查找使用阿拉丁产品的科研文献

Pharmacokinetic/pharmacodynamic relationship of a novel pleuromutilin derivative p-furoylamphenmulin against Mycoplasma gallisepticum in vivo in chickens

Xirui Xia,Huifang Zhao,Yaxi Li,Xiangyang Long,Xuezhen Liu,Mingyang Bai,Youzhi Tang,Xiangguang Shen,Huanzhong Ding

Mycoplasma gallisepticum ( M. gallisepticum , MG ) is the primary pathogen of chronic respiratory disease ( CRD ) in chickens and leads to pneumonia and air sacculitis in infected chickens and a corresponding economic loss for the poultry industry. The pleuromutilins have excellent anti-mycoplasmal activity and we evaluated the in vivo activity of a new derivative 22-((4-((2-furan-1-yl)acetamido)phenyl)thio) deoxypleuromutilin ( p- furoylamphenmulin ) against M. gallisepticum . A plasma pharmacokinetic ( PK ) study and an in vivo pharmacodynamic ( PD ) study of p -furoylamphenmulin were performed using an M. gallisepticum -infected chicken model. Based on the PK/PD results, a preliminary recommended dose was calculated. The minimum inhibitory concentration ( MIC ) of p -furoylamphenmulin against M. gallisepticum was 0.001953125 μg/mL. PK results indicated that the absorption half-life ( T 1/2ka ) in infected chicks was 0.10 h, elimination half-life ( T 1/2kel ) was 4.23 h. The areas under the concentration-time curve at 24h ( AUC 24h ) for 5, 40, and 80 mg/kg single-dose injections were 1.49, 10.15, and 18.56 μg·h/mL, respectively. The peak concentrations ( C max ) of 5, 40, and 80 mg/kg were 0.56, 5.79, and 9.53 μg/mL, respectively. The PD results indicated that at doses of 70 and 80 mg/kg, the mycoplasmal counts in lungs decreased by 3.39 and 3.28 Log 10 CFU/mL, respectively, achieving a bactericidal effect. Through PK/PD fitting, the target values corresponding to reducing the lung mycoplasma load by 3 Log 10 CFU/mL of AUC 24h /MIC and C max /MIC were 8288.29 h and 4299.30, respectively, and the calculated dosage using formula (2) was 62.64 mg/kg, under the regimen of intramuscular injection once every 24 h for 3 consecutive days. In addition, the effect of high-dose p -furoylamphenmulin on the relief of air sac lesions was significant. These results provide a basis for developing and applying p -furoylamphenmulin and provide a preliminary medication regimen.

Pharmacokinetic/pharmacodynamic relationship of a novel pleuromutilin derivative APTM against Mycoplasma gallisepticum

Weicong Yang,Huanzhong Ding,Xiaona Ma,Taiming Lv,Luoju Wang

Mycoplasma gallisepticum (MG) is a primary avian pathogen that causes chronic respiratory disease, leading to significant economic losses in the poultry industry. This study aimed to investigate the pharmacokinetic/pharmacodynamic (PK/PD) relationship of a novel pleuromutilin derivative, 14-O-[(4-amino-6-hydroxy-pyrimidine-2-yl) thioacetyl] mutilin (APTM), against MG in a chicken infection model to provide a basis for a rational dosage regimen. The in vitro activity of APTM against MG strain S6 was assessed by determining the minimum inhibitory concentration (MIC) and time-kill kinetics. An intratracheal MG infection model was established in chickens. The pharmacokinetic profile was evaluated after single oral administrations of APTM at 5, 15, and 40 mg/kg. The pharmacodynamic efficacy was determined by quantifying the bacterial reduction in the lungs after three consecutive days of oral treatment with doses ranging from 0 to 40 mg/kg. The PK/PD data were integrated and analyzed using an inhibitory sigmoid Emax model. The MIC of APTM against MG S6 was 0.03125 µg/mL, and in vitro time-kill assays demonstrated concentration-dependent bactericidal activity. In chickens, APTM was rapidly absorbed (T max : 0.25–0.5 h), with both C max and AUC 0-24h exhibiting excellent dose proportionality (R² > 0.99) over the tested range. In the efficacy study, APTM produced a dose-dependent reduction in lung bacterial load, with a maximum mean reduction of 2.80 log 10 CFU/mL observed at the 40 mg/kg dose, indicating a bactericidal effect. The PK/PD indices, AUC 0−24h /MIC and C max /MIC, were both highly correlated with the in vivo antimicrobial effect (R² = 0.9424 and 0.9428, respectively). To achieve a 2-log 10 CFU/mL reduction in bacterial load, the target AUC 0−24h /MIC value was determined to be 492.75, which corresponds to a calculated daily oral dose of 22 mg/kg. These findings demonstrate the potent efficacy of APTM against MG and provide a quantitative scientific foundation for its therapeutic use in poultry. Specifically, a daily oral dose of 22 mg/kg was identified as the breakpoint for a bactericidal effect (2-log10 reduction), suggesting APTM is a potent candidate for controlling MG infections in poultry.

Pharmacokinetic/pharmacodynamic integration of amphenmulin: a novel pleuromutilin derivative against Mycoplasma gallisepticum

Wenxiang Wang,Jiao Yu,Xuan Ji,Xirui Xia,Huanzhong Ding

Hydroxytyrosol Restrains NLRP3 Inflammasome Activation and Pyroptosis Through the TLR4/NF-κB Pathway to Prevent Mycoplasma gallisepticum-Inflammation

Shunxing Liu,Yanling Xiong,Zhentao Cheng,Anchun Cheng,Rutao Lin,Hui Li,Yao Huang,Binlan Zhou,Ting Yang,Chunlan Shan

Mycoplasma gallisepticum ( MG ), a significant pathogen, causes chronic respiratory disease (CRD) in poultry, characterized by coughing, wheezing, and dyspnea. This widespread disease severely impedes the healthy development of the poultry industry. Hydroxytyrosol (HT), a plant-derived monomeric compound, possesses diverse bioactivities, including antibacterial, antioxidant, and cardiovascular protective properties. This study aimed to investigate HT's protective effect against MG -induced inflammatory damage in HD11 cells. The findings revealed that MG infection activated the TLR4/NF-κB signaling pathway and the NLRP3 inflammasome, resulting in macrophage accumulation and inflammatory damage in the lung tissue of chicks. HT mitigated MG -induced inflammatory damage in HD11 cells, inhibited the M1 phenotype shift, and reduced the secretion of pro-inflammatory factors. Molecular docking and molecular dynamics simulations demonstrated HT's stable, spontaneous binding to NLRP3. Further investigations showed that HT alleviates oxidative stress-induced cellular damage, diminishes pathological apoptosis and pore formation, and concurrently reduces NLRP3 activation by regulating the TLR4/NF-κB pathway, thereby downregulating the expression of key pyroptosis factors. In summary, HT reduces NLRP3 inflammasome activation by specifically inhibiting the TLR4/NF-κB signaling axis, consequently alleviating inflammation-induced damage, oxidative stress, and pyroptosis in HD11 cells caused by MG infection.

Indirubin prevents structural damage to chicken lungs and trachea caused by Mycoplasma gallisepticum infection through attenuating oxidative stress and apoptosis

Y. S. Miao,Q. X. Han,K. X. Wang,X. D. Fan,Z. Zhang,L. Chen,D. Z. Zheng,S. Yue,L. Lei,L. Y. Liu,J. C. Li,G. J. Liu

1. This study evaluated the mechanism of action of indirubin in alleviating the structural damage induced by Mycoplasma gallisepticum (MG) in the lungs and trachea.2. A total of 250 one-day-old white leghorn chickens, specific-pathogen-free were divided into six treatment groups, including (A) indirubin high concentration treatment group (50 mg/kg; IHC); (B) indirubin medium concentration treatment group (25 mg/kg; IMC); (C) indirubin low concentration treatment group (12.5 mg/kg; ILC); (D) tylosin control group (0.5 g/l); (E) control group (CON) and (F) challenge model group (MG).3. Results from antioxidant activity analysis demonstrated that indirubin treatment significantly decreased the amount of MG-mediated oxidative stress in the lungs of chickens. Histopathological examination revealed abnormal morphological signs and cell damage in MG birds. This included lung lymphocytic infiltration, overlapping nuclear debris and inflammatory cell infiltration. In addition, ultrastructural examination revealed signs of apoptosis in the lungs. However, indirubin treatment partially relieved these abnormal morphological changes.4. The TUNEL analysis showed extensive apoptosis in the lungs of the model group compared to the control and positive drug control group. Apoptosis-related protein expression levels were significantly upregulated in the model group, which confirmed the phenomena of apoptosis induced by MG. The indirubin treatment significantly reduced apoptosis in the lungs and trachea compared to the model group. Meanwhile, the effect of MG challenge was reduced in the lungs by indirubin in a dose-dependent manner.5. These results showed that the inhibition of oxidative stress and apoptosis by indirubin contributed to its therapeutic effects against MG infection.

Methylsulfonylmethane ameliorates inflammation via NF-κB and ERK/JNK-MAPK signaling pathway in chicken trachea and HD11 cells during Mycoplasma gallisepticum infection

Yusong Miao,Dong Niu,Ze Wang,Jian Wang,Zhiyong Wu,Jiaxin Bao,Xiaodi Jin,Rui Li,Muhammad Ishfaq,Jichang Li

ABSTRACT Mycoplasma gallisepticum ( MG ) is an avian pathogen that commonly causes respiratory diseases in poultry. Methylsulfonylmethane ( MSM ) is a sulfur-containing natural compound that could alleviate inflammatory injury through its excellent anti-inflammatory and antioxidant properties. However, it is still unclear whether MSM prevents MG infection. The purpose of this study is to determine whether MSM has mitigative effects on MG-induced inflammatory injury in chicken and chicken like macrophages ( HD11 cells ). In this research, White Leghorn chickens and HD11 cells were used to build the MG-infection model. Besides, the protective effects of MSM against MG infection were evaluated by detecting MG colonization, histopathological changes, oxidative stress and inflammatory injury of trachea, and HD11 cells. The results revealed that MG infection induced inflammatory injury and oxidative stress in trachea and HD11 cells. However, MSM treatment significantly ameliorated oxidative stress, partially alleviated the abnormal morphological changes and reduced MG colonization under MG infection. Moreover, MSM reduced the mRNA expression of proinflammatory cytokines-related genes and decreased the number of death cells under MG infection. Importantly, the protective effects of MSM were associated with suppression of nuclear factor-kappa B ( NF-κB ) and extracellular signal-related kinases (ERK) /Jun amino terminal kinases (JNK) -mitogen-activated protein kinases ( MAPK ) pathway in trachea and HD11 cells. These results proved that MSM has protective effects on MG-induced inflammation in chicken, and supplied a better strategy for the protective intervention of this disease.

Quercetin alleviates Mycoplasma gallisepticum-induced inflammatory damage and oxidative stress through inhibition of TLR2/MyD88/NF-κB pathway in vivo and in vitro

Shun Wang,Xiaodi Jin,Hao Chen,Mingdong Han,Jiaxin Bao,Dong Niu,Yikang Wang,Rui Li,Zhiyong Wu,Jichang Li

Chronic respiratory disease (CRD) caused by Mycoplasma gallisepticum (MG) in chickens leads to enormous economic damage to the poultry industry yearly. The active components and mechanism of action of the traditional herbal remedy Ephedra houttuynia powder (EHP), which had been approved for clinical treatment against MG infection in China, remain unknown. In this study, the active components of EHP against MG were screened using a network pharmacological method, additionally, we studied the mechanism of action of the screened results (quercetin (QUE)). The findings demonstrated that QUE was an essential element of EHP against MG infection, effectively attenuating MG-induced oxidative stress and activation of the TLR2/MyD88/NF-κB pathway. Following QUE therapy, IL-1, IL-6, and TNF-α content and expression were downregulated, whereas IL-4 and IL-10 expression were upregulated, eventually suppressing the inflammatory response both in vitro and in vivo . Together, this study presents a strong rationale for using QUE as a therapeutic strategy to inhibit MG infection-induced inflammatory damage and oxidative stress.