1.Anti-frostbite effect of miglitol on cold-exposed mice through UCP1-mediated thermogenic activation
Xiang LI ; Hongyuan LU ; Mingyu ZHANG ; Huan GAO ; Dong YAO ; Zihua XU
Journal of Pharmaceutical Practice and Service 2025;43(1):1-5
Objective To investigate the effect and mechanism of miglitol on regulating the energy metabolism of brown adipocytes by activating UCP1 and preventing cold injury in mice after cold exposure. Methods Primary brown adipocytes were induced into mature adipocytes, the effect of miglitol on the viability of brown adipocytes was investigated by MTT method, the lipid droplet consumption level of cells after drug administration was investigated by Oil Red O staining technology, and the level of UCP1, a key protein of thermogenesis in brown adipocytes, was detected by Western blotting. The activity of anti-frostbite was investigated in cold exposure at 4 ℃ and −20 ℃. KM mice, which were randomly divided into control group, cold exposure group, miglitol group and all-trans retinoic acid group, and after 7 days of repeated administration, the body surface temperature of mice was detected by infrared thermal imaging system, the anal temperature change was detected by anal thermometer, and the expression levels of UCP1 and PGC1-α in adipose tissue were detected by immunoblotting. Results Compared with the control group, the lipid droplet consumption and UCP1 expression levels in brown adipocytes in the miglitol group were significantly increased. The levels of body surface temperature and rectal temperature increased significantly after cold exposure, and the levels of UCP1 and PGC1α in the brown adipose tissue of mice increased significantly, which indicated that the miglitol could activate the critical proteins UCP1 and PGC1α of the thermogenesis pathway, increase the thermogenesis of mice after cold exposure, and thus improve the effect of cold injury for toe swelling. Conclusion Miglitol could play a role in improving cold injury and body temperature in mice by increasing the level of UCP1 and PGC1α, which are key targets of the thermogenesis pathway to promote the thermogenesis of brown fat.
2.A new method for flow cytometry-based detection of ABO antigen expression levels
Yuyu ZHANG ; Xi LIU ; Junhua XIE ; Bin CAO ; Jiewei ZHENG ; Xinyi ZHU ; Zhongying WANG ; Dong XIANG
Chinese Journal of Blood Transfusion 2025;38(5):665-672
Objective: To design and establish a new method for flow cytometry-based detection of commonly observed highly expressed antigens on red blood cells, and to further evaluate the differences and distribution characteristics of antigen expression levels between ABO blood type homozygotes and heterozygotes in healthy individuals. Methods: Residual blood samples after donor blood type identification by Shanghai Blood Center in April 2024 were collected. Among them, samples of 19 homozygous and 19 heterozygous individuals of type A and type B were selected. Then the expression level of ABO antigen on red blood cells were detected using the new method established in this study and the traditional aldehyde fixed red blood cell method. Both methods were tested independently three times and the results were compared. Results: The mean values of the three detection results of the new method was (×10
/RBC): AA homozygous 3.3±0.5, AO heterozygous 2.8±0.3, BB homozygous 3.6±0.3, BO heterozygous 3.1±2.8. The mean values of the three detection results of the aldehyde fixation method were AA homozygous 5.9±0.9, AO heterozygous 5.0±1.4, BB homozygous 3.8±0.6, and BO heterozygous 3.3±0.4. The average antigen distribution of each genotype followed a normal distribution. Comparing the average antigen expression levels of homozygotes and heterozygotes, both methods showed that A/B homozygotes had higher antigen levels than heterozygotes, with AA being 1.17 to 1.18 times that of AO and BB being 1.15 to 1.16 times that of BO. Comparing the inter batch differences in the three test results of two methods, the new method showed no significant difference in the three test results for four genotypes (P>0.05). The aldehyde fixation method showed significant differences in the test results for all three genotypes (P<0.01) except for BB homozygotes (P>0.05). The reliability and reproducibility of the new method were better than those of the traditional aldehyde fixation method. Conclusion: The antigen expression level of ABO homozygotes is higher than that of heterozygotes, and the difference in antigen level between type A homozygotes and heterozygotes is slightly higher than that of type B. The new method is superior to traditional aldolization fixation methods.
3.Natural Products Treat Atopic Dermatitis via NF-κB Signaling Pathway: A Review
Xiang LI ; Lingling DONG ; Tao GUO ; Litao ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(4):271-280
Atopic dermatitis (AD) is a chronic, recurrent, inflammatory, and pruritus skin disease caused by multiple internal and external factors, ranking first in the global burden of skin diseases. Due to the adverse reactions and high costs of conventional treatments and biologics, the development of natural products has attracted much attention. The nuclear factor-κB (NF-κB) signaling pathway is a key pathway for inhibiting inflammation and modulating immunity. This paper summarizes the pharmacological effects and molecular mechanisms of natural products such as flavonoids, alkaloids, phenols, terpenoids, coumarins, glycosides, and anthraquinones via NF-κB signaling pathway, aiming to provide guidance for the development of natural products. Basic studies have shown that natural products have high safety and efficacy. Oral or topical administration of natural products can regulate the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), mitogen-activated protein kinase (MAPK), nuclear factor erythroid 2-related factor 2 (Nrf2), high mobility group box 1 protein (HMGB1)/receptor for advanced glycation endproducts (RAGE), and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) signaling pathways to exert anti-inflammatory, anti-allergy, antioxidant activities, thus reversing the pathological changes of AD. However, it is worth noting that the clinical application of natural products is still insufficient, and more rigorous clinical trials are still needed to verify their effects. The basic experiments and clinical evidence prove that natural products may play a role in alleviating AD, which provide a basis for evaluating the functioning mechanism of natural active substances and enrich the candidates for the development of potential drugs.
4.Modified Xiaoyaosan Alleviates Depression-like Behaviors by Regulating Activation of Hippocampal Microglia Cells in Rat Model of Juvenile Depression
Jiayi SHI ; Yun XIANG ; Ziyang ZHOU ; Dahua WU ; Feng QIU ; Chang LEI ; Hongyu ZENG ; Kaimei TAN ; Hongqing ZHAO ; Dong YANG ; Yuhong WANG ; Pengxiao GUO ; Xiuli ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(5):46-56
ObjectiveTo investigate the mechanism of Baihuan Xiaoyao Decoction (Xiaoyaosan added with Lilii Bulbus and Albiziae Cortex) in alleviating depression-like behaviors of juvenile rats by regulating the polarization of microglia. MethodSixty juvenile SD rats were randomized into normal control, model, fluoxetine, and low-, medium-, and high-dose (5.36, 10.71, 21.42 g·kg-1, respectively) Baihuan Xiaoyao decoction groups. The rat model of juvenile depression was established by chronic unpredictable mild stress (CUMS). The sucrose preference test (SPT) was carried out to examine the sucrose preference of rats. Forced swimming test (FST) was carried out to measure the immobility time of rats. The open field test (OFT) was conducted to measure the total distance, the central distance, the number of horizontal crossings, and the frequency of rearing. Morris water maze (MWM) was used to measure the escape latency and the number of crossing the platform. The immunofluorescence assay was employed to detect the expression of inducible nitric oxide synthase (iNOS, the polarization marker of M1 microglia) and CD206 (the polarization marker of M2 microglia). Real-time polymerase chain reaction was employed to determine the mRNA levels of iNOS, CD206, pro-inflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6] and anti-inflammatory cytokines (IL-4 and IL-10) in the hippocampus. Western blotting was employed to determine the protein levels of iNOS and CD206 in the hippocampus. The levels of IL-4 and IL-6 in the hippocampus were detected by enzyme-linked immunosorbent assay. ResultCompared with the normal control group, the model rats showed a reduction in sucrose preference (P<0.05), an increase in immobility time (P<0.05), decreased motor and exploratory behaviors (P<0.05), and weakened learning and spatial memory (P<0.05). In addition, the model rats showed up-regulated mRNA and protein levels of iNOS and mRNA levels of IL-1β, IL-6, and TNF-α (P<0.05). Compared with the model group, Baihuan Xiaoyao decoction increased the sucrose preference value (P<0.05), shortened the immobility time (P<0.01), increased the motor and exploratory behaviors (P<0.05), and improved the learning and spatial memory (P<0.01). Furthermore, the decoction down-regulated the positive expression and protein level of iNOS, lowered the levels of TNF-α, IL-1β, and IL-6 (P<0.01), promoted the positive expression of CD206, and elevated the levels of IL-4 and IL-10 (P<0.01) in the hippocampus of the high dose group. Moreover, the high-dose Baihuan Xiaoyao decoction group had higher sucrose preference value (P<0.01), shorter immobility time (P<0.01), longer central distance (P<0.01), stronger learning and spatial memory (P<0.01), higher positive expression and protein level of iNOS (P<0.01), lower levels of TNF-α, IL-1β, and IL-6 (P<0.05, P<0.01), lower positive expression and mRNA level of iNOS (P<0.05), and higher levels of IL-4 and IL-10 (P<0.05, P<0.01) than the fluoxetine group. ConclusionBaihuan Xiaoyao decoction can improve the depression-like behavior of juvenile rats by inhibiting the M1 polarization and promoting the M2 polarization of microglia in the hippocampus.
5.Clinical trial of brexpiprazole in the treatment of adults with acute schizophrenia
Shu-Zhe ZHOU ; Liang LI ; Dong YANG ; Jin-Guo ZHAI ; Tao JIANG ; Yu-Zhong SHI ; Bin WU ; Xiang-Ping WU ; Ke-Qing LI ; Tie-Bang LIU ; Jie LI ; Shi-You TANG ; Li-Li WANG ; Xue-Yi WANG ; Yun-Long TAN ; Qi LIU ; Uki MOTOMICHI ; Ming-Ji XIAN ; Hong-Yan ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(5):654-658
Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50%(140 cases/184 cases)and 82.40%(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P>0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P>0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P>0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00%vs.64.50%,P>0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.
6.Biological principles of "food and medicine homologous"
Jin-wen DING ; Xiang-yin CHI ; Yu ZHANG ; Lu-lu WANG ; Jian-dong JIANG ; Yuan LIN
Acta Pharmaceutica Sinica 2024;59(6):1509-1518
With the rapid society development and broad recognition of "Healthy China", the demands for good life and health are increasing. Accordingly, the concept of "food and medicine homologous" have been attractive. The concept of "food and medicine homologous" has a long history in China, and is an essence of various ideas in traditional Chinese medicine, such as diet therapy, medicated diet, regimen and preventive treatment of disease, representing an important field in health science. Many studies have found that the active ingredients of "food and medicine homologous" substances are multiple types, multiple mechanisms and multiple targets, exerting their biological effects after oral administration and chemical or metabolic transformation. In this review, the chemical basis and biological principles of various "food and medicine homologous" substances were summarized as compounds, biological macromolecules and intestinal flora. By focusing on the intestinal flora, we discussed the detailed biological principles of several classic "food and medicine homologous" substances. The scientific significance of "food and medicine homologous" concept were also discussed. This review explores the concept of "food and medicine homologous" from the perspective of modern medicine, in order to provide insights for future drug development and human health.
7.Two new isocoumarins from cave-derived Metarhizium anisopliae NHC-M3-2
Rong-xiang WU ; Jie-lan GUO ; Hua HUANG ; Jing-jing LIAO ; Yi HAO ; Fan-dong KONG ; Li-man ZHOU ; Chao-jun ZHANG
Acta Pharmaceutica Sinica 2024;59(9):2588-2593
Extracting extracts of secondary metabolites from the karst cave fungus
8.Determination of 19 components in Microctis Folium from different production areas based on UPLC-MS/MS
Min-you HE ; Li-wei WANG ; Lin LIU ; Po-yu ZHANG ; Jin-quan LAN ; Xin-ya WAN ; Zhen-yu LI ; Xiang-dong CHEN ; Dong-mei SUN
Acta Pharmaceutica Sinica 2024;59(5):1374-1381
The paper is to establish an UPLC-MS/MS method for the simultaneous determination of 19 components in Microctis Folium from different production areas. The 50% methanol was used as extraction solvent. The Agilent ZORBAX SB C18 (150 mm × 2.1 mm, 1.8 μm) column was used; mobile phase was acetonitrile - 0.1% acetic acid with gradient elution, flow rate was 0.3 mL·min-1, colume temperature was 30 ℃, and the injection volume was 2 μL; electrospray ionizaton source was used and detected in negative ion mode. The results showed that the established UPLC-MS/MS method could well separate the 19 components, and the methodological investigation results of 19 components were good. By means of orthogonal partial least squares discriminant analysis (OPLS-DA), 28 batches of Microctis Folium samples from different production areas can be divided into three categories, Guangdong, Guangxi and Hainan are each classified into one category, and 10 signature compounds which affecting the quality differences of different production areas were screened out. The established method is accurate, reliable, sensitive and reproducible. It can provide a basis for the establishment of the quality standard of Microctis Folium, as well as for safety and quality research.
9.A reporter gene assays for bioactivity determination of human chorinonic gonadotropin
Ying HUANG ; Xiao-ming ZHANG ; He-yang LI ; Lü-yin WANG ; Hui ZHANG ; Ping LÜ ; Jing LI ; Xiang-dong GAO ; Cheng-gang LIANG
Acta Pharmaceutica Sinica 2024;59(2):432-438
This study constructed a LHCGR-CRE-luc-HEK293 transgenic cell line according to the activation of the cAMP signaling pathway after recombinant human chorionic gonadotropin binding to the receptor. The biological activity of recombinant human chorionic gonadotropin was assayed using a luciferase assay system. The relative potency of the samples was calculated using four-parameter model. And the method conditions were optimized to validate the specificity, relative accuracy, precision and linearity of the method. The results showed that there was a quantitative potency relationship of human chorinonic gonadotropin (hCG) in the method and it was in accordance with the four-parameter curve. After optimization, the conditions were determined as hCG dilution concentration of 2.5 μg·mL-1, dilution ratio of 1∶4, cell number of 10 000-15 000 cells/well, and induction time of 6 h. The method had good specificity, relative accuracy with relative bias ranging from -8.9% to 3.4%, linear regression equation correlation coefficient of 0.996, intermediate precision geometric coefficient of variation ranging from 3.3% to 15.0%, and linearity range of 50% to 200%. This study successfully established and validated a reporter gene method to detect hCG biological activity, which can be used for hCG biological activity assay and quality control.
10.Clinical Study on Dingxuan Decoction Combined with Vestibular Function Rehabilitation Training in the Treatment of Meniere's Disease
Yu-Fang ZHANG ; Yan-Fang SONG ; Ying-Zhe CHEN ; Xiang-Dong WU ; Jing-Jing HAI ; Wen-Qing SUN
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(3):646-652
Objective To investigate the efficacy of Dingxuan Decoction combined with vestibular function rehabilitation training in the treatment of Meniere's disease and to observe its effect on clinical symptoms and blood flow of vertebral artery.Methods A total of 100 patients with Meniere's disease of liver-kidney yin deficiency complicated with wind-water upward stirring type were randomly divided into an observation group and a control group,with 50 patients in each group.The control group was given conventional treatment and vestibular function rehabilitation training,and the observation group was treated with Dingxuan Decoction on the basis of treatment for the control group.The two groups were treated for 4 weeks and then were followed up for 6 months.The changes of traditional Chinese medicine(TCM)syndrome score,Dizziness Handicap Inventory(DHI)score,Tinnitus Handicap Inventory(THI)score,hearing visual analogue scale(VAS)score and vertebral artery blood flow in the two groups were observed before and after the treatment.After treatment,the TCM syndrome efficacy,hearing improvement and follow-up results were compared between the two groups.Results(1)After 4 weeks of treatment,the total effective rate for TCM syndrome efficacy of the observation group was 86.00%(43/50),and that of the control group was 62.00%(31/50),and the intergroup comparison showed that the TCM syndrome efficacy in the observation group was significantly superior to that in the control group(P<0.01).(2)After 4 weeks of treatment,the hearing of patients in both groups was improved,and the total effective rate for the efficacy of hearing improvement in the observation group was 76.00%(38/50),while that in the control group was 46.00%(23/50).The intergroup comparison showed that the efficacy of hearing improvement in the observation group was significantly superior to that in the control group(P<0.01).(3)After treatment,the TCM syndrome scores,DHI score,THI score and hearing VAS scores in the two groups were all decreased compared with those before treatment(P<0.05 or P<0.01),and the decrease in the observation group was significantly superior to that in the control group(P<0.01).(4)After treatment,the average blood flow velocity of the left vertebral artery(LVA)and the right vertebral artery(RVA)in the two groups were both increased compared with those before treatment(P<0.05),and the increase in the observation group was significantly superior to that in the control group(P<0.05 or P<0.01).(5)The results of 6-month follow-up after treatment showed that the incidence of Meniere's disease and the frequency of attack in the observation group were significantly reduced compared with those in the control group,and the episode duration in the observation group was significantly shorter than that in the control group,the differences being all statistically significant(P<0.05 or P<0.01).Conclusion Dingxuan Decoction combined with vestibular function rehabilitation training exert certain effect in treating patients with Meniere's disease of liver-kidney yin deficiency complicated with wind-water upward stirring type,and the therapy is effective on improving patients'clinical symptoms and vertebral artery blood flow,reducing the risk of recurrence and improving the quality of life of the patients.

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