Intracellular Zn2+ promotes extracellular matrix remodeling in dexamethasone-treated trabecular meshwork.

Given the widespread application of glucocorticoids in ophthalmology, the associated elevation of intraocular pressure (IOP) has long been a vexing concern for clinicians, yet the underlying mechanisms remain inconclusive. Much of the discussion focuses on the extracellular matrix (ECM) of trabecular meshwork (TM). It is widely agreed that glucocorticoids impact the expression of matrix metalloproteinases (MMPs), leading to ECM deposition. Since Zn2+ is vital for MMPs, we explored its role in ECM alterations induced by dexamethasone (DEX). Our study revealed that in human TM cells treated with DEX, the level of intracellular Zn2+ significantly decreased, accompanied by impaired extracellular Zn2+ uptake. This correlated with changes in several Zrt-, Irt-related proteins (ZIPs) and metallothionein. ZIP8 knockdown impaired extracellular Zn2+ uptake, but Zn2+ chelation did not affect ZIP8 expression. Resembling DEX's effects, chelation of Zn2+ decreased MMP2 expression, increased the deposition of ECM proteins, and induced structural disarray of ECM. Conversely, supplementation of exogenous Zn2+ in DEX-treated cells ameliorated these outcomes. Notably, dietary zinc supplementation in mice significantly reduced DEX-induced IOP elevation and collagen content in TM, thereby rescuing the visual function of the mice. These findings underscore zinc's pivotal role in ECM regulation, providing a novel perspective on the pathogenesis of glaucoma.NEW & NOTEWORTHY Our study explores zinc's pivotal role in mitigating extracellular matrix dysregulation in the trabecular meshwork and glucocorticoid-induced ocular hypertension. We found that in human trabecular meshwork cells treated with dexamethasone, intracellular Zn2+ significantly decreased, accompanied by impaired extracellular Zn2+ uptake. Zinc supplementation rescues visual function by modulating extracellular matrix proteins and lowering intraocular pressure, offering a direction for further exploration in glaucoma management.

Exploring the role of flavonoids in caries-affected dentin adhesion: A comprehensive scoping review.

OBJECTIVES: The aim of this scoping review was to evaluate the available scientific evidence regarding the use of flavonoids in the treatment of caries-affected dentin focusing on bonding to dentin. METHODS: A comprehensive literature search was performed in five databases from March 2022 and updated in April 2023: PubMed, EMBASE, Scopus, Web of Science, and Scielo. Additionally, the references of included studies were manually searched. Gray literature was excluded from the review. STUDY SELECTION: Inclusion criteria included in vitro, in situ, and in vivo studies (animal or human) published in English. Abstracts, reviews, case reports, book chapters, doctoral dissertations, guidelines, and studies using pure plant extracts were excluded. Data collected from the selected studies were summarized and subjected to narrative and descriptive analysis. Out of the 91 studies identified, only 16 studies met the inclusion criteria. RESULTS: The review analyzed eight different flavonoids (hesperidin, galardin, proanthocyanidin, genipin, quercetin, naringin, epigallocatechin-3-gallate, and other catechins subtypes) used as pretreatment or loaded into adhesive systems, primers, and phosphoric acid. The use of flavonoids improved the mechanical properties of the materials and modified the biological properties of the dentin, reducing collagen loss by the inhibition of proteolytic activity of matrix metalloproteinases (MMPs). CONCLUSIONS: Based on the findings of this scoping review, it can be concluded that the use of flavonoids as pretreatment or incorporation into dental materials preserves collagen in the hybrid layer, inhibiting the MMPs activities, modifying the collagen fibrils of the dentin matrix and improving the mechanical properties of the dental adhesive systems. Therefore, it represents a promising approach for promoting dentin biomodification. This can result in more stable bonding of adhesive restorations to caries-affected dentin.

The mechanistic role of curcumin on matrix metalloproteinases in osteoarthritis.

A systematic mechanistic review was performed to determine mechanistic evidence for curcumin on pro-inflammatory matrix metalloproteinases and Osteoarthritis to understand the underlying pathophysiology, and to evaluate available human intervention evidence to inform clinical decision making. The systematic literature search was performed in 3 tranches (reviews, mechanistic, intervention studies) using PubMed, with no date limitations and using specific search terms. 65 out of 393 screened papers were accepted based on detailed inclusion and exclusion criteria. The mechanistic search was divided into three searches and the intervention searches were subdivided into four searches. Curcumin demonstrated significant inhibition of matrix metalloproteinases linked to cartilage degradation in Osteoarthritis through reduced activation of the nuclear factor kappa-B signaling pathway via suppressing phosphorylation of Iκßa and p65 nuclear translocation. Mechanistic evidence implicated matrix metalloproteinases in Osteoarthritis by decreasing Type II collagen, leading to cartilage damage. As a potential nutritional intervention for Osteoarthritis, curcumin could reduce inflammatory markers and improve pain and function scores. The evidence indicates most formulations of turmeric extract and curcumin extract, bio-enhanced and non-bio-enhanced, are effective at improving inflammatory markers and pain and function to a greater or lesser extent. Due to the high heterogeneity of the formulations, dosage, and duration of the studies, further research is needed to fully understand curcumin's potential as a promising non-pharmaceutical intervention for Osteoarthritis. This mechanism review identifies a gap in current research for the mechanism by which Type II collagen is mediated.

Metalloproteinases as Biomarkers and Sociomarkers in Human Health and Disease.

Metalloproteinases (MPs) are zinc-dependent enzymes with proteolytic activity and a variety of functions in the pathophysiology of human diseases. The main objectives of this review are to analyze a specific family of MPs, the matrix metalloproteinases (MMPs), in the most common chronic and complex diseases that affect patients' social lives and to better understand the nature of the associations between MMPs and the psychosocial environment. In accordance with the PRISMA extension for a scoping review, an examination was carried out. A collection of 24 studies was analyzed, focusing on the molecular mechanisms of MMP and their connection to the manifestation of social aspects in human disease. The complexity of the relationship between MMP and social problems is presented via an interdisciplinary approach based on complexity paradigm as a new approach for conceptualizing knowledge in health research. Finally, two implications emerge from the study: first, the psychosocial states of individuals have a profound impact on their overall health and disease conditions, which implies the importance of adopting a holistic perspective on human well-being, encompassing both physical and psychosocial aspects. Second, the use of MPs as biomarkers may provide physicians with valuable tools for a better understanding of disease when used in conjunction with "sociomarkers" to develop mathematical predictive models.

Amelioration of Rheumatoid Arthritis by Fragaria nubicola (Wild Strawberry) via Attenuation of Inflammatory Mediators in Sprague Dawley Rats.

Background and Objectives: Fragaria nubicola has never been evaluated scientifically for its anti-arthritic potential despite its use in folkloric systems of medicine. The research was conducted to assess the potential of F. nubicola against rheumatoid arthritis. Materials and Methods: The current study provided scientific evidence by evaluating the effects of plants using an in vivo CFA-induced model of arthritic rats and subsequent microscopic histopathological evaluation of ankle joints along with the determination of paw edema using a digital water displacement plethysmometer. The study also gave insight by determining levels of pro-inflammatory cytokines, matrix metalloproteinase enzymes (MMPs), prostaglandin E2 (PGE2), nuclear factor kappa B (NF-κB), vascular endothelial growth factor (VEGF), and biochemical and hematological parameters. GCMS analysis was also conducted for the identification of possible anti-inflammatory plant constituents. Results: The data showed that F. nubicola-treated groups attenuated the progression of arthritis and paw edema. Microscopic histopathological evaluation validated the anti-arthritic potential by showing amelioration of bone erosion, infiltration of inflammatory cells, and pannus formation. RT-PCR analysis displayed that treatment with F. nubicola down-regulated IL1ß, IL6, TNFα, NF-κB, VEGF, MMP2, MMP3, and MMP9 levels. Moreover, ELISA exhibited a reduction in levels of PGE2 levels in treatment groups. The levels of RBCs, platelets, WBCs, and Hb content were found to be nearly similar to negative control in the treated group. Statistically, a non-significant difference was found when all groups were compared for urea, creatinine, ALT, and AST analysis, indicating the safety of plant extract and fractions at test doses. GCMS analysis of extract and fractions showed the existence of many anti-inflammatory and antioxidant phytochemicals. Conclusion: In conclusion, F. nubicola possessed anti-arthritic properties that might be attributed to the amelioration of MMPs and pro-inflammatory cytokines.

Photothermal-Starvation Therapy Nanomodulator Capable of Inhibiting Colorectal Cancer Recurrence and Metastasis by Energy Metabolism Reduction.

The recurrence and metastasis of colorectal cancer (CRC) have been considered as a severe challenge in clinical treatment. Recent studies have demonstrated that matrix metalloproteinases (MMPs) and lactate can promote local tumor angiogenesis, recurrence, and metastasis. The expression of MMPs is highly dependent on energy metabolism, and lactate is considered an alternative energy source for tumor proliferation and metastasis. Therefore, using a rational approach, a photothermal-starvation therapy nanomodulator that can reduce energy metabolism to suppress CRC recurrence and metastasis is designed. To design a suitable nanomodulator, glucose oxidase (GOX), indocyanine green (IR820), and α-cyano-4-hydroxycinnamic acid (CHC) into nanoparticles by a coassembly method are combined. The photothermal properties of IR820 provide the appropriate temperature and oxygen supply for the enzymatic reaction of GOX to promote intracellular glucose consumption. CHC inhibits the expression of monocarboxylate transporter 1 (MCT1), the transporter of lactic acid into cells, and also reduces oxygen consumption and promotes the GOX reaction. Additionally, altering adenosine triphosphate synthesis to block heat shock proteins expression can be an effective means to prevent IR820-mediated photothermal therapy resistance. Thus, this dual photothermal-starvation therapy nanomodulator efficiently suppresses the recurrence and metastasis of CRC by depleting intracellular nutrients.

Matrix metalloproteinases are key targets of acupuncture in the treatment of ulcerative colitis.

The aim of this study was to elucidate the key targets of acupuncture in the colon of ulcerative colitis (UC) mice model using full-length transcriptome sequencing. 2.5% dextran sodium sulfate (DSS)-induced colitis mice were treated with or without acupuncture. Intestinal pathology was observed, and full transcriptome sequencing and bioinformatic analysis were performed. The results demonstrated that acupuncture treatment reduced the UC symptoms, disease activity index score, and histological colitis score and increased body weight, colon length, and the number of intestinal goblet cells. In addition, acupuncture can also decrease the expression of necrotic biomarker phosphorylates mixed lineage kinase domain-like pseudo kinase (p-MLKL). Full-length transcriptome analysis indicated that acupuncture reversed the expression of 987 of the 1918 upregulated differentially expressed genes (DEGs), and 632 of the 1351 downregulated DEGs induced by DSS. DEGs regulated by acupuncture were mainly involved in inflammatory responses and intestinal barrier pathways. The protein-protein interaction network analysis revealed that matrix metalloproteinases (MMPs) are important genes regulated by acupuncture. Gene set enrichment analysis revealed that extracellular matrix (ECM)-receptor interaction was an important target of acupuncture. In addition, alternative splicing analysis suggested that acupuncture improved signaling pathways related to intestinal permeability, the biological processes of xenobiotics, sulfur compounds, and that monocarboxylic acids are closely associated with MMPs. Overall, our transcriptome analysis results indicate that acupuncture improves intestinal barrier function in UC through negative regulation of MMPs expression.

Naringenin and proanthocyanidins pre-treatment decreases synthesis and activity of gelatinases induced by zoledronic acid in a dental implant surface in vitro model.

OBJECTIVE: To assess the effects of pre-treatment with proanthocyanidins (PA) flavonoids, from grape seed extract, and synthetic naringenin (NA) on the synthesis of matrix metalloproteinases (MMPs) gelatinases and their tissue inhibitors (TIMPs), as well as the gelatinolytic activity of MMPs by human gingival fibroblasts (HGF) and osteoblasts (Ob) exposed to zoledronic acid (ZA) in a dental implant surface in vitro model. DESIGN: The highest non-cytotoxic concentrations of NA and PA were determined for HGF (10 µg/mL; defined by previous study) and Ob (0.5 µg/mL; defined by prestoBlue assay). Then, HFG and Ob were individually seeded onto titanium discs, and after 24 h, cells were pre-treated (or not) with NA or PA, followed (or not) by exposure to ZA. Next, MMP-2, MMP-9, TIMP-1, TIMP-2 synthesis (ELISA), and gelatinolytic activity (in situ zymography) was evaluated. Data were analyzed by one-way ANOVA and Tukey tests (α = 0.05). RESULTS: ZA treatment increased the synthesis (p < 0.05) and activity of MMPs; flavonoids pre-treatment controlled ZA-induced gelatinolytic effects, down-regulating MMPs synthesis (p < 0.05) and activity by HGF and Ob. For HGF, NA and PA pre-treatment did not up-regulate TIMP synthesis after ZA exposure (p > 0.05); for Ob, TIMP-2 was up-regulated (p < 0.05) by flavonoids, followed by ZA. CONCLUSIONS: NA and PA pre-treatment provides interesting results in the modulation of ZA deleterious effects, down-regulating MMP-2 and MMP-9 synthesis and activity by HGF and Ob and up-regulating TIMP-2 by Ob.

Zhuidu Formula suppresses the migratory and invasive properties of triple-negative breast cancer cells via dual signaling pathways of RhoA/ROCK and CDC42/MRCK.

ETHNOPHARMACOLOGICAL RELEVANCE: Zhuidu Formula (ZDF) is composed of triptolide, cinobufagin and paclitaxel, which are the active ingredients of Tripterygium wilfordii Hook. F, dried toad skin and Taxus wallichiana var. chinensis (Pilg) Florin, respectively. Modern pharmacological studies show that triptolide, cinobufagin, and paclitaxel are well-known natural compounds that exert anti-tumor effects by interfering with DNA synthesis, inducing tumor cell apoptosis, and inhibiting the dynamic balance of the tubulin. However, the mechanism by which the three compounds inhibit triple-negative breast cancer (TNBC) metastasis is unknown. OBJECTIVE: The objective of this investigation was to examine the inhibitory essences of ZDF on the metastasis of TNBC and elucidate its potential mechanism. MATERIALS AND METHODS: Cell viability of triptolide (TPL), cinobufagin (CBF), and paclitaxel (PTX) on MDA-MB-231 cells was assessed employing a CCK-8 assay. The drug interactions of the three drugs on MDA-MB-231 cells were determined in vitro utilizing the Chou-Talalay method. MDA-MB-231 cells were identified for migration, invasion and adhesion in vitro through the implementation of the scratch assay, transwell assay and adhesion assay, respectively. The formation of cytoskeleton protein F-actin was detected by immunofluorescence assay. The expressions of MMP-2 and MMP-9 in the supernatant of the cells were determined by ELISA analysis. The Western blot and RT-qPCR were employed to explore the protein expressions associated with the dual signaling pathways of RhoA/ROCK and CDC42/MRCK. The anti-tumor efficacy of ZDF in vivo and its preliminary mechanism were investigated in the mouse 4T1 TNBC model. RESULTS: The results demonstrated that ZDF could significantly reduce the viability of the MDA-MB-231 cell, and the combination index (CI) values of actual compatibility experimental points were all less than 1, demonstrating a favorable synergistic compatibility relationship. It was found that ZDF reduces RhoA/ROCK and CDC42/MRCK dual signaling pathways, which are responsible for MDA-MB-231cell migration, invasion, and adhesion. Additionally, there has been a significant reduction in the manifestation of cytoskeleton-related proteins. Furthermore, the expression levels of RhoA, CDC42, ROCK2, and MRCKß mRNA and protein were down-regulated. ZDF significantly decreased the protein expressions of vimentin, cytokeratin-8, Arp2 and N-WASP, and inhibited actin polymerization and actomyosin contraction. Furthermore, MMP-2 and MMP-9 levels in the high-dose ZDF group were decreased by 30% and 26%, respectively. ZDF significantly reduced the tumor volume and protein expressions of ROCK2 and MRCKß in tumor tissues without eliciting any perceptible alterations in the physical mass of the mice, and the reduction was more pronounced than that of the BDP5290 treated group. CONCLUSION: The current investigation demonstrates that ZDF exhibits a proficient inhibitory impact on TNBC metastasis by regulating cytoskeletal proteins through the dual signaling pathways of RhoA/ROCK and CDC42/MRCK. Furthermore, the findings indicate that ZDF has significant anti-tumorigenic and anti-metastatic characteristics in breast cancer animal models.

1-Tetracosanol isolated from the leaves of Eupatorium glandulosum, accelerates wound healing by expressing inflammatory cytokines and matrix metalloproteinase.

ETHNOPHARMACOLOGICAL RELEVANCE: The leave paste of the plant, Eupatorium glandulosum H. B & K, has been traditionally used to treat cuts and wounds by the tribal community of the Nilgiris district of Tamilnadu, India. AIM OF THE STUDY: The present study was carried out to investigate the wound healing potential of this plant extract and the compound, 1-Tetracosanol, isolated from the ethyl acetate fraction. MATERIALS AND METHODS: An in vitro study was designed to compare the viability, migration and apoptosis of the fresh methanolic extract fractions and 1-Tetracosanol using mouse fibroblast NIH3T3 cell lines and human keratinocytes HaCaT cell lines, respectively. 1-Tetracosanol was evaluated for its viability, migration, qPCR analysis, in silico, in vitro and in vivo. RESULTS: 1-Tetracosanol at the concentration of 800, 1600, 3200 µM has significant wound closure of 99% at 24 h. The compound when screened in silico against various wound healing markers, TNF-α, IL-12, IL-18, GM-CSF and MMP-9, revealed high binding energy of -5, 4.9 and -6.4 kcal/mol for TNF-α, IL-18 and MMP-9, respectively. Gene expression and the release of cytokines increased at an early stage of the wound repair. 1-Tetracosanol, at 2% gel showed 97.35 ± 2.06% wound closure at 21st day. CONCLUSION: 1-Tetracosanol is a good lead for drug development targeted towards wound healing activity and work in this direction is in progress.

Protective Effects of Glycine soja Leaf and Stem Extract against Chondrocyte Inflammation and Osteoarthritis.

Wild soybean, also known as Glycine soja Sieb. et Zucc. (GS), has long been known for its various health benefits. Although various pharmacological effects of G. soja have been studied, the effects of GS leaf and stem (GSLS) on osteoarthritis (OA) have not been evaluated. Here, we examined the anti-inflammatory effects of GSLS in interleukin-1ß (IL-1ß)-stimulated SW1353 human chondrocytes. GSLS inhibited the expression of inflammatory cytokines and matrix metalloproteinases and ameliorated the degradation of collagen type II in IL-1ß-stimulated chondrocytes. Furthermore, GSLS played a protective role in chondrocytes by inhibiting the activation of NF-κB. In addition, our in vivo study demonstrated that GSLS ameliorated pain and reversed cartilage degeneration in joints by inhibiting inflammatory responses in a monosodium iodoacetate (MIA)-induced OA rat model. GSLS remarkably reduced the MIA-induced OA symptoms, such as joint pain, and decreased the serum levels of proinflammatory mediators, cytokines, and matrix metalloproteinases (MMPs). Our findings show that GSLS exerts anti-osteoarthritic effects and reduces pain and cartilage degeneration by downregulating inflammation, suggesting that it is a useful therapeutic candidate for OA.

Himalayan Citrus jambhiri juice reduced renal crystallization in nephrolithiasis by possible inhibition of glycolate oxidase and matrix metalloproteinases.

ETHNOPHARMACOLOGICAL RELEVANCE: Citrus fruits are a very rich source of electrolytes and citric acid. They have been used traditionally for treating urinary ailments and renal stones. Citrus jambhiri is indigenously used as a diuretic. AIM OF THE STUDY: Present study aimed at establishing the antiurolithiatic potential of the juice of Citrus jambhiri fruits along with the elucidation of the mechanism involved in the urolithiasis disease defying activity. METHODS: The antiurolithiatic activity was established by means of nucleation, growth and aggregation assay in the in vitro settings and by means of ethylene glycol mediated calcium oxalate urolithiasis in the male Wistar rats. Docking studies were performed in an attempt to determine the mechanism of the antiurolithiatic action. RESULTS: Present study revealed the role of C. jambhiri fruit juice in reducing nucleation, growth and aggregation of calcium oxalate crystals by possible reduction in the urinary supersaturation relative to calcium oxalate and raising the zeta potential of the calcium oxalate crystals. C. jambhiri fruit juice treatment in experimental rats produced significant amelioration of hypercalciuria, hyperoxaluria, hyperphosphaturia, hyperproteinuria, hyperuricosuria, hypocitraturia and hypomagnesiuria and ion activity product of calcium oxalate. It exhibited nephroprotection against calcium oxalate crystals induced renal tubular dilation and renal tissue deterioration. Docking studies further revealed high binding potential of the phytoconstituents of C. jambhiri viz. narirutin, neohesperidin, hesperidin, rutin and citric acid with glycolate oxidase and matrix metalloproteinase-9. CONCLUSION: C. jambhiri fruit juice possesses excellent antiurolithiatic activity. The study reveals antiurolithiatic mechanism that involves restoration of equilibrium between the promoters and inhibitors of stone formation; and inhibition of matrix metalloproteinases and glycolate oxidase.

Effects of Epigallocatechin-3-Gallate on Matrix Metalloproteinases in Terms of Its Anticancer Activity.

Epidemiological studies have shown that the consumption of green tea has beneficial effects against cancer. Basic studies have provided evidence that epigallocatechin gallate (EGCG) is a major contributor to these effects. Matrix metalloproteinases (MMPs) are zinc-dependent metalloproteinases with the ability to degrade the extracellular matrix proteins and are involved in various diseases including cancer in which MMPs have a critical role in invasion and metastasis. In this review, we discuss the effects of EGCG on several types of MMPs in the context of its anticancer activity. In the promoter region, MMPs have binding sites for at least one transcription factor of AP-1, Sp1, and NF-κB, and EGCG can downregulate these transcription factors through signaling pathways mediated by reactive oxygen species. EGCG can also decrease nuclear ERK, p38, heat shock protein-27 (Hsp27), and ß-catenin levels, leading to suppression of MMPs' expression. Other mechanisms by which EGCG inhibits MMPs include direct binding to MMPs to prevent their activation and downregulation of NF-κB to suppress the production of inflammatory cytokines such as TNFα and IL-1ß. Findings from studies on EGCG presented here may be useful in the development of more effective anti-MMP agents, which would give beneficial effects on cancer and other diseases.

Dose-Response Relationship of Photobiomodulation Therapy on Matrix Metalloproteinase in Healing Dynamics of Diabetic Neuropathic Ulcers-An in vivo Study.

Individuals with diabetic foot ulcers have overlapped the inflammatory, proliferative and remodeling phase, making the tissue vulnerable to delayed healing responses. We aimed to establish the dose-response relationship of photobiomodulation therapy of different doses and matrix metalloproteinases in the healing dynamics of diabetic neuropathic ulcers. Diabetes was induced in 126 Albino Wistar rats, and neuropathy was induced to the hind paw by a sciatic nerve injury method. An excisional wound was created on the neuropathy-induced leg. Photobiomodulation therapy of dosages 4, 6, 8, 10, 12 and 15 J cm-2 and wavelength 655 nm and 808 nm was irradiated. Photobiomodulation therapy of dosages 4, 6 and 8 J cm-2 showed better wound healing properties with optimized levels of matrix metalloproteinases-1 and 8. We observed a strong dose response in the experimental group treated with 6 and 8 J cm-2 . The findings from the present study conclude that photobiomodulation therapy of dosages 4, 6 and 8 J cm-2 is suggestive of usefulness in diabetic neuropathic ulcer healing. Markers like matrix metalloproteinases may give a clear direction on response to the therapy. Based on the findings from the present study, we recommend to validate the findings for safety and efficacy in future through human prospective randomized controlled clinical trials.

Effect of A. polygama APEE (Actinidia polygama ethanol extract) or APWE (Actinidia polygama water extract) on wrinkle formation in UVB-irradiated hairless mice.

BACKGROUND: Actinidia polygama (silver vine) is considered a medical plant which has been used in oriental medicine. It has been used for the treatment of pain, gout, rheumatoid arthritis, and inflammation. Few studies reported on the effect of Actinidia polygama (silver vine) on skin photoaging. OBJECTIVE: To evaluate the anti-photoaging effect of the ethanol and water extracts of A. polygama (APEE and APWE, respectively) in UVB-irradiated hairless mice. METHODS: SKH-1 hairless mice were exposed to UVB irradiation (30-60 mJ/cm2 ), following orally APEE or APWE oral administration for 10 weeks. We examined the effect on winkle improvement by a measuring Fullscope, PRIMOS, Craniometer, and Cutometer. Furthermore, we analyzed histological changes in mouse dorsal skin through hematoxylin and eosin (H&E) and Masson's trichrome (MT) staining. The expression of matrix metalloproteinase (1, 3, and 9) was analyzed by immunoblotting. RESULTS: Oral administration of APEE or APWE at 100 or 200 mg/kg in UVB-irradiated mice alleviated the symptoms of skin aging, such as wrinkling, epidermal hyperplasia, and water loss. In addition, the APEE or APWE oral administration increased skin elasticity by enhancing the production of type I collagen, elastin, and hyaluronic acid synthase and downregulating matrix metalloproteinase (1, 3, and 9) expression. CONCLUSION: Based on results for our study, APEE or APWE could protect the UVB-mediated skin wrinkle and is new target for the developing anti-wrinkle cosmetics.

Targeting matrix metalloproteases: A promising strategy for herbal medicines to treat rheumatoid arthritis.

As a type of metalloproteinase, matrix metalloproteinases (MMPs) can be divided into collagenase, gelatinase, stromelysins, membrane-type (MT)-MMPs and heterogeneous subgroups according to their structure and function. MMP contents in the human body are strictly regulated, and their synthesis, activation and inhibition processes should be kept in a certain balance; otherwise, this would result in the occurrence of various diseases. Rheumatoid arthritis (RA) is a known immune-mediated systemic inflammatory disease that is affected by a variety of endogenous and exogenous factors. In RA development, MMPs act as important mediators of inflammation and participate in the degradation of extracellular matrix substrates and digestion of fibrillar collagens, leading to the destruction of joint structures. Interestingly, increasing evidence has suggested that herbal medicines have many advantages in RA due to their multitarget properties. In this paper, literature was obtained through electronic databases, including the Web of Science, PubMed, Google Scholar, Springer, and CNKI (Chinese). After classification and analysis, herbal medicines were found to inhibit the inflammatory process of RA by regulating MMPs and protecting joint structures. However, further preclinical and clinical studies are needed to support this view before these herbal medicines can be developed into drugs with actual application to the disease.

Fallopia Japonica and Prunella vulgaris inhibit myopia progression by suppressing AKT and NFκB mediated inflammatory reactions.

BACKGROUND: The increased global incidence of myopia requires the establishment of therapeutic approaches. This study aimed to investigate the effect of Fallopia Japonica (FJ) and Prunella vulgaris (PV) extract on myopia caused by monocular form deprivation (MFD). METHODS: We used human retinal pigment epithelial cell to study the molecular mechanisms on how FJ extract (FJE) and PV extract (PVE) lowering the inflammation of the eye. The effect of FJE and PVE in MFD induced hamster model and explore the role of inflammation cytokines in myopia. RESULTS: FJE + PVE reduced IL-6, IL-8, and TNF-α expression in RPE cells. Furthermore, FJE and PVE inhibited inflammation by attenuating the phosphorylation of protein kinase B (AKT), and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) pathway. In addition, we report two resveratrol + ursolic acid compounds from FJ and PV and their inhibitory activities against IL-6, IL-8, and TNF-α expression levels in RPE cells treated with IL-6 and TNF-α. FJE, PVE, and FJE + PVE were applied to MFD hamsters and their axial length was measured after 21 days. The axial length showed statistically significant differences between phosphate-buffered saline- and FJE-, PVE-, and FJE + PVE-treated MFD eyes. FJE + PVE suppressed expressions of IL-6, IL-8, and TNF-α. They also inhibited myopia-related transforming growth factor-beta (TGF)-ß1, matrix metalloproteinase (MMP)-2, and NF-κB expression while increasing type I collagen expression. CONCLUSIONS: Overall, these results suggest that FJE + PVE may have a therapeutic effect on myopia and be used as a potential treatment option.

Alpinia officinarum Rhizome ameliorates the UVB induced photoaging through attenuating the phosphorylation of AKT and ERK.

BACKGROUND: Chronic ultraviolet (UV) exposure is one of the major external factors in skin aging, and repetitive UVB exposure induces extracellular matrix (ECM) damage as well as metabolic disease. Alpinia officinarum Rhizome (AOR) is a medicinal plant that has been traditionally used for treating rheumatism and whooping cough. However, the antiphotoaging effects of AOR remain unclear. We investigated the protective effects of water extracts of AOR (WEAOR) in terms of UVB-mediated ECM damage, wrinkle formation, inflammatory responses, and intracellular signaling on hairless mice and NIH-3T3 skin fibroblast cells. METHODS: WEAOR was administered to UVB-irradiated hairless mice. Wrinkle formation was assessed using the replica assay, epidermal changes through H&E staining, and collagen contents in mice skin through Masson's trichrome staining. The expression of procollagen type-1 (COL1A1), metalloproteinase-1a (MMP-1a), and inflammatory cytokines (IL-6, IL-8, and MCP-3) in hairless mice skin and NIH-3T3 cells was investigated through qRT-PCR. The effects of WEAOR or signaling inhibitors on UVB-induced expression of intracellular mitogen-activated protein kinases (MAPKs) were estimated by Western blotting and qRT-PCR, respectively. RESULTS: Topical WEAOR significantly attenuated the UVB-induced wrinkle formation and epidermal thickening in the skin of hairless mice. WEAOR treatment also attenuated the UVB-induced expression of MMP-1a and COL1A1 and recovered the reduction of collagen content in mouse skin. These effects were confirmed in NIH-3T3 skin fibroblast cells. WEAOR treatment restored the UVB-induced COL1A1 and MMP-1a gene expression and attenuated the UVB-induced expression of IL-6, IL-8, and MCP-3 in NIH-3T3 cells. Notably, WEAOR attenuated UVB-induced phosphorylation of AKT and ERK, but not that of p38 and JNK in NIH-3T3 cells. In addition, the administration of AKT and ERK inhibitors restored the UVB-induced expression of MMP-1a and COL1A1 to an equal extent as WEAOR in NIH-3T3 cells. CONCLUSIONS: The antiphotoaging properties of WEAOR were first evaluated in this study. Our results suggest that WEAOR may be a potential antiphotoaging agent that ameliorates UVB-induced photoaging processes via the AKT and ERK signaling pathways.

Photobiomodulation effects in metalloproteinases expression in zymosan-induced arthritis.

Matrix metalloproteinases (MMPs) play a crucial role in the degenerative course of rheumatic disorders. They are responsible for cartilage and other joint-associated tissues breakdown. Amid arthritis treatments, photobiostimulation (PBM), a non-thermal and non-invasive low-power laser application, appears to be an outstanding therapy alternative once it has succeeded in MMPs modulation. Thus, this study aimed to evaluate the PBM effects of low infrared laser (830 nm), testing two different energy densities (3 and 30 Jcm-2) in MMP-2, MMP-9, MMP-13, and MMP-14 as well as the inhibitor TIMP-2 expressions using zymosan-induced arthritis model. C57BL/6 mice were distributed into four groups (n = 8): zymosan-induced arthritis without treatment; zymosan-induced arthritis and dexamethasone-treated; zymosan-induced arthritis and PBM at energy density of 3 Jcm-2 treated; and zymosan-induced arthritis and PBM at energy density of 30 Jcm-2 treated. MMPs and TIMP-2 mRNA relative levels by qRT-PCR and proteins expression by immunohistochemical and Western blotting techniques were performed after PBM treatment in the inflamed joint. Our results demonstrated PBM could modulate both mRNA relative levels and proteins expression of the MMP-2, -9, -13, -14, and TIMP-2 in joint tissues, decreasing MMP-9 protein expression and increasing TIMP-2 protein expression. PBM promotes a better arthritis prognostic, modulating metalloproteinase and its inhibitor, especially MMP-9 and TIMP-2 protein expression that is important inflammatory markers. These findings may also corroborate that PBM may regulate MMPs expression using different pathways.

Enzyme-responsive nano-drug delivery system for combined antitumor therapy.

Efficient drug loading, tumor targeting, intratumoral penetration, and cellular uptake are the main factors affecting the effectiveness of drug delivery systems in oncotherapy. Based on the tumor microenvironment, we proposed to develop Curcumin (Cur)-loaded matrix metalloproteinase (MMP)-responsive nanoparticles (Cur-P-NPs) by static electricity, to enhance tumor targeting, cellular uptake, and drug loading efficiency. These nanoparticles combine the properties of both PEG-peptides (cleaved peptide + penetrating peptide) and star-shaped polyester (DPE-PCL) nanoparticles. Cur-P-NPs displayed good entrapment efficiency, drug loading and biocompatibility. Additionally, they showed an enhanced release rate, cellular uptake, and anti-proliferative activity by activating peptides under the simulated tumor microenvironment. Furthermore, intraperitoneal injection of losartan (LST) successfully enhanced intratumoral drug penetration by collagen I degradation. In vivo studies based on the systematic administration of the synergistic LST + Cur-P-NPs combination to mice confirmed that combined antitumor therapy with LST and Cur-P-NPs could further improve intratumor distribution, enhance anticancer efficacy, and reduce the toxicity and side effects. Therefore, LST + Cur-P-NPs represent a new and efficient system for clinical oncotherapy.