INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Mei Bai,Ning An,Meng Cheng,Jia Qin,Jie Wang,Rumeng Jia,Wentao Liu,Jingcai Cheng,Qiang Xu,Xuefeng Wu
Neutrophil extracellular traps (NETs) play a key role in the development of psoriasis, a chronic inflammatory skin condition. We demonstrate the effects and possible mechanisms of phenethyl isothiocyanate (PEITC) in inhibiting NETs and alleviating psoriasis. In response to imiquimod (IMQ), multiple symptoms including scaly plaques and associated skin inflammations were induced in mice. IMQ additionally promotes the formation of NETs and the levels of inflammatory factors. Interestingly, a natural compound PEITC exerted an intensive activity in the treatment of psoriasis. It improved lesions and ameliorated ischemic coagulation symptoms in the dorsal skin of mice. PEITC also significantly reduced the expression of inflammatory factors in mice skin with an inhibition on NETs-related molecules, such as myeloperoxidase, neutrophil elastase and citrullinated histone H3. 16S rRNA sequencing analysis demonstrated that IMQ treatment induced significant gut microbiota dysbiosis in mice, suggesting potential detrimental effects on intestinal microbial homeostasis. However, PEITC administration did not show a statistically significant ameliorative effect on this IMQ-induced microbial imbalance. In vitro experiments demonstrated that PEITC significantly suppressed lipopolysaccharide (LPS)-induced NET formation, suggesting that its therapeutic effects in psoriasis may be due to the inhibition of bacterially driven neutrophil activation. Therefore, we identified PAD4, an important enzyme for post-translational modification of proteins in the production of NETs, as a new potential target of PEITC. Taken together, our findings suggest that PEITC could be a novel potential therapeutic drug to relieve psoriasis via the inhibition of NETs both in vitro and in vivo .
研究领域:
免疫学
·
皮肤病学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2025
·
IF 7.7
Yu-Chen Jiang,Jia Guo,Sai-Hu Liu,Xu Dai,Chen-Yu Wang,Li-Hua Lian,Zhen-Yu Cui,Ji-Xing Nan,Yan-Ling Wu
Background and Purpose Vincamine has extensive biological and pharmaceutical activity. We examined the hepatoprotective effects and mechanisms by which vincamine suppresses hepatic fibrosis. Experimental Approach Hepatic stellate cells (HSCs), TGF- β stimulated, were cultured with either vincamine, farnesoid X receptor (NR1H4; FXR) agonist or antagonist. Further, C57BL/6 mice were given thioacetamide (TAA) to induce hepatic fibrosis and subsequently treated with vincamine or curcumin. Key Results Vincamine regulated the deposition of extracellular matrix (ECM), inflammatory factors and S100A4, and up-regulated FXR and TGR5 (GPBA receptor) in activated HSCs, by activating FXR. FXR deficiency blocked vincamine effect on FXR, TGR5, α -smooth muscle actin ( α -SMA) and IL1R1 in activated LX-2 cells. Vincamine corrected ECM imbalance, inflammatory secretion and FXR/TGR5 down-regulation in activated LX-2 cells with stimulating medium from LPS-primed THP-1 cells. S100A4 deficiency increased FXR and TGR5, and decreased IL-1β expression in activated THP-1. Further, S100A4 deficiency in activated macrophages could elevate FXR and TGR5 expression in activated LX-2, strengthening the impact of vincamine on α -SMA and IL-1β expression. Further, vincamine reduced serum ALT/AST levels, liver and intestinal histopathological changes, and caused ECM accumulation and protected the intestinal barrier in thioacetamide-induced hepatic fibrosis mice. Vincamine decreased inflammatory factors e.g. caspase 1 and IL-1β, and inhibited the S100A4-mediated FXR-TGR5 pathway. Conclusion and Implications Vincamine significantly reverses hepatic fibrosis via inhibiting S100A4 involved in the crosstalk between macrophages and HSCs, and by activating the FXR-TGR5 pathway. Targeting the S100A4-mediated FXR dependence on modulating the liver environment may be the key target of vincamine in inhibiting hepatic fibrosis. Graphical
研究领域:
药理学
·
肝脏病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Junfeng Li,Min Guo,Cuiping Yuan,Tiezhu Li,Jie Zhang,Li Ren
ABSTRACT Peroxisome proliferator-activated receptor γ (PPARγ) was a major transcription factor and performed an essential function in the regulation of lipid metabolism. Ellagic acid (EA) was a natural phytochemical extracted from berries and pomegranates, and research had demonstrated its ameliorative effects on lipid metabolism disorders. We intended to explore the interventional effect and mechanism of action of EA on hyperlipidemia. In vitro experiments revealed that EA could reduce lipid accumulation in HepG2 cells. EA was found to bind stably to PPARγ, suppressing its nuclear translocation as well as its luciferase activity. It could also down-regulate the expression of genes and proteins related to lipid metabolism upstream and downstream of PPARγ. To explore the impact of EA on hyperlipidemia in vivo from different levels and perspectives, we established hyperlipidemia mice and hyperlipidemia zebrafish models. Consistent with the in vitro results, in vivo experiments revealed that EA attenuated lipid accumulation in hyperlipidemia mice and reduced the levels of related inflammatory factors in their serum. EA also inhibited lipid accumulation by decreasing the expression of upstream and downstream lipid-associated genes of pparg in hyperlipidemia zebrafish. In conclusion, EA could effectively improve hyperlipidemia by regulating PPARγ.
研究领域:
药理学
·
分子生物学
·
营养学
✓ 已验证
产品关联
DOI
高影响因子
CYTOTHERAPY
·
2025
·
IF 3.2
Jiaqi Lin,Ziwei Lin,Anqi Huang,Xinyi Wu,Wei Yan,Daojun Liu,Chiju Wei,Wencan Xu
Introduction The treatment of chronic refractory skin wounds still remains a serious clinical challenge. Stem cells and hydrogels are widely used in healing of skin wound of various types due to their superior bioactivities and biocompatibility. This study aimed to demonstrate the wound healing effect of a hydrogel compound loaded with enucleated stem cells expressing the platelet-derived growth factor (PDGF). Methods An injectable hydrogel was formulated using 22% poloxamer 407, 1% poloxamer 188 and 1% hyaluronic acid. A PDGF-B transgenic cell line of mouse bone marrow mesenchymal stem cells (BMSCs) was generated by lentiviral infection. Cells were enucleated and embedded in hydrogel. The healing effects of the compound was tested in a full-thickness skin wound model of Balb/c mice. The wound models were randomly divided into four groups: the control group applied with PBS buffer; the hydrogel group with hydrogel only; the BMSC group with hydrogel mixed with normal BMSCs; and the BMSC-PDGF group with hydrogel mixed with enucleated BMSCs expressing PDGF. Results Overexpression of PDGF-B in transgenic cell line of BMSCs was verified by RT-PCR, immunofluorescence staining and western blot. When enucleated, the viability measured by Calcein-AM staining reduced to 54.29% at 48 h. Conditioned medium was collected with or without hydrogel layered over cells. PDGF concentration measured by ELISA reached 14.66 ng/μL and 257.89 ng/μL respectively after 48-h cultivation, suggesting a possible slow releasing effect in the presence of hydrogel. When applied to the skin wound, the healing rates of the BMSC-PDGF group was significantly higher than that of the control group on day 3. BMSC-PDGF group had significantly more neovascularization and cutaneous appendages from day 7. The proliferation of collagen fibers in BMSC-PDGF group was significantly higher than the control group on day 3 and day 7. Finally, BMSC-PDGF group had significantly lower amount of the inflammatory factors TNF-α, IL-1β, IL-6, MMP-3 and MMP-9 than that of the control group on day 7. Conclusion PDGF-stem cell-hydrogel compound significantly improved wound healing and reduced wound inflammatory factor expression in Balb/c mice. This biomaterial-based approach provides a new powerful reference for the treatment of chronically wounded skin.
研究领域:
生物医学
·
再生医学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Heliyon
·
2024
·
IF 3.4
Xin Yang,Junxian Li,Chunlan Shan,Xuqin Song,Jian Yang,Hao Xu,Deyuan Ou
In the present study, we investigated whether baicalin could reduce the damage caused to RAW264.7 cells following infection with H6N6 avian influenza virus. In addition, we studied the expression of autophagy-related genes. The morphological changes in cells were observed by hematoxylin and eosin (H&E) staining, and the inflammatory factors in the cell supernatant were detected by enzyme-linked immunosorbent assay (ELISA). Transmission electron microscopy (TEM) was used to detect the levels of RAW264.7 autophagosomes, and western blotting and immunofluorescence were used to detect the protein expression of autophagy marker LC3. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to detect the mRNA transcription levels of autophagy key factors. The results showed that different doses of baicalin significantly reduced the H6N6 virus-induced damage of RAW264.7 cells. The contents of interleukin (IL)-1β, IL-2, IL-6, and tumor necrosis factor (TNF)-α in the cell supernatant significantly decreased. In addition, the protein expression of LC3 and Beclin-1, ATG12, ATG5 the mRNA levels were significantly decreased. This study showed that baicalin can reduce cell damage and affect the H6N6-induced autophagy level of RAW264.7 cells.
研究领域:
病毒学
·
药理学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Chinese Medicine
·
2024
·Vol. 19
·期 1
·1-12
·
IF 5.3
Zhou Hongyan,Hu Dingxin,Zhao Xian,Qin Siyuan,Nong Qiyao,Tian Yuan,Zhang Zunjian,Dong Haijuan,Zhang Pei,Xu Fengguo
Background Irinotecan (CPT-11) is a first-line treatment for advanced colorectal cancer (CRC). Four components (baicalin, baicalein, wogonin, and glycyrrhizic acid) derived from Huangqin Decoction (HQD) have been proven to enhance the anticancer activity of CPT-11 in our previous study. Objective This study aimed to determine the optimal combination of the four components for sensitizing CPT-11 as well as to explore the underlying mechanism. Methods The orthogonal design method was applied to obtain candidate combinations (Cmb1-9) of the four components. The influence of different combinations on the anticancer effect of CPT-11 was first evaluated in vitro by cell viability, wound healing ability, cloning formation, apoptosis, and cell cycle arrest. Then, a CRC xenograft mice model was constructed to evaluate the anticancer effect of the optimal combination in vivo. Potential mechanisms of the optimal combination exerting a sensitization effect combined with CPT-11 against CRC were analyzed by targeted metabolomics. Results In vitro experiments determined that Cmb8 comprised of baicalin, baicalein, wogonin, and glycyrrhizic acid at the concentrations of 17 μM, 47 μM, 46.5 μM and 9.8 μM respectively was the most effective combination. Importantly, the cell viability assay showed that Cmb8 exhibited synergistic anticancer activity in combination with CPT-11. In in vivo experiments, this combination (15 mg/kg of baicalin, 24 mg/kg of baicalein, 24 mg/kg of wogonin, and 15 mg/kg of glycyrrhizic acid) also showed a synergistic anticancer effect. Meanwhile, inflammatory factors and pathological examination of the colon showed that Cmb8 could alleviate the gastrointestinal damage induced by CPT-11. Metabolic profiling of the tumors suggested that the synergistic anticancer effect of Cmb8 might be related to the regulation of fatty acid metabolism. Conclusion The optimal combination of four components derived from HQD for the synergistic sensitization of CPT-11 against CRC was identified.
研究领域:
肿瘤学
·
药理学
·
代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Polymer Chemistry
·
2025
·
IF 3.9
Yanlin Wang,Fan Rong,Xiaoyi Sun,Duohang Bi,Yin Wang,Yijing Liu,Jintao Zhu
Psoriasis is a common chronic skin disease. Current psoriasis treatments face challenges such as low drug bioavailability and side effects. Hydrogen sulfide (H2S) can be a potential therapeutic for psoriasis, while developing an effective delivery system and a controlled release strategy is essential to guarantee its efficacy and safety. We report a responsive microneedle (MN)-mediated transdermal H2S gas therapy for treating psoriasis. The phenylboronic acid-modified hyaluronic acid (HP) and a peptide H2S donor (AlaCOS) are synthesized, which assemble into H2S donating nanoparticles (HP-AC NPs). The HP-AC NPs efficiently release AlaCOS in aqueous solution or acidic conditions, which can further release H2S triggered by aminopeptidase N (APN) and carbonic anhydrase (CA). Moreover, the HP-AC NPs can effectively downregulate the pro-inflammatory cytokines in macrophages. Furthermore, the HP-AC NP-loaded MNs (HP-AC MN) are prepared with sufficient mechanical strength to penetrate the stratum corneum barrier. In the psoriatic mouse model, the mice receiving the HP-AC MN treatment exhibit decreased epidermal thickness, reduced levels of pro-inflammatory cytokines, and induced M2 polarization of macrophages. This MN-mediated H2S gas therapy represents a promising alternative for treating psoriasis.
研究领域:
皮肤病学
·
纳米医学
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
Discovery Medicine
·
2024
·Vol. 36
·期 181
·266-277
·
IF 2
Luo X,Liao H,Peng J,Jiang X
Background Osteoarthritis (OA) is a common disease that causes pain to many older adults. Because the pathogenesis is not fully elucidated, effective drug therapies are currently lacking. This study aimed to determine how salidroside (Sal)-mediated reduction of osteoarthritis development in mice worked and to identify the underlying mechanism. Methods Using in vitro experiments, ATDC5 cells were treated with various concentrations of Sal and interleukin (IL)-1β for 24 hours to mimic OA. An enzyme-linked immunosorbent assay (ELISA) was conducted to detect the production of pro-inflammatory cytokines and reactive oxygen species (ROS). Western blotting was performed to observe the nuclear factor-kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2) pathways. In in vivo experiments, pathological examination was used to assess the effects of Sal on alleviating OA progression in mice. Nrf2 signaling and its downstream proteins were further tested by immunofluorescence analysis. Results The results showed that both pro-inflammatory cytokines and ROS were significantly reduced following Sal treatment in a concentration-dependent manner. Western blotting revealed that Sal could inhibit the expression of the NF-κB/hypoxia-inducible factor-2α pathway and activate the Nrf2/heme oxygenase-1 pathway. In vivo experiments showed that the cartilage surface in the saline-treated group eroded to a greater extent than the Sal-treated groups ( p < 0.001). Immunohistochemistry analysis revealed that matrix metallopeptidase (MMP) 9, MMP13, and a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5) decreased expression level. In contrast, collagen-II and aggrecan increased in the Sal-treated groups compared to the saline-treated group. Conclusions Our findings indicate that Sal can alleviate OA progression by promoting anti-oxidant expression and inhibiting degradation enzyme expression. These findings suggest that Sal inhibits the NF-κB pathway and its downstream targets through up-regulating the Nrf2 pathway.
研究领域:
医学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Junsong Jing,Yi Sun,Yiyang Shui,Junyi Wang,Wenjing Ye,Ranran Chen,Lianhao Wu,Lijuan Xing,Rongrong Huang,Ting Zhou,Wenwen Zhu,Yueguo Wu,Sheng Zhang,Jing Shi,Yuanyuan Li,Yan Liu,Zhenqiang You
Background Viral pneumonia is an infection of the lungs caused by numerous different viruses, which can lead to severe respiratory distress and even life-threatening conditions. In the absence of specific treatments for viral pneumonia, natural traditional medicines offer an alternative in terms of innovative drug therapies. Morus alba L. (common name mulberry leaf) is a Chinese medicine that has been used clinically as an antiviral. Purpose The therapeutic effect of M. alba on viral pneumonia was investigated along with its mechanism of action. Methods Network pharmacology and molecular docking were used to analyze the mechanism of action of M. alba in the treatment of viral pneumonia. Histology, immunofluorescence, Western blotting, qPCR, and flow cytometry were used to evaluate the protective effect of MLE (the ethanol extract of Morus alba L. ) on PR8 (A/Puerto Rico/8/1934 H1N1, a murine lung-adapted influenza A virus strain)-induced viral pneumonia. SiRNA was used to validate the relationship between the therapeutic effects of MLE on viral pneumonia and the target Syk (a crucial non-receptor tyrosine kinase). Results MLE alleviated PR8-induced viral pneumonia by reducing inflammatory factor expression in the lungs, decreasing NF-κB pathway activation, slowing oxidative damage in the lungs, and inhibiting lung tissue cell apoptosis. Meanwhile, MLE for viral pneumonia was significantly associated with Syk targets. Notably, knockdown of the Syk gene not only reduced the therapeutic effect of MLE, but also suppressed PR8-induced viral pneumonia. Conclusion MLE can alleviate PR8-induced viral pneumonia through inhibiting the Dectin-1/Syk pathway.
研究领域:
药理学
·
分子生物学
·
病毒学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
·
2021
·
IF 2.63
Yuling Tong,Manyi Jing,Xu Zhao,Honghong Liu,Shizhang Wei,Ruisheng Li,Xia Liu,Min Wang,Hongtao Song,Yanling Zhao
The classic prescription Zuojin Pill (ZJP) shows a good therapeutic effect on chronic atrophic gastritis (CAG); it is of great significance to clarify its specific mechanism. Therefore, we explore the mechanism of ZJP on MNNG-induced CAG by integrating approaches. First of all, through the pathological changes of gastric tissue and the expression level of PGI and PGI/II in serum, the expression of inflammation-related factors was determined by RT-PCR to determine the efficacy. Then, UPLC-Q-TOF/MS was used for plasma and urine metabolomic analysis to screen the specific potential biomarkers and metabolic pathway of ZJP in ameliorating CAG and to explore its possible mechanism. ZJP significantly ameliorate the pathological injury of gastric tissue, increase levels of PGI and PGI/II, and reduce the expression level of proinflammatory factors. Through metabolomic analysis, 9 potential metabolic differences were identified and 6 related metabolic pathways were enriched. These findings indicate for the first time the potential mechanism of ZJP in improving CAG induced by MNNG and are of great significance to the clinical development and application of ZJP-related drugs.
研究领域:
中药学
·
代谢组学
·
病理学
✓ 已验证
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Aining Yin,Yu Fu,Tingxin Wang,Honglin Li,Xiufang Wang,Xueke Ye,Peipei Dong,Wei Yao
Ethnopharmacological relevance FZLFR was derived from a classic traditional Chinese medicine recipe, the Shiquan-Dabu decoction. FZLFR is commonly used in clinical practice to address muscle loss and associated cancer cachexia. However, the mechanism of by which FZLFR acts in cancer cachexia remains unclear. Aim This study aimed to assess the effects and explore the potential mechanism of action of FZLFR in treating cancer cachexia. Methods Cancer cachexia was induced by inoculating Lewis lung carcinoma cells into the right flank of male C57BL/6 mice. The efficacy of FZLFR was evaluated by comparing changes in body weight, tumor mass, food intake, survival time, weight, and cross-sectional area of the gastrocnemius and anterior tibial muscles. Moreover, inflammatory cytokines, such as TNF-α and IL-6, were detected by ELISA. The chemical components of FZLFR were analyzed using ultra-performance liquid chromatography-coupled with time-of-flight mass spectrometry. Network pharmacology analysis was performed to screen the core targets and potential pathways involved in FZLFR treatment of cancer cachexia. Molecular docking was used to analyze the binding ability of the core targets and key compounds. The expression levels of core targets and targets correlated with skeletal muscle atrophy were also assessed using western blotting. Results FZLFR enhanced the food intake and survival rate of mice with cancer cachexia. It also alleviated tumor-induced body weight loss, tumor growth, and muscle fiber atrophy in these mice. Additionally, it improved the weight and cross-sectional area of the gastrocnemius and anterior tibial muscles. FZLFR down-regulated the serum levels of TNF-α and IL-6. UPLC-ESI-Q-TOF-MS analysis identified 184 compounds in FZLFR. Network pharmacology analysis predicted that TNF signaling pathway, ErbB signaling pathway and VEGF signaling pathway might be essential in FZLFR action. Molecular docking showed that kaempferol, upafolin, apigenin, and luteolin might play key roles in FZLFR treatment. Moreover, FZLFR decreased MAFBx1, MURF1, NF-κB, TWEAK, MAPK8, and EGFR expression levels. FZLFR enhanced the expression of VEGFA and ESR1, as demonstrated by western blotting. Conclusions FZLFR increased food intake and alleviated muscle atrophy in mice with cancer cachexia. The potential pharmacological mechanisms underlying its anticachexia effects include reducing inflammation, enhancing muscle vascular growth, inhibiting tumor angiogenesis, and modulating estrogen receptors.
研究领域:
民族药理学
·
肿瘤学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
·
2025
·
IF 4.2
Shibo Zhu,Sunwei Tang,Zijie Ye,Wei Jia
One of the most prevalent male urogenital anomalies is hypospadias. The general etiology of hypospadias is still not completely clear, despite the fact that the number of patients with the hypospadias is rising. HNF-1α was predicted as the most activated upstream regulator of severe hypospadias in our previous research. Our study aims to investigate the mechanism by which HNF-1α regulates hypospadias. We found that HNF-1α was highly expressed in hypospadias tissues, and was positively associated with fibrinogen related genes FGA and FGB, respectively. In animal experiments, silencing of HNF-1α resulted in a more narrow urethral groove, and a decreased periurethral pathologic fibrosis. Meanwhile, the inflammation cytokines and oxidative stress related factors were significantly reduced after inhibition of HNF-1α expression. In addition, the protein levels of STAT3, FGA and FGB were also depressed after HNF-1α knockdown. Mechanistically, we showed that the HNF-1α transcriptionally activated STAT3, and subsequently increased the expressions of FGA and FGB. Additionally, suppression of HNF-1α improved the murine hypospadias via inactivating the STAT3. Therefore, our findings confirmed that HNF-1α promoted hypospadias and periurethral fibrosis by activating STAT3. Targeting HNF-1α might the future direction for hypospadias treatment.
研究领域:
医学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）