Aflatoxin B1 (AFB1) is a potent hepatotoxin that induces oxidative stress, inflammation, and mitochondrial dysfunction. Dipsacoside B (DB), a bioactive triterpenoid saponin from Flos Lonicerae (Shanyinhua), is recognized for its antioxidant, anti-inflammatory, and cytoprotective properties. This study investigates the protective effects of DB against AFB1-induced liver injury and the underlying mechanisms. Male C57BL/6 mice were assigned to control, AFB1, DB, and AFB1 + DB groups, receiving oral treatments for 4 weeks. The results showed that DB significantly alleviated AFB1-induced weight loss and liver damage, as evidenced by histopathological changes and serum biochemical markers. DB reduced hepatic H₂O₂ and MDA levels, enhanced the activities of antioxidant enzymes such as T-SOD, GSH-Px, CAT, and total antioxidant capacity (T-AOC), inhibited the expression of IL-6, IL-1β, and TNF-α genes, and modulated metabolic enzymes by downregulating Phase I genes (CYP1A2, CYP3A11) while upregulating the Phase II gene GSTA3. Notably, DB upregulated AFB1-suppressed Nrf2 and its downstream targets (HO-1, NQO1, SOD1, GCLC, GCLM, GSS). DB also reversed AFB1-induced mitochondrial damage, including swelling and cristae disruption, and inhibited apoptosis by restoring Bcl-2 and reducing p53, Bax, Cyt-c, caspase-9, and caspase-3 expression. These findings suggest that DB protects against AFB1-induced liver injury by regulating oxidative stress, inflammation, apoptosis, and metabolic enzymes, suggesting it has significant potential as a therapeutic strategy for aflatoxin-related hepatic disorders.

Objective Non-alcoholic fatty liver disease (NAFLD) represents a significant global health challenge, predominantly managed through non-pharmacological interventions. Heat therapy (HT) has been shown to effectively reduce hepatic lipid accumulation; however, the underlying mechanisms remain incompletely understood. This study aims to elucidate the mechanism by liver metabolomics. Methods This animal study utilized a high-fat diet to induce hepatic lipid accumulation in mice, combined with long-term HT intervention. Subsequently, metabolomic profiling and Western blot analysis were performed to assess hepatic metabolic alterations and elucidate the underlying mechanisms of HT action, followed by in vitro validation using L02 human hepatocytes. Results HT significantly decreased body weight, fat levels, and hepatic lipid accumulation while preventing excessive glycogen depletion in HFD-fed mice. Metabolomics analysis revealed that HT reduced diacylglycerol (DAG), triacylglycerol (TAG), free fatty acids (FFA), and saturated ceramides (CER); it also increased taurine levels, enhanced the utilization of vitamins B2, B5, and B6, and corrected amino acid imbalances. Furthermore, HT upregulated the expression of CSAD, ACADL, and ATP5A. In vitro studies demonstrated that heat treatment increased CSAD levels in L02 cells. Overexpression of CSAD elevated taurine levels and, under palmitic acid induction, reduced FFA levels while upregulating VDAC1 and ATP5A. Conclusions HT enhances mitochondrial function and promotes fatty acid oxidation by upregulating taurine synthesis via CSAD, thereby inhibiting hepatic lipid accumulation and correcting metabolic disorders, ultimately improving NAFLD.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, with current therapies often limited by significant drug resistance. Owing to the Warburg effect, targeting cancer-specific metabolic vulnerabilities is a promising therapeutic strategy. This study aims to investigate the role of RNF114 in HCC progression and its regulatory mechanism, as well as its clinical translational potential as a therapeutic target. We evaluated the clinical significance of RNF114 using tissue microarrays and database analysis. RNF114 function in promoting HCC progression by regulating glucose uptake was investigated using knockdown experiments in cell lines and subcutaneous xenograft models. Furthermore, a therapeutic xenograft model was employed to assess the potential of RNF114 knockdown in overcoming Sorafenib resistance. RNF114 was highly expressed in HCC and correlated with poor prognosis. Knockdown of RNF114 significantly suppressed HCC cell proliferation, migration, invasion, and glycolysis. Co-immunoprecipitation identified PACSIN3 as a key substrate of RNF114. RNF114 interacted with the SH3 domain of PACSIN3, promoting its ubiquitination and proteasomal degradation. Subcellular fractionation revealed that the F-BAR domain of PACSIN3 facilitated GLUT1 vesicular trafficking. Consequently, RNF114 impaired this process, leading to increased plasma membrane retention of GLUT1 and enhanced glycolytic flux. Consistently, in both HCC cells and subcutaneous xenograft models, RNF114 knockdown sensitized tumors to Sorafenib treatment. Collectively, our findings reveal that the RNF114–PACSIN3–GLUT1 axis regulates glucose uptake and metabolic reprogramming in HCC, thereby promoting tumor progression and contributing to therapy resistance. Targeting this signaling axis provides a novel insight into metabolic therapy for HCC.

Oxylipins are bioactive lipid metabolites that may bridge immune dysregulation and depressive symptomatology. However, systematic alterations of oxylipin networks in MDD and their therapeutic implications remain unclear. In this study, a plasma oxylipidomics analysis was performed in 154 patients with MDD and 134 healthy controls (HC). Findings were validated in a chronic restraint stress (CRS) mouse model of depression, followed by pharmacological inhibition of lipoxygenase (LOX) pathways using ML-355 and zileuton. Behavioral tests and immunofluorescence analysis of microglial activation were conducted to assess therapeutic effects. MDD patients exhibited significantly elevated plasma levels of 22 oxylipins compared to HCs, including oxylipins derived from lipoxygenase (LOX), cytochrome P450 (CYP450), cyclooxygenase (COX), and non-enzymatic pathways. Notably, non-responders to antidepressant treatment displayed higher baseline levels of 20 oxylipins than both responders and HCs, and baseline oxylipin levels negatively correlated with Hamilton Depression Rating Scale (HAMD) score reduction rates. In CRS mice, the LOX pathway was activated, as evidenced by increased LOX levels in the blood and brain, as well as elevated plasma levels of LOX-derived oxylipins. Pharmacological inhibition of 12-lipoxygenase (12-LOX) with ML-355 significantly alleviated depressive-like and anxiety-like behaviors and reversed stress-induced microglial activation in the hippocampus and medial prefrontal cortex. The 5-LOX inhibitor zileuton reduced microglial activation in a region-dependent manner but did not significantly improve behavioral outcomes. These findings reveal elevated LOX-derived oxylipins as potential biomarkers predicting poor antidepressant response in MDD. Targeting the LOX pathway, particularly 12-LOX, represents a promising therapeutic strategy for depression by ameliorating neuroinflammatory processes.

Sleep deprivation (SD) disrupts intestinal homeostasis through excessive reactive oxygen species (ROS) accumulation. Tibetan tea is a potential dietary intervention for inflammation, it's effect on SD-induced intestinal inflammation remains unclear. This study investigates the alleviating effects of Tibetan tea water-soluble extract (TTE) on intestinal dysfunction in SD mice. After TTE supplementation, the physiological activity, inflammatory cytokines, and oxidative stress levels were assessed in SD-induced intestinal dysfunction mice. SD increased ROS levels and pro-inflammatory cytokines in plasma and small intestine, causing intestinal injury characterized by reduced goblet cells, decreased Mucin2 (MUC2) expression, and impaired tight junction proteins. Conversely, TTE reversed these disorders and improved mucosal injury in the small intestine. Furthermore, TTE modulated gut microbiota by enriching probiotics linked to SCFA production and restored SD-induced metabolic disturbances in the small intestine and systemic circulation, particularly affecting tricarboxylic acid (TCA) cycle, urea cycle, and TAG-related metabolites. Overall, TTE remarkably ameliorated SD-induced intestinal dysfunction through reducing ROS, restoring intestinal barrier function, and regulating the gut microbiome, which suggested that Tibetan tea could contribute to the treatment of intestinal inflammation.

3D printed vascular stent (3D-PVS) fabricated based on the specific vascular structure has provided an excellent solution in therapy of cardiovascular disease (CVD). However, the 3D-PVS-based biocompatibility analysis was still remained at the phenotypic level stage while deeper molecular mechanism was urgent to be explored in order to provide theoretical and technical support for the clinical application of 3D-PVS. Fortunately, nanometabolomics proposed and applied in our latest research could offer an excellent alternative for elucidating detailed molecular mechanisms involved in "3D-PVS-organism" interaction through 3D-PVS-related untargeted/ targeted aqueous metabolomics, lipidomics, and spatial metabolomics. In this work, the biological response and relevant molecular mechanism of 3D-PVS was elucidated by nanometabolomics. Thereinto, untargeted nanometabolomics was performed for primary profiling of 3D-PVS-induced alteration in cell metabolism, then targeted nanometabolomics was carried out in rat model for in-depth investigation of 3D-PVS-induced metabolic reprogramming based on above untargeted nanometabolomics results. The untargeted nanometabolomics results revealed that the in vitro safe range of concentration (including low concentration (5 mg/mL) and high concentration (15 mg/mL)) of 3D-PVS could lead to strong disturbance of amino acids or organic acids-related metabolism and phospholipids, sphingolipids or glycerolipids-related metabolism. In addition, targeted nanometabolomics results further elucidated the in vivo 3D-PVS-induced promotion in glycolysis and amino acid metabolism and homeostasis of some lipid classes. This work could be consider as a far-reaching exploration on 3D-PVS at a phenotypic and molecular level, which also shed light on its further biomedical application based on nanometabolomics bioinformation.

Lung cancer (LC) remains the leading cause of cancer death worldwide. Chemical combined photothermal therapy (PTT) offers an innovative therapeutic strategy for LC. However, the mechanistic understanding of PTT-based LC treatment lacks deep mechanistic insights into photothermal therapy. In this work, we developed a paclitaxel/Mo4/3B2-x bifunctional nanomedicine (Taxol/Mo4/3B2-x-BN) for the treatment of LC. Mo4/3B2-x nanosheets could reduce drug resistance or degradation of Taxol, while Taxol could enhance post-PTT residual cell elimination. Furthermore, nanometabolomics was leveraged to investigate metabolic reprogramming, specifically alterations in the metabolome and lipidome, at the molecular level following treatment. Results demonstrated that 1 mg/mL Taxol/Mo4/3B2-x-BN exhibited excellent biocompatibility and synergistic efficacy, inducing a rapid tumor volume regression (from 0.214 cm3 to complete resolution on day 4). Subsequent nanometabolomics revealed significant alteration in amino acids and lipid metabolism, which demonstrated that Taxol/Mo4/3B2-x-BN could regulate the homeostasis of amino acid and lipids metabolism. Key amino acid metabolic pathways induced by treatment were further delineated. These findings indicate the clinical anticancer potential of Taxol/Mo4/3B2-x-BN. In addition, nanometabolomics could provide multidimensional bioinformation for nanomedicine-based mechanism exploration.

BACKGROUND:Radix Linderae is a traditional Chinese herb used to treat diabetes and gastrointestinal disorders related to Qi deficiency. Excessive production of reactive oxygen species (ROS) plays a crucial role in the pathogenesis and progression of diabetes. In tissues affected by ROS, the intestine is a common site prone to dysfunction, and ROS is considered a key player in intestinal physiological and metabolic disorders in diabetes. Modern pharmacological studies have found that Radix Linderae possesses excellent antioxidant capacity and exerts its antidiabetic activity through its antioxidant effects. The development and utilization of Radix Linderae for the treatment of diabetes-induced ROS-related intestinal metabolic disorders hold great potential. OBJECTIVE:The present research aimed to identify chemical components of the Radix Linderae Alkaloids-enriched fraction (RLA) and to clarify the underlying therapeutic mechanisms against diabetes and associated complications by regulating intestinal ROS-induced metabolic disturbances. A combined strategy employing multimodel metabolomics and gut microbiomics analyses was employed. METHODS:The α-glucosidase inhibition experiment, along with pathological, imaging, and biochemical studies on diabetic mice, was carried out to confirm the hypoglycemic activity, intestinal ROS clearance ability, and alleviative effect of RLA on ROS-induced intestinal metabolic disorders in diabetes. Microbial modulation induced by RLA was evaluated via 16S rRNA sequencing (rRNA-seq) and quantification of short-chain fatty acids (SCFAs). Subsequently, a multimodel metabolomics approach, including spatial metabolomics, aqueous metabolomics, and lipidomics, was applied to investigate the underlying mechanisms of RLA on modulating the ROS-related abnormal metabolic pathways and lipid metabolism. Finally, the intestinal cell model experiment was performed to verify that RLA exerted its antidiabetic activity through antioxidant effects. RESULTS:Oral administration of RLA effectively eliminated intestinal ROS overproduction in diabetes, rehabilitated probiotic diversity, especially the SCFA-producing bacteria in the intestine, and restored homeostasis to metabolism-related biological processes. CONCLUSIONS:These findings indicated that the accumulation of ROS led to dysbiosis of the gut microbiota and ROS-related metabolic disorders in diabetes. RLA alleviated diabetes and its symptoms by clearing intestinal ROS and restoring intestinal disturbances. RLA demonstrates significant promise as an adjunctive therapy for diabetes.

Objective:To establish a viable bacteria assay for Helicobacter pylori (H. pylori) by assessing the cgt gene expression, and to develop accordingly a rapid and novel testing method for clinical precision treatment. Methods:Viable bacteria count was determined in bacterial cultures. The transcriptional expression level of cgt (hp0421), the conserved gene that encodes cholesterol-α-glucosyltransferase (CGT) in H. pylori, was measured by RT-PCR. The correlation between the number of colonies and cgt gene transcription expression was analyzed and the regression model was constructed. The linear range, sensitivity, and specificity of the new method were examined accordingly. The bactericidal action of clarithromycin was assessed using this method to verify the performance of the method in determining clinical bacterial drug resistance. Results:The Ct values of cgt for H. pylori colony counts of 102, 104, 106, and 108 CFU/mL were 29.67±0.14, 23.37±0.36, 17.65±0.37, and 11.38±0.39, respectively. In the range of 101-108 CFU/mL, the regression equation for cgt gene expression and viable bacterial counts determined by RT-qPCR was y=-0.3501x+12.49, with the correlation coefficient being R 2=0.9992 and the sensitivity being 101 CFU/mL, showing no cross-reaction with 13 other bacteria. The lg values of live H. pylori bacteria treated with clarithromycin at 0, 5, 10, 20, and 40 μg/mL for 12 h were 2.57±0.02, 2.45±0.01, 2.19±0.02, 1.91±0.07, and 1.33±0.05, respectively. The corresponding cgt gene Ct values were 27.76±0.09, 28.37±0.24, 29.51±0.14, 30.11±0.12, and 31.66±0.11. By applying the cgt gene expression in the equation, the estimated counts of viable bacteria were found to be 2.73±0.03, 2.52±0.08, 2.11±0.05, 1.89±0.02, and 1.33±0.04, showing no significant difference in statistical analysis (P>0.05). Conclusion:The method for assessing viable bacteria account by evaluating cgt gene expression in H. pylori was successfully established, significantly reducing the time required to determine viable bacteria count and providing a new method for clinical viable bacteria testing.

Mo4/3B2-x nanosheets are newly developed, and 2D transition metal borides (MBene) were reported in 2021, but there is no report on their further applications and modification; hence, this article sheds light on the significance of potential biological prospects for future biomedical applications. Therefore, elucidation of the biocompatibility, biotoxicology, and bioactivity of Mo4/3B2-x nanosheets has been an urgent need to be fulfilled. Nanometabolomics (also referred as nanomaterials-based metabolomics) was first proposed and utilized in our previous work, which specialized in interpreting nanomaterials-induced metabolic reprogramming through aqueous metabolomics and lipidomics approach. Hence, nanometabolomics could be considered as a novel concept combining nanoscience and metabolomics to provide bioinformation on nanomaterials' biomedical applications. In this work, the safe range of concentration (<50 mg/L) with good biosafety toward human umbilical vein endothelial cells (HUVECs) was discovered. The low concentration (5 mg/L) and high concentration (50 mg/L) of Mo4/3B2-x nanosheets were utilized for the in vitro Mo4/3B2-x-cell interaction. Nanometabolomics has elucidated the biological prospective of Mo4/3B2-x nanosheets via monitoring its biocompatibility and metabolic shift of HUVECs. The results revealed that 50 mg/L Mo4/3B2-x nanosheets could lead to a stronger alteration of amino acid metabolism with disturbance of the corresponding amino acid-related pathways (including amino acid metabolism, amino acid degradation, fatty acid biosynthesis, and lipid biosynthesis and metabolism). These interesting results were closely involved with the oxidative stress and production of excess ROS. This work could be regarded as a pathbreaking study on Mo4/3B2-x nanosheets at a biological level, which also designates their further biochemical, medical, and industrial application and development based on nanometabolomics bioinformation.

In this work, Mo 2 C nanosheet-based photothermal therapy toward melanoma was investigated through integrated metabolomics in the mice model.

IntroductionMacranthoidin B (MB) is a primary active component of Flos Lonicerae. In Chinese veterinary clinics, Flos Lonicerae is frequently used in combination with florfenicol to prevent and treat infections in livestock and poultry. However, potential interactions between Flos Lonicerae and florfenicol remain unclear. To systematically study these interactions, it is crucial to investigate the individual phytochemicals within Flos Lonicerae. Therefore, MB was selected for this study to assess its effect on the pharmacokinetics of florfenicol in vivo and to explore the underlying mechanisms involved.MethodsMale Sprague-Dawley rats were administered MB (60 mg/kg BW) or sterile water orally for 7 consecutive days. On the 8th day, a single oral dose of florfenicol (25 mg/kg BW) was given. Florfenicol pharmacokinetics were analyzed using ultra-high performance liquid chromatography. The hepatic expression levels of cytochrome P450 (CYP1A2, CYP2C11, CYP3A1), UDP-glucuronosyltransferase (UGT1A1), P-glycoprotein (P-gp), and nuclear receptors, including constitutive androstane receptor (CAR), pregnane X receptor (PXR), and retinoid X receptor alpha (RXRα), were quantified via reverse transcription-quantitative polymerase chain reaction and Western blotting (WB). Hepatic CYP1A2 and CYP2C11 activities were measured using a cocktail method. Additionally, the subcellular expression and localization of CAR, PXR, and RXRαin hepatocytes was assessed using WB and immunofluorescence staining.ResultsMB significantly reduces the AUC(0-∞) and MRT(0-∞) of florfenicol. MB also markedly upregulates the mRNA and protein expression of hepatic CYP1A2 and CYP2C11, along with their catalytic activities. Substantial upregulation of CAR and PXR proteins occurs in the hepatocyte nucleus, along with significant nuclear colocalization of the transcriptionally active CAR/RXRα and PXR/RXRαheterodimers, indicating MB-induced nuclear translocation of both CAR and PXR.DiscussionThese findings suggest that MB-induced alterations in florfenicol pharmacokinetics, particularly its accelerated elimination, may be due to increased expression and activities of CYP1A2 and CYP2C11, with CAR and PXR potentially involved in these regulatory effects. Further investigation is yet needed to fully elucidate the clinical implications of these interactions concerning the efficacy of florfenicol in veterinary medicine.

In brief The metabolic processes of the gestation period in pandas remain poorly understood. Our study comprehensively characterizes the metabolism of giant pandas during gestation and proposes arginine and histidine as potential novel biomarkers for detecting the pregnancy state of giant pandas. Abstract There has been remarkable progress in the conservation and reproduction of giant pandas. However, the physiology of the gestation period in pandas remains poorly understood. The metabolic processes from estrus to pregnancy are dynamic and precisely regulated, playing a crucial role in pregnancy and related dysfunctions. In this study, we conducted a metabolomic analysis of 37 blood samples collected from pandas in estrus, acyclic, and potential pregnant states, employing rigorous screening to minimize the influence of diet. Our findings suggest that a reduced appetite can serve as an indicator for evaluating implantation time, representing a characteristic response to pregnancy and aiding in the prediction of delivery time in pregnant pandas. Metabolomic results indicate great metabolism variation from estrus to pregnancy, highlighting the association between amino acid metabolism and pregnancy outcomes. Compared to other pandas, individuals who successfully bred exhibit significantly elevated levels of arginine and histidine, even 2 months before experiencing a reduced appetite. Furthermore, the lipid profile undergoes distinct dynamic changes only in estrus samples. In summary, our study comprehensively characterizes the metabolism of giant pandas during gestation and proposes arginine and histidine as potential novel biomarkers for detecting the pregnancy state of giant pandas.

Mycobacterium abscessus is a non-tuberculous mycobacterial pathogen known to cause pulmonary and skin infections worldwide. Renowned for its multidrug resistance, M. abscessus infections often result in unfavorable clinical outcomes. Clarithromycin plays a pivotal role in treating M. abscessus infections, with resistance commonly leads to treatment failure. While canonical mutations in 23S rRNA residue 2270/2271 are recognized as a major mechanism for acquired clarithromycin resistance, resistant isolates devoid of such mutations have been widely reported. In this study, we conducted a comprehensive investigation into acquired clarithromycin resistance using spontaneous mutants derived from two parental strains characterized by erm(41) T28 and C28 sequevars respectively. A total of 135 resistant mutants were selected from the parental strains. Sequencing of the 78 mutants lacking canonical 2270/2271 mutations identified mutations within the peptidyl-transferase center and in hairpin loops 35, 49, and 74 of the 23S rRNA. Moreover, these noncanonical mutations were identified in 57 out of 1875 genomes of clinical isolates. Thirteen representative mutations were introduced into the bacterial genome via site-directed mutagenesis, and their contribution to macrolide resistance was verified. Mapping these mutations onto the three-dimensional structure of 23S rRNA revealed their localization at the entrance of the nascent peptide exit tunnel, potentially contributing to resistance by disrupting the macrolide binding pocket. The identification of these noncanonical 23S rRNA mutations advances our understanding of macrolide resistance in M. abscessus and underscores their importance as potential markers for detecting clarithromycin resistance.

Wound rehabilitation is invariably time-consuming, scar formation further weakens therapeutic efficacy, and detailed mechanisms at the molecular level remain unclear. In this work, a Mo4/3B2-x nanoscaffold was fabricated and utilized for wound healing and scar removing in a mice model, while metabolomics was used to study the metabolic reprogramming of metabolome during therapy at the molecular level. The results showed that transition metal borides, called Mo4/3B2-x nanoscaffolds, could mimic superoxide dismutase and glutathione peroxidase to eliminate excess reactive oxygen species (ROS) in the wound microenvironment. During the therapeutic process, the Mo4/3B2-x nanoscaffold could facilitate the regeneration of wounds and removal of scars by regulating the biosynthesis of collagen, fibers, and blood vessels at the pathological, imaging, and molecular levels. Subsequent metabolomics study revealed that the Mo4/3B2-x nanoscaffold effectively ameliorated metabolic disorders in both wound and scar microenvironments through regulating ROS-related pathways including the amino acid metabolic process (including glycine and serine metabolism and glutamate metabolism) and the purine metabolic process. This study is anticipated to illuminate the potential clinical application of the Mo4/3B2-x nanoscaffold as an effective therapeutic agent in traumatic diseases and provide insights into the development of analytical methodology for interrogating wound healing and scar removal-related metabolic mechanisms.

To reveal dysregulated metabolism hallmark that was associated with a severe acute pancreatitis (SAP) phenotype. In this study, LC-MS/MS-based targeted metabolomics was used to analyze plasma samples from 106 acute pancreatitis (AP) patients (34 mild, 38 moderate, and 34 severe) admitted within 48 hours from abdominal pain onset and 41 healthy controls. Temporal metabolic profiling was performed on days 1, 3, and 7 after admission. A random forest (RF) was performed to significantly determine metabolite differences between SAP and non-SAP (NSAP) groups. Mass spectrometry imaging (MSI) and immunohistochemistry were conducted for the examination of pancreatic metabolite and metabolic enzyme alterations, respectively, on necrosis and paracancerous tissues. Simultaneously determination of serum and pancreatic tissue metabolic alterations using an L-ornithineinduced AP model to discover metabolic commonalities. Twenty-two significant differential metabolites screened by RF were selected to build an accurate model for the prediction of SAP from NSAP (AUC = 0.955). Six of 22 markers were found by MSI with significant alterations in pancreatic lesions, reduced ornithine-related metabolites were also identified. The abnormally expressed arginase2 and ornithine transcarboxylase were further discovered in combination with time-course metabolic profiling in the SAP animal models, the decreased ornithine catabolites were found at a late stage of inflammation, but ornithine-associated metabolic enzymes were activated during the inflammatory process. The plasma metabolome of AP patients is distinctive, which shows promise for early SAP diagnosis. AP aggravation is linked to the activated ornithine metabolic pathway and its inadequate levels of catabolites in in-situ lesion.

为了探究川射干提取物对急性肺损伤的防治效果及其对TLR4/NF-κB信号通路相关蛋白表达的影响,试验将 24 只雌性 Balb/c 小鼠随机分为空白对照(CTR)组、模型(LPS)组、地塞米松(DEX)组及川射干提取物(ITR)组,每组 6 只.ITR 组每只每天灌胃 12.5 mg/mL 川射干提取物0.2 mL,其他组灌胃等体积生理盐水,连续7 d.末次给药 1 h后,LPS组、DEX组和ITR组每只小鼠腹腔注射1 mg/mL脂多糖0.2 mL造模,CTR组腹腔注射等体积生理盐水.DEX组于造模前 1 小时每只小鼠腹腔注射0.5 mg/mL地塞米松0.2 mL.造模6 h后采集血液,制备血清;处死各组小鼠,分别采集肺泡灌洗液(BALF)和肺脏,通过ELISA法检测血清和肺泡灌洗液中趋化因子 1(CXCL1)、肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β、IL-6、IL-8 和IL-10 的含量;对肺脏组织进行H.E.染色,观察肺脏病理变化;通过Western-blot检测Toll样受体4(TLR4)、核因子κB(NF-κB)信号通路相关蛋白的表达情况.结果表明:与LPS组相比,ITR组血清和肺泡灌洗液中CXCL1、TNF-α、IL-1β、IL-6、IL-8 含量均显著或极显著下降(P<0.05 或P<0.01),IL-10 含量显著或极显著升高(P<0.05 或P<0.01);与LPS组比较,ITR组肺泡内炎症细胞浸润程度明显减轻,仅局部肺泡腔内出现少量巨噬细胞或淋巴细胞浸润.与LPS组比较,ITR组肺脏TLR4、MyD88、TRIF和NF-κB p-p65 蛋白表达量显著或极显著降低(P<0.05 或P<0.01).说明川射干提取物可通过调节TLR4/NF-κB信号通路缓解脂多糖诱导的小鼠急性肺损伤.

Abstract Coptisine (COP) is the main active ingredient of Coptis chinensis. In Chinese veterinary clinics, Coptis chinensis is commonly used alongside florfenicol to treat intestinal infections. The goal of this study was to investigate the impact of COP co-administration on the pharmacokinetics of florfenicol in rats. Male Sprague-Dawley rats were orally administered COP (50 mg/kg BW) or sterile water for 7 consecutive days, followed by a single oral dose of florfenicol (25 mg/kg BW) on the 8th day. Pharmacokinetics of florfenicol were analysed using non-compartmental methods, while expression levels of cytochrome P450 (CYP) isoforms in the liver and P-glycoprotein (P-gp) in the jejunum were measured using real-time RT-PCR, Western blot and immunohistochemical analyses. Co-administration of COP and florfenicol significantly increased AUC(0-∞), MRT(0-∞), and Cmax of florfenicol, while CLz/F was significantly decreased. COP down-regulated the expression of CYP1A2, CYP2C11, and CYP3A1 in the liver, as well as P-gp in the jejunum. These findings suggest that co-administration of COP with florfenicol alters the pharmacokinetics of florfenicol in rats. The down-regulation of CYP and P-gp expression may contribute to this effect. Therefore, the co-administration of COP with florfenicol may enhance the prophylactic or therapeutic efficacy of florfenicol in veterinary practice.

川续断属于川产道地药材,主产于四川攀西等盆周山地,用于防治跌打损伤、崩漏安胎,是临床常用中药材.文章在充分查阅川续断相关文献的基础上对川续断资源分布、化学成分、药理药效、种植现状进行全面的综述,同时对其壮阳、补肝肾、壮筋骨、安胎等药理活性在畜牧业生产中用于种畜保健、母畜保胎及蛋鸡产蛋性能等良好的应用前景进行了阐述,为扩大川续断药材资源在畜禽健康养殖中合理利用以及动保行业开发利用川续断资源提供参考.

Belamcanda chinensis (L.) DC, commonly used with florfenicol in Chinese veterinary clinics for respiratory tract infections, contains the major effective isoflavone, tectoridin (TEC). This study aimed to investigate the impact of TEC co-administration on the pharmacokinetics of florfenicol in vivo. Male rats received oral TEC (50 mg/kg BW) or sterile water for seven days, followed by a single oral dose of florfenicol (25 mg/kg BW) on the 8th day. Non-compartmental methods analysed the pharmacokinetics of florfenicol, while real-time reverse transcription polymerase chain reaction (RT-PCR), Western blot, and immunohistochemical analyses measured expression levels of cytochrome P450 (CYP) isoforms in the liver and P-glycoprotein (P-gp) in the jejunum. TEC significantly decreased florfenicol's AUC(0-infinity), MRT(0-infinity), t 1/2z, Vz/F, and C max by 24.75%, 18.43%, 55.47%, 43.05%, and 19.48%, while increasing CLz/F by 33.33%. TEC also up-regulated hepatic CYP1A2 and CYP3A1 mRNA expression, as well as intestinal MDR1, by 1.39-fold, 1.85-fold, and 1.65-fold. This coincided with a respective increase in protein expression by 1.37-fold, 1.39-fold, and 1.43-fold. These findings suggest that TEC-induced alterations in the pharmacokinetics of florfenicol may be attributed to increased CYP and P-gp expression. Further investigations are warranted to understand the implications of these findings on the clinical effectiveness of florfenicol in veterinary practice.