Nutricosmetic effects of Asparagus officinalis: a potent matrix metalloproteinase-1 inhibitor.

This study aimed to investigate the nutricosmetic effect of Asparagus officinalis extracts. The tip and spear of A. officinalis were successively extracted with 95% ethanol. The rutin, phenolic, and flavonoid contents of A. officinalis extracts were investigated. The antioxidant activities were determined by 2,2-azinobis (3-ethylbenzothiazoline-6-sulphonic acid) and a ferric reducing antioxidant power assay. Matrix metalloproteinase-1 (MMP-1), elastase, and hyaluronidase inhibition were determined by in vitro enzyme reaction assay. The cytotoxicity was analyzed on peripheral blood mononuclear cellss. Findings revealed that drying temperature and drying duration had significant effects on the chemical composition and biological activity of A. officinalis extract. A. officinalis tips dried at 50 °C for 24 h contained the (significantly) highest flavonoid and rutin content. The most potent extract was from A. officinalis spears since it possessed the (significantly) highest MMP-1, elastase, and hyaluronidase inhibition rates of 83.4 ± 1.5%, 70.4 ± 4.1%, and 75.2 ± 1.0%, respectively. Interestingly, at the same concentration, the A. officinalis spear extract was more potent in MMP-1 inhibition than oleanolic acid and epigallocatechin gallate, the well-known natural MMP-1 inhibitors. The results show that A. officinalis extract is an attractive source of natural anti-skin-wrinkle ingredients.

Glycosyl flavones from Humulus japonicus suppress MMP-1 production via decreasing oxidative stress in UVB irradiated human dermal fibroblasts.

Exposure to Ultraviolet (UV) light induces photoaging of skin, leading to wrinkles and sunburn. The perennial herb Humulus japonicus, widely distributed in Asia, is known to have antiinflammatory, antimicrobial, and antioxidant effects. However, the physiological activities of isolated compounds from H. japonicus have rarely been investigated. This study focused on the isolation of active compounds from H. japonicus and the evaluation of their effects on photoaging in UVB-irradiated human fibroblast (Hs68) cells. When the extract and four fractions of H. japonicus were treated respectively in UVB-irradiated Hs68 cells to investigate anti-photoaging effects, the ethyl acetate (EtOAc) fraction showed the strongest inhibitory effect on MMP- 1 secretion. From EtOAc fraction, we isolated luteolin-8-C-glucoside (1), apigenin-8-C-glucoside (2), and luteolin-7-O-glucoside (3). These compounds suppressed UVB-induced MMP-1 production by inhibiting the phosphorylation of the mitogen-activated protein kinases (MAPKs) and activator protein-1 (AP-1). When the antioxidant activity of the compounds were estimated by conducting western blot, calculating the bond dissociation energies of the O-H bond (BDE) at different grade, and measuring radical scavenging activity, we found luteolin-8-C-glucoside (1) showed the strongest activity on the suppression of UVB-induced photoaging. These results demonstrate the inhibitory effect of three flavone glycosides derived from H. japonicus on MMP-1 production, MAPK and AP-1 signaling, and oxidative stress; this could prove useful in suppressing UVB induced photoaging. [BMB Reports 2020; 53(7): 379-384].

Effects of 12-Week Exercise Program on Enzyme Activity of Serum Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 in Female Patients with Postmenopausal Osteoporosis: A Randomized Control Study.

BACKGROUND: Osteoporosis is a disease characterized by decreased bone density and destruction of bone microarchitecture. Indicators for altered bone homeostasis are changes in the serum level of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). The purpose of the current study was to evaluate the effect of a 12-week exercise program on enzyme activity of serum MMP-9 and TIMP-1 in postmenopausal osteoporotic patients. Materials and methods. Participants were randomized in two groups: exercise (EG) (N = 37) and control (CG) (N = 37) and control (CG) (. RESULTS: Significant differences between pretreatment and posttreatment enzyme activities of serum MMP-9 (p=0.009), TIMP-1 (p=0.009), TIMP-1 (p=0.009), TIMP-1 (. CONCLUSION: Our results suggest that a 12-week exercise program has an influence on enzyme activity of serum MMP-9, revealing a possible role of MMPs in initiating training-specific adaptation. Although measurements of circulating MMP-9 and TIMP-1 allowed us to detect effects of exercise, as of today, they have no real role in the diagnosis of osteoporosis and/or follow-up of osteoporotic patient's response to treatment. MMP-9 might be used as an important prognostic marker for the evaluation of patient's response to exercise. Larger-randomized controlled studies need to be performed to expand this area of knowledge. This trial is registered with trial registration number: NCT03816449).

Down-regulation of mir-27b promotes angiogenesis and fibroblast activation through activating PI3K/AKT signaling pathway.

To study the effects of mir-27b on angiogenesis and fibroblast activation and to explore its further mechanism. Humanmicrovascular endothelial cell (HMEC)-1 and humannormal skin fibroblast (BJ) cells were treated with mir-27b inhibitor negative control reagent, mir-27b inhibitor, LY294002, and mir-27b inhibitor + LY294002, respectively. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) was used to detect the T-cell proliferation. The migration ability was detected by Scratch assays. The angiogenesis of HMEC-1 cells was observed by in vitro tube formation assay. The mRNA and protein expression of vascular endothelial growth factor (VEGF) in HMEC-1 cells and the mRNA and protein expression of collagen I, collagen III, α-SMA, and MMP1 in BJ cells were detected by quantitativereal-time polymerase chain reaction (qRT-PCR) and Western blot, respectively. Meanwhile, the PI3K/protein kinase B (AKT) pathway-related proteins were also detected by Western blot. The proliferation, migration, angiogenesis, the mRNA and protein expression of VEGF and the protein expression of p-PI3K and p-AKT in HMEC-1 cells were increased after treated with mir-27b inhibitor. Meanwhile, the proliferation, migration, and the protein expression of collagen I, collagen III, α-SMA, MMP1, p-PI3K, and p-AKT in BJ cells were increased after treated with mir-27b inhibitor. However, the angiogenesis and fibroblast activation of mir-27b inhibitor was reversed by LY294002, and the activate effect to PI3K/AKT pathway was also inhibited. Down-regulation of mir-27b could promote angiogenesis and fibroblast activation, and its mechanism is related to activate PI3K/AKT signaling pathway.

Design, synthesis and biological evaluation of some new 1,3,4-thiadiazine-thiourea derivatives as potential antitumor agents against non-small cell lung cancer cells.

New 1,3,4-thiadiazine-thiourea derivatives have been synthesized. All the synthesized compounds were examined for in vitro cytotoxic activity against Non-Small Cell Lung Cancer (NSCLC) cell line A549, using MTT bioassay. Compounds 5d, 5i, 5j showed the highest cytotoxic activity with IC50 values of 0.27 ±â€¯0.01, 0.30 ±â€¯0.02, and 0.32 ±â€¯0.012 µM respectively with sorafenib as reference (IC50 3.85 ±â€¯0.27 µM). These compounds were chosen for further investigations against various biological targets known to play roles in NSCLC specifically: vascular endothelial growth factor receptor 2 (VEGFR2), B-RAF and matrix metalloproteinase 9 (MMP9). Encouraging results were exhibited by the three compounds against the selected targets. Compound 5j was specially promising as it exhibited inhibitory activity of VEGFR2 close to sorafenib (IC50 0.11 ±â€¯0.01 µM), most potent B-RAF activity inhibition (IC50 0.178 ±â€¯0.004 µM) and MMP9 inhibition (IC50 0.08 ±â€¯0.004 µM). Moreover, cell cycle analysis of A549 cells treated with 5j exhibited cell cycle arrest at G2-M phase and pro-apoptotic activity as indicated by Annexin V-FITC staining. Also, it reflected antinvasive and antimigration properties to A549 cells. Additionally, docking study of 5j on VEGFR2, B-RAF and MMP9 revealed that it binds to the target enzymes in a similar way as the co-crystallized ligand. The three compounds exhibited significantly high selectivity to A549 cancer cells against the normal human fetal lung fibroblast cell line WI-38 with higher selectivity index compared to sorafenib (5d IC50 136.76 ±â€¯2.38 µM, SI = 506.52; 5i IC50 89.20 ±â€¯2.11 µM, SI = 297.33; 5j IC50 79.60 ±â€¯3.8 µM, SI = 248.75; sorafenib IC50 30.32 ±â€¯2.41 µM, SI = 7.88). In conclusion, compounds 5d, 5i and 5j, specially 5j are promising anticancer agents targeting important pathways in NSCLC and warrant further preclinical and clinical trials.

Sudachitin Inhibits Matrix Metalloproteinase-1 and -3 Production in Tumor Necrosis Factor-α-Stimulated Human Periodontal Ligament Cells.

Sudachitin, a polymethoxylated flavonoid found in the skin of Citrus sudachi, is a biologically active substance. The aim of this study was to examine whether sudachitin could be used to inhibit the expression of matrix metalloproteinase (MMP)-1 and MMP-3, which are involved in the destruction of periodontal tissues in periodontal lesions, in tumor necrosis factor (TNF)-α-stimulated human periodontal ligament cells (HPDLC). Sudachitin suppressed TNF-α-induced MMP-1 and MMP-3 production in HPDLC. On the other hand, it enhanced tissue inhibitor of metalloproteinase (TIMP)-1 expression. The level of Akt phosphorylation in the TNF-α-stimulated HPDLC was decreased by sudachitin treatment. Moreover, an Akt inhibitor reduced MMP-1 and MMP-3 production and increased TIMP-1 production. These findings indicate that sudachitin reduces MMP-1 and MMP-3 production in TNF-α-stimulated HPDLC by inhibiting the Akt pathway.

Doxycycline-loaded nanotube-modified adhesives inhibit MMP in a dose-dependent fashion.

OBJECTIVES: This article evaluated the drug loading, release kinetics, and matrix metalloproteinase (MMP) inhibition of doxycycline (DOX) released from DOX-loaded nanotube-modified adhesives. DOX was chosen as the model drug, since it is the only MMP inhibitor approved by the U.S. Food and Drug Administration. MATERIALS AND METHODS: Drug loading into the nanotubes was accomplished using DOX solution at distinct concentrations. Increased concentrations of DOX significantly improved the amount of loaded DOX. The modified adhesives were fabricated by incorporating DOX-loaded nanotubes into the adhesive resin of a commercial product. The degree of conversion (DC), Knoop microhardness, DOX release kinetics, antimicrobial, cytocompatibility, and anti-MMP activity of the modified adhesives were investigated. RESULTS: Incorporation of DOX-loaded nanotubes did not compromise DC, Knoop microhardness, or cell compatibility. Higher concentrations of DOX led to an increase in DOX release in a concentration-dependent manner from the modified adhesives. DOX released from the modified adhesives did not inhibit the growth of caries-related bacteria, but more importantly, it did inhibit MMP-1 activity. CONCLUSIONS: The loading of DOX into the nanotube-modified adhesives did not compromise the physicochemical properties of the adhesives and the released levels of DOX were able to inhibit MMP activity without cytotoxicity. CLINICAL SIGNIFICANCE: Doxycycline released from the nanotube-modified adhesives inhibited MMP activity in a concentration-dependent fashion. Therefore, the proposed nanotube-modified adhesive may hold clinical potential as a strategy to preserve resin/dentin bond stability.

The effect of dehydroglyasperin C on UVB-mediated MMPs expression in human HaCaT cells.

BACKGROUND: The ultraviolet B (UVB) from solar radiation increases the generation of reactive oxygen species (ROS), which mediate the production of matrix metalloproteinases (MMPs), and acts mainly on the epidermis layer of the skin. This study was aimed at assessing the anti-photoaging effects of dehydroglyasperin C isolated from Glycyrrhiza uralensis Fisch on MMPs levels in HaCaT human keratinocytes and to elucidate the underlying mechanism. METHODS: The cell viability was measured by MTT assay. Expression, phosphorylation and enzymatic activity of the protein were examined using ELISA, Western blot or gelatin zymography. Intracellular ROS measurement was evaluated by fluorescent ELISA and 2',7'-dichlorodihydrofluorescein diacetate (H2DCF-DA) assay. RESULTS: In the present study, we found that dehydroglyasperin C markedly inhibited UVB-mediated expression of collagenase (MMP-1) and gelatinase (MMP-9) by inhibiting ROS generation. Dehydroglyasperin C treatment also decreased the UVB irradiation-mediated activation of mitogen-activated protein kinase (MAPK), c-Jun phosphorylation, and c-Fos expression. In addition, the down-regulation of UVB-induced c-Jun phosphorylation caused by dehydroglyasperin C treatment was more than the down-regulation of c-Fos expression in the HaCaT human keratinocytes. CONCLUSION: Our results indicated that dehydroglyasperin C may function as a potential anti-photoaging agent by inhibiting UVB-mediated MMPs expression via suppression of MAPK and AP-1 signaling.

Leonurine attenuates fibroblast-like synoviocyte-mediated synovial inflammation and joint destruction in rheumatoid arthritis.

Objective: To explore the role of leonurine in the regulation of synovial inflammation and joint destruction inRA. Methods: Fibroblast-like synoviocytes were isolated from synovial tissue from RA patients. Pro-inflammatory cytokine and MMP expression was evaluated using real-time PCR and a cytometric bead array. Cell migration and invasion in vitro were measured using the Boyden chamber method and the scratch assay, respectively. Protein expression was measured by western blotting. Nuclear factor kappa B (NF-κB) nuclear translocation was detected by immunofluorescence. The in vivo effect of leonurine was evaluated in mice with CIA. Results: Leonurine treatment significantly decreased the production of pro-inflammatory cytokines (IL-1ß, IL-6, IL-8 and TNFα) and MMPs (MMP-1 and MMP-3) and suppressed the migration and invasion of RA fibroblast-like synoviocytes. The molecular analysis revealed that leonurine impaired TNFα-induced NF-κB signalling by inhibiting the phosphorylation and degradation of inhibitor of NF-κB alpha (IκBα) and subsequently preventing the nuclear translocation of the NF-κB p65 subunit. Leonurine also inhibited the p38 and Jun N-terminal kinase mitogen-activated protein kinases signalling pathways without affecting ERK signalling. Intraperitoneal injection of leonurine reduced synovial inflammation, joint destruction and the serum IL-1ß, IL-6 and TNFα levels in mice with CIA. Conclusion: Our findings show that leonurine reduces synovial inflammation and joint destruction in RA through the NF-κB and mitogen-activated protein kinases pathways. Leonurine has potential as a therapeutic agent for RA.

ROS Scavenging and Anti-Wrinkle Effects of Clitocybin A Isolated from the Mycelium of the Mushroom Clitocybe aurantiaca.

Clitocybin A, an isoindolinone from Clitocybe aurantiaca, was investigated to assess its anti-wrinkle properties, through reactive oxygen species (ROS)-scavenging and elastase inhibitory activities, procollagen synthesis, and matrix metalloproteinase-1 (MMP-1) expression, in human primary dermal fibroblast-neonatal (HDF-N) cells. Clitocybin A exhibited no significant cytotoxicity up to 10 ppm in HDF-N cells, with cell viability and cell proliferation activity greater than 94.6% and 91.9%, respectively. Strong and concentration-dependent ROS radical scavenging activities of clitocybin A were observed following irradiation with UVB at 30 mJ/cm2. Furthermore, clitocybin A treatment of cells at 0.1, 1, and 10 ppm exhibited decreased elastase activity, in a concentration-dependent manner, by 1.97%, 6.6%, and 8.31%, respectively, versus the control group. The effects of clitocybin A on procollagen synthesis and MMP-1 expression were investigated. Clitocybin A treatment of cells at 1, 5, and 10 ppm increased procollagen synthesis, by 67.9%, 74.4%, and 112.9%, respectively, versus the control group. At these concentrations, MMP-1 expression decreased significantly following UV irradiation. Together, these findings suggest that clitocybin A may be an effective ingredient for use in anti-wrinkle cosmetic products.

The effect of potassium diclofenac and dexamethasone on MMP-1 gene transcript levels during experimental tooth movement in rats.

OBJECTIVES: The aim of this study was to analyze MMP-1 transcript levels in periodontal tissues of rats that underwent orthodontic treatment using potassium diclofenac and dexamethasone at different stages of tooth movement. SETTING AND SAMPLE POPULATION: The sample comprised of ninety male Wistar rats. MATERIAL AND METHODS: A closed nickel-titanium coil spring was used to apply a force of 50 cN to move the maxillary right first molars mesially. One group received daily doses of 0.9% saline solution, the second group received daily doses of 5 mg/kg potassium diclofenac, and the third group received daily doses of 0.5 mg/kg dexamethasone. Tooth movement was observed on days 0, 1, 3, 7, and 14. MMP-1 transcript levels were evaluated by real-time polymerase chain reaction and the results were compared between groups by three-way ANOVA, with a significance level of 0.05. RESULTS: Transcript levels increased in groups that received the coil spring treatment on all days of the experiment. MMP-1 expression was found to be decreased in groups treated with potassium diclofenac and dexamethasone compared to that in the control group, on days 1, 3, 5, and 7. CONCLUSIONS: The application of orthodontic forces significantly increased MMP-1 transcript levels. The use of anti-inflammatory drugs may have an inhibitory effect on MMP-1 expression.

Licoricidin, an isoflavonoid isolated from Glycyrrhiza uralensis Fisher, prevents UVA-induced photoaging of human dermal fibroblasts.

OBJECTIVE: Licoricidin is an isoflavonoid isolated from Glycyrrhiza uralensis Fisher. In this study, we investigated the effects of licoricidin on photoaging of UVA-irradiated human dermal fibroblasts (HDFs). METHODS: In vitro reactive oxygen species (ROS) scavenging activity, cellular protective effect and inhibition of elastase activity was determined by Fe3+ -EDTA/H2 O2 systems, photohaemolysis and elastase activity assay, respectively. Anti-oxidative capacity of the compound was evaluated by fluorescent ELISA and 2', 7'-dichlorofluorescin-diacetate (DCF-DA) assay. The expression of protein and phosphorylation was examined using Western blot. RESULTS: The ROS scavenging activity (OSC50 ) of licoricidin was 2.77 µM. It was 3.1-fold higher than that of L-ascorbic acid. Its protective effects were confirmed in a study of 1 O2 -induced cellular damage to human erythrocytes. The τ50 value of 10 µM of licoricidin was 71.0 min; this was markedly higher than that obtained with α-tocopherol (37.0 min). The elastase inhibitory activity of licoricidin (IC50 of 61.2 µM) was 2.1-fold more potent than that of oleanolic acid. Licoricidin markedly reduced the UVA-induced intracellular ROS in a concentration-dependent manner. Western blot revealed that licoricidin attenuated the UVA-dependent induction of MMP-1 protein. Mechanistically, this appeared to be due to licoricidin-dependent inhibition of mitogen-activated protein kinases (MAPK) phosphorylation, which resulted in decreased c-Jun activation and reduced c-Jun and c-Fos expression. CONCLUSION: Licoricidin blocks UVA-induced photoaging via ROS scavenging. This activity converges to limit the activity of MMP-1. These data suggest that licoricidin may be considered as an active ingredient in new topically applied anti-ageing formulations.

IL37 dampens the IL1ß-induced catabolic status of human OA chondrocytes.

Objective: A crucial feature of OA is cartilage degradation. This process is mediated by pro-inflammatory cytokines, among other factors, via induction of matrix-degrading enzymes. Interleukin 37 (IL37) is an anti-inflammatory cytokine and is efficient in blocking the production of pro-inflammatory cytokines during innate immune responses. We hypothesize that IL37 is therapeutic in treating the inflammatory cytokine cascade in human OA chondrocytes and can act as a counter-regulatory cytokine to reduce cartilage degradation in OA. Methods: Human OA cartilage was obtained from patients undergoing total knee or hip arthroplasty. Immunohistochemistry was applied to study IL37 protein expression in cartilage biopsies from OA patients. Induction of IL37 expression by IL1ß, OA synovium-conditioned medium and TNFα was investigated in human OA chondrocytes. Adenoviral overexpression of IL37 followed by IL1ß stimulation was performed to investigate the anti-inflammatory potential of IL37. Results: IL37 expression was detected in cartilage biopsies of OA patients and induced by IL1ß. After IL1ß stimulation, increased IL1ß, IL6 and IL8 expression was observed in OA chondrocytes. Elevated IL37 levels diminished the IL1ß-induced IL1ß , IL6 and IL8 gene levels and IL1ß and IL8 protein levels. In addition to the reduction in pro-inflammatory cytokine expression, IL37 reduced MMP1 , MMP3 , MMP13 and disintegrin and metalloproteinase with thrombospondin motifs 5 gene levels and MMP3 and MMP13 protein levels. Conclusion: IL37 is induced by IL1ß, and IL37 itself reduced IL1ß, IL6 and IL8 production, indicating that IL37 is able to induce a counter-regulatory anti-inflammatory feedback loop in chondrocytes. In addition, IL37 dampens catabolic enzyme expression. This supports IL37 as a potential therapeutic target in OA.

SB-431542, a specific inhibitor of the TGF-ß type I receptor inhibits hypoxia-induced proliferation of pulmonary artery adventitial fibroblasts.

The vascular remodeling process plays an important role in the pathology of hypoxia-induced pulmonary hypertension, and it includes cell proliferation, cell motility, cell synthesis and collagen coagulation. Due to their proliferation and synthesis ability, the adventitial fibroblasts are thought to be critical in the vascular remodeling process initiated in response to hypoxia. However, the factors driving hypoxia-induced fibroblast proliferation and synthesis have yet to be elucidated, and the treatment regimens to treat hypoxia remain ineffective. As forthis study, its purpose was to examine the effects exerted by SB-431542, a small-molecule antagonist of transforming growth factor-ß-receptor, on the proliferation, synthesis and collagen coagulation in cultured adventitial fibroblasts. Another aim of this study was to assess the inhibitory ability of SB-431542 on pulmonary vascular remodeling in chronic hypoxia in vivo.The cell morphology and proliferation of cultured adventitial fibroblasts was assessed by laser confocal microscopy and the MTT assay, respectively. Additionally, collagen synthesis was determined by hydroxyproline chromatography, while the expression of cytokines in adventitial fibroblasts and lung tissues was evaluated by immunohistochemical and reverse transcription PCR analyses. The results indicated that the exposure of cultured fibroblasts to 1% oxygen led to the up regulation of cell proliferation, cell synthesis. In addition, increased expression of cytokines and collagen was detected in vivo in the pulmonary artery adventitia of rats exposed to chronic hypoxia. Conversely, SB-431542 inhibited fibroblast proliferation and synthesis in the process of hypoxia-induced pulmonary hypertension (P < 0.01). Thus, the results suggested that by reducing cell proliferation, cell synthesis of vascular adventitia, small molecule inhibitors of the TGF-ß1 receptors may offer a novel therapy for pulmonary hypertension.

Effects of chitin and sepia ink hybrid sponge on the healing of burning wound rats and its impact on macrophages in vitro.

PURPOSE: To detect whether chitin and sepia ink sponge (CS) can promote wound healing and elevate impact of CS on phagocytosis ability of macrophages. METHODS: Forty-eight rats were assigned to four groups: Normal group (Normal), negative control group (Con), chitin and sepia ink sponge group (CS) and positive control Surgicel Gauze(r) group (SG). Deep second-degree burn model was created in rats. Wound area was recorded by digital imaging and determined using Image J software. Samples were collected and kept at -80oC on 3d, 7d, 14d and 21d for cytokines detecting. Transforming growth factor (TGF)-ß1, interleukin (IL)-6, matrix metalloproteinase (MMP)-1, hydroxyproline (Hyp) and macrophage activity reflected by tumor necrosis factor (TNF)-α were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Comparing to Con and SG, scabs in CS group fell off and basically healed on 21 day. TGF-ß1, IL-6, MMP-1 and Hyp were significantly increased by CS and SG comparing to Con (p < 0.05), CS had more apparently adjustment on TGF-ß1 and MMP-1 compared to SG; results in vitro indicated CS significantly promoted phagocytosis ability of macrophages reflected in TNF-α (p < 0.05). CONCLUSION: CS improved wound healing through exerting significant influences on secretion of kinds of cytokines and activating macrophages.

Effects of chitin and sepia ink hybrid sponge on the healing of burning wound rats and its impact on macrophages in vitro

PURPOSE: To detect whether chitin and sepia ink sponge (CS) can promote wound healing and elevate impact of CS on phagocytosis ability of macrophages. METHODS: Forty-eight rats were assigned to four groups: Normal group (Normal), negative control group (Con), chitin and sepia ink sponge group (CS) and positive control Surgicel Gauze(r) group (SG). Deep second-degree burn model was created in rats. Wound area was recorded by digital imaging and determined using Image J software. Samples were collected and kept at -80oC on 3d, 7d, 14d and 21d for cytokines detecting. Transforming growth factor (TGF)-β1, interleukin (IL)-6, matrix metalloproteinase (MMP)-1, hydroxyproline (Hyp) and macrophage activity reflected by tumor necrosis factor (TNF)-α were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Comparing to Con and SG, scabs in CS group fell off and basically healed on 21 day. TGF-β1, IL-6, MMP-1 and Hyp were significantly increased by CS and SG comparing to Con (p < 0.05), CS had more apparently adjustment on TGF-β1 and MMP-1 compared to SG; results in vitro indicated CS significantly promoted phagocytosis ability of macrophages reflected in TNF-α (p < 0.05). CONCLUSION: CS improved wound healing through exerting significant influences on secretion of kinds of cytokines and activating macrophages.

What do we know about sulforaphane protection against photoaging?

Sulforaphane (SFN), a natural compound occurring in cruciferous vegetables, has been known for years as a chemopreventive agent against many types of cancer. Recently, it has been investigated as an antioxidant and anti-aging agent, and interesting conclusions have been made over the last decade. SFN demonstrated protective effects against ultraviolet (UV)-induced skin damage through several mechanisms of action, for example, decrease of reactive oxygen species production, inhibition of matrix metalloproteinase expression, and induction of phase 2 enzymes. SFN used as a protective agent against UV damage is a whole new matter, and it seems to be a very promising ingredient in upcoming anti-aging drugs and cosmetics.

Identification of MMP-1 and MMP-9 inhibitors from the roots of Eleutherococcus divaricatus, and the PAMPA test.

The purpose of this study was the isolation of metalloproteinases MMP-1 and MMP-9 inhibitors from the chloroform extract of the Eleutherococcus divaricatus roots. Using GC-MS, (1)H and (13)C NMR, HMQC, HMBC, COSY and DEPT, (+)-sesamin has been identified as a new anti-MMP inhibitor. We report for the first time that (+)-sesamin inhibited MMP-1 and MMP-9 activity in 40% and 17%, respectively. The high inhibitory potential has been shown by ursolic acid (90.9% and 89.8% for MMP-1 and MMP-9). In the PAMPA test, the Pe value for sesamin was established as 17.4 × 10(-6) cm/s, that for ursolic acid as 30.0 × 10(- 6) cm/s. Verapamil and theophylline were used as a positive and negative control (Pe 42.1 and 2.9 × 10(-6) cm/s). To our best knowledge, no information was available on this activity of sesamin and other compounds. These studies provide a biochemical basis for the regulation of MMP-1 and MMP-9 by E. divaricatus compounds.

Flt3 is a target of coumestrol in protecting against UVB-induced skin photoaging.

While skin aging is a naturally occurring process by senescence, exposure to ultraviolet (UV) radiation accelerates wrinkle formation and sagging of skin. UV induces skin aging by degrading collagen via activating matrix metalloproteinases (MMPs). In this study, we show that coumestrol, a metabolite of the soybean isoflavone daidzein, has a preventive effect on skin photoaging in three-dimensional human skin equivalent model. Coumestrol inhibited UVB-induced MMP-1 expression and activity. Whole human kinase profiling assay identified FLT3 kinase as a novel target protein of coumestrol in UVB-induced signaling pathway in skin. Coumestrol suppresses FLT3 kinase activity, and subsequently, Ras/MEK/ERK and Akt/p70 ribosomal S6 kinase pathway. This suppresses AP-1 activity and in turn, diminishes MMP-1 gene transcription. Using X-ray crystallography, the binding of coumestrol to FLT3 was defined and implied ATP-competitive inhibition. Residues Lys644 and Phe830 showed local changes to accommodate coumestrol in the ATP-binding pocket. 4-APIA, a pharmacological inhibitor of FLT3, inhibited MMP-1 expression and induced signal transduction changes similar to coumestrol. Taken together, coumestrol inhibits UVB-induced MMP-1 expression by suppressing FLT3 kinase activity. These findings suggest that coumestrol is a novel dietary compound with potential application in preventing and improving UVB-associated skin aging.

Opuntia Extract Reduces Scar Formation in Rabbit Ear Model: A Randomized Controlled Study.

The purpose of this article is to investigate the effect of Opuntia stricta H (Cactaceae) extract on suppression of hypertrophic scar on ventral surface wounds of rabbit ears. Full thickness skin defection was established in a rabbit ear to simulate hypertrophic scar. Opuntia extract was sprayed on the wounds in the experimental group, and normal saline was used in the control group. After the wounds healed with scar formation, the hypertrophic scar tissue was harvested on days 22, 39, and 54 for histological analysis. The expression of type I and type III collagen and matrix metalloproteinase-1 (MMP-1) were evaluated by immunohistochemistry and real-time quantitative polymerase chain reaction. The results indicated that the scar of the control group is more prominent compared with the opuntia extract group. The expression of type I collagen in the opuntia extract group was lower than the control group, while type III collagen in opuntia extract group gradually increased and exceeded control group. The expression of MMP-1 decreased in the opuntia extract group, while the control group increased over time, but the amount of MMP-1 was much higher than that in the control group on day 22. In conclusion, opuntia extract reduces hypertrophic scar formation by means of type I collagen inhibition, and increasing type III collagen and MMP-1.T he novel application of opuntia extract may lead to innovative and effective antiscarring therapies.