1.Modified Guishenwan Alleviates Inflammation in Rat Model of Polycystic Ovary Syndrome by Inhibiting MAPK/NF-κB Pathway
Jiayu TIAN ; Wenyi QIN ; Juan YANG ; Xiaofeng RONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):86-94
ObjectiveTo explore the mechanism by which modified Guishenwan alleviates inflammation in the rat model of polycystic ovary syndrome (PCOS) by regulating the mitogen-activated protein kinase (MAPK)/nuclear factor kappa B (NF-κB) pathway. MethodsAccording to the random number table method, 60 SPF female SD rats were randomized into a normal group (n=10) and a modeling group (n=50). The normal group received routine feeding, while the modeling group was administrated with letrozole (1 mg·kg-1·d-1) by gavage for 21 days for the modeling of PCOS. The successfully modeled rats were randomized into model, diane-35 (0.2 g·kg-1·d-1), high- (16.04 g·kg-1·d-1), medium- (8.02 g·kg-1·d-1), low- (4.01 g·kg-1·d-1) dose modified Guishenwan groups. The drug intervention groups were administrated with modified Guishenwan at corresponding doses by gavage, and the normal group and model group were given equal volumes of normal saline. All the groups were continuously treated for 28 days. After treatment, Gram staining of vaginal smears was employed to observe the estrous cycle in each group. Enzyme-linked immunosorbent assay was employed to determine the levels of follicle-stimulating hormone (FSH), estradiol (E2), luteinizing hormone (LH), testosterone (T), and progesterone (PROG) in the plasma, as well as interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin-10 (IL-10) in the plasma and ovarian tissue. The LH/FSH ratio was calculated. The morphological changes in the ovarian tissue were observed by hematoxylin-eosin (HE) staining. Western blot was employed to determine the protein levels of extracellular-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), p38 MAPK, NF-κB p65, IκBα, p-JNK, p-ERK, p-p38 MAPK, p-NF-κB p65, and p-IκBα in the ovarian tissue. Real-time quantitative polymerase chain reaction was used to determine the mRNA levels of ERK, JNK, p38 MAPK, NF-κB p65, and IκBα in the ovarian tissue. ResultsCompared with the normal group, the model group was in the estrus phase, with an increase in the number of ovarian vesicles and decreases in granulosa cells and corpus luteum formation (P<0.05), and lowered levels of FSH and E2 and elevated levels of LH, T, and LH/FSH in the plasma (P<0.05). Compared with the model group, high-, medium-, and low-dose modified Guishenwan recovered the estrous cycle, increased the generation of granulosa cells and corpus luteum, reduced the number of vesicles, elevated the levels of FSH and E2, and lowered the levels LH, T, and LH/FSH (P<0.05, P<0.01) in a dose-dependent manner. High-dose modified Guishenwan demonstrated the best therapeutic effect. Therefore, subsequent experiments for exploring the treatment mechanism were conducted in the normal group, model group, and high-dose modified Guishenwan group. The results showed that compared with the model group, high-dose modified Guishenwan lowered the levels of IL-1β, TNF-α, and IL-10 and elevated the level of IL-10 in the plasma and ovarian tissue (P<0.05, P<0.01), down-regulated the protein levels of p-ERK, p-JNK, p-p38 MAPK, p-NF-κB p65, and p-IκBα, while up-regulating the protein level of IκBα (P<0.01). At the same time, the mRNA levels of ERK, JNK, p38 MAPK, and NF-κB p65 in the high-dose modified Guishenwan group were down-regulated (P<0.05, P<0.01). ConclusionModified Guishenwan can improve the ovarian function in rat model of PCOS induced by letrozole and has anti-inflammatory effects, which may be related to inhibition of the MAPK/NF-κB pathway.
2.Mechanism of Modified Guishenwan in Regulating AMPK/Akt/Nrf2 Pathway to Improve Glucose and Lipid Metabolism and Oxidative Stress in Polycystic Ovary Syndrome Rats
Jiayu TIAN ; Wenyi QIN ; Juan YANG ; Xiaofeng RONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):1-8
ObjectiveBased on the adenosine 5'-monophosphate (AMP)-activated protein kinase/protein kinase B/nuclear factor erythroid 2-related factor 2 (AMPK/Akt/Nrf2) pathway, this study aims to explore the mechanism by which modified Guishenwan improves glucose and lipid metabolism and oxidative stress in polycystic ovary syndrome (PCOS) rats. MethodsA PCOS rat model was established by continuous oral administration of letrozole (1 mg·kg-1·d-1) for 21 days. Successfully modeled rats were randomly divided into a model group, a metformin group (0.25 g·kg-1), and low-, medium-, and high-dose modified Guishenwan groups (4.01, 8.02, and 16.04 g·kg-1·d-1), with 8 rats in each group. Ten normal rats were assigned to the normal group. The drug groups were given their respective doses, while the normal and model groups were given an equal volume of normal saline. Intervention lasted for 4 weeks. Testosterone (T), estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were measured by enzyme-linked immunosorbent assay (ELISA), and the LH/FSH ratio was calculated. Fasting blood glucose (FPG), fasting insulin (FINS), triglyceride (TG), and total cholesterol (TC) levels were measured using an automatic biochemical analyzer, and the insulin resistance index (HOMA-IR) and insulin sensitivity index (HOMA-ISI) were calculated. Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were conducted. Malondialdehyde (MDA), advanced glycation end products (AGEs), and superoxide dismutase (SOD) levels in serum and ovarian tissue were measured using a chemical fluorescence method. Hematoxylin-eosin (HE) staining was used to assess ovarian tissue pathology. Real-time quantitative fluorescent polymerase chain reaction (Real-time PCR) and Western blot were used to measure the expression of AMPK/Akt/Nrf2 pathway-related genes and proteins in ovarian tissue. ResultsCompared with the normal group, the model group exhibited significantly increased levels of T, LH, LH/FSH, FPG, FINS, TG, TC, and HOMA-IR, while FSH, E2, and HOMA-ISI were significantly decreased (P<0.05, P<0.01). MDA and AGEs levels were significantly higher in both serum and ovarian tissue, and SOD levels were significantly reduced (P<0.05). AMPK, Akt, and Nrf2 mRNA and protein expression in ovarian tissue was also significantly reduced (P<0.05). The OGTT and ITT results showed significantly higher blood glucose levels at each time point (P<0.05, P<0.01), with impaired glucose and insulin tolerance. Ovarian follicles showed polycystic changes, reduced corpus luteum, and sparse granulosa cell layers. Compared with the model group, the metformin group and the high-dose modified Guishenwan group showed significant decreases in T, LH, LH/FSH, FPG, FINS, TG, TC, and HOMA-IR, while FSH, E2, and HOMA-ISI were significantly increased (P<0.05, P<0.01). In the high-dose modified Guishenwan group, MDA and AGEs levels in serum and ovarian tissue were significantly reduced, and SOD levels were significantly increased (P<0.05). The mRNA and protein expression of AMPK, Akt, and Nrf2 in ovarian tissue was significantly increased (P<0.05). OGTT and ITT results showed that blood glucose levels in rats decreased significantly at each time point (P<0.05, P<0.01). No obvious abnormalities were observed in ovarian tissue. Compared with the low-dose modified Guishenwan group, the high-dose group showed significant decreases in T, LH, LH/FSH, FPG, FINS, TG, TC, and HOMA-IR, while FSH, E2, and HOMA-ISI were significantly increased (P<0.05). OGTT and ITT results indicated that the high-dose modified Guishenwan group significantly improved glucose and insulin tolerance in rats. No significant abnormalities were observed in ovarian tissue. ConclusionModified Guishenwan effectively improves glucose and lipid metabolism abnormalities and inhibits oxidative stress in PCOS rats, potentially through regulation of the AMPK/Akt/Nrf2 pathway.
6.Prevalence trends of elevated blood pressure and its association with nutritional status among primary and secondary school students in Inner Mongolia
Chinese Journal of School Health 2025;46(9):1342-1345
Objective:
To analyze the prevalence trends of different types of elevated blood pressure and their association with nutritional status among primary and secondary school students in Inner Mongolia from 2019 to 2024, providing references for targeted prevention strategies.
Methods:
From September 2019 to 2024, a stratified random cluster sampling method was used to select 12 primary and secondary schools from each league city in Inner Mongolia Autonomous Region. A total of 177 108, 137 758, 190 182, 180 084 , 188 056, 180 351 primary and secondary school students (excluding grades one to three of primary school) were included for physical examination. The correlation between their nutritional status and high blood pressure was analyzed based on the basic situation of 129 821 primary and secondary school students who completed a questionnaire survey at the same time in 2024. Statistical analysis was conducted using a Chi-square test and multiple Logistic regression model.
Results:
From 2019 to 2024, the detection rates of elevated blood pressure were 13.60%, 13.68%, 17.60%, 17.24%, 14.77% and 15.96%, respectively. The rates for isolated systolic hypertension were 4.24%, 5.83%, 7.26%, 7.19%, 6.24% and 6.93%; isolated diastolic hypertension rates were 6.38%, 4.99%, 6.23 %, 6.41%, 5.39% and 5.66%; and combined systolic and diastolic hypertension rates were 2.97%, 2.86%, 4.11%, 3.65%, 3.14 % and 3.36%. Multivariate Logistic regression analysis showed that girls, junior high school, senior high school, overweight, and obesity were positively associated with elevated blood pressure risk ( OR =1.27, 1.25, 1.32, 1.66, 3.07, all P <0.05); conversely, county residence, Mongolian ethnicity, and other ethnicities showed negative associations ( OR =0.90, 0.93, 0.90, all P <0.05).
Conclusions
Overweight and obesity among children and adolescents are closely related to various types of elevated blood pressure. Prevention strategies should prioritize effectively controlling weight issues among children and adolescents, thereby effectively reducing the incidence of elevated blood pressure.
7.Consensus on low-altitude transport and delivery services for emergency medicines via drones (2025 edition)
Qinshui WU ; Yanfang CHEN ; Tao LIU ; Xiaoyan LI ; Yumin LIANG ; Xin LI ; Zhong LI ; Rong LI ; Xiaoman WANG ; Shuyao ZHANG ; Huishu TIAN
China Pharmacy 2025;36(18):2221-2225
OBJECTIVE To promote the application of drones in emergency rescue and related fields, expand “low-altitude+ medical” rescue services, and advance the standardization of “low-altitude+medical” distribution services. METHODS The Consensus on Low-altitude Transport and Delivery Services for Emergency Medicines via Drones (2025 Edition) (hereinafter referred to as the Consensus) was jointly initiated by the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society and the Expert Committee on Precision Medication of the Guangdong Pharmaceutical Association. Guangzhou Red Cross Hospital served as the leading unit, organizing 53 multidisciplinary experts nationwide to participate in drafting and reviewing. A nominal group technique was employed to discuss and finalize the consensus outline, resulting in a preliminary draft. Delphi method was employed, and 11 external review experts were invited to conduct the evaluation. After the experts’ opinions were analyzed and integrated, the Consensus was finalized. RESULTS & CONCLUSIONS The finalized Consensus includes its purpose, principles, and applicable scenarios, basic requirements, and operational procedures for low-altitude transport and delivery of emergency medications; distribution requirements and precautions for controlled substances, fragile medications, and temperature-sensitive medications; and recommendations for emergency medications supplies suitable for the low-altitude transportation and distribution. The release of this Consensus is expected to provide guidance and support for the standardization of “low-altitude+medical” distribution services and the application of low-altitude economy in the healthcare sector.
8.Guideline for the workflow of clinical comprehensive evaluation of drugs
Zhengxiang LI ; Rong DUAN ; Luwen SHI ; Jinhui TIAN ; Xiaocong ZUO ; Yu ZHANG ; Lingli ZHANG ; Junhua ZHANG ; Hualin ZHENG ; Rongsheng ZHAO ; Wudong GUO ; Liyan MIAO ; Suodi ZHAI
China Pharmacy 2025;36(19):2353-2365
OBJECTIVE To standardize the main processes and related technical links of the clinical comprehensive evaluation of drugs, and provide guidance and reference for improving the quality of comprehensive evaluation evidence and its transformation and application value. METHODS The construction of Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs was based on the standard guideline formulation method of the World Health Organization (WHO), strictly followed the latest definition of guidelines by the Institute of Medicine of the National Academy of Sciences of the United States, and conformed to the six major areas of the Guideline Research and Evaluation Tool Ⅱ. Delphi method was adopted to construct the research questions; research evidence was established by applying the research methods of evidence-based medicine. The evidence quality classification system of the Chinese Evidence-Based Medicine Center was adopted for evidence classification and evaluation. The recommendation strength was determined by the recommendation strength classification standard formulated by the Oxford University Evidence-Based Medicine Center, and the recommendation opinions were formed through the expert consensus method. RESULTS & CONCLUSIONS The Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs covers 4 major categories of research questions, including topic selection, evaluation implementation, evidence evaluation, and application and transformation of results. The formulation of this guideline has standardized the technical links of the entire process of clinical comprehensive evaluation of drugs, which can effectively guide the high-quality and high-efficient development of this work, enhance the standardized output and transformation application value of evaluation evidence, and provide high-quality evidence support for the scientific decision-making of health and the rationalization of clinical medication.
9.Effects of different processing methods on traits and chemical constituents of Forsythiae Fructus.
Rong-Rong XU ; Rui LI ; Chu-Han ZHANG ; Wei TIAN ; Xin-Guo WANG ; Li-Ying NIU ; Wei FENG
China Journal of Chinese Materia Medica 2025;50(2):465-471
This study aims to investigate the correlations of the appearance traits, total antioxidant capacity, and component content of Forsythiae Fructus processed by different methods, explore the effects of different processing methods on the abovementioned three aspects of Forsythiae Fructus, and screen out the internal and external indicators that have important effects on its quality. It determined the length, diameter, stem length, chroma value L~*, a~*, b~*, and other appearance indexes and antioxidant activity of Forsythiae Fructus processed by different methods. The content of forsythiaside A, rutin, forsythin, pinoresinol, and phillygenin was determined by ultra performance liquid chromatography(UPLC). Correlation analysis, principal component analysis(PCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and independent sample t-test analysis were performed on the appearance indexes and the component content. The correlation analysis showed that there were differences in the appearance traits and the component content. L~* and E~* had highly significant negative correlations with pinoresinol and phillygenin(P<0.01) and significant positive correlations with forsythiaside A(P<0.05). There were a highly significant negative correlation between a~* and forsythiaside A(P<0.01) and highly significant positive correlations of a~* with pinoresinol and phillygenin(P<0.01). There were a highly significant positive correlation between b~* and forsythiaside A(P<0.01) and highly significant negative correlations of b~* with pinoresinol and phillygenin(P<0.01). The total antioxidant capacity had highly significant negative correlations with pinoresinol and phillygenin(P<0.01). The PCA results showed that there were differences among Forsythiae Fructus samples processed by different methods. OPLS-DA marked five important indicators, which were forsythiaside A, stem length, E~*, L~*, and b~*. The results of independent sample t-test showed that the content of forsythiaside A, pinoresinol, and phillygenin, the total antioxidant capacity, and the appearance traits such as L~*, a~*, b~*, and E~* were significantly different between the Forsythiae Fructus samples processed by steaming and boiling(P<0.05). According to content determination and a related biological activity analysis, steaming is a good choice from the perspective of improving the stability of chemical constituents and antioxidant activity of Forsythiae Fructus. From the point of view of improving the stability of chemical constituents and anti-inflammatory and anti-cancer activities of Forsythiae Fructus, it is recommended to use boiling as the processing method. Based on the above analysis methods, the main indexes for the appearance traits of Forsythiae Fructus processed by different methods are powder chroma value(L~*, a~*, b~*, E~*), stem length, and total antioxidant capacity, and those for chemical constituents are the content of forsythiaside A, pinoresinol, and phillygenin. This study provides reference for seeking scientific processing methods of Forsythiae Fructus.
Forsythia/chemistry*
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Drugs, Chinese Herbal/isolation & purification*
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Fruit/chemistry*
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Antioxidants/analysis*
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Chromatography, High Pressure Liquid
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Glycosides/analysis*
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Principal Component Analysis
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Furans
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Lignans
10.Verification of resveratrol ameliorating vascular endothelial damage in sepsis-associated encephalopathy through HIF-1α pathway based on network pharmacology and experiment.
Rong LI ; Yue WU ; Wen-Xuan ZHU ; Meng QIN ; Si-Yu SUN ; Li-Ya WANG ; Mei-Hui TIAN ; Ying YU
China Journal of Chinese Materia Medica 2025;50(4):1087-1097
This study aims to investigate the mechanism by which resveratrol(RES) alleviates cerebral vascular endothelial damage in sepsis-associated encephalopathy(SAE) through network pharmacology and animal experiments. By using network pharmacology, the study identified common targets and genes associated with RES and SAE and constructed a protein-protein interaction( PPI) network. Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed to pinpoint key signaling pathways, followed by molecular docking validation. In the animal experiments, a cecum ligation and puncture(CLP) method was employed to induce SAE in mice. The mice were randomly assigned to the sham group, CLP group, and medium-dose and high-dose groups of RES. The sham group underwent open surgery without CLP, and the CLP group received an intraperitoneal injection of 0. 9% sodium chloride solution after surgery. The medium-dose and high-dose groups of RES were injected intraperitoneally with 40 mg·kg-1 and 60 mg·kg~(-1) of RES after modeling, respectively, and samples were collected 12 hours later. Neurological function scores were assessed, and the wet-dry weight ratio of brain tissue was detected. Serum superoxide dismutase(SOD), catalase( CAT) activity, and malondialdehyde( MDA) content were measured by oxidative stress kit. Histopathological changes in brain tissue were examined using hematoxylin-eosin(HE) staining. Transmission electron microscopy was employed to evaluate tight cell junctions and mitochondrial ultrastructure changes in cerebral vascular endothelium. Western blot analysis was performed to detect the expression of zonula occludens1( ZO-1), occludin, claudins-5, optic atrophy 1( OPA1), mitofusin 2(Mfn2), dynamin-related protein 1(Drp1), fission 1(Fis1), and hypoxia-inducible factor-1α(HIF-1α). Network pharmacology identified 76 intersecting targets for RES and SAE, with the top five core targets being EGFR, PTGS2, ESR1, HIF-1α, and APP. GO enrichment analysis showed that RES participated in the SAE mechanism through oxidative stress reaction. KEGG enrichment analysis indicated that RES participated in SAE therapy through HIF-1α, Rap1, and other signaling pathways. Molecular docking results showed favorable docking activity between RES and key targets such as HIF-1α. Animal experiment results demonstrated that compared to the sham group, the CLP group exhibited reduced nervous reflexes, decreased water content in brain tissue, as well as serum SOD and CAT activity, and increased MDA content. In addition, the CLP group exhibited disrupted tight junctions in cerebral vascular endothelium and abnormal mitochondrial morphology. The protein expression levels of Drp1, Fis1, and HIF-1α in brain tissue were increased, while those of ZO-1, occludin, claudin-5, Mfn2, and OPA1 were decreased. In contrast, the medium-dose and high-dose groups of RES showed improved neurological function, increased water content in brain tissue and SOD and CAT activity, and decreased MDA content. Cell morphology in brain tissue, tight junctions between endothelial cells, and mitochondrial structure were improved. The protein expressions of Drp1, Fis1, and HIF-1α were decreased, while those of ZO-1, occludin, claudin-5, Mfn2, and OPA1 were increased. This study suggested that RES could ameliorate cerebrovascular endothelial barrier function and maintain mitochondrial homeostasis by inhibiting oxidative stress after SAE damage, potentially through modulation of the HIF-1α signaling pathway.
Animals
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Mice
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Network Pharmacology
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Resveratrol/administration & dosage*
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Male
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Sepsis-Associated Encephalopathy/genetics*
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Signal Transduction/drug effects*
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Hypoxia-Inducible Factor 1, alpha Subunit/genetics*
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Endothelium, Vascular/metabolism*
;
Molecular Docking Simulation
;
Protein Interaction Maps/drug effects*
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Humans
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Sepsis/complications*
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Oxidative Stress/drug effects*


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