Bailixiang tea, an herbal medicine formula, co-suppresses TLR2/MAPK8 and TLR2/NF-κB signaling pathways to protect against LPS-triggered cytokine storm in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) has shown notable effectiveness and safety in managing illnesses linked to cytokine storm(CS). Bailixiang tea (BLX), an herbal medicine formula, which is a compound Chinese medicine composed of Thymus mongolicus (Ronniger) Ronniger (Bailixiang), Glycyrrhiza uralensis Fisch. (Gancao), Citrus reticulata Blanco (Chenpi), Cyperus rotundus L. (Xiangfu), and Perilla frutescens (L.) Britton (Zisu). The objective of this study was to explore the capacity of BLX in improving LPS-induced CS. AIM OF THE STUDY: This study aimed to validate the mitigating effect of BLX on CS and to further investigate its mechanism. MATERIALS AND METHODS: mice were orally administered BLX for 24 h after being treated with 5 mg/kg lipopolysaccharide (LPS). Histopathological observations further confirmed the significant protective effect of BLX treatment against LPS-induced lung and spleen damage. Additionally, we aimed to explore the molecular mechanism underlying its effects through blood proteomics and transcriptomics analyses. Real-Time Quantitative PCR (RT-qPCR) was utilized to detect the levels of Toll-like receptor 2 (TLR2), Matrix metalloproteinase 8 (MMP8), Matrix metalloproteinase 9 (MMP9), Integrin beta 2 (ITGB2), Mitogen-activated protein kinase 8 (MAPK8), Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, epsilon (NFKBIE), Nuclear factor of kappa light polypeptide gene enhancer in B-cells 2 (NFKB2), and Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH)expressions in the lung tissue. RESULTS: The results demonstrated that BLX effectively down-regulated the overproduction of interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) in both the serum and lung and spleen tissues. Furthermore, BLX effectively mitigated the overproduction of monocyte chemoattractant protein-1 (MCP-1) in the serum. Through comprehensive multi-omics analysis, it was revealed that BLX specifically targeted and regulated TLR2/MAPK8 and TLR2/NF-κB signaling pathways, which play a crucial role in the production of key cytokines. CONCLUSIONS: The findings of this study demonstrate that Bailixiang tea possesses the ability to alleviate lung tissue damage and inhibit the development of LPS-induced cytokine storm in mice. These effects are attributed to the tea's ability to suppress the TLR2/MAPK8 and TLR2/NF-κB pathways. Consequently, this research highlights the potential application of Bailixiang tea as a treatment option for cytokine storm.

In-situ evaluation the fluctuation of hypochlorous acid in acute liver injury mice models with a mitochondria-targeted NIR ratiometric fluorescent probe.

Acute liver injury (ALI) is a frequent and devastating liver disease that has been made more prevalent by the excessive use of chemicals, drugs, and alcohol in modern life. Hypochlorous acid (HClO), an important biomarker of oxidative stress originating mainly from the mitochondria, has been shown to be intimately connected to the development and course of ALI. Herein, a novel BODIPY-based NIR ratiometric fluorescent probe Mito-BS was constructed for the specific recognition of mitochondrial HClO. The probe Mito-BS can rapidly respond to HClO within 20 s with a ratiometric fluorescence response (from 680 nm to 645 nm), 24-fold fluorescence intensity ratio enhancement (I645/I680), a wide pH adaptation range (5-9) and the low detection limit (31 nM). The probe Mito-BS has been effectively applied to visualize endogenous and exogenous HClO fluctuations in living zebrafish and cells based on its low cytotoxicity and prominent mitochondria-targeting ability. Furthermore, the fluorescent probe Mito-BS makes it possible to achieve the non-invasive in-situ diagnosis of ALI through in mice, and provides a feasible strategy for early diagnosis and drug therapy of ALI and its complications.

A ratiometric fluorescent probe with a large Stokes shift for the detection of Hg2+ and its applications in environmental sample and living system analysis.

Toxic mercury ions (Hg2+) can cause serious environmental pollution and accumulate in living organisms via the food chain. Therefore, monitoring Hg2+ is crucial in ensuring the safety of ecosystems and organisms. In this work, a novel ratiometric fluorescent probe CMT (5-(4-(diphenylamino)phenyl)-1-(7-hydroxy-coumarin-3-yl)-4-pentene-1,3-dione) based on coumarin was developed for detecting Hg2+, which displayed obvious fluorescence changes, a low detection limit (2.24 × 10-7 M), good selectivity, and a large Stokes shift (255 nm). The CMT probe could detect Hg2+ in real environmental soil and water samples. Furthermore, the CMT probe enabled the naked-eye detection of Hg2+ using test paper experiments. CMT was also applied for fluorescence imaging in living zebrafish and plants. This work provides a highly efficient tool for monitoring Hg2+ in environmental samples and biological systems.

Xinshubao tablet ameliorates myocardial injury against heart failure via the DCN/PPARα/PGC-1α/P300 pathway.

Heart failure (HF) is a complex clinical syndrome with impaired ventricular ability due to structural or functional cardiac disorders. A traditional Chinese formula named Xinshubao tablet (XSB) is reported to protect cardiomyocytes and decrease the risk of HF clinically; however, the underlying mechanism of XSB on decreasing HF risk is not elucidated yet. Therefore, our study aimed to investigate the therapeutic efficacy and underlying mechanism of XSB by using HF model rats and H9c2 cells with oxygen glucose deprivation. Echocardiographic and pathological features of animal experiment showed that XSB treatment effectively improved cardiac function and ameliorated myocardial injury after 4 weeks of treatment. Cellular experiments indicated that XSB pretreatment significantly inhibited apoptosis and increased mitochondrial energy metabolism. Furthermore, in vivo and in vitro experiments both demonstrated that XSB suppressed oxidative stress and inflammatory response. Our results further revealed that the potential protective mechanism of XSB was closely associated with the DCN/PPARα/PGC-1α/P300 signaling pathway. Our findings provide novel mechanistic insights for HF treatment and a pharmacological basis for the therapeutic application of XSB against cardiovascular disorders.

Fluorescent probe for sensitive discrimination of GSH and Hcy/Cys with single-wavelength excitation in biological systems via different emission.

Biothiols (GSH, Hcy, Cys) are important active sulfur substances in biological systems and widely participate in various physiological processes. The three kinds of biothiols have similar chemical structures, including the sulfhydryl group (-SH) and an amino group (-NH2), so distinguishing two or more of them simultaneously is an important challenge. Herein, a nopinone-based fluorescent probe 3-(3-((4-nitrobenzoxadiazole vinyl) nopinyl difluoride (NF-NBD) was designed to distinguish GSH and Hcy/Cys by generating different fluorescence channels with a single excitation wavelength. The nitrobenzodioxazole (NBD) was introduced in the fluorescent probe by ether bounds that can quench fluorescence and selectively discriminate GSH and Hcy/Cys. After reacting with GSH and Hcy/Cys, NF-NBD exhibited strong fluorescence (green for GSH and yellow for Hcy/Cys). NF-NBD displayed a wide linear range, low detection limit, a rapid response time, and superior selectivity for biothiols. Furthermore, NF-NBD was applied to image and distinguish different biothiols in living cells and zebrafish via different fluorescence signals at a single excitation wavelength.

Advances in Fluorescent Sensing Carbon Dots: An Account of Food Analysis.

Illuminating the use of nanomaterials, carbon quantum dots (CQDs) have transfigured the food safety arena because of their bright luminescence, optical properties, low toxicity, and enhanced biocompatibility. Therefore, fluorescent resonance energy transfer, photoinduced electron transfer, and an internal filtering effect mechanism allow precise detection of food additives, heavy metal ions, pathogenic bacteria, veterinary drug residues, and food nutrients. In this review, we describe the primal mechanism of CQD-based fluorescence sensors for food safety inspection. This is an abridged description of the nanodesign and future perspectives of more advanced CQD-based sensors for food safety analysis.

Therapeutic effects of total saikosaponins from Radix bupleuri against Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by memory loss and cognitive dysfunction in the elderly, with amyloid-beta (Aß) deposition and hyperphosphorylation of tau protein as the main pathological feature. Nuclear factor 2 (Nrf2) is a transcription factor that primarily exists in the cytosol of hippocampal neurons, and it is considered as an important regulator of autophagy, oxidative stress, and inflammation. Total saikosaponins (TS) is the main bioactive component of Radix bupleuri (Chaihu). In this study, it was found that TS could ameliorate cognitive dysfunction in APP/PS1 transgenic mice and reduce Aß generation and senile plaque deposition via activating Nrf2 and downregulating the expression of ß-secretase 1 (BACE1). In addition, TS can enhance autophagy by promoting the expression of Beclin-1 and LC3-II, increasing the degradation of p62 and NDP52 and the clearance of phosphorylated tau (p-tau), and reducing the expression of p-tau. It can also downregulate the expression of nuclear factor-κB (NF-κB) to inhibit the activation of glial cells and reduce the release of inflammatory factors. In vitro experiments using PC12 cells induced by Aß, TS could significantly inhibit the aggregation of Aß and reduce cytotoxicity. It was found that Nrf2 knock-out weakened the inhibitory effect of TS on BACE1 and NF-κB transcription in PC12 cells. Moreover, the inhibitory effect of TS on BACE1 transcription was achieved by promoting the binding of Nrf2 and the promoter of BACE1 ARE1. Results showed that TS downregulated the expression of BACE1 and NF-κB through Nrf2, thereby reducing the generation of Aß and inhibiting neuroinflammation. Furthermore, TS can ameliorate synaptic loss and alleviate oxidative stress. In gut microbiota analysis, dysbiosis was demonstrated in APP/PS1 transgenic mice, indicating a potential link between gut microbiota and AD. Furthermore, TS treatment reverses the gut microbiota disorder in APP/PS1 mice, suggesting a therapeutic strategy by remodeling the gut microbe. Collectively, these data shows that TS may serve as a potential approach for AD treatment. Further investigation is needed to clarify the detailed mechanisms underlying TS regulating gut microbiota and oxidative stress.

Qinbaohong Zhike Oral Liquid Attenuates LPS-Induced Acute Lung Injury in Immature Rats by Inhibiting OLFM4.

Acute respiratory infections (ARIs) are a common public safety threat with high morbidity and mortality in pediatric patients worldwide. Qinbaohong Zhike oral liquid (QBH), a marketed traditional Chinese medicine product, has been widely used to cure respiratory diseases. QBH is reported to have antitussive, expectorant, and antiasthmatic properties. However, its treatment effect against ARIs is not elucidated. This study aimed to explore the therapeutic efficacy of QBH in the treatment of ARIs-induced pneumonia. Network pharmacology was used to predict the possible targets of QBH against ARIs. Next, the tracheal lipopolysaccharide (LPS-)-induced acute lung injury (ALI) immature rat model was constructed to evaluate the therapeutic effect of QBH. Tandem mass tag (TMT-)-based quantitative proteomics was then used to screen the in-depth disease targets of QBH. QBH exerted a protective effect against LPS-induced ALI by inhibiting pulmonary pathological damage. QBH also reduced the levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and granulocyte macrophage colony-stimulating factor (GM-CSF) in the serum and IL-1ß, IL-6, IL-8, TNF-α, IFN-γ, and GM-CSF in the lung tissue. Based on proteomic data, olfactomedin 4 (OLFM4) related to immunity and inflammation was selected as a potential target. Western blot analysis further confirmed the moderating effect of QBH downregulation on OLFM4 in the lung tissue. Our findings demonstrated that QBH alleviated lung tissue damage and inflammatory reaction via inhibiting OLFM4 expression in LPS-challenged immature rats. Our research indicates that QBH may have therapeutic potential for treating ARIs-related ALI in pediatric patients, which also serves as a candidate target for drug therapy of ALI by intervening OLFM-related signaling pathways.

The Alleviation of LPS-Induced Murine Acute Lung Injury by GSH-Mediated PEGylated Artesunate Prodrugs.

Acute lung injury (ALI) or its aggravated stage acute respiratory distress syndrome (ARDS) is a common severe clinical syndrome in intensive care unit, may lead to a life-threatening form of respiratory failure, resulting in high mortality up to 30-40% in most studies. Nanotechnology-mediated anti-inflammatory therapy is an emerging novel strategy for the treatment of ALI, has been demonstrated with unique advantages in solving the dilemma of ALI drug therapy. Artesunate (ART), a derivative of artemisinin, has been reported to have anti-inflammatory effects. Therefore, in the present study, we designed and synthesized PEGylated ART prodrugs and assessed whether ART prodrugs could attenuate lipopolysaccharide (LPS) induced ALI in vitro and in vivo. All treatment groups were conditioned with ART prodrugs 1 h before challenge with LPS. Significant increased inflammatory cytokines production and decreased GSH levels were observed in the LPS stimulated mouse macrophage cell line RAW264.7. Lung histopathological changes, lung W/D ratio, MPO activity and total neutrophil counts were increased in the LPS-induced murine model of ALI via nasal administration. However, these results can be reversed to some extent by treatment of ART prodrugs. The effectiveness of mPEG2k-SS-ART in inhibition of ALI induced by LPS was confirmed. In conclusion, our results demonstrated that the ART prodrugs could attenuate LPS-induced ALI effectively, and mPEG2k-SS-ART may serve as a novel strategy for treatment of inflammation induced lung injury.

Red ginseng extract improves skeletal muscle energy metabolism and mitochondrial function in chronic fatigue mice.

Background: Skeletal muscles are organs with high energy requirements, especially during vigorous exercise. Adequate mitochondrial function is essential to meet the high energy needs of skeletal muscle cells. Recent studies have reported that red ginseng can significantly improve chronic fatigue; however, the specific mechanism of action is still not clear. Methods: A chronic fatigue syndrome mouse model was developed using C57BL/6J mice through long-term compound stimulation of stress factors. Following this, the animals were orally administered 200, 400, or 600 mg/kg red ginseng extracts for 28 days. Skeletal muscle lactate acid, serum lactate dehydrogenase, urea concentrations, ATP level, mitochondrial membrane potential, activities of Na+-K+-ATPase and cytochrome c oxidase were determined using assay kits or an automatic biochemical analyser detection system. Skeletal muscle mitochondria morphology was observed using electron microscopy and the expression of p-AMPK, PGC-1α, ACO2 and complex I in skeletal muscle protein was determined by western blotting. Results: Oral administration of 400 or 600 mg/kg red ginseng extract in mice with chronic fatigue reduced lactic acid, lactate dehydrogenase and urea, rescued the density and morphology of skeletal muscle mitochondria, increased the activities of Na+-K+-ATPase and cytochrome c oxidase, and activated the AMPK/PGC-1α cascade pathway, resulting in improved skeletal muscle mitochondrial function by restoring ATP level, mitochondrial membrane potential, complex I and mitochondrial biogenesis. Conclusion: The anti-fatigue effects of red ginseng are partly related to its potent mitochondrial improving activity, including decreasing mitochondrial swelling and mitochondrial membrane permeability, increasing mitochondrial biogenesis, thus ameliorating mitochondrial dysfunction.

[Study on potential effective components and mechanism of Zhishe Tongluo Capsules in treatment of ischemic stroke].

To explore the potential effective components and mechanism of Zhishe Tongluo Capsules in the treatment of ischemic stroke via network pharmacology, molecular docking and cellular experiment. The chemical constituents of Zhishe Tongluo Capsules were found by TCMSP, BATMAN-TCM and literatures. The constituents-target network was predicted by BATMAN-TCM database. Key words such as cerebral stroke, ischemic stroke and cerebral ischemic stroke were used to search ischemic stroke related targets, and then Venny Map was constructed based on the targets of traditional Chinese medicine and the targets of ischemic stroke. The overlapping targets were imported into STRING database to establish the interaction network. Furthermore, the core targets were screened out by Cytoscape software. Go and KEGG enrichment analysis were performed through DVIAD database. The results showed a total of 193 potential chemical constituents, 985 drug targets and 6 035 disease targets. There were 631 potential targets, 44 core targets and 55 potential active components for treating ischemic stroke through Venny mapping. GO enrichment analysis mainly involved response to hypoxia and positive regulation of ERK1/ERK2. KEGG pathway enrichment analysis mainly involved cholinergic synapse, cAMP signaling pathway, and calcium signaling pathway. Molecular docking data revealed that TP53, EGFR, IL6, INS, TNF and SRC had a good capability to bind with their corresponding active components. To ensure the protective effect Zhishe Tongluo Capsules on the inflammation reaction, an in vitro model of lipopolysaccharide(LPS)-induced RAW264.7 cells was built. The contents of IL-1α, IL-1ß, IL-6 and TNF-α in the supernatant were significantly decreased by enzyme linked immunosorbent assay(ELISA). The findings suggested that Zhishe Tongluo Capsules could prevent the injury of ischemic stroke by inhibiting the inflammation.

[A novel flavanone from Thymus przewalskii].

This study was to investigate the chemical constituents from the aerial parts of Thymus przewalskii. The chemical consti-tuents were separated and purified by column chromatography on silica gel, ODS, Sephadex LH-20 and semi-prepared HPLC, and their structures were determined by physicochemical properties and spectroscopic data. Four flavanones were isolated from the ethanol extract of the aerial parts of T. przewalskii, and identified as(2S)-5,6-dihydroxy-7,8,4'-trimethoxyflavanone(1), 5,4'-dihydroxy-6,7-dimethoxyflavanone(2),(2S)-5,4'-dihydroxy-7,8-dimethoxyflavanone(3), sakuranetin(4), respectively. Compound 1 was a new compound and its configuration was determined by CD spectrum, compound 3 was natural product which was isolated for the first time and their configurations were determined by CD spectra. Compound 2 was isolated from the genus Thymus for the first time and compound 4 was isolated from T. przewalskii for the first time. Furthermore, cytotoxicity test was assayed for the four flavanones. They exhibited weak cytotoxicity against human lung cancer cells(A549), with the IC_(50) from 74.5 to 135.6 µmol·L~(-1).

Photochemical synthesis of noble metal (Ag, Pd, Au, Pt) on graphene/ZnO multihybrid nanoarchitectures as electrocatalysis for H2O2 reduction.

For the first time, a series of noble metal (Ag, Au, Pd, and Pt) nanoparticles (NPs) based on new functional graphene were successfully achieved via UV-assisted photocatalytic reduction by ZnO nanorods. The whole preparation strategy for constructing noble metal deposited graphene sheets/ZnO (GS/ZnO) was elucidated in detail in this work. First, graphene oxide based two-dimensional carbon nanostructures served as a support to disperse ZnO nanorods through a hydrothermal route. The ZnO nanorods were self-assembled onto the surface of graphene sheets, forming GS/ZnO nanocomposite, and the graphene oxide was reduced, yielding reduced graphene sheets in this synthetic procedure. Second, the GS/ZnO films were further employed as supporting materials for the dispersion of metal nanoparticles. Photogenerated electrons from UV-irradiated ZnO were transported across GS to stepwise and respectively reduce v µL metal ions (Ag(+), Pd(2+), AuCl4(-), PtCl6(2-), 20 mg/mL) into metal (Ag, Pd, Au, Pt) NPs at a location distinct from the ZnO anchored site, forming five graphene-based hybrid nanocomposites designated as GS/ZnO, GS/ZnO@Agv, GS/ZnO@Pdv, GS/ZnO@Auv, GS/ZnO@Ptv, respectively. The obtained mutihybrid nanoarchitectured materials were clearly characterized by transmission electron microscopy (TEM) and X-ray diffraction (XRD). According to the diameters and distribution, the four metal NPs on GS/ZnO were divided into two categories: Ag&Au and Pd&Pt. Their difference was rooted in the rival abilities of gathering electron between graphene and different metal islands in the photochemical reduction process. The electrochemical behaviors of the five resultant hybrid nanocomposites were investigated in H2O2 as well as in potassium ferricyanide (Fe(CN)6(3-/4-)) and displayed distinct electrocatalytic activity.