1.Comparison of the efficacy and safety of vedolizumab versus infliximab in Bio-naive patients with ulcerative colitis
Duidui YAO ; Feixue LI ; Jiaqi WU ; Xiaobing LIU ; Hongping WEN
China Pharmacy 2026;37(10):1307-1312
OBJECTIVE To compare the efficacy and safety of vedolizumab (VDZ) versus infliximab (IFX) in biologic-naive(Bio-naive) patients with moderate-to-severe active ulcerative colitis (UC), and to analyze the factors influencing efficacy. METHODS Clinical data were retrospectively collected from Bio-naive patients with moderate-to-severe active UC who received treatment in the Department of Gastroenterology at Shanxi Provincial People’s Hospital from June 2023 to June 2024. Based on the type of biologic agent administered, the patients were divided into the IFX group (41 cases) and the VDZ group (30 cases). Patients in the two groups received IFX (5 mg/kg) or VDZ (300 mg) for induction and maintenance of remission therapy. The two groups were compared regarding modified Mayo score, serological indicators (hemoglobin, albumin, platelet count, erythrocyte sedimentation rate, C-reactive protein), combined medication, efficacy-related indexes (clinical response rate/remission rate, and endoscopic response rate/remission rate), and the occurrence of adverse drug reactions (ADR). Based on Logistic regression model, univariate and multivariate analyses were conducted to identify potential factors influencing clinical remission at week 14 and endoscopic remission at week 38. RESULTS There were no statistically significant differences in clinical response rate/remission rate, or endoscopic response rate/remission rate between the two groups at weeks 14 and 38 ( P >0.05). However, at week 14 of treatment, the proportion of patients using concomitant corticosteroids in VDZ group was 26.67%, significantly higher than the 7.50% in IFX group ( P <0.05). There was no statistical significance in the overall incidence of ADR between the two groups ( P >0.05); all ADRs in the IFX group were grade 3 and led to treatment discontinuation (6 cases), whereas ADR in the VDZ group was grade 2 and did not interrupt therapy (1 case). Univariate and multivariate regression analyses revealed that disease type (relapsing) was significantly associated with clinical remission at week 14 of treatment, and a history of smoking was significantly associated with endoscopic remission at week 38 of treatment (the odds ratios were 0.08 for both, with 95% confidence intervals of 0.01-0.77 and 0.01-0.91 respectively, P <0.05). CONCLUSIONS For Bio-naive patients with moderate-to-severe active UC, VDZ and IFX demonstrate comparable efficacy in inducing and maintaining clinical remission and promoting mucosal healing, as well as overall safety. Although IFX can achieve faster control of inflammation in the early stage of the disease, it causes more severe ADR. Disease type (relapsing) and smoking history are identified as independent negative predictors for short-term clinical remission and long-term endoscopic remission, respectively.
2.Semaphorin 3A promotes pathological cardiac hypertrophy: an experimental study
Lifei WU ; Jiaojiao ZHANG ; Xing ZHANG ; Donghang LI ; Hongbo WANG ; Jimin CAO
Acta Universitatis Medicinalis Anhui 2026;61(7):1215-1222
ObjectiveTo investigate the effect of Semaphorin 3A (Sema3A) on the progression of pathological cardiac hypertrophy. MethodsWild-type C57BL 6J mice, Sema3A global overexpressing (Sema3A/Cre-ERTM) mice, and their littermate controls (Cre-ERTM) were used, with 6 mice per group. A pressure-overload induced cardiac hypertrophy model was established via transverse aortic constriction (TAC), with a sham-operated group (Sham) as the control. Cardiac hypertrophy was assessed by gross morphology, heart weight/body weight ratio (HW/BW), heart weight/tibia length ratio (HW/HL), and heart weight/lung weight ratio (HW/PW). Cardiac function was evaluated by measuring ejection fraction (EF) and fractional shortening (FS) via echocardiography. In heart tissues, the mRNA level of atrial natriuretic peptide (ANP) and Sema3A were detected by RT-qPCR, Sema3A protein level was detected by western blot, morphological structure was detected by hematoxylin and eosin (HE) staining, level of fibrosis was detected by Masson’s trichrome staining, and angiogenesis was detected by immunohistochemical detection of CD31. For in vitro experiments, rat H9C2 cardiomyocytes were treated with angiotensin Ⅱ (Ang Ⅱ) to induce hypertrophy, with PBS-treated cells as the control. After 48 hours, the mRNA expression of ANP, B-type natriuretic peptide (BNP) and Sema3A were measured by RT-qPCR, and Sema3A protein level was assessed by western blot. ResultsAt the animal level, compared with the sham group, mice subjected to TAC showed significantly increased mRNA levels of ANP in cardiac tissue, as well as markedly elevated mRNA and protein levels of Sema3A (all P<0.05). Compared with the Cre-ERTM + TAC group, the Sema3A/Cre-ERTM + TAC group exhibited more pronounced cardiac hypertrophy, greater ventricular wall thickening, higher HW/BW, HW/HL, and HW/PW ratios, more significant reductions in EF and FS, more severe cardiac fibrosis, and a significant decrease in cardiac CD31 expression levels (all P<0.05). At the cellular level, compared with the control group, H9C2 cells treated with Ang Ⅱ displayed significantly increased mRNA levels of ANP and BNP, along with markedly elevated mRNA and protein levels of Sema3A (all P<0.05). ConclusionSema3A promotes the progression of pressure overload-induced cardiac hypertrophy by inhibiting angiogenesis.
3.Analysis of Animal Models of Allergic Asthma Based on Data Mining
Han WU ; Zhixiang HU ; Meiqi JI ; Hao YIN ; Yu'e LYU ; Chuntao ZHAI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):211-217
ObjectiveTo provide a basis for the establishment of an ideal animal model of allergic asthma by statistically analyzing the modeling characteristics and the selection of indicators of the available models. MethodsWe retrieved the relevant articles from China National Knowledge Infrastructure(CNKI), VIP, Wanfang Data, SinoMed, and PubMed with "allergic asthma" as the keyword and the time interval from January 2019 to January 2024. Through integrating the literature and extracting data, we used Excel 2021 to create a personal database and sorted out the animal strains, genders, allergenic substances, modeling routes, and test indicators and methods. Excel 2021, Cytoscape 3.10.2, and SPSS Modeler 18.0 were then used to analyze the relevant characteristics of the animal models. ResultsA total of 418 articles were included in the database, and the comparative analysis showed that the most frequently used animal strain for modeling was BALB/c mice, and female animals were mostly used. The main modeling method was sensitization by intraperitoneal injection of ovalbumin (OVA), which was combined with intranasal inhalation. The test indicators mainly included appearance signs, cellular analysis, lung histopathology, lung function indicators, and protein and gene expression in the lung. The test methods mainly involved pathological staining, enzyme-linked immunosorbent assay, immunohistochemistry, immunofluorescence, Western blot, and polymerase chain reaction(PCR) assays. ConclusionThere is no recognized modeling method or evaluation standard for the animal models of allergic asthma. Based on the results of data analysis, the OVA-induced allergic asthma model in BALB/c mice is recommended. The main criteria for evaluating the success of modeling are the general behavioral changes, the morphological changes of the airway and inflammatory cell infiltration in the lung tissue, the changes of pro-inflammatory and anti-inflammatory cytokines in the serum, and the alterations of inflammatory cells in the bronchoalveolar lavage fluid.
4.Effect and mechanism of embryonic intervention with Zuogui pill on the glucose tolerance in offsprings of pregnant rats with gestational diabetes mellitus
Min YANG ; Yujie WU ; Kainan SUN ; Yonghui WANG ; Chaoqun WANG ; Kaixia XU
China Pharmacy 2025;36(16):1981-1987
OBJECTIVE To explore the effect and mechanism of embryonic intervention with Zuogui pill on the glucose tolerance in offsprings of pregnant rats with gestational diabetes mellitus. METHODS Pregnant rats were randomly divided into blank group, model group, positive control group (insulin glargine), Zuogui pill low-, medium- and high-dose groups (4.725, 9.45, 18.9 g/kg). In addition to the blank group, streptozotocin was injected intraperitoneally to establish a gestational diabetes mellitus rat model. From day 6 to day 18 of pregnancy, each group was given relevant medicine and distilled water intragastrically, once a day. After 21 days of birth, the body weight and body length of offsprings were recorded, and the area under the curve (AUC) was calculated through a glucose tolerance test. After 22 days of birth, fasting blood glucose (FBG), fasting insulin (FINS) levels in serum, insulin sensitivity index (ISI), and homeostasis model assessment of insulin resistance (HOMA-IR) were measured, and the morphological structure of pancreatic tissue was observed. The protein spectrum of pancreatic tissue was analyzed by tandem mass tag-based proteomics, and protein and mRNA expression levels of apolipoprotein A1(ApoA1), solute carrier family 27 member 1 (Slc27a1), kininogen 1(Kng1) and sodium/potassium-transporting ATPase subunit alpha 2 (Atp1a2), solute carrier family 7 member 5 (Slc7a5), solute carrier family 3 member 2 (Slc3a2), bile acid-coenzyme A: amino acid N- acyltransferase (Baat), eukaryotic translation initiation factor 2 subunit gamma (Eif2s3) were detected. RESULTS Compared with the model group, the body weight, body length and ISI of offsprings in the positive control group and Zuogui pill medium-dose group were significantly increased (P<0.05), while the glucose tolerance and islet cell proliferation were significantly improved, and the AUC, FBG, FINS and HOMA-IR were significantly decreased (P<0.05). There were 88 potential target proteins for the embryonic intervention of Zuogui pill in offsprings of pregnant rats with gestational diabetes mellitus,involving multiple pathways such as peroxisome proliferator-activated receptor (PPAR), cyclic guanosine monophosphate-protein kinase G (cGMP-PKG), fat digestion and absorption, and bile secretion. The proteins closely related to glucose metabolism and insulin resistance mainly included ApoA1, Slc27a1, Kng1, Atp1a2, Slc7a5, Slc3a2, Baat, and Eif2s3. Among them, compared with the model group, protein and mRNA expressions of Slc7a5, Slc3a2, and Baat in the pancreatic tissues of pregnant rat offsprings in the Zuogui pill medium-dose group were significantly up-regulated (P<0.05); protein and mRNA expressions of ApoA1, Slc27a1, Kng1, Atp1a2 and Eif2s3 were all significantly down-regulated (P<0.05). CONCLUSIONS The intervention of Zuogui pill in the embryonic period on offsprings of pregnant rats with gestational diabetes mellitus can improve their blood glucose levels and pancreatic pathological morphology. The mechanism may be related to the upregulation of the expressions of Slc7a5, Slc3a2, and Baat and the down-regulation of ApoA1, Slc27a1, Kng1, Atp1a2 and Eif2s3 expressions in the PPAR, cGMP-PKG, fat digestion and absorption, and bile secretion pathways.
5.Effects of peripheral blood-derived exosomes intervened by Naozhenning on injury of neuron induced by microglia
Li GAO ; Le ZHAO ; Liya WU ; Weiyi ZHANG ; Nan LI ; Nannan WEI ; Yonghui WANG
China Pharmacy 2025;36(19):2393-2398
OBJECTIVE To study the effects of peripheral blood-derived exosomes (Exo) intervened by Naozhenning (NZN) on injury of neuron cells HT22 induced by microglia BV-2 cells. METHODS Wistar rats were selected to prepare peripheral blood- derived Exo intervened by NZN (66.83 g/kg), referred to as NZN-Exo; peripheral blood-derived Exo intervened by normal saline and piracetam (PLXT, 1.62 g/kg) were prepared using the same method, denoted as KB-Exo and PLXT-Exo respectively, and all Exo were subsequently identified. Meanwhile, BV-2 cells were stimulated with 1 μg/mL lipopolysaccharide (LPS) to prepare LPS- stimulated supernatant, and non-LPS-stimulated supernatant was prepared following the same protocol. HT22 cells were divided into four groups: KB-Exo group (treated with non-LPS-stimulated supernatant+KB-Exo), model group (treated with LPS-stimulated supernatant+KB-Exo), PLXT-Exo group (treated with LPS-stimulated supernatant+PLXT-Exo), and NZN-Exo group (treated with LPS-stimulated supernatant+NZN-Exo), with the concentration of the corresponding Exo in all groups being 50 μg/mL. After 24 hours of culture, the proliferation of HT22 cells was detected by the CCK-8 assay and EdU assay; the apoptosis of HT22 cells was detected; the microstructure of HT22 cells was observed; the contents of interleukin-1β (IL-1β), IL-10, nuclear factor-κB (NF- κB), and tumor necrosis factor-α (TNF-α) in HT22 cells were measured, as well as the expression levels of TNF-α, NOD-like receptor thermal protein domain associated protein 3 (NLRP3), Caspase-1, B-cell lymphoma-2( Bcl-2), and Bcl-2-associated X protein (Bax). RESULTS KB-Exo, PLXT-Exo and NZN-Exo were successfully prepared, and all Exo exhibited typical cup-shaped contours and membrane-enclosed characteristics. Compared with KB-Exo group, model group showed significantly decreased cell proliferation rates (detected by CCK-8 and EdU), intracellular IL-10 levels, and Bcl-2 protein expression levels (P<0.05); while the cell apoptosis rate, intracellular levels of IL-1β, TNF-α, and NF-κB, as well as the expression levels of NLRP3, TNF-α, Caspase-1, and Bax proteins were significantly increased (P<0.05). Additionally, in the model group, the cells showed volume swelling, incomplete cell membrane, nucleolar rupture, significant swelling and deformation of mitochondria, and severe vacuolization. Compared with model group, the above quantitative indicators in the PLXT-Exo group and NZN-Exo group were significantly reversed (P<0.05), with large and round cell nuclei, intact nuclear membranes, and reduced mitochondrial vacuolization. CONCLUSIONS Peripheral blood-derived Exo intervened by naozhenning can alleviate the injury of neuronal cells HT22 by inhibiting inflammatory responses and cell apoptosis.
6.Effects of electroacupuncture at changbing fang on autophagy of colonic cells and gut microbiota in ulcerative colitis of rats.
Huichao XU ; Tian WU ; Jianheng HAO ; Ronglin WU ; Bingbei YAN ; Haijun WANG ; Laixi JI
Chinese Acupuncture & Moxibustion 2025;45(5):657-669
OBJECTIVE:
To observe the effects of electroacupuncture (EA) at changbing fang (prescription for intestinal disease) on autophagy of colonic cells and gut microbiota in rats with ulcerative colitis (UC), and to explore the mechanism of EA in the treatment of UC.
METHODS:
Thirty-two SD male rats were randomly divided into a control group, a model group, an EA group and a sham-EA group, with 8 rats in each group. Except the control group, the UC rat model was established by free drinking of 5% dextran sulfate sodium solution for 7 days in the other groups. In the EA group, changbing fang was adopted, in which, EA was applied at "Tianshu" (ST25) and "Shangjuxu" (ST37), at disperse-dense wave and frequency of 10 Hz/50 Hz, for 20 min in each intervention. In the sham-EA group, shallow transcutaneous puncture was performed at the sites, 5 mm away from the points as the EA group, with the same parameters as the EA group. The intervention was delivered once daily for 3 consecutive days. The body weight was measured daily and the disease activity index (DAI) score was calculated before and after intervention. After intervention completion, the colon length was measured. Using HE staining, the colon morphology was observed and the score of colonic pathology was assessed. With ELISA adopted, the contents of tumor necrosis factor (TNF-α), interleukin (IL)-1β, IL-2 and IL-10 in the serum of the rats were detected. The ultrastructure of the colon tissue was observed under electron microscopy. Using Western blotting, the protein expression was detected for microtubule-associated protein 1 light chain 3 (LC3)Ⅱ, LC3Ⅰ, autophagy-related genes (ATG) 5, ATG12, sequestosome 1 (p62), phosphatidylinositol 3-kinase (PI3K), phosphorylated protein kinase B (p-AKT), protein kinase B (AKT), and phosphorylated mammalian target of rapamycin (p-mTOR), mammalian target of rapamycin (mTOR) in the colon tissue. The mRNA expression of PI3K, AKT and m-TOR in the colon tissue was detected by real-time fluorescence quantitative PCR. The 16S rRNA gene sequencing was used to analyze the structure of gut flora in the feces of rats.
RESULTS:
From day 1 to day 7, compared with the control group, the body weight decreased in the model group, EA group, and SEA group (P<0.05, P<0.01). From day 9 to day 10, the EA group showed an increase in body weight compared with the model group and SEA group (P<0.05, P<0.01). Before intervention, the DAI score in the model group, EA group, and SEA group was higher than the score of the control group, respectively (P<0.01). After intervention, the DAI score in the EA group was reduced compared with the model group and SEA group (P<0.01). Compared with the control group, in the model group, the colon length of rats was shorter (P<0.01); it showed the distorted crypts, thinner mucosal layer, reduced goblet cells, inflammatory cell infiltration and the disarranged histological structure; and the pathological score of the colon tissue increased (P<0.01); the serum contents of TNF-α and IL-1β increased (P<0.01), and those of IL-2 and IL-10 decreased (P<0.01). The structure of colon epithelial cells was disarranged, with cilia pelt off, and a large number of vacuoles in the cytoplasm; the mitochondria were swollen, with unclear structure and cristae partially disappeared; and few autophagosomes were observed. The value of LC3Ⅱ/LC3Ⅰand the protein expression of ATG5 and ATG12 in the colon tissues were reduced (P<0.01), the protein expression of p62 and PI3K, and the values of p-AKT/AKT, and p-mTOR/mTOR increased (P<0.01), and mRNA expression of PI3K, AKT and mTOR was elevated (P<0.01). The indexes of Chao1, Ace and Shannon decreased (P<0.01). At the phylum level, the relative abundance of Firmicutes decreased (P<0.05), that of Bacteroidetes and Proteobacteria increased (P<0.05, P<0.01). At the genus level, the relevant abundance of Lactobacillus decreased (P<0.05), while that of Lachnospiraceae_NK4A136_group and Phascolarctobacterium increased (P<0.01, P<0.05 ). Compared with the model group and SEA group, in the EA group, the colon length increased (P<0.01), the infiltration of inflammatory cells was reduced, the arrangement of intestinal epithelial cells was arranged regularly, with a small amount of shedding, and the pathological score of the colon tissue decreased (P<0.01). The serum contents of TNF-α and IL-1β decreased (P<0.01), and those of IL-2 and IL-10 increased (P<0.01). The colonic epithelial cells were arranged relatively, the morphology of organelles was basically normal, and autophagosomes were visible. The value of LC3Ⅱ/LC3Ⅰand the protein expression of ATG5 and ATG12 in colon tissue increased (P<0.01, P<0.05), the protein expression of p62 and PI3K, and the values of p-AKT/AKT, and p-mTOR/mTOR decreased (P<0.01); and mRNA expression of PI3K, AKT, m-TOR was reduced (P<0.01). The indexes of Chao1, Ace and Shannon increased (P<0.01). At the phylum level, the relative abundance of Firmicutes increased (P<0.01), while that of Bacteroidetes decreased (P<0.01). At the genus level, the relative abundance of Lactobacillus increased (P<0.05), whereas that of Lachnospiraceae_NK4A136_group decreased (P<0.01). When compared with the model group, the relative abundance of Proteobacteria decreased (P<0.05), and that of Phascolarctobacterium was reduced (P<0.05) in the EA group.
CONCLUSION
EA at changbingfang alleviates UC symptoms probably through inhibiting the PI3K/AKT/mTOR signaling pathway to regulate colonic autophagy and improve the intestinal flora.
Animals
;
Electroacupuncture
;
Colitis, Ulcerative/metabolism*
;
Male
;
Rats
;
Gastrointestinal Microbiome
;
Rats, Sprague-Dawley
;
Colon/metabolism*
;
Humans
;
Autophagy
;
Acupuncture Points
;
Tumor Necrosis Factor-alpha/genetics*
;
Interleukin-10/genetics*
7.Effect of Naozhenning Granules on Energy Metabolism of Cortical Mitochondria in Rat Model of Post-concussion Syndrome
Nannan WEI ; Liya WU ; Tiantian WANG ; Qizhao LIU ; Weiyi ZHANG ; Yonghui WANG ; Li GAO ; Le ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(14):107-113
ObjectiveTo explore the effects of Naozhenning granules on the memory function and neuron cells in the rat model of post-concussion syndrome based on mitochondrial biosynthesis. MethodSPF-grade Wistar rats were used to establish the multiple cerebral concussion (MCC) model by the weight-drop method. The successfully modeled rats were assigned into model, piracetam (0.324 g·kg-1), and low-, medium-, and high-dose (2.25, 4.5, and 9 g·kg-1, respectively) Naozhenning groups. The rats were administrated with corresponding drugs by gavage and those in the blank group and model group were administrated the same volume of normal saline once a day for 14 days. The general state of rats was observed before and after treatment. The open field test and new object recognition test were conducted to examine the motor and memory abilities of rats. Hematoxylin-eosin staining was employed to observe the pathological changes of cortical neurons in rats. Western blot and real-time polymerase chain reaction were employed to determine the protein and mRNA levels, respectively, of peroxisome proliferator-activated receptor γ-coactivator-1α (PGC-1α), nuclear respiratory factor-1 (NRF-1), and transcription factor A mitochondrial (TFAM) in rat cortex. ResultCompared with the blank group, the model group showed anxious and manic mental status, yellow and messy fur, and reduced food intake. In the open field experiment, the model group showed reduced total movement distance, times of entering the central grid, and times of rearing decreased and increased resting time compared with the blank group (P<0.01). The model group had lower recognition index of new objects than the blank group (P<0.01). In addition, the modeling caused reduced neurons with sparse distribution and deformed, broken, and irregular nucleoli and down-regulated the mRNA and protein levels of PGC-1α, NRF-1, and TFAM in the cortex (P<0.01). Compared with the model group, piracetam and Naozhenning improved the mental state, coat color, food intake, and activities of rats. In the open field test, piracetam and Naozhenning increased the total movement distance, the times of entering the central grid, and the times of rearing and shortened the resting time (P<0.05, P<0.01). The piracetam and Naozhenning groups had higher recognition index of new objects than the model group (P<0.05, P<0.01). Compared with the model group, the piracetam and Naozhenning groups showed increased neurons with tight arrangement and large and round nuclei, and some cells with irregular morphology and turbid cytoplasm. Furthermore, piracetam and medium-dose Naozhenning upregulated the protein levels of PGC-1α, NRF-1, and TFAM (P<0.01). Low-dose Naozhenning upregulated the protein levels of NRF-1 and TFAM (P<0.01), and high-dose Naozhenning upregulated the protein levels of PGC-1α and TFAM in the cortex (P<0.01). The mRNA levels of PGC-1α, NRF-1, and TFAM in the cortex were upregulated in the piracetam group and Naozhenning groups (P<0.05, P<0.01). ConclusionNaozhenning granules can improve the motor, memory, and learning, repair the neuronal damage, and protect the nerve function in the rat model of MCC by promoting mitochondrial biosynthesis.
8.Mechanism of Naozhenning granules in regulating mitochondrial energy metabolism in multiple cerebral concussion rats
Li GAO ; Le ZHAO ; Nannan WEI ; Liya WU ; Tiantian WANG ; Weiyi ZHANG ; Yonghui WANG
China Pharmacy 2024;35(9):1050-1056
OBJECTIVE To explore the mechanism of Naozhenning granules in regulating mitochondrial energy metabolism in hippocampal tissue of multiple cerebral concussion (MCC) model rats. METHODS SPF grade Wistar rats were used to prepare MCC models using the “free fall impact method”. The successfully modeled rats were divided into model group, piracetam group, and Naozhenning granule low-dose, medium-dose and high-dose groups, and a normal group was also set up, with 8 rats in each group. Rats in each treatment group orally administered corresponding drugs at doses of 0.324 g/kg for the piracetam group and 2.25, 4.5 and 9 g/kg for the Naozhenning granule low-dose, medium-dose and high-dose groups; the normal group and model group were given equal volumes of normal saline; once a day, for 14 consecutive days. The motor exploration ability, learning and memory ability of rats were tested; the adenosine triphosphate (ATP) content in the hippocampal tissue of rat was detected; the changes in the mitochondrial structure of hippocampal tissue was observed; the fluorescence intensity of mitochondrial dynamin- related protein 1 (Drp1), mitochondrial fission protein 1 (Fis1), mitochondrial fusion 1 (Mfn1), and optic atrophy protein 1 (Opa1) were detected in the hippocampal tissue of rat; the protein expression levels of peroxisome proliferator activated receptor gamma coactivator-1α(PGC-1α), nuclear respiratory factor-1(NRF-1),mitochondrial transcription factor A(TFAM), Wnt-3a,β-catenin in hippocampal tissue of rat were detected. RESULTS Compared with the normal group, the total exercise distance, number of central grid entries, number of upright positions, new object recognition index, mitochondrial ATP content, fluorescence intensity of Mfn1 and Opa1, the protein expression levels of PGC-1α、NRF-1、TFAM、Wnt-3a、 β-catenin in the model group were significantly reduced (P<0.01), while the rest time and fluorescence intensity of Drp1 and Fis1 in hippocampal tissue were significantly increased (P<0.01). The results of transmission electron microscopy showed that the mitochondria in the hippocampal tissue were significantly swollen, with a large number of broken and reduced cristae, and some mitochondria had myeloid changes in the membrane. Compared with the model group, the levels/contents of the above indicators in rats of each administration group showed varying degrees of reversal, and most of the differences were statistically significant (P<0.05 or P<0.01); the degree of mitochondrial swelling in the hippocampal tissue was reduced, with a small amount of broken and reduced cristae, fuzzy fractures appeared in local areas of the rough endoplasmic reticulum. CONCLUSIONS Naozhenning granules can improve the motor exploration, learning and memory abilities of MCC model rats, repair neuronal damage, and exert neuroprotective effects. Its mechanism may be related to activating Wnt/β-catenin signaling pathway,maintaining the balance of mitochondrial division and fusion,and promoting mitochondrial biosynthesis.
9.Anti-fatigue activity of selenium nanoparticles functionalized by polysaccharides from Pleurotus tuber-regium sclerotium
Si ZOU ; Yanbin WU ; Jinzhong WU ; Jianguo WU ; Jiaxing HUANG
Journal of Pharmaceutical Practice and Service 2024;42(10):426-432
Objective To investigate the anti-fatigue effect of PTR-SeNPs in vivo by measuring the muscle relative length of hindlimb,load-bearing swimming time as well as serum and liver indexes of mice.Methods 48 male C57/BL6 mice were randomly assigned into 4 groups with 12 mice in each group,including vehicle control group(control group),swimming training exercise group(EC group)with vehicle treatment,swimming training exercise with low dose of PTR-SeNPs group(LPTR-SeNPs)and high dose of PTR-SeNPs group(HPTR-SeNPs).The mice were intragastrically administrated with normal saline in both control group and EC group,as well as 2.5 and 10 μmol/(kg·bw)PTR-SeNPs in LHPTR-SeNPs group,respectively,once per day for consecutively 21 days.After swimming training exercise,the muscle structures in the hind limb of mice were examined by magnetic resonance imaging.Furthermore,the burdened swimming time was measured,the serum content of blood lactic acid(BLA),urea nitrogen(BUN),alanine aminotransferase(ALT),glutamic oxalate aminotransferase(AST)and lactate dehydrogenase(LDH),as well as the hepatic level of glycogen(HG),malondialdehyde(MDA)and activity of catalase(CAT)and superoxide dismutase(SOD)were determined.Results Compared with the control group,the serum contents of BLA,BUN,ALT,AST and LDH in EC group(P<0.05 or P<0.01)and hepatic CAT in HPTR-SeNPs group(P<0.01)were significantly increased.The muscle relative length of hind limbs and the burdened swimming time were extended by HPTR-SeNPs markedly(P<0.05).There was no significant difference in MDA level in LHPTR-SeNPs group.Compared with EC group,the burdened swimming time of mice was significantly prolonged(P<0.01),the contents of BLA and BUN were obviously decreased in the HPTR-SeNPs group(P<0.05 or P<0.01),the level of HG was significantly increased in the LHPTR-SeNPs groups(P<0.05 or P<0.01),the serum content of ALT,AST and LDH were markedly decreased in the HPTR-SeNPs group(P<0.05 or P<0.01).Hepatic SOD activity was remarkably increased in LPTR-SeNPs group(P<0.05),the level of CAT was evidently increased(P<0.01)and AST was decreased(P<0.05)in the HPTR-SeNPs group.Conclusion PTR-SeNPs could improve the liver physiological function,increase glycogen storage,reduce the accumulation of metabolites and enhance the body's antioxidant capacity to ameliorate fatigue significantly,which could present the potential to be developed into health care products or drugs.
10.Role and mechanism of action of Yinchenhao Decoction in inhibiting ferroptosis of hepatocytes in mice with autoimmune hepatitis
Zhurong LI ; Chen CHEN ; Di GUO ; Sixue LYU ; Jiawen WU ; Na YANG ; Yang LIU
Journal of Clinical Hepatology 2024;40(3):502-508
ObjectiveTo investigate the role and mechanism of action of Yinchenhao Decoction in inhibiting ferroptosis of hepatocytes in mice with autoimmune hepatitis. MethodsA total of 18 specific pathogen-free female C57BL/6 mice were selected and divided into normal group, model group, and treatment group using a random number table, with 6 mice in each group. The mice in the model group and the treatment group were injected with concanavalin A (Con A) via the caudal vein to establish a mouse model of autoimmune hepatitis, and those in the normal group were injected with normal saline. The mice in the treatment group were given prophylactic treatment with Yinchenhao Decoction (4.68 g crude drug/kg) by gavage at 14 days before modeling, and Con A was injected after the last gavage. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), interferon gamma (IFN-γ), tumor necrosis factor-α (TNF-α), iron ion, glutathione (GSH), reactive oxygen species (ROS), adenosine triphosphate (ATP), and malondialdehyde (MDA) were measured; liver index and spleen index were calculated; the expression levels of GPX4 and SLC7A11 were measured; liver histopathological changes were compared between groups. A one-way analysis of variance was used for comparison of normally distributed continuous data between three groups, and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the normal group, the model group had significant increases in liver index, spleen index, ALT, AST, IFN-γ, TNF-α, iron ion, ROS and MDA (all P<0.05) and significant reductions in the content of GSH and ATP and the protein expression levels of GPX4 and SLC7A11 (all P<0.05). Compared with the model group, the treatment group had significant reductions in liver index, spleen index, ALT, AST, IFN-γ, TNF-α, iron ion, ROS and MDA (all P<0.05) and significant increases in the content of GSH and ATP and the protein expression levels of GPX4 and SLC7A11 (all P<0.05). HE staining showed that compared with the normal group, the model group showed massive hepatocyte degeneration and necrosis and inflammatory cell aggregation at the portal area, and compared with the model group, the treatment group had alleviation of liver necrosis and inflammatory infiltration. ConclusionLiver injury induced by Con A may be associated with ferroptosis. Yinchenhao Decoction can increase the protein expression levels of SLC7A11 and GPX4 protein and thus inhibit ferroptosis of hepatocytes induced by Con A.

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