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NEPHROLOGY · 2023 · IF 2.5

Baicalin and baicalein attenuate hyperuricemic nephropathy via inhibiting PI3K/AKT/NF-κB signalling pathway

Ziyuan Liu,Huilong Xiang,Qin Deng,Wanting Fu,Yang Li,Zejun Yu,Yinsheng Qiu,Zhinan Mei,Lingyun Xu

Aim Inflammation and apoptosis are main pathological processes that lead to the development of hyperuricemic nephropathy (HN). This study aims to explore whether baicalin (BA) and baicalein (BAI) can relieve the damage through PI3K/AKT/NF-κB signal pathway and provide more reliable and precise evidence for the treatment of HN. Methods HN mice were induced by yeast extract with potassium oxonate (PO), and HK-2 cells were induced by monosodium urate (MSU). Molecular docking, western blot, q-PCR, and other methods were used to explore the changes of various indicators in HN mice and HK-2 cells. Results Molecular docking results showed that BA and BAI had good binding ability with PI3K, AKT, p65 and IκBα. BA and BAI significantly ameliorated the levels of renal function, decreased the p-PI3K, p-AKT and p-p65 expression, down-regulated the BAX/BCL2 and CASP3, and blunted the mRNA levels of tumour necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-18 in both renal tissue of HN mice and HK-2 cells induced by MSU. BA and BAI also decreased the oxidative stress level of MSU-induced HK-2 cells. Conclusion BA and BAI were confirmed to attenuate HN through alleviating renal inflammatory and apoptosis in cells and tissues by inhibiting PI3K/AKT/NF-κB pathway. BA and BAI were expected to be developed as new anti-HN drugs.

CAS / MDL: 50-02-2 2207-75-2
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Journal of Functional Foods · 2023 · IF 5.6

Geniposide improves bleomycin-induced pulmonary fibrosis by inhibiting NLRP3 inflammasome activation and modulating metabolism

Yi Wei,Chao Liu,Lujia Li

Geniposide (Gen) is a natural compound derived from Gardenia jasminoides that has anti-inflammatory, antioxidative stress, antiapoptotic, and antitumour properties. However, its mechanisms of action in idiopathic pulmonary fibrosis (IPF) have not been well studied. Recent studies have found that the progression of IPF is influenced by host metabolism. This study investigated the antifibrotic effects and metabolic modulation of Gen. Gen significantly ameliorated pathological injury in the IPF mouse model. Gen reduced the expression of proinflammatory cytokines and inhibited oxidative stress levels. Gen also inhibited NLRP3 inflammasome activation. Untargeted metabolomics analysis revealed that metabolites were affected in the lung. These metabolites were associated with the regulation of arachidonic acid metabolism, histidine metabolism, and tryptophan metabolism. Gen reduced the inflammatory response and oxidative stress and inhibited NLRP3 inflammasome activation in IPF mice. Mechanistically, Gen-mediated treatment of IPF may be linked to the regulation of host metabolism.

CAS / MDL: 50-02-2 1403-66-3
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CHEMICAL ENGINEERING JOURNAL · 2023 · IF 15.1

Switching the primary mechanism from a radical to a nonradical pathway in electrocatalytic ozonation by onsite alternating anode and cathode

Yahan Yu,Chunxiu Yu,Zelin Wu,Bingkun Huang,Peng Zhou,Heng Zhang,Wen Liu,Yucheng Liu,Zhaokun Xiong,Bo Lai

Concurrently elevating the degradation efficiency of pollutants and realizing the reduction of iron sludge in Fe-based catalytic ozonation is important but still challenging. Herein, we developed an electrocatalytic ozonation (ECO) system with iron plate cathode and graphite felt anode (ECO-Fe-cathode), which was free from added chemical reagents. Unlike the iron plate as a sacrificial anode in the ECO (ECO-Fe-anode) system, this delicately designed system shows a much higher degradation rate of ibuprofen ( k obs  = 1.490 min −1 ) than that of the ECO-Fe-anode system ( k obs  = 0.345 min −1 ). Simultaneously, the effluent was totally limpid without the corrosion of iron plates and the formation of iron sludge in the ECO-Fe-cathode system. Unexpectedly, the generation of singlet oxygen ( 1 O 2 ) which is indirectly generated by the single-electron transfer derived from superoxide ion (O 2 •- ) is the primary reactive oxygen species (ROS) in the ECO-Fe-cathode system, which is different from the ECO-Fe-anode system with hydroxyl radicals ( • OH). Moreover, linear sweep voltammetry (LSV) was applied to reveal the oxygen evolution reaction (OER) performance of the iron plate and graphite felt, and the results showed that graphite felt as anode has better electrocatalytic performance. The electrochemical analysis and density functional theory (DFT) calculation revealed that ozone adsorbed on the iron plate surface is more conducive to facilitating and triggering subsequent reactions. Finally, the different degradation pathways of ibuprofen in both systems were proposed. This work represents a fundamental breakthrough toward the design of an efficient and harmless ECO system for wastewater treatment.

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MOLECULES · 2022 ·Vol. 28 ·期 1 ·295 · IF 4.927

Screening and Identification of Anti-Inflammatory Compounds from Erdong Gao via Multiple-Target-Cell Extraction Coupled with HPLC-Q-TOF-MS/MS and Their Structure–Activity Relationship

Mengyu Li,Hui Luo,Zhen Huang,Jin Qi,Boyang Yu

Erdong Gao (EDG), consisting equally of roots of Asparagi Radix and Ophiopogonis Radix, is a well-known traditional Chinese formulation that has been used to treat cough and throat pain for centuries. However, the bioactive components in EDG remain to be elucidated. In this study, a rapid and effective method involving live cell bio-specific extraction and HPLC-Q-TOF-MS/MS was established to rapidly screen and identify the anti-inflammatory compounds of an EDG extract. One hundred and twenty-four components were identified in EDG extract using HPLC-Q-TOF-MS/MS analysis. After co-incubation with 16HBE, HPAEpiCs and HUVECs, which have been validated as the key target cells for pulmonary diseases, sixteen components were demonstrated to exhibit an affinity for binding to them. Furthermore, fifteen components were subsequently verified to exert anti-inflammatory effects on lipopolysaccharide (LPS)-induced 16HBE, HPAEpiCs and HUVECs via inhibiting the release of TNF-α and IL-6, indicating that nine steroidal saponins may possess potential for the treatment of lung-related diseases. Taken together, our study provides evidence that live cell biospecific extraction combined with the HPLC-Q-TOF-MS/MS technique was an efficient method for rapid screening potential bioactive components in traditional Chinese medicines and the structure activity relationship of steroidal saponins in EDG was summarized for the first time.Keywords:Erdong Gao;anti-inflammatory;steroidal saponins;structure activity relationship;cell extraction

CAS / MDL: 50-02-2
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CELLULAR SIGNALLING · 2022 · IF 4.85

Osteoclast-derived extracellular miR-106a-5p promotes osteogenic differentiation and facilitates bone defect healing

Yutong Wu,Hongbo Ai,Yuchi Zou,Qiankun Yang,Ce Dou,Jianzhong Xu

Small extracellular vesicles (sEVs) are considered to play critical roles in intercellular communications during normal and pathological processes since they are enriched with miRNAs and other signal molecules. In bone remodeling , osteoclasts generate large amounts of sEVs. However, there is very few research studying whether and how osteoclast-derived sEVs (OC-sEVs) affect surrounding cells. In our study, microarray analysis identified miR-106a-5p as highly enriched in OC-sEV. Further experiments confirmed that OC-sEVs inhibited Fam134a through miR-106a-5p and significantly promoted bone mesenchymal stem cell (BMSC) osteogenic mineralization in vitro . Next, we prepared an sEV-modified demineralized bone matrix (DBM) as scaffold treating calvarial defect mouse model to evaluate the pro-osteogenic activities of the scaffold. In vivo results indicated that DBM modified with miR-106a-5p-sEVs showed an enhanced capacity for bone regeneration . This important finding further emphasizes that sEV-mediated miR-106a-5p transfer plays a critical role in osteogenesis and indicates a novel communication mode between osteoclasts and BMSCs.

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EUROPEAN JOURNAL OF PHARMACOLOGY · 2022 · IF 5.195

Quinacrine attenuates diet-induced obesity by inhibiting adipogenesis via activation of AMPK signaling

Xiangxiang Li,Jing Zhou,Zhuozhou Hu,Liang Han,Wenyang Zhao,Tongyu Wu,Chun Li,Jingjing Liu,Jia Kang,Xinping Chen

Obesity, a global epidemic chronic metabolic disease , urgently demands novel therapies. As an antimalarial drug , quinacrine has not been reported for its anti-obesity effect to our knowledge. This study aimed to explore the ability of quinacrine to attenuate obesity. In an in vitro adipogenic model, quinacrine exhibited an outstanding suppression on adipogenesis of 3T3-L1 cells, mainly by activating the AMPK (Adenosine 5′-monophosphate (AMP)-activated protein kinase) signaling pathway to regulate preadipocytes differentiation and lipid accumulation. In addition, C57BL/6N female mice were fed with high-fat diet and high-fructose water for 14 weeks to establish an obesity model, followed by oral administration of quinacrine or orlistat . After 9 weeks of treatment, quinacrine significantly reduced the body weight and energy intake, ameliorated the impaired glucose tolerance and restored the homeostasis of serum lipids. Also, quinacrine improved lipid profile and optimized the expression of AMPK signaling pathway related proteins in livers and adipose tissues of obese mice . Quinacrine reverses obesity through activating AMPK phosphorylation to down-regulate adipogenesis, along with lowering the risk of type 2 diabetes and atherosclerosis . It should be a novel application for the treatment of obesity and its associated diseases.

CAS / MDL: 50-02-2
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BIOMACROMOLECULES · 2023 · IF 6.2

Investigating the Biodegradation Mechanism of Poly(trimethylene carbonate): Macrophage-Mediated Erosion by Secreting Lipase

Lihuang Wu,Yuqi Wang,Xinyue Zhao,Hongli Mao,Zhongwei Gu

Poly(trimethylene carbonate) (PTMC), as one of the representatives of biodegradable aliphatic polycarbonates, has been found to degrade in vivo via surface erosion. This unique degradation behavior and the resulting nonacidic products make it more competitive with aliphatic polyesters (e.g., polylactide) in clinical practice. However, this surface degradation mechanism is complicated and not fully understood to date despite the findings that several reactive oxygen species and enzymes can specifically degrade PTMC in vitro. Herein, the biodegradation mechanism of PTMC was investigated by using possible degradation factors, distinct cell lines, and the inhibitors of these factors. The results demonstrate that PTMC undergoes a specific macrophage-mediated erosion. Macrophages tend to fuse into giant cells and elicit a typical inflammatory response by releasing proinflammatory cytokines. In addition, macrophages are suggested to primarily secrete enzymes (lipase specifically) to erode the PTMC bulk extracellularly as inhibiting their activity effectively prevented this eroding process. The clarification of the biodegradation mechanism in this work suggests that the degradation of PTMC highly depends on the foreign body response. Thus, it reminds the researchers to consider the effect of the microenvironment on the degradation and drug release of PTMC-based implantation devices and localized drug delivery systems.

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CARBOHYDRATE POLYMERS · 2022 · IF 10.723

A triple-network carboxymethyl chitosan-based hydrogel for hemostasis of incompressible bleeding on wet wound surfaces

Zheng Chen,Jiulong Zhao,Hang Wu,Haibin Wang,Xuhua Lu,Mohammad-Ali Shahbazi,Shige Wang

Hydrogel is a kind of hemostatic agent with good application prospect. However, the water molecules on the wound made the hydrogel less adhesive to wet wound tissue. Herein, the carboxymethyl chitosan (CMCS)/oxidized dextran (OD)/γ-polyglutamic acid (γ-PGA) hydrogel was prepared using a double-barreled syringe for hemostasis of diffuse and incompressible wound bleeding. The hydrogel formation was based on the intramolecular lactam bonds, intermolecular amide bonds, and Schiff base bonds. In the hydrogel, the super hydrophilic γ-PGA could drain the surface moisture of the wound and create a local dry environment for enhanced surface adhesion. In vivo study showed that the CMCS/ODex/γ-PGA hydrogel possesses a good biosafety and biodegradability . Interestingly, the CMCS/ODex/γ-PGA hydrogel exhibited excellent hemostatic abilities in dynamic humid environment and resisted a high blood pressure of 238 mmHg, which exceeds the threshold systolic blood pressure of healthy adults ( i.e. , 120 mmHg). Together with the antibacterial and reactive nitrogen species scavenging activities, this study is expected to provide a new method to design the wet-surface adhesives for the efficient hemostatic application.

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JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES · 2022 · IF 3.318

Efficacy identification and active compounds screening of topically administration of Scutellaria Radix in oral ulcer

Hui Luo,Yi Yu,Ming Liang,Zhen Huang,Heng Jiang,Yufei Wang,Jin Qi

Scutellaria Radix (SR) is often added to various preparations for the treatment of oral ulcer, but its own efficacy and active compounds are still unknown while topically administration for oral ulcer, bring obstacles in further research. We expected to demonstrate the anti-oral ulcer effect of SR and find out its hallmark compounds, so as to provide reference for its material basis research. In this study, in vivo and in vitro models were used to prove the efficacy of SR, and spectrum-effect analysis was used to figure out the active compounds. In oral ulcer rats, SR significantly reduced TNF-α and IL-8 level, raised IL-2 level in both serum and mucosa, enhanced SOD activity and decreased MDA level of serum, reduced inflammatory reaction and showed good therapeutic effect. As for in vitro models, SR increased the survival rates of H 2 O 2 damaged HOK, inhibited the release of IL-1β and NO of LPS induced HOK and LPS induced RAW 264.7, demonstrating good efficacy on oral ulcer. Subsequently, fingerprints and cellular pharmacodynamic data for 18 batches of SR were acquired, and spectrum-effect analysis were carried out by grey correlation analysis (GRA), partial least squares regression (PLSR) and “spider-web” mode. Five potential compounds were screened out and validated by comparing with SR activity, and baicalin, baicalein, and wogonoside were finally identified as active compounds of SR. These results explained the material basis of SR in treating oral ulcer and provided a scientific evidence for the clinical application of SR in oral administration.

CAS / MDL: 616-91-1 50-02-2
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2022 · IF 8.025

Injectable wound dressing based on carboxymethyl chitosan triple-network hydrogel for effective wound antibacterial and hemostasis

Zheng Chen,Jinpeng Yao,Jiulong Zhao,Shige Wang

Currently, hydrogels are widely studied for wound dressings. However, wound healing is often hindered by bacterial infection. In this study, in situ cross-linked carboxymethyl chitosan (CMCS)/oxidized dextran (OD)/poly-γ-glutamic acid (γ-PGA) (COP) hydrogel was prepared for antimicrobial and hemostasis of diffuse wounds. In the COP hydrogel, γ-PGA was able to drain the surface moisture of the wound to enhance the surface adhesion. Moreover, γ-PGA could concentrate blood by absorbing plasma, and CMCS could electrostatically adsorb negative RBCs. The antibacterial properties of CMCS and OD endowed the COP hydrogel with certain antibacterial effects. In the inhibition zone experiment, an obvious inhibition zone appeared around the COP hydrogel. In vivo studies showed that the COP hydrogel significantly inhibited bacterial growth and promoted wound healing. In the rat tail diffuse hemorrhage wound model, the COP hydrogel showed superior hemostasis ability. Therefore, the multifunctional COP hydrogel is expected to find different applications in wound hemostasis and healing.

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JOURNAL OF ETHNOPHARMACOLOGY · 2022 · IF 5.195

Effect of CYP3A inducer/inhibitor and licorice on hepatotoxicity and in vivo metabolism of main alkaloids of Euodiae Fructus based on UPLC-Q-Exactive-MS

Kun Ren,Ruijie Wang,Shinuo Fang,Shumeng Ren,Huiming Hua,Dongmei Wang,Yingni Pan,Xiaoqiu Liu

Ethnopharmacological relevance As a traditional Chinese medicine , Euodiae Fructus (EF) has been used to treat stomachache, belching, and emesis for more than a thousand years. Ancient records and modern research have shown that EF has mild toxicity, which needs to be processed with licorice juice to reduce its toxicity. Research suggested that the toxicity of EF can be caused by in vivo metabolism , but whether its metabolites are related to hepatotoxicity and whether licorice can affect the metabolism of EF have not been reported, which needed an effective strategy to clarify the correlation between metabolites and toxicity and the attenuation mechanism of licorice processing. Aim of the study The poisonous substances and metabolic pathways were clarified by comparing the mechanism in vivo process of the main alkaloids of EF in normal rats and rats treated with dexamethasone (DXMS), ketoconazole (KTC), and EF processed with licorice (EFP). Materials and methods Rats were given EF and EFP by oral administration, respectively. The EF + DXMS and EF + KTC groups were pretreated with DXMS and KTC, respectively, by i. p. for seven days, and their toxicity differences were compared. The comprehensive strategy based on UPLC-Q-Exactive-MS and Orthogonal Partial Least Squares Discriminant Analysis was developed to compare the types and contents of metabolites and clarify the metabolic pathways of alkaloids among EF, EFP, EF + KTC, and EF + DXMS groups. Results EF + DXMS group significantly increased the hepatotoxicity, whereas the EF + KTC and EFP groups reduced the hepatotoxicity compared with the EF group. One hundred and thirty-five metabolites were detected, and the metabolic pathways of the main alkaloid components related to toxicity were inferred in the plasma, urine, feces, and bile of rats. KTC and licorice similarly inhibited the production of toxic metabolites, changed metabolism in vivo, and produced many new II and a few phases I metabolites, while the contents of toxic metabolites increased in the DXMS group. Conclusion Licorice and KTC could inhibit the production of metabolites of EF related to toxicity, increase the production of other metabolites and promote the excretion of alkaloids, which may be why licorice and KTC can minimize EF toxicity.

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International Journal of Polymeric Materials and Polymeric Biomaterials · 2023 · IF 3.2

Study on fully cross-linked poly(cyclotriphosphazene-co-epigallocatechin) nanospheres and their application as drug delivery carriers

Sahid Mehmood,Md Alim Uddin,Haojie Yu,Li Wang,Bilal Ul Amin,Fazal Haq,Shah Fahad,Muhammad Haroon

In this research, hexachlorocyclotriphosphazene (HCCP) was cross-linked with epigallocatechin (EGC) via one-pot precipitation polymerization. The synthesis was confirmed using FT-IR spectroscopy. The cross-linking density of the nanospheres was investigated by EPR spectroscopy. The mole ratio of HCCP:EGC had a major effect on the nanospheres’ formation, growth, particle size, and shape. The thermal properties of the nanospheres were improved due to their cross-linked polymeric structures. The PCTPEC-3 nanospheres were used as anti-cancer drug carriers and the in vitro drug release profile was studied. The findings revealed that the cumulative release of drugs was dependent on the pH environment.

CAS / MDL: 50-02-2 970-74-1
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