Oral intake of collagen hydrolysate from mackerel scad (Decapterus macarellus) attenuates skin photoaging by suppressing the UVB-induced expression of MMP-1 and IL-6.

OBJECTIVES: Excessive skin exposure to UVB radiation can induce photoaging caused by an imbalance in oxidative stress and inflammatory responses, damaging the skin's structure and surface layer. A previous study revealed that collagen hydrolisate extracted from the skin of mackarel scads (Decapterus macarellus) had antiaging properties that were tested in vitro, which serves as a foundation for a subsequent study of its use in vivo. This study aimed at investigating the repair effect of the mackerel scad's skin collagen hydrolysate (MSS-CH) in photoaging conditions in a mouse model. METHODS: MSS-CH was given orally in mice model of skin photoaging under chronic exposure to UVB irradiation for 12 weeks. Morphological and histological changes on the skin were evaluated using SEM and HE staining, along with the measurement of the expression of matrix metalloproteinases (MMP-1) and cytokine pro-inflammatory interleukin 6 (IL-6) using ELISA. RESULTS: MSS-CH inhibits the occurrence of epidermal thickening and damage to the dermal layer of the skin. As a result, it restores the epidermis' barrier function and reduces surface damage caused by photoaging. The skin of the MSS-CH treated group exhibited improved physical appearance with reduced fine lines, wrinkles, and enhanced smoothness. Additionally, administering MSS-CH to the mice groups reduced the expression of MMP-1 and IL-6 in UVB-exposed skin. CONCLUSIONS: Altogether, this in vivo study demonstrates the photoaging-protective properties of CH-MSS, aligning with previous in vitro data. Thus, MSS-CH emerges as a strong candidate for use as an ingredient in nutraceuticals and biocosmetics.

Quantitative evaluation of warm acupuncture-moxibustion in improvement of cartilage damage in rabbits with early knee osteoarthritis based on MR T2 mapping. / åŸºäºŽæ ¸ç£å ±æŒ¯T2 mappingå®šé‡è¯„ä»·æ¸©é’ˆç¸å¯¹æ—©æœŸå ”è†å ³èŠ‚éª¨å ³èŠ‚ç‚Žè½¯éª¨æŸä¼¤çš„ä¿®å¤ä½œç”¨.

OBJECTIVES: To observe the application value of MR T2 mapping for evaluating the effect of warm acupuncture-moxibustion on articular cartilage degeneration, and to observe the relationship between T2 value and expression of matrix metalloproteinases (MMP)-1 and MMP-13 of chondrocytes in rabbits with early knee osteoarthritis (KOA). METHODS: Thirty male New Zealand rabbits were randomly divided into blank control, KOA model and warm acupuncture-moxibustion groups, with 10 rabbits in each group. The early KOA model was established by right hind limb tubular plaster extension fixation method for 2 weeks. The rabbits of the warm acupuncture-moxibustion group received warm acupuncture-moxibustion stimulation at "Heding"(EX-LE2), "Neixiyan"(EX-LE4), "Waixiyan" (EX-LE5) and"Zusanli"(ST36) on the right hind limb for 15 min, once a day for 2 weeks. After intervention, MR T2 mapping of the right knee joint was performed in each group. The H.E. staining was used to evaluate the histopathological changes of cartilage, followed by giving a score according to the standards of Mankin scoring. The TUNEL method was used to analyze the apoptosis state of chondrocytes, and the positive expressions of MMP-1 and MMP-13 in the articular cartilage were detected by immunohistochemical staining. RESULTS: Compared with the blank control group, the Mankin score, chondrocyte apoptosis index, T2 value and the positive expressions of MMP-1 and MMP-13 in the cartilage tissue were significantly increased in the model group (P<0.01). Compared with the model group, the Mankin score, chondrocyte apoptosis index, T2 value and the positive expressions of MMP-1 and MMP-13 in the cartilage tissue were markedly decreased in the warm acupuncture-moxibustion group (P<0.01). The T2 value was positively correlated with the expression levels of MMP-1 and MMP-13 (P<0.01). H.E. staining showed disordered arrangement of chondrocytes and thinner cartilage layer in the model group, and a clear and relative ordered arrangement of chondrocyte in the warm acupuncture-moxibustion group. CONCLUSIONS: Warm acupuncture-moxibustion can reduce the T2 value of articular cartilage in early KOA rabbits, which is positively correlated with the decreased expression of MMP-1 and MMP-13 in the extracellular matrix of cartilage. The MR T2 mapping has certain value in evaluating the effect of warm acupuncture-moxibustion on KOA rabbits with early cartilage degeneration.

Protective Effects of a Mixed Medicinal Herb Extract (NUC1) on Collagenase-Induced Osteoarthritis in Rabbits.

NUC1 (Nutraceutical compound 1) is an ethanol extract composed of a formulation based on medicinal herbs traditionally used for the treatment of arthritis in Korea and China. This study investigated the therapeutic effects of NUC1 on osteoarthritis (OA). The protective effect of NUC1 on OA was tested in a rabbit model of collagenase-induced arthritis (CIA) for 4 weeks. Results were compared among four groups (n = 9 per group): the normal group (untreated), the CIA group (vehicle control), the NUC1 group (CIA rabbits treated with 200 mg/kg NUC1), and the JOINS group (positive control, CIA rabbits treated with 200 mg/kg JOINS tablet). NUC1 significantly inhibited NO production (p < 0.05 at 125 µg/ml, p < 0.01 at 250 µg/ml, and p < 0.001 at 500 µg/ml) and iNOS expression in macrophages, in a concentration-dependent manner. NUC1 also inhibited the release and protein expression of MMP-1, 3, and 13, in TNF-α-induced chondrosarcoma cells in a concentration-dependent manner. In vivo, the MMP-1 and MMP-3 levels in synovial fluids were significantly (p < 0.05) lower in NUC1 group (77.50 ± 20.56 and 22.50 ± 7.39 pg/ml, respectively) than in the CIA group (148.33 ± 68.58 and 77.50 ± 20.46 pg/ml, respectively). Also, in histopathological, NUC1 ameliorated articular cartilage damage in OA by increasing the abundance of chondrocytes and proteoglycan in the articular cartilage. Thus, NUC1 showed promise as a potential therapeutic agent, and it can be generalized to a broader study population in different OA animal models.

Protective effect of Salvia plebeia R. Br ethanol extract on UVB-induced skin photoaging in vitro and in vivo.

BACKGROUND: UV exposure is one of the primary factors responsible for photoaging, causing the increase in matrix metalloproteinases (MMPs) and the reduction in collagen. Salvia plebeia R. Br (SP), as an herbaceous plant, contains abundant flavonoids and possesses excellent anti-inflammatory and antioxidant activities. This study aimed to investigate the photoprotective effects of SP on UVB-induced photodamage in immortalized human keratinocytes (HaCaTs) and Kunming mice, as well as its main active components such as homoplantaginin (HP). METHODS: CCK-8 was applied to detect the cell viability in UVB-irradiated or non-irradiated HaCaTs. Commercial kits were used to evaluate the levels of ROS, MDA, SA-ß-Gal, MMP-1, and IL-6. The expression of MAPK and TGF-ß/Smad pathways was detected by western blot. HE and Masson's trichrome staining were performed to examine the epidermis thickness and collagen degradation of Kunming mice. RESULTS: Our results found that SP and HP notably decreased UVB-induced ROS, MDA, and SA-ß-Gal production, and inhibited MMP-1 and IL-6 secretion by inhibiting the MAPK signaling pathway. In addition, SP and HP significantly promoted type I procollagen synthesis by activation of TGF-ß/Smad pathway. Consistently, the in vivo experiments also indicated that SP and HP had a photoprotective effect, which significantly reversed UVB-induced epidermis thickness and collagen degradation. CONCLUSION: This study demonstrated that SP effectively could protect skin from UVB-induced photoaging, while HP acted as the active substance in SP. All these findings provided a new strategy for skin photoaging treatment.

S-1-propenyl-L-cysteine suppresses lipopolysaccharide-induced expression of matrix metalloproteinase-1 through inhibition of tumor necrosis factor-α converting enzyme-epidermal growth factor receptor axis in human gingival fibroblasts.

Periodontal disease is the most common dental health problem characterized by the destruction of connective tissue and the resorption of alveolar bone resulting from a chronic infection associated with pathogenic bacteria in the gingiva. Aged garlic extract has been reported to improve gingival bleeding index and probing pocket depth score in patients with mild to moderate periodontitis. Although our previous study found that aged garlic extract and its constituents suppressed the tumor necrosis factor-α-induced inflammatory responses in a human gingival epithelial cell line, the mechanism underlying the effect of aged garlic extract on the destruction of the gingiva remains unclear. The present study investigated the effect of S-1-propenyl-L-cysteine, one of the major sulfur bioactive compounds in aged garlic extract, on the lipopolysaccharide-induced expression of matrix metalloproteinases in human gingival fibroblasts HGF-1 cells. Matrix metalloproteinases are well known to be closely related to the destruction of the gingiva. We found that S-1-propenyl-L-cysteine suppressed the lipopolysaccharide-induced expression and secretion of matrix metalloproteinase-1 in HGF-1 cells. In addition, S-1-propenyl-L-cysteine inhibited the lipopolysaccharide-induced phosphorylation of epidermal growth factor receptor and expression of the active form of tumor necrosis factor-α converting enzyme. Furthermore, the inhibitors of epidermal growth factor receptor tyrosine kinase and tumor necrosis factor-α converting enzyme, AG-1478 and TAPI-1, respectively, reduced the lipopolysaccharide-induced protein level of matrix metalloproteinase-1, as did S-1-propenyl-L-cysteine. Taken together, these results suggested that S-1-propenyl-L-cysteine suppresses the lipopolysaccharide-induced expression of matrix metalloproteinase-1 through the blockade of the tumor necrosis factor-α converting enzyme-epidermal growth factor receptor axis in gingival fibroblasts.

Effects and Mechanism of the Leontopodium alpinum Callus Culture Extract on Blue Light Damage in Human Foreskin Fibroblasts.

Leontopodium alpinum is an important source of raw material for food, medicine, and modern cosmetics. The purpose of this study was to develop a new application for protection against blue light damage. To investigate the effects and mechanism of action of Leontopodium alpinum callus culture extract (LACCE) on blue light damage, a blue-light-induced human foreskin fibroblast damage model was established. The contents of collagen (COL-I), matrix metalloproteinase 1 (MMP-1), and opsin 3 (OPN3) were detected using enzyme-linked immunosorbent assays and Western blotting. The calcium influx and reactive oxygen species (ROS) levels were measured via flow cytometry and the results showed that the LACCE (10-15 mg/mL) promoted the production of COL-I, inhibited the secretion of MMP-1, OPN3, ROS and calcium influx, and may play a role in inhibiting the activation of blue light on the OPN3-calcium pathway. Thereafter, high-performance liquid chromatography and ultra-performance liquid chromatography-tandem mass spectrometry were used to quantitatively analyze the contents of nine active ingredients in the LACCE. The results indicated that LACCE has an anti-blue-light-damage effect and provides theoretical support for the development of new raw materials in the natural food, medicine, and skin care industries.

Biophotonic Effects of Low-Level Laser Therapy on Adipose-Derived Stem Cells for Soft Tissue Deficiency.

PURPOSES: The objectives of this study are to use diode lasers for low-level laser therapy (LLLT) and to assess its applicability and effects in adipose-derived stem cell (ADSC) growth processes. METHODS: Studies were conducted on the diode laser with wavelengths of 622.7, 527.1, and 467.3 nm. The mechanism of action of LLL illumination was studied on ADSCs, isolated from human tissue, and then cultured by examining different wavelengths to determine the relevant light parameters for optimal responses. We used enzyme-linked immunosorbent assay and real-time polymerase chain to determine the percentages of fibroblast-mediated procollagen type 1 and matrix metallopeptidase 1 (MMP-1), MMP-2, and MMP-9 production at different wavelengths. The levels of lactate dehydrogenase produced by ADSCs after LLL illumination were assessed as well. Clinical results from 20 patients treated for soft tissue deficiency were collected for assessment of ADSC-assisted lipotransfer. RESULTS: Low-level laser (622.7 nm) illumination on cell cultures in vitro increased ADSCs proliferation, type 1 procollagen expression, collagen production, as well as MMP-1, MMP-2, and MMP-9 relative expression. Statistical analysis demonstrated a significant difference in red light (622.7 nm) versus green light (527.1 nm) and blue light (467.3 nm, P < 0.05). No significant differences were noted between the effects of green and blue lights. In clinical application, all patients attained significant improvement with treatment in the final outcome assessment after 6 months. CONCLUSIONS: Low-level laser illumination may affect ADSCs growth processes and ADSC-assisted lipotransfer for soft tissue deformity, scar treatment, wound healing, and other reconstructive surgery.

Overexpression of estrogen receptor ß inhibits cellular functions of human hepatic stellate cells and promotes the anti-fibrosis effect of calycosin via inhibiting STAT3 phosphorylation.

BACKGROUND: Estrogen receptor ß (ERß) is the major ER subtype in hepatic stellate cells (HSCs). Previously we reported phytoestrogen calycosin suppressed liver fibrosis progression and inhibited HSC-T6 cell functions, suggesting the effects may be related to ERß. Here, we explore the effect of overexpressed ERß on human HSCs and the role of ERß in pharmacological action of calycosin. METHODS: LX-2 cells were transfected with lentivirus to overexpress ERß. In the presence or absence of overexpressed ERß, the effects of ERß and calycosin on proliferation, migration, activation, collagen production and degradation of TGF-ß1-induced LX-2 cells and the role of ERß in the inhibition effect of calycosin were investigated. LX-2 cells overexpressed with ERß or treated with ER non-selective antagonist ICI182,780 were used to investigate the regulation of ERß on JAK2/STAT3 signaling pathway. CCK-8 method was used to screen effective doses of calycosin and investigate cell proliferation. The cell migration was detected by transwell chamber assay. The expression of α-SMA was detected by immunofluorescence and western blot. The protein expressions of Col-I, MMP1, TIMP1, JAK2, p-JAK2, STAT3 and p-STAT3 were detected by western blot. RESULTS: ERß overexpressed lentivirus was successfully transfected into LX-2 cells with high efficiency. Overexpressed ERß or calycosin alone inhibited the TGF-ß1-induced LX-2 cell proliferation and migration, downregulated the protein expressions of α-SMA, Col-I, TIMP-1, p-STAT3 and upregulated MMP-1. Both overexpressed ERß and calycosin had no significant effect on JAK2, p-JAK2 and STAT3 expressions. ERß overexpression further enhanced the above effects of calycosin. However, after the cells were treated with ICI182,780, downregulation of STAT3 phosphorylation induced by calycosin was reversed. CONCLUSIONS: ERß mediated the inhibition of major functions of LX-2 cell possibly by inhibiting the phosphorylation of STAT3, and was an important pathway through which calycosin exerted anti-liver fibrosis effect.

Protective role of Caesalpinia sappan extract and its main component brazilin against blue light-induced damage in human fibroblasts.

BACKGROUND: Ultraviolet (UV) radiation is a well-known factor that causes skin aging. Recently, with the development of technology, the skin has been exposed to not only the UV radiation but also the blue light from electronic devices. Blue light is a high-energy visible light that penetrates deep into the dermal layer, producing reactive oxygen species (ROS) and resulting in skin aging. In this study, we searched for candidate materials that can inhibit blue light-induced skin aging and found Caesalpinia sappan extract (CSE) to be effective. METHODS: Human dermal fibroblasts (HDFs) were treated with various concentrations of CSE and brazilin and exposed to blue light. We measured that antioxidant activity, MMP-1 levels using MMP-1 ELISA, changes in collagen type 1, collagen type 3, MMP-1, and MMP-3 mRNA expressions, and ROS generation. RESULTS: We confirmed that CSE has high absorption of blue light and antioxidant activity. Blue light irradiation at 30 J/cm2 decreased the expression of collagen types 1 and 3, increased the expression of matrix metalloproteinase (MMP)-1 and 3, and decreased the production of ROS in human dermal fibroblasts as compared to those of the nonirradiated group. However, pretreatment with CSE protected against the damage caused by the blue light. Brazilin, a major constituent of C. sappan, had high absorbance in the blue light region and antioxidant activities. Pretreatment with brazilin also inhibited the damage caused by the blue light in the cells. CONCLUSION: CSE and brazilin are potential agents for inhibiting skin aging caused by blue light-induced damage.

Umbilicaria esculenta Extract Exhibits Antiwrinkle Activity by Suppressing ErbB2 Phosphorylation.

Umbilicaria esculenta (UE), an edible lichen, is widespread in northeast Asian countries, including China, Japan, and Korea. In the present study, we examined the antiwrinkle activity of UE. We observed that the UE extract (UEE) suppressed ultraviolet (UV)-induced matrix metalloprotein-1 (MMP-1) expression and reactive oxygen species (ROS) generation in a human keratinocyte cell line (HaCaT) and human skin tissue. In addition, UEE reversed the UV-induced decrease in collagen in the human skin tissue. Excessive and chronic UV exposure is a key factor underlying skin wrinkle formation via MMP-1 expression. As treatment with UEE disrupted the UV-activated mitogen-activated protein kinase (MAPK) signaling pathway, we applied an antibody array to unveil the underlying mechanism of UEE. Interestingly, UEE treatment inhibited ErbB2 phosphorylation, but not epidermal growth factor receptor phosphorylation, a heterodimerization partner with ErbB2. Furthermore, UEE treatment enhanced UV-suppressed phosphatase activity via ROS suppression. Collectively, our findings indicate that UEE enhances ErbB2 dephosphorylation to suppress UV-induced MMP-1 expression.

Transcriptomic profiling revealed the role of apigenin-4'-O-α-L-rhamnoside in inhibiting the activation of rheumatoid arthritis fibroblast-like synoviocytes via MAPK signaling pathway.

BACKGROUND: Activated fibroblast-like synoviocyte (FLS) played a significant role in the pathogenesis and progression of rheumatoid arthritis (RA). Apigenin-4'-O-α-L-rhamnoside showed remarkable effects against RA, however, no relevant studies on pharmacology of apigenin-4'-O-α-L-rhamnoside yet, the effects and underlying molecular mechanism of apigenin-4'-O-α-L-rhamnoside on RA are still unclear. PURPOSE: This study aimed to investigate the therapeutic effects and mechanisms of apigenin-4'-O-α-L-rhamnoside on RA-FLS cells by transcriptomic analysis. METHODS: In vitro, RA-FLS cell viability and migration were measured by CCK-8 and scratch assays, respectively. The effects of apigenin-4'-O-α-L-rhamnoside on inflammatory levels of MMP-1, MMP-3, RANKL and TNF-α in RA-FLS cells were detected using ELISA kits. High-throughput transcriptome analysis was performed to screen the key genes and related pathways of apigenin-4'-O-α-L-rhamnoside inhibit RA-FLSs, and the result of which were validated by RT-qPCR and western blot. Furthermore, in vivo, we also evaluated the effects of apigenin-4'-O-α-L-rhamnoside in rat with CIA. RESULTS: Apigenin-4'-O-α-L-rhamnoside significantly suppressed RA-FLS migration, exerted remarkable inhibiting effects on the expression levels on MMP-1, MMP3, RANKL and TNF-α in RA-FLS cells. It seemed that MAPK signaling pathway might be closely related to the pathogenesis of RA by down-regulated relevant core targets (MAPK1, HRAS, ATF-2, p38 and JNK). Moreover, apigenin-4'-O-α-L-rhamnoside attenuated the severity of arthritis in CIA rat. CONCLUSION: Apigenin-4'-O-α-L-rhamnoside inhibited pro-inflammatory cytokine, chemokine and MMPs factors production of RA-FLS by targeting the MAPK signaling pathway, which provided a scientific basis for potential application in the treatment of RA.

Aqueous Extracts of Pleurotus ostreatus and Hericium erinaceus Protect against Ultraviolet A-Induced Damage in Human Dermal Fibroblasts.

Pleurotus ostreatus (PO) and Hericium erinaceus (HE) have been traditionally used to treat various diseases, owing to their antioxidant, antimicrobial, neuroprotective, and antitumor effects. However, few studies have been reported on their antiaging effects. In this study, the antioxidant and antiaging activities of PO and HE aqueous extracts were investigated in ultraviolet A (UVA)-induced human dermal fibroblast cells (HDFs). The antioxidant properties of PO and HE aqueous extracts were measured by total polyphenol and ergothioneine content, and their antioxidant activity was analyzed with the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical-scavenging assays. To demonstrate the antiaging effect of PO and HE aqueous extracts in UVA-induced HDFs, the secretion and mRNA expression of matrix metalloproteinase-1 (MMP-1), procollagen type I (PC1), and elastase were assessed by enzyme-linked immunosorbent assay (ELISA) and real-time PCR, respectively. The total polyphenol content in each extract was 13.6 and 11.7 mg gallic acid equivalents/g dry weight (DW), respectively, and the total ergothioneine content in each extract was 3.43 and 2.18 mg/g DW, respectively. The PO and HE extracts increased DPPH and ABTS radical-scavenging activity in a dose-dependent manner. In UVA-damaged HDFs, the extracts increased PC1 production but decreased MMP-1 production and elastase-1 activity. Furthermore, the mRNA levels of PC1, MMP-1, and elastase were recovered in the PO- and HE-treated UVA-irradiated HDFs compared to those in the irradiated control group. PO and HE aqueous extracts may be potentially used as a promising antiphotoaging agent.

Effects of ginger (Zingiber officinale) on gingival fibroblasts: An in vitro study.

OBJECTIVES: Ginger, the powdered rhizome of the herb Zingiber officinale, is commonly used as a traditional medicine in many areas around the world. Anti-inflammatory actions of its extract have been previously reported. The aim of this study was to investigate the effect of ginger extract on matrix metalloproteinase (MMP) and interleukin (IL) expression from human gingival fibroblasts (HGFs) in vitro. MATERIAL AND METHODS: HGFs were obtained from subcultures of biopsies from clinically healthy gingival tissues of 10 patients. Ginger extract was prepared from commercial powder of rhizome of Z. officinale (GZO) and its effect on cell viability was assessed using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide cytotoxicity assay. Cells were then incubated and treated (except for the control samples) with either GZO, lipopolysaccharides (LPS), and GZO before or after LPS stimulation. Culture supernatants of all five samples were collected for the Milliplex analysis to measure MMP-1, MMP-2, MMP-8, MMP-9, IL-1ß, and IL-8. One-way analysis of variance and Duncan multiple range tests were used to compare the mean values of all groups. RESULTS: The gingerextract showed minimal cytotoxicity to HGFs even with the maximum tested concentration. Compared to the control group, GZO treatment alone caused little or no effect on the levels of expression of MMP-1, MMP-2, MMP-8, MMP-9, IL-1ß, and IL-8. While GZO treatment after LPS stimulation significantly reduced the expression of MMP-1, MMP-2, MMP-8, MMP-9, and IL-8 when compared to LPS alone. Comparing the control to LPS stimulation after GZO treatment, significant differences were detected for all tested MMPs and cytokines. CONCLUSIONS: These findings suggest a potential role for ginger extract in inhibiting MMP and IL HGFs' expression in inflamed gingival tissues.

Mechanism of Action of Ermiao San on Rheumatoid Arthritis Based on Bioinformatics and Molecular Dynamics.

BACKGROUND: Ermiao San, one of the Chinese medicine formulas, has been widely used to treat rheumatoid arthritis (RA). Our previous study has demonstrated that Ermiao San is effective in treating RA. However, its pharmacological mechanisms remain unclear. Therefore, the purpose of this study was to decipher the potential mechanism of action of Ermiao San in rheumatoid arthritis (RA) by bioinformatics, network pharmacology, molecular docking, and molecular dynamics. METHODS: Gene expression data (GSE77298) were obtained from the GEO database. Differentially expressed genes (DEGs) were analyzed by R. The active ingredients of Huangbai (Phellodendron) and Cangshu (Atractylodes), two main constituents of Ermiao San, and their predicted target genes were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the overlapping genes between DEGs of the RA dataset and the predicted target genes of Ermiao San. The gene-gene interaction network was analyzed and visualized by Cytoscape. Molecular docking and dynamics simulations were performed to study the interaction between selected target genes (Chemokine ligand 2 (CCL2) and matrix metalloproteinase 1 (MMP1)) and active ingredients (quercetin and wogonin) of Ermiao San. RESULTS: A total of 16 potential targets for Ermiao San were identified, with significantly enriched GO terms, such as cytokine-mediated signaling pathways, oxidoreductase activity, cell space, etc., and IL-17 signaling pathway, rheumatoid arthritis pathway, and NF-κB signaling pathway were identified as enriched pathways through KEGG analysis. CCL2 and MMP1 were identified and verified to be the targets of both quercetin and wogonin, the two active ingredients of Ermiao San, by molecular docking and molecular dynamics. CONCLUSION: Ermiao San may target CCL2 and MMP1 via its active ingredients by exerting therapeutic effects on RA.

Maternal omega-3 polyunsaturated fatty acids supplementation in pregnancy decreases MMP-1 levels in breastmilk: a cross-sectional study.

INTRODUCTION: Anti-inflammatory properties of fish-oil are well known and suggested during pregnancy. MMP-1 is involved in inflammation and tissue remodelling. There have been studies focused on anti-inflammatory effect of maternal omega use on human milk while little is known about the effect of omega use on breastmilk proteases. Leptin is an important hormone that influences MMP levels in various tissues and exerts its metabolic effects. In our study we assessed the levels of MMP-1, TIMP-1, leptin, IL-6 and FA's including PUFA in breastmilk from women who used omega-3. MATERIALS AND METHODS: Our study was a cross-sectional study included 67(Group 1, n = 32, omega user; Group 2 n = 35, non-user)lactating women and their infan MMP-1, TIMP-1, leptin, IL-6 and FA's were evaluated in breastmilk of both groups. MMP-1, TIMP-1, IL-6 and leptin were measured by enzyme-linked immunoabsorbent assay (ELISA) method. Breastmilk fatty acids were measured by gas chromatography flame ionisation detector (GC-FID). RESULTS: Matrix metalloproteinase-1 (MMP-1) levels in breastmilk were significantly lower in breastmilk from omega users (mean ± SD, 0.455 ± 0.1) than non-users (mean ± SD, 0.677 ± 0.289) (p=.0001). MMP-1 and omega 6:3 ratio were positively correlated (r: 0.301, p=.01). MMP levels were correlated with IL-6 (Pearson's r: 0.411, p<.001). MMP-1 and leptin levels were positively correlated (r: .388, p=.001). CONCLUSION: MMP-1 levels in breastmilk, may be modified by maternal omega use in pregnancy which may help to redirect extracellular matrix remodelling and metabolic programming in early infancy.

Acer tataricum subsp. ginnala Inhibits Skin Photoaging via Regulating MAPK/AP-1, NF-κB, and TGFß/Smad Signaling in UVB-Irradiated Human Dermal Fibroblasts.

Skin, the organ protecting the human body from external factors, maintains structural and tensile strength by containing many collagen fibrils, particularly type I procollagen. However, oxidative stress by ultraviolet (UV) exposure causes skin photoaging by activating collagen degradation and inhibiting collagen synthesis. Acer tataricum subsp. ginnala extract (AGE) is a herbal medicine with anti-inflammatory and anti-oxidative effects, but there is no report on the protective effect against skin photoaging. Therefore, we conducted research concentrating on the anti-photoaging effect of Acer tataricum subsp. ginnala (AG) in UVB (20 mJ/cm2)-irradiated human dermal fibroblasts (HDF). Then, various concentrations (7.5, 15, 30 µg/mL) of AGE were treated in HDF for 24 h following UVB irradiation. After we performed AGE treatment, the matrix metalloproteinase1 (MMP1) expression was downregulated, and the type I procollagen level was recovered. Then, we investigated the mitogen-activated protein kinases/activator protein 1 (MAPK/AP-1) and nuclear factor-κB (NF-κB) pathway, which induce collagen breakdown by promoting the MMP1 level and pro-inflammatory cytokines. The results indicated that AGE downregulates the expression of the MAPK/AP-1 pathway, leading to MMP1 reduction. AGE inhibits nuclear translocation of NF-κB and inhibitor of nuclear factor-κB (IκB) degradation. Therefore, it downregulates the expression of MMP1 and pro-inflammatory cytokines such as TNF-α, IL-1ß, and IL-6 increased by UVB. Besides, the TGFß/Smad pathway, which is mainly responsible for the collagen synthesis in the skin, was also analyzed. AGE decreases the expression of Smad7 and increases TGFßRII expression and Smad3 phosphorylation. This means that AGE stimulates the TGFß/Smad pathway that plays a critical role in promoting collagen synthesis. Thus, this study suggests that AGE can be a functional material with anti-photoaging properties.

Synthesis, Molecular Docking, and In Vitro Boron Neutron Capture Therapy Assay of Carboranyl Sinomenine.

In comparison with pristine sinomenine and carborane precursors, the calculations of molecular docking with matrix metalloproteinases (MMPs) and methylcarboranyl-n-butyl sinomenine showed improved interactions. Accordingly, methylcarboranyl-n-butyl sinomenine shows a high potential in the treatment of rheumatoid arthritis (RA) in the presence of slow neutrons. The reaction of potassium salt of sinomenie, which is generated from the deprotonation of sinomenine (1) using potassium carbonate in a solvent of N,N-dimethyl formamide, with 4-methylcarboranyl-n-butyl iodide, (2) forms methylcarboranyl-n-butyl sinomenine (3) in 54.3% yield as a new product. This new compound was characterized by 1H, 13C, and 11B NMR spectroscopy, FT-IR spectroscopy, and elemental analyses to confirm its molecular composition. In addition to molecular docking interactions with MMPs, the in vitro killing effects of 3, along with its toxicity measurements, exhibited its potential to be the new drug delivery agent for boron neutron capture synovectomy (BNCS) and boron neutron capture therapy (BNCT) for the treatment of rheumatoid arthritis (RA) and cancers in the presence of slow neutrons, respectively.

Protection against UVB-Induced Photoaging by Nypa fruticans via Inhibition of MAPK/AP-1/MMP-1 Signaling.

Ultraviolet B (UVB) irradiation is major causative factor in skin aging. The aim of the present study was to investigate the protective effect of a 50% ethanol extract from Nypa fruticans (NF50E) against UVB-induced skin aging. The results indicated that NF50E exerted potent antioxidant activity (IC50 = 17.55 ± 1.63 and 10.78 ± 0.63 µg/mL for DPPH and ABTS-radical scavenging activity, respectively) in a dose-dependent manner. High-performance liquid chromatography revealed that pengxianencin A, protocatechuic acid, catechin, chlorogenic acid, epicatechin, and kaempferol were components of the extract. In addition, the extract exhibited elastase inhibitory activity (IC50 = 17.96 ± 0.39 µg/mL). NF50E protected against UVB-induced HaCaT cell death and strongly suppressed UVB-stimulated cellular reactive oxygen species generation without cellular toxicity. Moreover, topical application of NF50E mitigated UVB-induced photoaging lesions including skin erythema and skin thickness in BALB/C mice. NF50E treatment inhibited UVB-induced collagen degradation as well as MMP-1 and IL-1ß expressions and significantly stimulated SIRT1 expression. Furthermore, the extract treatment markedly suppressed the activation of NF-κB and AP-1 (p-c-Jun) by deactivating the p38 and JNK proteins. Taken together, current data suggest that NF50E exhibits potent antioxidant potential and protection against photoaging by attenuating MMP-1 activity and collagen degradation possibly through the downregulation of MAPK/NF-κB/AP-1 signaling and SIRT1 activation.

Mixture of enzyme-processed Panax ginseng and Gastrodia elata extract prevents UVB-induced decrease of procollagen type 1 and increase of MMP-1 and IL-6 in human dermal fibroblasts.

According to the previously described anti-photoaging effect of the enzyme-processed Panax ginseng extract and Gastrodia elata extract, we hypothesized that the combination of the two extracts would have superior effect to protect human skin from UVB radiation. Besides, the mixture of active components isolated from herbal extracts, ginsenoside F2, and α-gastrodin was investigated on the photo-protective capability. The expression of aging-related markers including matrix metalloproteinase-1 (MMP-1), interleukin-6 (IL-6), and procollagen type 1 was evaluated using ELISA kits. It was reported that the herbal extract at a Panax ginseng extract to Gastrodia elata extract ratio of 1:10 (w/w) and the compound mixture with equal proportion of ginsenoside F2 and α-gastrodin exhibited significant inhibition of MMP-1 and IL-6 production, and marked upregulation of procollagen type 1 formation. Thus, the combination of either the enzyme-processed herbal extracts or their active components would enhance the properties of prevention and treatment of UVB-induced skin damage.

Role of HSP70 in response to (thermo)radiotherapy: analysis of gene expression in canine osteosarcoma cells by RNA-seq.

Pre-treatment of tumors with hyperthermia is often used to increase the efficacy of radiotherapy. One of the main proteins induced in response to hyperthermia is heat shock protein 70 (HSP70). The aim of our study was to investigate up- and down-regulated genes in response to (thermo)radiotherapy in HSP70 proficient and deficient canine osteosarcoma cell line (Abrams), and functional role of HSP70 in the mechanism of thermoradiosensitization. Cells were transfected with negative control siRNA or siRNA targeting HSP70 and treated with hyperthermia (HT), radiotherapy (RT), and thermoradiotherapy (HTRT). RNA sequencing was used to analyze gene expression. Hyperthermia and thermoradiotherapy, but not radiotherapy alone, induced differential gene expression. We identified genes differentially expressed only in HSP70 knockdown (thus HSP70-dependent) cells in response to hyperthermia and thermoradiotherapy. Interestingly, cell proliferation but not clonogenicity and apoptosis/necrosis was affected by the HSP70 knockdown in response to thermoradiotherapy. The results suggest that HSP70 regulates expression of specific genes in response to hyperthermia and thermoradiotherapy. Further investigations into the role of specific genes regulated in a HSP70-dependent manner in response to thermoradiotherapy could pave a way into new, combinatorial treatment options for (canine) osteosarcoma and other cancer types.