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Medicina (Kaunas, Lithuania) Apr 2024: Tacrolimus is a macrolide lactone compound derived from the bacterium , widely known as an immunosuppressant. In basic research, the effects of tacrolimus on...
: Tacrolimus is a macrolide lactone compound derived from the bacterium , widely known as an immunosuppressant. In basic research, the effects of tacrolimus on osteogenic differentiation have been tested using mesenchymal stem cells. In this study, tacrolimus's effects on the cellular survival and osteogenic differentiation of stem cell spheroids were investigated. : Concave microwells were used to form stem cell spheroids in the presence of tacrolimus at final concentrations of 0 μg/mL, 0.1 μg/mL, 1 μg/mL, 10 μg/mL, and 100 μg/mL. A microscope was used to test cellular vitality qualitatively, and an assay kit based on water-soluble tetrazolium salt was used to measure cellular viability quantitatively. Alkaline phosphatase activity and an anthraquinone dye test for measuring calcium deposits were used to assess osteogenic differentiation. To assess the expression of osteogenic differentiation, a quantitative polymerase chain reaction, Western blot, and RNA sequencing were performed. : Spheroids across all concentrations maintained a relatively uniform and spherical shape. Cell viability assay indicated that tacrolimus, up to a concentration of 100 μg/mL, did not significantly impair cell viability within spheroids cultured in osteogenic media. The increase in calcium deposition, particularly at lower concentrations of tacrolimus, points toward an enhancement in osteogenic differentiation. There was an increase in COL1A1 expression across all tacrolimus concentrations, as evidenced by the elevated mean and median values, which may indicate enhanced osteogenic activity. : This study showed that tacrolimus does not significantly impact the viability of stem cell spheroids in osteogenic media, even at high concentrations. It also suggests that tacrolimus may enhance osteogenic differentiation, as indicated by increased calcium deposition and COL1A1 expression. These findings advance our understanding of tacrolimus's potential roles in tissue repair, regeneration, and stem cell-based therapeutic applications.
Topics: Tacrolimus; Osteogenesis; Spheroids, Cellular; Cell Differentiation; Cell Survival; Humans; RNA, Messenger; Immunosuppressive Agents; Stem Cells; Mesenchymal Stem Cells
PubMed: 38792884
DOI: 10.3390/medicina60050702 -
Molecules (Basel, Switzerland) May 2024Yinhua Pinggan Granule (YPG) is an approved compounded traditional Chinese medicine (TCM) prescription for the treatment of cold, cough, viral pneumonia, and related...
Qualitative and Quantitative Analysis of Chemical Components in Yinhua Pinggan Granule with High-Performance Liquid Chromatography Coupled with Q-Exactive Mass Spectrometry.
Yinhua Pinggan Granule (YPG) is an approved compounded traditional Chinese medicine (TCM) prescription for the treatment of cold, cough, viral pneumonia, and related diseases. Due to its complicated chemical composition, the material basis of YPG has not been systematically investigated. In this study, an analytical method based on high-performance liquid chromatography (HPLC) coupled with Q-Exactive mass spectrometry was established. Together with the help of a self-built compound database and Compound Discoverer software 3.1, the chemical components in YPG were tentatively identified. Subsequently, six main components in YPG were quantitatively characterized with a high-performance liquid chromatography-diode array detector (HPLC-DAD) method. As a result, 380 components were annotated, including 19 alkaloids, 8 organic acids, 36 phenolic acids, 27 other phenols, 114 flavonoids, 75 flavonoid glycoside, 72 terpenes, 11 anthraquinones, and 18 other compounds. Six main components, namely, chlorogenic acid, puerarin, 3'-methoxypuerarin, polydatin, glycyrrhizic acid, and emodin, were quantified simultaneously. The calibration curves of all six analytes showed good linearity (R > 0.9990) within the test ranges. The precision, repeatability, stability, and recovery values were all in acceptable ranges. In addition, the total phenol content and DPPH scavenging activity of YPG were also determined. The systematic elucidation of the chemical components in YPG in this study may provide clear chemical information for the quality control and pharmacological research of YPG and related TCM compounded prescriptions.
Topics: Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Mass Spectrometry; Flavonoids; Medicine, Chinese Traditional; Phytochemicals
PubMed: 38792164
DOI: 10.3390/molecules29102300 -
International Journal of Molecular... May 2024The most common malignancy in women is breast cancer. During the development of cancer, oncogenic transcription factors facilitate the overproduction of inflammatory... (Review)
Review
The most common malignancy in women is breast cancer. During the development of cancer, oncogenic transcription factors facilitate the overproduction of inflammatory cytokines and cell adhesion molecules. Antiapoptotic proteins are markedly upregulated in cancer cells, which promotes tumor development, metastasis, and cell survival. Promising findings have been found in studies on the cell cycle-mediated apoptosis pathway for medication development and treatment. Dietary phytoconstituents have been studied in great detail for their potential to prevent cancer by triggering the body's defense mechanisms. The underlying mechanisms of action may be clarified by considering the role of polyphenols in important cancer signaling pathways. Phenolic acids, flavonoids, tannins, coumarins, lignans, lignins, naphthoquinones, anthraquinones, xanthones, and stilbenes are examples of natural chemicals that are being studied for potential anticancer drugs. These substances are also vital for signaling pathways. This review focuses on innovations in the study of polyphenol genistein's effects on breast cancer cells and presents integrated chemical biology methods to harness mechanisms of action for important therapeutic advances.
Topics: Humans; Genistein; Breast Neoplasms; Female; Signal Transduction; Apoptosis; Animals; Polyphenols
PubMed: 38791595
DOI: 10.3390/ijms25105556 -
International Journal of Molecular... May 2024can be a substantial concern, as it causes various diseases in aquaculture. An effective and green method for inhibiting is urgently required. Emodin, a naturally...
can be a substantial concern, as it causes various diseases in aquaculture. An effective and green method for inhibiting is urgently required. Emodin, a naturally occurring anthraquinone compound, was exploited as a photo-antimicrobial agent against . At the minimum inhibitory concentration of emodin (256 mg/L) to inactivate in 30 min, an 11.32% survival rate was observed under 45 W white compact fluorescent light irradiation. In addition, the antibacterial activity under natural sunlight (0.78%) indicated its potential for practical application. Morphological observations demonstrated that the cell walls and membranes of were susceptible to damage by emodin when exposed to light irradiation. More importantly, the photoinactivation of was predominantly attributed to the hydroxyl radicals and superoxide radicals produced by emodin, according to the trapping experiment and electron spin resonance spectroscopy. Finally, a light-dependent reactive oxygen species punching mechanism of emodin to photoinactivate was proposed. This study highlights the potential use of emodin in sunlight-mediated applications for bacterial control, thereby providing new possibilities for the use of Chinese herbal medicine in aquatic diseases prevention.
Topics: Emodin; Aeromonas hydrophila; Sunlight; Anti-Bacterial Agents; Microbial Sensitivity Tests; Reactive Oxygen Species
PubMed: 38791482
DOI: 10.3390/ijms25105444 -
Biomedicine & Pharmacotherapy =... Jul 2024Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by skin barrier dysfunction and chronic inflammatory responses. Reynoutria japonica, known as...
Reynoutria japonica consisted of emodin-8-β-D-glucoside ameliorates Dermatophagoides farinae extract-induced atopic dermatitis-like skin inflammation in mice by inhibiting JAK/STAT signaling.
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by skin barrier dysfunction and chronic inflammatory responses. Reynoutria japonica, known as Huzhang in traditional Chinese Medicine, can enhance blood circulation to eliminate wind pathogens and terminate coughing. Despite pharmacological evidence supporting the efficacy of R. japonica in suppressing edema-induced skin inflammation or connective tissue diseases, its pharmaceutical potential for treating AD-like skin inflammation remains unexplored. This study investigated the possible effects of R. japonica ethanol extract (RJE) on Dermatophagoides farinae extract (DfE)-induced AD-like skin inflammation in NC/Nga mice. To elucidate the underlying mechanisms by which RJE inhibits skin inflammation, we examined the effect of RJE on IFN-γ/TNF-α-induced signal transducer and activator of transcription (STAT) signaling in human epidermal keratinocytes (HEKs) and human dermal fibroblasts (HDFs). Our findings revealed that RJE mitigates DfE-induced AD-like symptoms and skin barrier disruptions in mouse skin lesions. Moreover, RJE attenuated DfE-induced mast cell infiltration and serum levels of inflammatory cytokines (IL-1α, IL-1β, IL-6, IL-23, IFN-γ, TNF-α, and GM-CSF). RJE also inhibited IFN-γ/TNF-α-induced chemokine levels and STAT3 phosphorylation in HEKs and HDFs. Virtual binding analysis of the RJE components suggested that emodin-8-β-D-glucoside binds to Janus kinase (JAK) 1/2, thereby suppressing STAT signaling, which was confirmed by Western blot analysis. In conclusion, our results suggest that RJE may alleviate DfE-induced skin barrier dysfunction by inhibiting JAK/STAT signaling and the proinflammatory immune response through the suppression of inflammatory mediators in AD-like skin disease. These findings suggest that RJE has potential as an effective therapy for AD management.
Topics: Animals; Dermatitis, Atopic; Signal Transduction; Mice; Dermatophagoides farinae; STAT Transcription Factors; Janus Kinases; Humans; Glucosides; Cytokines; Male; Skin; Emodin; Keratinocytes; Plant Extracts; Inflammation
PubMed: 38788600
DOI: 10.1016/j.biopha.2024.116765 -
Ecotoxicology and Environmental Safety Jul 2024Oxidative stress and inflammation play a fundamental role in the beginning and advancement of silicosis. Hence, questing active phytocompounds (APCs) with anti-oxidative...
Oxidative stress and inflammation play a fundamental role in the beginning and advancement of silicosis. Hence, questing active phytocompounds (APCs) with anti-oxidative and anti-inflammatory properties such as diosgenin (DG) and emodin (ED) can be a therapeutic intervention targeting silica-induced pulmonary inflammation and fibrosis. Hydrophobicity and low bioavailability are the barriers that restrict the therapeutic efficacy of DG and ED against pulmonary defects. Encapsulating these APCs in polymeric nanoparticles can overcome this limitation. The present study has thus explored the anti-inflammatory and anti-fibrotic effects of polylactic-co-glycolic acid (PLGA) nanoparticles (NPs) individually loaded with DG (DGn) or ED (EDn) and in combine DG+ED [(DG+ED)n] in respirable silica dust (RSD)-induced pulmonary fibrosis silicosis rat model. Our study found that individual and combined NPs revealed physiochemical characteristics appropriate for IV administration with sustained-drug release purposes. Physiological evaluations of RSD-induced silicosis rats suggested that no treatment could improve the body weight. Still, they reduced the lung coefficient by maintaining lung moisture. Only (DG+ED)n significantly cleared free lung silica. All interventions were found to attribute the increased per cent cell viability in BALF, reduce cytotoxicity via minimizing LDH levels, and balance the oxidant-antioxidant status in silicotic rats. The expression of inflammatory cytokines (TNF-α, IL-1β, IL-6, MCP-1, and TGF-β1) were efficiently down-regulated with NPs interventions compared to pure (DG+ED) treatment. All drug treatments significantly declined, the 8-HdG and HYP productions indicate that RSD-induced oxidative DNA damage and collagen deposition were successfully repaired. Moreover, histopathological investigations proposed that individual or combined drugs NPs interventions could decrease the fibrosis and alveolitis grades in RSD-induced silicosis rats. However, (DG+ED)n intervention significantly inhibited pulmonary fibrosis and alveolitis compared to pure (DG+ED) treatment. In conclusion, the RSD can induce oxidative stress and inflammation in rats, producing reactive oxygen species (ROS)-mediated cytotoxicity to pulmonary cells and leading to silicosis development. The IV administration of combined NP suppressed lung inflammation and collagen formation by maintaining oxidant-antioxidant status and effectively interrupting the fibrosis-silicosis progression. These results may be attributed to the improved bioavailability of DG and ED through their combined nano-encapsulation-mediated targeted drug delivery.
Topics: Animals; Diosgenin; Silicosis; Silicon Dioxide; Pulmonary Fibrosis; Rats; Emodin; Nanoparticles; Male; Dust; Oxidative Stress; Anti-Inflammatory Agents; Rats, Wistar; Lung; Polylactic Acid-Polyglycolic Acid Copolymer
PubMed: 38788565
DOI: 10.1016/j.ecoenv.2024.116483 -
Marine Drugs Apr 2024Marine symbiotic and epiphyte microorganisms are sources of bioactive or structurally novel natural products. Metabolic blockade-based genome mining has been proven to...
Metabolic Blockade-Based Genome Mining of Sea Anemone-Associated sp. S1502 Identifies Atypical Angucyclines WS-5995 A-E: Isolation, Identification, Biosynthetic Investigation, and Bioactivities.
Marine symbiotic and epiphyte microorganisms are sources of bioactive or structurally novel natural products. Metabolic blockade-based genome mining has been proven to be an effective strategy to accelerate the discovery of natural products from both terrestrial and marine microorganisms. Here, the metabolic blockade-based genome mining strategy was applied to the discovery of other metabolites in a sea anemone-associated sp. S1502. We constructed a mutant sp. S1502/Δ that switched to producing the atypical angucyclines WS-5995 A-E, among which WS-5995 E is a new compound. A biosynthetic gene cluster () of the angucyclines was identified through gene knock-out and heterologous expression studies. The biosynthetic pathways of WS-5995 A-E were proposed, the roles of some tailoring and regulatory genes were investigated, and the biological activities of WS-5995 A-E were evaluated. WS-5995 A has significant anti- activity with an IC value of 2.21 μM. The production of antibacterial streptopyrroles and anticoccidial WS-5995 A-E may play a protective role in the mutual relationship between sp. S1502 and its host.
Topics: Streptomyces; Animals; Sea Anemones; Multigene Family; Anti-Bacterial Agents; Biosynthetic Pathways; Genome, Bacterial; Biological Products; Anthraquinones; Angucyclines and Angucyclinones
PubMed: 38786587
DOI: 10.3390/md22050195 -
Frontiers in Microbiology 2024Cassia seeds, originating from the mature seeds of leguminous cassia species, possess pharmacological effects attributed to their rich composition of various active...
INTRODUCTION
Cassia seeds, originating from the mature seeds of leguminous cassia species, possess pharmacological effects attributed to their rich composition of various active ingredients, notably anthraquinones. While current research predominantly focuses on pharmaceutical extractions, there has been limited progress in fermentation studies.
METHODS
Our study aimed to enhance the content of active compounds such as anthraquinones, flavonoids, and polyphenols using microbial fermentation techniques. We specifically optimized a fermentation system through a single-factor experimental design.
RESULTS
The antioxidant properties of the fermentation solution were validated through assays involving HaCaT cells and zebrafish. We observed effective suppression of inflammatory reactions in both RAW264.7 cells and transgenic zebrafish by the fermentation solution. Moreover, significant inhibition of tyrosinase activity and melanin production was evident in B16-F10 cells and zebrafish. Positive outcomes were also obtained in antibacterial assays and chick embryo experiments.
DISCUSSION
These findings highlight the potential of cassia seed fermentation solution as a safe and eco-friendly material in food chemistry and biomedical sciences.
PubMed: 38784817
DOI: 10.3389/fmicb.2024.1400505 -
International Journal of Biological... Jun 2024Wound infections, posing a grave risk of severe physical consequences and even mortality, exact a substantial financial toll on society, rendering them among the most...
Wound infections, posing a grave risk of severe physical consequences and even mortality, exact a substantial financial toll on society, rendering them among the most formidable challenges confronting our world today. A critical imperative is the development of hydrogel dressings endowed with immune-regulating and antibacterial properties. This study is founded upon the symbiotic physical and efficacious attributes of two small natural molecules. An injectable hydrogel is meticulously crafted by encapsulating puerarin (PUE) into tyramine-modified hyaluronic acid, subsequently introducing rhein (RHE), and catalyzing the formation of inter-phenol crosslinks with HO/horseradish peroxidase (HA-Tyr-R@P). Exhibiting a favorable microenvironmental impact the developed hydrogel attains an antibacterial efficacy exceeding 95 %, coupled with a wound closure rate twice that of the control group. HA-Tyr-R@P hydrogels not only inhibit bacterial growth but also mitigate inflammation, fostering wound healing, owing to their harmonized physicochemical characteristics and synergistic therapeutic effects. This work underscores the creation of a singular, versatile hydrogel platform, negating the complexities and side effects associated with pharmaceutical preparations. Furthermore, it offers new ideas for the formulation of RHE-based hydrogels for wound healing, emphasizing the pivotal role of natural small molecules in advancing biological materials.
Topics: Tyramine; Hyaluronic Acid; Hydrogels; Anti-Bacterial Agents; Animals; Isoflavones; Anti-Inflammatory Agents; Wound Healing; Mice; Anthraquinones; Bandages
PubMed: 38777027
DOI: 10.1016/j.ijbiomac.2024.132527 -
PloS One 2024In the search for better anticancer drugs, computer-aided drug design (CADD) techniques play an indispensable role in facilitating the lengthy and costly drug discovery...
BACKGROUND
In the search for better anticancer drugs, computer-aided drug design (CADD) techniques play an indispensable role in facilitating the lengthy and costly drug discovery process especially when natural products are involved. Anthraquinone is one of the most widely-recognized natural products with anticancer properties. This review aimed to systematically assess and synthesize evidence on the utilization of CADD techniques centered on the anthraquinone scaffold for cancer treatment.
METHODS
The conduct and reporting of this review were done in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) 2020 guideline. The protocol was registered in the "International prospective register of systematic reviews" database (PROSPERO: CRD42023432904) and also published recently. The search strategy was designed based on the combination of concept 1 "CADD or virtual screening", concept 2 "anthraquinone" and concept 3 "cancer". The search was executed in PubMed, Scopus, Web of Science and MedRxiv on 30 June 2023.
RESULTS
Databases searching retrieved a total of 317 records. After deduplication and applying the eligibility criteria, the final review ended up with 32 articles in which 3 articles were found by citation searching. The CADD methods used in the studies were either structure-based alone (69%) or combined with ligand-based methods via parallel (9%) or sequential (22%) approaches. Molecular docking was performed in all studies, with Glide and AutoDock being the most popular commercial and public software used respectively. Protein data bank was used in most studies to retrieve the crystal structure of the targets of interest while the main ligand databases were PubChem and Zinc. The utilization of in-silico techniques has enabled a deeper dive into the structural, biological and pharmacological properties of anthraquinone derivatives, revealing their remarkable anticancer properties in an all-rounded fashion.
CONCLUSION
By harnessing the power of computational tools and leveraging the natural diversity of anthraquinone compounds, researchers can expedite the development of better drugs to address the unmet medical needs in cancer treatment by improving the treatment outcome for cancer patients.
Topics: Anthraquinones; Humans; Neoplasms; Antineoplastic Agents; Drug Design; Molecular Docking Simulation; Computer-Aided Design; Drug Discovery
PubMed: 38776291
DOI: 10.1371/journal.pone.0301396