Clinical Implications of Interleukin-4 and C-reactive Protein in Atopic Dermatitis and Their Changes Before and after Dupilumab Treatment.

Objective: To analyze the clinical implications of C-reactive protein (C-reactive protein) and interleukin-4 (IL-4) in atopic dermatitis and their correlations with the therapeutic effect of Dupilumab (DU). Methods: Seventy-four cases of atopic dermatitis (intervention group) were admitted to Xingtai Third Hospital between May 2021 and January 2023, and 55 concurrent healthy controls (control group) were selected as research participants. Atopic dermatitis patients were treated with a DU injection of 600 mg for the first time after diagnosis. Peripheral blood IL-4 and C-reactive protein levels before and after treatment in the intervention group and their levels at admission in the control group were comparatively analyzed, and their predictive value for the occurrence, clinical efficacy, and adverse reactions of atopic dermatitis were determined. Additionally, alterations in C-reactive protein and IL-4 levels before and after treatment in the intervention group and their relationship with the Scoring Atopic Dermatitis (SCORAD) index were discussed. Results: The intervention group exhibited higher C-reactive protein and IL-4 levels than the control group. The diagnostic sensitivity and specificity of C-reactive protein + IL-4 detection for atopic dermatitis were 74.32% and 94.55%, respectively (P < .05). The post-treatment C-reactive protein and IL-4 were lower in the intervention group, and the test results were positively correlated with SCORAD before and after treatment (P < .05). In addition, C-reactive protein + IL-4 detection showed excellent predictive effects on the therapeutic efficacy of DU and adverse reactions. Conclusions: IL-4 and C-reactive protein are closely related to atopic dermatitis, which can be used as the evaluation indexes for disease development of atopic dermatitis and therapeutic effects of DU in the future.

Effects of Astragalus, Epimedium, and Fructus Ligustri Lucidi extractive on antioxidant capacity, production performance, and immune mechanism of breeding pigeons under stress.

With the large-scale and intensive development of pigeon breeding industry and the improvement of production level, stress factors have an important impact on the immune, antioxidant capacity, and productivity of pigeons. In this study, the extenuating effect of Astragalus, Epimedium, and Ligustrum lucidum (AEF) on the antioxidant, production performance, and immune mechanism was investigated in breeding pigeons. Eighty pairs of 11-month-old healthy breeding pigeons with the same egg production batch were randomly divided into 4 groups: control group (C group), treated with AEF (AEF group), in restraint stress (S group) and treated with AEF and in restraint stress (S+AEF group). Results showed that AEF reduces weight loss during lactation and increases spleen weight, increased IgA, IgG, T4, GSH-Px, and SOD in serum and decreased T3 and MDA (P < 0.05). Furthermore, treatment with AEF declined HSP60, HSP70, HSP90, GR levels in liver and cFOS, GR mRNA levels in the Hypothalamus, GR mRNA levels in the pituitary (P < 0.05). Meanwhile, the results of the intestine studies showed that AEF promoted relative abundances of Firmicutes and relieve intestinal injury in the colon of pigeons. These results indicated AEF enhanced stress resistance, immunity, production performance and antioxidant capacity of pigeons.

Terrestrosin D, a spirostanol saponin from Tribulus terrestris L. with potential hepatorenal toxicity.

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Tribuli (FT) has been commonly used as a traditional medicine for thousands of years. With the diverse uses of FT, more attention has been paid to its hepatorenal toxicity. However, the compounds causing the hepatorenal toxicity of FT remain undetermined. Terrestrosin D (TED), a major spirostanol saponin isolated from FT, may exert hepatorenal toxicity. AIM OF THE STUDY: This study aimed to evaluate the potential hepatorenal toxicity of TED, and preliminarily explore the possible mechanism of TED-induced hepatorenal toxicity. MATERIALS AND METHODS: Cytotoxicity assays, a repeated-dose 28-day in-vivo study, a toxicokinetic study, and a tissue distribution study were used to evaluate the potential hepatorenal toxicity of TED. Furthermore, network pharmacology was applied to preliminarily explore the possible mechanism of TED-induced hepatorenal toxicity. RESULTS: Both the in vitro and in vivo studies showed that the spirostanol saponin TED had potential hepatorenal toxicity. Nonetheless, hepatorenal toxicity induced by oral treatment with TED at a dosage range of 5 - 15 mg/kg daily for 28 consecutive days to Sprague-Dawley (SD) rats was reversible after 14 days of TED withdrawal. The toxicokinetic study demonstrated that the systematic exposure of SD rats to TED had an accumulation phenomenon and a dose-dependent trend after a 28-day repeated-dose oral administration. The tissue distribution study revealed that TED had a targeted distribution in the liver and kidneys accompanied by a phenomenon of accumulation in SD rats. Network pharmacology combined with molecular docking methods was used to screen for the key targets (HSP90AA1, CNR1, and DRD2) and the key pathways of TED-induced hepatorenal toxicity. CONCLUSIONS: The spirostanol saponin TED, a major spirostanol saponin isolated from FT, had potential hepatorenal toxicity.

Pharmacokinetic comparisons of six steroid saponins in rat plasma following oral administration of crude and stir-fried Fructus Tribuli extracts by UHPLC-MS/MS.

Modern pharmacological studies have shown that Fructus Tribuli can improve sexual function and treat cardiovascular diseases. In this study, we focused on comparing the pharmacokinetics of crude Fructus Tribuli (CFT) and stir-fried Fructus Tribuli (SFT) to further clarify the changes in chemical composition in vivo. The quantitation of six analytes was performed in a triple quadrupole mass spectrometer using the multiple reaction monitoring mode. Separation was performed on a Halo® C18 column using 0.05% formic acid and 5 µmol/L sodium formate in water, and 0.05% formic acid and 5 µmol/L sodium formate in acetonitrile as the mobile phase. The selectivity, precision, accuracy, extraction recovery, matrix effect and stability of the method were fully validated. Compared with the crude group, the parameters Cmax and AUC0-t of terrestroside B and terrestrosin K increased significantly (P < 0.05), but the Cmax and AUC0-t of polianthoside D, terrestrinin D, tribuluside A and terrestrosin D were decreased, terrestrosin D being especially decreased (P < 0.05), after oral administration of SFT extract. These results showed that the developed method was suitable for pharmacokinetic analysis of the six steroid saponins of CFT and SFT in rat plasma, and can be used to facilitate future clinical studies.

Study on the Potential Mechanism of Fructus Tribuli in the Treatment of Hypertensive Vascular Remodeling Based on Network Pharmacology and Molecular Docking.

BACKGROUND: Hypertensive vascular remodeling (HVR) is the pathophysiological basis of hypertension, which is also an important cause of vascular disease and target organ damage. Treatment with Fructus Tribuli (FT), a traditional Chinese medicine, has a positive effect on HVR. However, the pharmacological mechanisms of FT are still unclear. Therefore, this study aimed to reveal the potential mechanisms involved in the effects of FT on HVR based on network pharmacology and molecular docking. MATERIALS AND METHODS: We selected the active compounds and targets of FT according to the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the Swiss Target Prediction database, and the targets of HVR were collected from the Online Mendelian Inheritance in Man (OMIM), GeneCards, and DrugBank databases. The protein-protein interaction network (PPI) was established using the STRING database. Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses and network analysis were performed to further explore the potential mechanisms. Finally, molecular docking methods were used to evaluate the affinity between the active compounds and the main target. RESULTS: Seventeen active compounds of FT and 164 potential targets for the treatment of HVR were identified. Component-target and PPI networks were constructed, and 12 main active components and 33 main targets were identified by analyzing the topological parameters. Additionally, GO analysis indicated that the potential targets were enriched in 483 biological processes, 52 cellular components, and 110 molecular functions. KEGG analysis revealed that the potential targets were correlated with 122 pathways, such as the HIF-1 signaling pathway, ErbB signaling pathway, and VEGF signaling pathway. Finally, molecular docking showed that the 12 main active components had a good affinity for the top five main targets. CONCLUSION: This study demonstrated the multiple compounds, targets, and pathway characteristics of FT in the treatment of HVR. The network pharmacology method provided a novel research approach to analyze potential mechanisms.

[Study on transformation rules of terrestrosin D in course of Tribuli Fructus stir-frying based on simulated processing technology].

The contents of terrestrosin D and hecogenin from Tribuli Fructus were determined before and after stir-frying. The results showed that the content of terrestrosin D was decreased significantly,and the content of hecogenin was increased significantly after such processing. In order to verify the inference that terrestrosin D was converted to hecogenin by stir-frying,the quantitative variation rules of terrestrosin D and hecogenin were studied by simulated processing technology,and the simulated processing product of terrestrosin D was qualitatively characterized by ultra performance liquid chromatography/time of flight mass spectrometry( UPLC-TOF/MS) to clarify its transformation process during stir-frying. The results showed that the content of terrestrosin D was decreased significantly at first and then a platform stage appeared with the prolongation of processing time at a certain temperature. Raising the stir-frying temperature could further decrease the content of terrestrosin D and delay the time that the platform stage appeared. When the processing was simulated at higher temperatures( 220 ℃ and 240 ℃),the content of hecogenin was increased gradually with the increase of processing temperature and the prolongation of processing time. In the process of stir-frying,the deglycosylation reaction of terrestrosin D to hecogenin was not completed in one step. The deglycosylation reaction occurred first at the end of the sugar chain,and then other glycosyl units in the sugar chain were sequentially removed from the outside to the inside to finally form the hecogenin. This study provides a basis for further revealing the detoxification mechanism of stir-fried Tribuli Fructus.

[Changes and mechanisms of terrestroside B and terrestrosin K in stir-frying Tribuli Fructus].

The contents of terrestroside B and terrestrosin K in Tribuli Fructus with different degree of stir-frying were determined by high performance liquid chromatography with evaporative light-scattering detector( HPLC-ELSD). The results showed that the contents of terrestroside B and terrestrosin K were increased at first and then decreased,and both of them had the highest content at the best time of heating. The results of simulated processing of Tribulus Terrestris saponins showed that when the processing time kept constant,the contents of terrestroside B and terrestrosin K were decreased gradually with the increase of processing temperature from 180 ℃ to240 ℃. At a certain temperature,the content of terrestrosin K was increased first and then decreased with the prolongation of processing time,and reached the highest level at 5 min. However,the content of terrestroside B was increased first and then decreased with the increase of processing time only at 180 ℃,and reached the highest level at 10 min. When the processing temperature was controlled at200,220 and 240 ℃ respectively,the content of terrestroside B was decreased gradually with the increase of processing time. The simulated processing products of tribuluside A,terrestroside B and terrestrosin K were qualitatively characterized by ultra-performance liquid chromatography-time of flight mass spectrometry( UPLC-TOF/MS). It was proved that tribuluside A and terrestrosin Ⅰ containing C-22-OH were dehydroxylated in the processing of Tribuli Fructus and transformed respectively into terrestroside B and terrestrosin K containing C-20-C-22 double bond. As a result,the contents of terrestroside B and terrestrosin K were increased. The sugar chains at C-3 and C-26 positions of terrestroside B and terrestrosin K could be deglycosylated and converted into monosaccharide chain saponins and short sugar chain saponins,so the contents of terrestroside B and terrestrosin K were reduced. The study provides reference for further revealing the processing principle of Tribuli Fructus.