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International Journal of Pharmaceutics Jun 2024Rhein, a natural anthraquinone compound derived from traditional Chinese medicine, exhibits potent anti-inflammatory properties via modulating the level of Reactive...
Rhein, a natural anthraquinone compound derived from traditional Chinese medicine, exhibits potent anti-inflammatory properties via modulating the level of Reactive oxygen or nitrogen species (RONS). Nevertheless, its limited solubility in water, brief duration of plasma presence, as well as its significant systemic toxicity, pose obstacles to its in vivo usage, necessitating the creation of a reliable drug delivery platform to circumvent these difficulties. In this study, an esterase-responsive and mitochondria-targeted nano-prodrug was synthesized by conjugating Rhein with the polyethylene glycol (PEG)-modified triphenyl phosphonium (TPP) molecule, forming TPP-PEG-RH, which could spontaneously self-assemble into RPT NPs when dispersed in aqueous media. The TPP outer layer of these nanoparticles enhances their pharmacokinetic profile, facilitates efficient delivery to mitochondria, and promotes cellular uptake, thereby enabling enhanced accumulation in mitochondria and improved therapeutic effects in vitro. The decline in RONS was observed in IL-1β-stimulated chondrocyte after RPT NPs treating. RPT NPs also exert excellent anti-inflammatory (IL-1β, TNF-α, IL-6 and MMP-13) and antioxidative effects (Cat and Sod) via the Nrf2 signalling pathway, upregulation of cartilage related genes (Col2a1 and Acan). Moreover, RPT NPs shows protection of mitochondrial membrane potential and inhibition of chondrocyte apoptosis. Moreover, These findings suggest that the mitochondria-targeted polymer-Rhein conjugate may offer a therapeutic solution for patients suffering from chronic joint disorders, by attenuating the progression of osteoarthritis (OA).
PubMed: 38945463
DOI: 10.1016/j.ijpharm.2024.124397 -
Neuroscience Jun 2024Neonatal hypoxic-ischemic brain damage (HIBD) can lead to mortality and severe neurological dysfunction. Emodin is a natural anthraquinone derivative that is easy to...
Neonatal hypoxic-ischemic brain damage (HIBD) can lead to mortality and severe neurological dysfunction. Emodin is a natural anthraquinone derivative that is easy to obtain and has good neuroprotective effects. This study aimed to investigate the neuroprotective effect of emodin on neonatal mouse HIBD. The modified Rice-Vannucci method was used to induce HIBD in mouse pups. Eighty postnatal 7-day (P7) C57BL/6 neonatal mice were randomly divided into the sham group (sham), vehicle group (vehicle), and emodin group (emodin). TTC staining and whole-brain morphology were used to evaluate the infarct volume and morphology of the brain tissue. The condition of the neurons was observed through Nissl staining, HE staining, FJC staining, immunofluorescence and Western blot for NeuN, IBA-1, and GFAP. The physiological status of the mice was evaluated using weight measurements. The neural function of the mice was assessed using the negative geotaxis test, righting reflex test, and grip test. TUNEL staining was used to detect apoptosis in brain cells. Finally, Western blot and immunofluorescence were used to detect the expression levels of apoptosis-related proteins, such as P53, cleaved caspase-3, Bax and Bcl-2, in the brain. Experiments have shown that emodin can reduce the cerebral infarct volume, brain oedema, neuronal apoptosis, and degeneration and improve the reconstruction of brain tissue morphology, neuronal morphology, physiological conditions, and neural function. Additionally, emodin inhibited the expression of proapoptotic proteins such as P53, Bax and cleaved caspase-3 and promoted the expression of the antiapoptotic protein Bcl-2. Emodin attenuates HIBD by inhibiting neuronal apoptosis in neonatal mice.
PubMed: 38944149
DOI: 10.1016/j.neuroscience.2024.06.030 -
Journal of Integrative Neuroscience Jun 2024root, cataloged as "" in the Korean Pharmacopeia, is rich in various anthraquinones known for their anti-inflammatory and antioxidant properties. Formulations...
BACKGROUND
root, cataloged as "" in the Korean Pharmacopeia, is rich in various anthraquinones known for their anti-inflammatory and antioxidant properties. Formulations containing are traditionally employed for treating neurological conditions. This study aimed to substantiate the antiepileptic and neuroprotective efficacy of root extract (RTE) against trimethyltin (TMT)-induced epileptic seizures and hippocampal neurodegeneration.
METHODS
The constituents of RTE were identified by ultra-performance liquid chromatography (UPLC). Experimental animals were grouped into the following five categories: control, TMT, and three TMT+RTE groups with dosages of 10, 30, and 100 mg/kg. Seizure severity was assessed daily for comparison between the groups. Brain tissue samples were examined to determine the extent of neurodegeneration and neuroinflammation using histological and molecular biology techniques. Network pharmacology analysis involved extracting herbal targets for and disease targets for epilepsy from multiple databases. A protein-protein interaction network was built using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and pivotal targets were determined by topological analysis. Enrichment analysis was performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) tool to elucidate the underlying mechanisms.
RESULTS
The RTE formulation was found to contain sennoside A, sennoside B, chrysophanol, emodin, physcion, (+)-catechin, and quercetin-3-O-glucuronoid. RTE effectively inhibited TMT-induced seizures at 10, 30, and 100 mg/kg dosages and attenuated hippocampal neuronal decay and neuroinflammation at 30 and 100 mg/kg dosages. Furthermore, RTE significantly reduced mRNA levels of tumor necrosis factor (), glial fibrillary acidic protein (), and in hippocampal tissues. Network analysis revealed TNF, Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Protein c-fos (FOS), RAC-alpha serine/threonine-protein kinase (AKT1), and Mammalian target of rapamycin (mTOR) as the core targets. Enrichment analysis demonstrated significant involvement of components in neurodegeneration ( = 4.35 × 10-5) and TNF signaling pathway ( = 9.94 × 10-5).
CONCLUSIONS
The and analyses performed in this study suggests that RTE can potentially modulate TMT-induced epileptic seizures and neurodegeneration. Therefore, root is a promising herbal treatment option for antiepileptic and neuroprotective applications.
Topics: Animals; Neuroprotective Agents; Trimethyltin Compounds; Plant Extracts; Rheum; Plant Roots; Male; Anticonvulsants; Epilepsy; Hippocampus; Disease Models, Animal; Neurodegenerative Diseases; Computer Simulation; Network Pharmacology; Protein Interaction Maps; Rats
PubMed: 38940090
DOI: 10.31083/j.jin2306122 -
Chemical Science Jun 2024Hydrogen peroxide (HO) is one of the most valuable clean energy sources with a rapidly growing requirement in industry and daily life. The direct synthesis of HO from...
Hydrogen peroxide (HO) is one of the most valuable clean energy sources with a rapidly growing requirement in industry and daily life. The direct synthesis of HO from hydrogen and oxygen is considered to be an economical and environmentally friendly manufacturing route to replace the traditional anthraquinone method, although it remains a formidable challenge owing to low HO selectivity and production. Here, we report a catalyst consisting of Pd(111) nanocrystals on TiO modified with single Pt atoms (PtPd(111)/TiO), which displays outstanding reactivity, producing 1921.3 μmol of HO, a H conversion of 62.2% and HO selectivity of 80.3% over 30 min. Kinetic and isotope experiments confirm that the extraordinary catalytic properties are due to stronger H activation (the rate-determining step). DFT calculations confirm that PtPd(111) exhibits lower energy barriers for H dissociation and two-step O hydrogenation, but higher energy barriers for side reactions than PtPd(100), demonstrating clear facet dependence and resulting in greater selectivity and amount of HO produced.
PubMed: 38939129
DOI: 10.1039/d4sc01560f -
Frontiers in Nutrition 2024Rhubarb is a popular food that relieves constipation and aids with weight loss. The traditional method of preparation, includes steaming and sun-drying rhubarb nine...
INTRODUCTION
Rhubarb is a popular food that relieves constipation and aids with weight loss. The traditional method of preparation, includes steaming and sun-drying rhubarb nine times (SDR-9) to reduce its toxicity and increase efficacy.
METHODS
Flavor analysis includes odor analysis by gas chromatography-ion mobility spectrometry and taste characterization using an electronic tongue.
RESULTS
Odor analysis of the samples prepared through SDR-9 identified 61 volatile compounds, including aldehydes, esters, alcohols, ketones, acids, alkenes, and furans. Of these, 13 volatile components were the key substances associated with odor. This enabled the process to be divided into two stages: 1-5 times of steaming and sun-drying and 6-9 times. In the second stage, SDR-6 and SDR-9 were grouped together in terms of odor. Analysis using electronic tongue revealed that the most prominent taste was bitterness. A radar map indicated that the bitterness response was the highest for raw rhubarb, whereas that for processed (steamed and sun-dried) rhubarb decreased. Orthogonal partial least squares discriminant analysis (OPLS-DA) clustering results for SDR-6 and SDR-9 samples indicated that their tastes were similar. Anthraquinones were analyzed via high-performance liquid chromatography; moreover, analysis of the taste and components of the SDR samples revealed a significant correlation.
DISCUSSION
These results indicate that there are similarities between SDR-6 and SDR-9 in terms of smell, taste, and composition, indicating that the steaming and sun-drying cycles can be conducted six times instead of nine.
PubMed: 38933883
DOI: 10.3389/fnut.2024.1406430 -
International Journal of Molecular... Jun 2024Chemotherapy resistance in cancer is an essential factor leading to high mortality rates. Tumor multidrug resistance arises as a result of the autophagy process. Our...
Chemotherapy resistance in cancer is an essential factor leading to high mortality rates. Tumor multidrug resistance arises as a result of the autophagy process. Our previous study found that compound 1-nitro-2 acyl anthraquinone-leucine (C2) exhibited excellent anti-colorectal cancer (CRC) activity involving autophagy and apoptosis-related proteins, whereas its underlying mechanism remains unclear. A notable aspect of this study is how C2 overcomes the multidrug susceptibility of HCT116/L-OHP, a colon cancer cell line that is resistant to both in vitro and in vivo oxaliplatin (trans-/-diaminocyclohexane oxalatoplatinum; L-OHP). In a xenograft tumor mouse model, we discovered that the mixture of C2 and L-OHP reversed the resistance of HCT116/L-OHP cells to L-OHP and inhibited tumor growth; furthermore, C2 down-regulated the gene expression levels of and and decreased drug efflux activity. It is important to note that while C2 re-sensitized the HCT116/L-OHP cells to L-OHP for apoptosis, it also triggered a protective autophagic pathway. The expression levels of cleaved caspase-3 and Beclin 1 steadily rose. Expression of PI3K, phosphorylated AKT, and mTOR were decreased, while p53 increased. We demonstrated that the anthraquinone derivative C2 acts as an L-OHP sensitizer and reverses resistance to L-OHP in HCT116/L-OHP cells. It suggests that C2 can induce autophagy in HCT116/L-OHP cells by mediating p53 and the PI3K/AKT/mTOR signaling pathway.
Topics: Humans; TOR Serine-Threonine Kinases; Proto-Oncogene Proteins c-akt; Animals; Oxaliplatin; Phosphatidylinositol 3-Kinases; Autophagy; Anthraquinones; Signal Transduction; Mice; HCT116 Cells; Apoptosis; Xenograft Model Antitumor Assays; Antineoplastic Agents; Drug Resistance, Neoplasm; Mice, Nude; Cell Line, Tumor
PubMed: 38928176
DOI: 10.3390/ijms25126468 -
Journal of Nanobiotechnology Jun 2024Hypoxia-activated prodrugs present new opportunities for safe and effective tumor drug resistance therapy due to their high selectivity for hypoxic cells. However, the...
BACKGROUND
Hypoxia-activated prodrugs present new opportunities for safe and effective tumor drug resistance therapy due to their high selectivity for hypoxic cells. However, the uneven distribution of oxygen in solid tumor and insufficient hypoxia in the tumor microenvironment greatly limit its therapeutic efficacy.
RESULTS
In this paper, a novel AQ4N-Mn(II)@PDA coordination nanoplatform was designed and functionalized with GMBP1 to target drug-resistant tumor cells. Its excellent photothermal conversion efficiency could achieve local high-temperature photothermal therapy in tumors, which could not only effectively exacerbate tumor hypoxia and thus improve the efficacy of hypoxia-activated chemotherapy of AQ4N but also significantly accelerate Mn-mediated Fenton-like activity to enhance chemodynamic therapy. Moreover, real-time monitoring of blood oxygen saturation through photoacoustic imaging could reflect the hypoxic status of tumors during treatment. Furthermore, synergistic treatment effectively inhibited tumor growth and improved the survival rate of mice bearing orthotopic drug-resistant tumors.
CONCLUSIONS
This study not only provided a new idea for PTT combined with hypoxia-activated chemotherapy and CDT for drug-resistant tumors but also explored a vital theory for real-time monitoring of hypoxia during treatment.
Topics: Animals; Mice; Drug Resistance, Neoplasm; Cell Line, Tumor; Humans; Photothermal Therapy; Mice, Inbred BALB C; Nanoparticles; Antineoplastic Agents; Tumor Microenvironment; Mice, Nude; Prodrugs; Tumor Hypoxia; Manganese; Female; Neoplasms; Anthraquinones
PubMed: 38926723
DOI: 10.1186/s12951-024-02653-8 -
Angewandte Chemie (International Ed. in... Jun 2024The electrochemical production of hydrogen peroxide (H2O2) using metal-free catalysts has emerged as a viable and sustainable alternative to the conventional...
The electrochemical production of hydrogen peroxide (H2O2) using metal-free catalysts has emerged as a viable and sustainable alternative to the conventional anthraquinone process. However, the precise architectural design of these electrocatalysts poses a significant challenge, requiring intricate structural engineering to optimize electron transfer during the oxygen reduction reaction (ORR). Herein, we introduce a novel design of covalent organic frameworks (COFs) that effectively shift the ORR from a four-electron to a more advantageous two-electron pathway. Notably, the JUC-660 COF, with strategically charge-modified benzyl moieties, achieved a continuous high H2O2 yield of over 1200 mmol g-1 h-1 for an impressive duration of over 85 hours in a flow cell setting, marking it as one of the most efficient metal-free and non-pyrolyzed H2O2 electrocatalysts reported to date. Theoretical computations alongside in-situ infrared spectroscopy indicate that JUC-660 markedly diminishes the adsorption of the OOH* intermediate, thereby steering the ORR towards the desired pathway. Furthermore, the versatility of JUC-660 was demonstrated through its application in the electro-Fenton reaction, where it efficiently and rapidly removed aqueous contaminants. This work delineates a pioneering approach to altering the ORR pathway, ultimately paving the way for the development of highly effective metal-free H2O2 electrocatalysts.
PubMed: 38924241
DOI: 10.1002/anie.202410417 -
Marine Drugs Jun 2024A new dimeric C-glycoside polyketide chrysomycin F (), along with four new monomeric compounds, chrysomycins G (), H (), I (), J (), as well as three known analogues,...
A new dimeric C-glycoside polyketide chrysomycin F (), along with four new monomeric compounds, chrysomycins G (), H (), I (), J (), as well as three known analogues, chrysomycins A (), B (), and C (), were isolated and characterised from a strain of sp. obtained from a sediment sample collected from the South China Sea. Their structures were determined by detailed spectroscopic analysis. Chrysomycin F contains two diastereomers, whose structures were further elucidated by a biomimetic [2 + 2] photodimerisation of chrysomycin A. Chrysomycins B and C showed potent anti-tuberculosis activity against both wild-type and a number of clinically isolated MDR strains.
Topics: Streptomyces; Mycobacterium tuberculosis; Antitubercular Agents; Polyketides; Microbial Sensitivity Tests; Glycosides; China; Molecular Structure; Anthraquinones
PubMed: 38921570
DOI: 10.3390/md22060259 -
Journal of Fungi (Basel, Switzerland) May 2024Biocolourants could be a sustainable option for dyes that require fossil-based chemicals in their synthesis. We studied the in vitro toxicity of anthraquinone aglycone...
Biocolourants could be a sustainable option for dyes that require fossil-based chemicals in their synthesis. We studied the in vitro toxicity of anthraquinone aglycone extract obtained from fungus and compared it to the toxicity of its two main components, emodin and previously studied dermocybin. Cell viability, cytotoxicity, and oxidative stress responses in HepG2 liver and THP-1 immune cell lines were studied along with skin sensitisation. In addition, genotoxicity was studied with comet assay in HepG2 cells. Cellular viability was determined by MTT, propidium iodide, and lactate dehydrogenase assays, which showed that the highest doses of both the aglycone extract and emodin affected the viability. However, the effect did not occur in all of the used assays. Notably, after both exposures, a dose-dependent increase in oxidative stress factors was observed in both cell lines as measured by MitoSOX and dihydroethidium assays. extract was not genotoxic in the comet assay. Importantly, both emodin and the extract activated the skin sensitisation pathway in the KeratinoSens assay, suggesting that they can induce allergy in humans. As emodin has shown cytotoxic and skin-sensitising effects, it is possible that the adverse effects caused by the extract are also mediated by it since it is the main component present in the fungus.
PubMed: 38921356
DOI: 10.3390/jof10060369