1.Buzhong Yiqitang Regulates Mitochondrial Homeostasis of Skeletal Muscle via PINK1 Pathways to Resist Exercise-induced Fatigue
Huani WEI ; Ting JIANG ; Juan PENG ; Chunxiang JING ; Wei LIU ; Huashan PAN ; Daorui CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):31-39
ObjectiveTo explore the effect of Buzhong Yiqitang on exercise-induced fatigue and its potential mechanism. MethodsSixty male SPF-grade C57BL/6J mice were randomized into blank, model, low-, medium-, high-dose (4.1, 8.2, 16.4 g·kg-1, respectively) Buzhong Yiqitang, and vitamin C (0.04 g·kg-1) groups. The blank and model groups were administrated with normal saline. Each group was administrated with corresponding agents by gavage at a dose of 0.2 mL once a day. Except the blank group, other groups underwent a 6-weeks exhaustive swimming test under negative gravity. At the end of the experiment, blood was collected, and the thymus, spleen, liver, and kidney weights were measured. Serum levels of lactic acid (LD), blood urea nitrogen (BUN), creatine kinase (CK), and malondialdehyde (MDA) were assessed by kits to evaluate fatigue. Hematoxylin-eosin staining was performed to observe pathological changes in the skeletal muscle. Electron microscopy was used to examine the skeletal muscle cell ultrastructure, with a focus on mitochondrial morphological changes. The adenosine triphosphate (ATP) content and activities of mitochondrial respiratory chain complexes Ⅰ, Ⅱ, and Ⅴ in skeletal muscle were determined by kits. The expression levels of key genes and proteins in the PTEN-induced putative kinase 1 (PINK1)-mediated mitochondrial homeostasis pathways in the skeletal muscle were evaluated via Real-time PCR and Western blot, respectively. ResultsCompared with the blank group, the model group showed reductions in weight gain rate (P<0.01) and thymus index (P<0.01), rises in serum levels of LD, BUN, MDA, and CK (P<0.01), disarrangement of skeletal muscle, broken muscle fibers, inflammatory cell infiltration in muscle fiber gaps, abnormal morphological changes (increased vacuolated mitochondria and disappearance of cristae) of mitochondria in skeletal muscle cells, and decreased mitochondria. In addition, the skeletal muscle in the model group showed reduced content of ATP, weakened activities of mitochondrial respiratory chain complexes Ⅰ, Ⅱ, and Ⅴ (P<0.05), up-regulated mRNA levels of PINK1, E3 ubiquitin-protein ligase (Parkin), hairy/enhancer-of-split related with YRPW motif 1 (HEY1), dynamin-related protein 1 (Drp1), sequestosome 1 (p62), and hypoxia-inducible factor 1 alpha (HIF-1α) (P<0.05), and down-regulated protein level of microtubule-associated protein 1-light chain 3B (LC3B) (P<0.01). Compared with the model group, Buzhong Yiqitang prolonged the swimming exhaustion time (P<0.01), increased the weight gain rate (P<0.01) and thymus index (P<0.01), lowered the serum levels of LD, BUN, MDA, and CK (P<0.05, P<0.01). The skeletal muscle in the Buzhong Yiqitang groups showed neat arrangement, reduced inflammatory cells, intact mitochondria with dense cristae, and increased mitochondria. In addition, the skeletal muscle in the Buzhong Yiqitang groups showcased increased ATP content, enhanced activities of mitochondrial respiratory chain complexes Ⅰ, Ⅱ, and Ⅴ (P<0.05, P<0.01), up-regulated protein levels of PINK1, Parkin, HEY1, LC3B, and Drp1 and mRNA level of HIF-1α (P<0.05, P<0.01), and down-regulated expression level of p62 (P<0.05, P<0.01). ConclusionBuzhong Yiqitang can prevent and treat exercise-induced fatigue by regulating the mitochondrial homeostasis of skeletal muscle via the HIF-1α/PINK1/Parkin and HIF-1α/HEY1/PINK1 signaling pathways.
2.Buzhong Yiqitang Regulates Mitochondrial Homeostasis of Skeletal Muscle via PINK1 Pathways to Resist Exercise-induced Fatigue
Huani WEI ; Ting JIANG ; Juan PENG ; Chunxiang JING ; Wei LIU ; Huashan PAN ; Daorui CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):31-39
ObjectiveTo explore the effect of Buzhong Yiqitang on exercise-induced fatigue and its potential mechanism. MethodsSixty male SPF-grade C57BL/6J mice were randomized into blank, model, low-, medium-, high-dose (4.1, 8.2, 16.4 g·kg-1, respectively) Buzhong Yiqitang, and vitamin C (0.04 g·kg-1) groups. The blank and model groups were administrated with normal saline. Each group was administrated with corresponding agents by gavage at a dose of 0.2 mL once a day. Except the blank group, other groups underwent a 6-weeks exhaustive swimming test under negative gravity. At the end of the experiment, blood was collected, and the thymus, spleen, liver, and kidney weights were measured. Serum levels of lactic acid (LD), blood urea nitrogen (BUN), creatine kinase (CK), and malondialdehyde (MDA) were assessed by kits to evaluate fatigue. Hematoxylin-eosin staining was performed to observe pathological changes in the skeletal muscle. Electron microscopy was used to examine the skeletal muscle cell ultrastructure, with a focus on mitochondrial morphological changes. The adenosine triphosphate (ATP) content and activities of mitochondrial respiratory chain complexes Ⅰ, Ⅱ, and Ⅴ in skeletal muscle were determined by kits. The expression levels of key genes and proteins in the PTEN-induced putative kinase 1 (PINK1)-mediated mitochondrial homeostasis pathways in the skeletal muscle were evaluated via Real-time PCR and Western blot, respectively. ResultsCompared with the blank group, the model group showed reductions in weight gain rate (P<0.01) and thymus index (P<0.01), rises in serum levels of LD, BUN, MDA, and CK (P<0.01), disarrangement of skeletal muscle, broken muscle fibers, inflammatory cell infiltration in muscle fiber gaps, abnormal morphological changes (increased vacuolated mitochondria and disappearance of cristae) of mitochondria in skeletal muscle cells, and decreased mitochondria. In addition, the skeletal muscle in the model group showed reduced content of ATP, weakened activities of mitochondrial respiratory chain complexes Ⅰ, Ⅱ, and Ⅴ (P<0.05), up-regulated mRNA levels of PINK1, E3 ubiquitin-protein ligase (Parkin), hairy/enhancer-of-split related with YRPW motif 1 (HEY1), dynamin-related protein 1 (Drp1), sequestosome 1 (p62), and hypoxia-inducible factor 1 alpha (HIF-1α) (P<0.05), and down-regulated protein level of microtubule-associated protein 1-light chain 3B (LC3B) (P<0.01). Compared with the model group, Buzhong Yiqitang prolonged the swimming exhaustion time (P<0.01), increased the weight gain rate (P<0.01) and thymus index (P<0.01), lowered the serum levels of LD, BUN, MDA, and CK (P<0.05, P<0.01). The skeletal muscle in the Buzhong Yiqitang groups showed neat arrangement, reduced inflammatory cells, intact mitochondria with dense cristae, and increased mitochondria. In addition, the skeletal muscle in the Buzhong Yiqitang groups showcased increased ATP content, enhanced activities of mitochondrial respiratory chain complexes Ⅰ, Ⅱ, and Ⅴ (P<0.05, P<0.01), up-regulated protein levels of PINK1, Parkin, HEY1, LC3B, and Drp1 and mRNA level of HIF-1α (P<0.05, P<0.01), and down-regulated expression level of p62 (P<0.05, P<0.01). ConclusionBuzhong Yiqitang can prevent and treat exercise-induced fatigue by regulating the mitochondrial homeostasis of skeletal muscle via the HIF-1α/PINK1/Parkin and HIF-1α/HEY1/PINK1 signaling pathways.
3.Study on the modeling method of general model of Yaobitong capsule intermediates quality analysis based on near infrared spectroscopy
Le-ting SI ; Xin ZHANG ; Yong-chao ZHANG ; Jiang-yan ZHANG ; Jun WANG ; Yong CHEN ; Xue-song LIU ; Yong-jiang WU
Acta Pharmaceutica Sinica 2025;60(2):471-478
The general models for intermediates quality analysis in the production process of Yaobitong capsule were established by near infrared spectroscopy (NIRS) combined with chemometrics, realizing the rapid determination of notoginsenoside R1, ginsenoside Rg1, ginsenoside Re, ginsenoside Rb1, ginsenoside Rd and moisture. The spray-dried fine powder and total mixed granule were selected as research objects. The contents of five saponins were determined by high performance liquid chromatography and the moisture content was determined by drying method. The measured contents were used as reference values. Meanwhile, NIR spectra were collected. After removing abnormal samples by Monte Carlo cross validation (MCCV), Monte Carlo uninformative variables elimination (MC-UVE) and competitive adaptive reweighted sampling (CARS) were used to select feature variables respectively. Based on the feature variables, quantitative models were established by partial least squares regression (PLSR), extreme learning machine (ELM) and ant lion optimization least squares support vector machine (ALO-LSSVM). The results showed that CARS-ALO-LSSVM model had the optimum effect. The correlation coefficients of the six index components were greater than 0.93, and the relative standard errors were controlled within 6%. ALO-LSSVM was more suitable for a large number of samples with rich information, and the prediction effect and stability of the model were significantly improved. The general models with good predicting effect can be used for the rapid quality determination of Yaobitong capsule intermediates.
4.Effectiveness of autologous platelet-rich plasma for blood conservation and its prognostic impact in patients with type A aortic dissection
Qian ZHENG ; Shoumei CHEN ; Ming XIE ; Shenshen ZHI ; Kun LIU ; Ting JIANG
Chinese Journal of Blood Transfusion 2025;38(8):1035-1042
Objective: To investigate the effects of autologous platelet-rich plasma (aPRP) collected using a continuous blood cell separator on blood conservation and prognosis in patients with type A aortic dissection. Methods: The clinical data of patients who underwent emergency aortic replacement for acute type A aortic dissection at our hospital from January 2020 to December 2023 were respectively analyzed. Patients were divided into two groups based on whether they received aPRP collection before surgery for subsequent reinfusion: the aPRP group (n=32) and the control group (n=35). The volume of aPRP collected and the platelet concentration in the aPRP were recorded. The volumes of allogeneic blood and blood products transfused, and the associated costs during hospitalization were compared between two groups. Intraoperative blood loss, perioperative laboratory parameter changes, 24-hour postoperative drainage volume, duration of ICU stay and mechanical ventilation, length of hospital stay, and mortality rate of the two groups were also compared. Results: The platelet concentration in aPRP was (491.5±85.4)×10
/L, accounting for (24.1±9.6)% of the patient's total platelet count. The volume of aPRP collected accounted for (23.0±6.3)% of the patient's total plasma volume. Compared with the control group, the aPRP group demonstrated significantly reduced transfusion volumes of allogeneic red blood cells, plasma, and platelets (P<0.05), along with significantly lower blood-related costs during hospitalization (P<0.05). Postoperative coagulation parameters (APTT, PT, INR, and TEG) were significantly improved (P<0.05), and platelet counts were markedly increased (P<0.05) in aPRP group as compared with the control group. No statistically significant differences were observed in postoperative use of prothrombin complex concentrate and fibrinogen between the two groups. Similarly, there were no significant differences in postoperative 24-hour drainage volume, 24-hour extubation rate, ICU length of stay, duration of mechanical ventilation, or total hospital length of stay. The incidence of complications and mortality did not differ significantly between the two groups. Conclusion: The administration of aPRP significantly reduces the requirement for perioperative allogeneic blood transfusion in patients undergoing surgery for type A aortic dissection. Furthermore, it enhances coagulation function and reduces associated transfusion costs, thereby establishing itself as an effective and safe strategy for blood conservation.
5.Mechanism of Shenkang injection in treatment of renal fibrosis based on bioinformatics and in vitro experimental verification
Gao-Quan MENG ; Ming-Liang ZHANG ; Xiao-Fei CHEN ; Xiao-Yan WANG ; Wei-Xia LI ; Dai ZHANG ; Lu JIANG ; Ming-Ge LI ; Xiao-Shuai ZHANG ; Wei-Ting MENG ; Bing HAN ; Jin-Fa TANG
Chinese Pharmacological Bulletin 2024;40(10):1953-1962
Aim To explore the mechanism and mate-rial basis of Shenkang injection(SKI)in the treatment of renal fibrosis(RF)by bioinformatics and in vitro experiments.Methods The differentially expressed genes of RF were screened by GEO database.With the help of CMAP database,based on the similarity princi-ple of gene expression profile,the drugs that regulated RF were repositioned,and then the components of SKI potential treatment RF were screened by molecular fin-gerprint similarity analysis.At the same time,the core targets and pathways of SKI regulating RF were predic-ted based on network pharmacology.Finally,it was verified by molecular docking and cell experiments.Results Based on the GEO database,two RF-related data sets were screened,and CMAP was relocated to three common RF therapeutic drugs(saracatinib,da-satinib,pp-2).Molecular fingerprint similarity analysis showed that RF therapeutic drugs had high structural similarity with five SKI components such as salvianolic acid B and hydroxysafflor yellow A.Molecular docking results showed that salvianolic acid B,hydroxysafflor yellow A and other components had good binding abili-ty with MMP1 and MMP13,which were the core targets of SKI-regulated potential treatment of RF.Network pharmacology analysis suggested that the core targets of SKI were mainly enriched in signaling pathways such as Relaxin and AGE-RAGE.Cell experiments showed that SKI could significantly reduce the mRNA expres-sion levels of AGER,NFKB1,COL1A1,SERPINE1,VEGFC in AGE-RAGE signaling pathway and MMP1 and MMP13 in Relaxin signaling pathway in RF model cells,and significantly increase the mRNA expression level of RXFP1.Conclusions SKI can play a role in the treatment of RF by regulating Relaxin and AGE-RAGE signaling pathways,and its material basis may be salvianolic acid B,hydroxysafflor yellow A and other components.
6.Effect of salidroside combined with rosavin on ischemic brain injury in rats
Wen-Fang LAI ; Yu-Ting JIANG ; Hui-Ling WU ; Qing-Qing WU ; Jing-Quan CHEN ; Xue-Rui ZHENG ; Gui-Zhu HONG
Chinese Pharmacological Bulletin 2024;40(12):2303-2311
Aim To study the effect of salidroside combined with rosavin on ischemic stroke in rats.Methods The model of MCAO was established by u-sing thread-embolic method.The rats were divided into the sham group,MCAO group,salidroside combined with rosavin group,positive control group,and the drug was given continuously for seven days.The infarct volume was measured by MRI and neurological deficit score was evaluated by Zea-Longa.The levels of Ne-uN,BDNF,TGF-β1,p-Smad were observed by West-ern blot and immunofluorescence staining.The expres-sions of IL-1β,TNF-α and IL-6 were performed by RT-qPCR/ELISA.The primary cortical neurons were isolated,OGD/R inducted,divided into the normal group,OGD/R group,salidroside combined with rosa-vin group,and TGF-β1 inhibitor+salidroside com-bined with rosavin group,the drug was given for 24 hours,and the expressions of NeuN,BDNF,IL-1β,TNF-α and IL-6 were measured.Results Salidroside combined with rosavin could decrease the infarct vol-ume,improve the neurological function,promote the levels of Neun,BDNF,TGF-β1,p-Smad,and inhibit the expressions of IL-1β,TNF-α and IL-6.Salidroside combined with rosavin could promote NeuN,BDNF,inhibit IL-1β,TNF-α,IL-6 in primary nerve cells in-duced by OGD/R,and these effects were blocked by TGF-β1 inhibitor.Conclusions Salidroside combined with rosavin has neuroprotective effects on MCAO rats,and primary neurons are induced by OGD/R,and these effects are closely related to the TGF-β pathway.
7.Study on Down-regulation of Interleukin-1β Secretion by Inhibiting ABCC1/MRP1 Transporter
Yuan-Yuan CHEN ; Pei-Ting YING ; Wen-Wen WENG ; Mei-Xin FANG ; Jiang LI ; Ze-Bin LUO ; Ming JIA ; Xiao-Ping GUO ; Ling-Yan ZHANG ; Xiao-Jun XU ; Yong-Min TANG
Journal of Experimental Hematology 2024;32(3):911-919
Objective:To screen interleukin(IL)-1β secretion-related membrane transporters by macrophage experiment in vitro and conventional knockout mice.Methods:THP-1 cell line was differentiated to obtain human THP-1-derived macrophages,and the primary macrophages were obtained from human peripheral blood.FVB wild-type mice with the same sex and age were used as the controls of MRP1 knockout mice.The macrophages in abdominal cavity and bone marrow of mice were cultivated.The cells were treated with ABCC1/MRP1,ABCG2/BCRP,ABCB1/P-gp,OATP1B1,and MATE transporter inhibitors,then stimulated by lipopolysaccharide and adenosine triphosphate.The secretion level of IL-iβ was detected by ELISA,Western blot,and immunofluorescence.Results:After inhibiting ABCC1/MRP1 transporter,the secretion of IL-1β decreased significantly,while inhibition of the other 4 transporters had no effect.In animal experiment,the level of IL-1 β secreted by macrophages in bone marrow of MRP1 knockout mice was significantly lower than control group(P<0.05).Conclusion:ABCC1/MRP1 transporter is a newly discovered IL-1β secretion pathway,which is expected to become a new target for solving clinical problems such as cytokine release syndrome.
8.Sertraline hydrochloride combined with compound chamomile lidocaine gel for the treatment of premature ejaculation
Shu-Gen LI ; Shang GAO ; Zhen-Wei GU ; Dao-Hua ZHAO ; Jie JIANG ; Xiao-Ting LU ; Lan-Xiang LIU ; Hao-Ran LIU ; Ze CHEN
National Journal of Andrology 2024;30(9):809-812
Objective:To investigate the effect of sertraline hydrochloride combined with compound chamomile lidocaine gel in the treatment of premature ejaculation(PE).Methods:We selected 80 cases of PE treated in our hospital from June 2021 to May 2023 and equally randomized them into a control and an observation group,the former medicated with compound chamomile lidocaine gel while the latter with sertraline hydrochloride in addition,both for 6 weeks.We recorded and compared the intravaginal ejaculation latency time(IELT),the number of successful sexual intercourses per week,the Premature Ejaculation Diagnostic Tool(PEDT)scores,and the incidence of adverse reactions between the two groups of patients.Results:After the treatment,the IELT was signif-icantly longer([5.39±1.17]vs[2.49±0.73]min,P<0.05),the weekly number of successful sexual intercourses remarkably higher(1.82±0.45 vs 0.93±0.19,P<0.05)and the PEDT scores markedly lower(7.42±2.04 vs 9.85±2.36,P<0.05)in the observation than in the control group,but no statistically significant differences were observed in the baseline PEDT scores or the incidence of adverse reactions between the two groups(P>0.05).Conclusion:Sertraline hydrochloride combined with com-pound chamomile lidocaine gel is definitely effective in the treatment of PE,which can significantly improve the patients'quality of sexual life,with a high safety and low incidence of adverse reactions.
9.Efficacy of 595-nm pulsed dye laser in the treatment of port-wine stains in 155 infants and toddlers: a retrospective analysis
Ting ZHANG ; Lian LIU ; Haotian CHEN ; Danfeng WEI ; Xu LIU ; Ping DIAO ; Qingfeng LIU ; Xian JIANG
Chinese Journal of Dermatology 2024;57(7):610-615
Objective:To investigate the clinical efficacy of 595-nm pulsed dye laser (PDL) in the treatment of port-wine stains (PWS) in infants and toddlers.Methods:A retrospective analysis was conducted based on clinical data from 155 infants and toddlers with PWS treated with 595-nm PDL at West China Hospital of Sichuan University from January 2013 to October 2023, and the efficacy was evaluated according to pre- and post-treatment photographs. The children were grouped according to gender, age, lesion color, lesion area, lesion sites, and number of treatment sessions, separately, and the differences were analyzed between different groups. Further analysis was conducted to determine factors affecting efficacy of PDL for PWS. Adverse reactions after treatment were recorded. The Mann-Whitney U test and Kruskal-Wallis H test were used to analyze unidirectional ordered R × C contingency table data, the Bonferroni approach was used for multiple comparisons, and multivariate ordered logistic regression analysis was performed for multifactorial analysis. Results:After the treatment with 595-nm PDL, 135 infants and toddlers with PWS showed good response, with an overall response rate of 87.1%. Univariate analysis indicated that the efficacy was associated with the lesion area ( P = 0.016) and the number of treatment sessions ( P < 0.001), but not with age ( P = 0.340), gender ( P = 0.164), lesion color ( P = 0.530), or lesion sites ( P = 0.077), and the smaller the lesion area, the more the treatment sessions, the better the therapeutic effect. Multivariate ordered logistic regression analysis further confirmed the correlations of efficacy with lesion area ( P = 0.010) and number of treatment sessions ( P < 0.001). Adverse reactions occurred in 5 (3.2%) cases of PWS, including 2 (1.3%) of hypopigmentation, 2 (1.3%) of hyperpigmentation, and 1 (0.6%) of scar formation. Conclusion:The 595-nm PDL was safe and effective for the treatment of PWS in infants and toddlers with few adverse reactions, making it a reliable therapeutic option.
10.Diagnosis and treatment of port-wine stains-associated syndromes
Qingfeng LIU ; Lian LIU ; Ping DIAO ; Xiaoxue LI ; Ting ZHANG ; Haotian CHEN ; Xu LIU ; Xian JIANG
Chinese Journal of Dermatology 2024;57(7):656-660
Port-wine stains (PWS) are one of the common congenital vascular malformations in dermatology, clinically manifesting as pink or red irregular patches occurring on the skin or mucosa at birth or shortly thereafter, which are often not elevated above the skin surface. In a minority of patients, vascular malformations not only affect the skin, but also involve the eyes, brain, limbs and viscera. These patients are at risk for glaucoma, epilepsy, limb pain, and other clinical conditions. In general, these conditions are referred to as PWS-associated syndromes. These syndromes are rare diseases, can affect multiple systems and exhibit a variety of clinical manifestations, which pose challenges in their diagnosis and treatment. This review focuses on the clinical manifestations, diagnoses, pathogenesis and treatment of PWS-associated syndromes.

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