showed decreased lipid accumulation indicating a diminished adipocyte phenotype. Treatment with HNG also suppressed the mRNA and protein expressions of PPARγ, C/EBPα, and SREBP1c, and three adipogenic marker genes. Further analysis of MAPK signaling pathway exhibited that HNG treatment elevated ERK activation and suppressed the JNK-mediated cFos and cJun phosphorylation, which inhibits PPARγ transcriptional activity. Taken together, HNG treatment was shown to inhibit adipogenesis via suppressed PPARγ expression as a result of altered MAPK signaling. Therefore, it was suggested that HNG might prevent bone marrow adiposity by inhibiting hBM-MSC adipogenesis and can be utilized as a drug or nutraceutical with beneficial effects on bone. Thus, further studies should be conducted to analyze its effect in vivo.
PDF
