1.Effect and mechanism of Prunus mume against hepatic fibrosis
Feng HAO ; Ji LI ; Jing DU ; Yuchen OUYANG ; Yichun CUI ; Shuang WEI
China Pharmacy 2025;36(2):172-178
OBJECTIVE To explore the effect and mechanism of Prunus mume against hepatic fibrosis (HF). METHODS Male SD rats were randomly divided into normal control group (n=10) and modeling group (n=50). The modeling group established HF model using carbon tetrachloride. The modeled rats were randomly divided into model group (normal saline), positive control group [colchicine, 0.09 mg/(kg·d)], and P. mume low-dose, medium-dose and high-dose groups [1.35, 2.70, 5.40 g/(kg·d)], with 9 rats in each group. They were given the corresponding drug/normal saline intragastrically, once a day, for 8 consecutive weeks. After the last medication, the liver index was calculated, while liver function indexes, liver fiber indexes, oxidative stress indicators and inflammatory factors of rats were measured. HE staining was used to observe the pathological changes in liver tissue of rats; Masson staining was used to observe the degree of HF in liver tissue of rats; transmission electron microscopy was used to observe the ultrastructure of liver tissue in rats; TUNEL staining was used to detect liver cell apoptosis in each group of rats. Western blot method was used to detect the protein expressions of transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor (PDGF) in liver tissue of rats. RESULTS Compared with normal control group, the levels of alanine transaminase, alkaline phosphatase, aspartate transaminase, total bilirubin, malondialdehyde, procollagen type Ⅲ protein, Ⅳ-type pre collagenase, laminin, hyaluronic acid, interleukin-6, tumor necrosis factor-α, as well as the protein expressions of TGF-β1 and PDGF in model group were increased significantly, while the levels of superoxide dismutase and glutathione peroxidase were significantly reduced (P<0.01); the HE, Masson staining and transmission electron microscopy observation results showed obvious HF characteristics in rats of model group. Compared with model group, varying degrees of improvement in above indexes were observed in P. mume groups, and the above 2021BSZR011) indicators of rats in P. mume medium-dose and high-dose groups were reversed significantly (P<0.05 or P<0.01). CONCLUSIONS P. mume has an anti-HF effect, which may be achieved through mechanisms such as antioxidation, anti-inflammation, reduction of collagen production, inhibition of PDGF protein expression, and regulation of TGF- β1 signaling pathway.
2.Effect and mechanism of Prunus mume against hepatic fibrosis
Feng HAO ; Ji LI ; Jing DU ; Yuchen OUYANG ; Yichun CUI ; Shuang WEI
China Pharmacy 2025;36(2):172-178
OBJECTIVE To explore the effect and mechanism of Prunus mume against hepatic fibrosis (HF). METHODS Male SD rats were randomly divided into normal control group (n=10) and modeling group (n=50). The modeling group established HF model using carbon tetrachloride. The modeled rats were randomly divided into model group (normal saline), positive control group [colchicine, 0.09 mg/(kg·d)], and P. mume low-dose, medium-dose and high-dose groups [1.35, 2.70, 5.40 g/(kg·d)], with 9 rats in each group. They were given the corresponding drug/normal saline intragastrically, once a day, for 8 consecutive weeks. After the last medication, the liver index was calculated, while liver function indexes, liver fiber indexes, oxidative stress indicators and inflammatory factors of rats were measured. HE staining was used to observe the pathological changes in liver tissue of rats; Masson staining was used to observe the degree of HF in liver tissue of rats; transmission electron microscopy was used to observe the ultrastructure of liver tissue in rats; TUNEL staining was used to detect liver cell apoptosis in each group of rats. Western blot method was used to detect the protein expressions of transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor (PDGF) in liver tissue of rats. RESULTS Compared with normal control group, the levels of alanine transaminase, alkaline phosphatase, aspartate transaminase, total bilirubin, malondialdehyde, procollagen type Ⅲ protein, Ⅳ-type pre collagenase, laminin, hyaluronic acid, interleukin-6, tumor necrosis factor-α, as well as the protein expressions of TGF-β1 and PDGF in model group were increased significantly, while the levels of superoxide dismutase and glutathione peroxidase were significantly reduced (P<0.01); the HE, Masson staining and transmission electron microscopy observation results showed obvious HF characteristics in rats of model group. Compared with model group, varying degrees of improvement in above indexes were observed in P. mume groups, and the above 2021BSZR011) indicators of rats in P. mume medium-dose and high-dose groups were reversed significantly (P<0.05 or P<0.01). CONCLUSIONS P. mume has an anti-HF effect, which may be achieved through mechanisms such as antioxidation, anti-inflammation, reduction of collagen production, inhibition of PDGF protein expression, and regulation of TGF- β1 signaling pathway.
3.Health Economic Analysis of Central Line-associated Bloodstream Infections in Critically Ill Patients in Intensive Care Unit
Li CAI ; Xiaomin FENG ; Jing HUANG ; Huichao CHEN ; Jian LI ; Honglian OUYANG
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(2):301-310
ObjectiveTo explore the incremental cost of central line-associated bloodstream infections (CLABSI) after central venous catheterization (CVC) in critically ill patients in the intensive care unit (ICU), as well as the main cost of nosocomial infection prevention and control. By comparing these two costs, the medical personnel to pay more attention should CLABSI prevention and control from the perspectives of medical quality and economic benefits, and promote the implementation of prevention and control measures. MethodsCluster sampling was used to select 126 critically ill patients who underwent CVC in the ICU of a tertiary traditional Chinese medicine hospital from January 2021 to December 2023, including 65 cases in the CLABSI group and 61 in the non-CLABSI group. Patients’ data were retrospectively collected from the hospital medical records, including the disease type, gender, age, length of hospital stay, outcome, and hospitalization expenses. The costs of different hand hygiene methods and differing approaches to environmental cleaning and disinfection were analyzed and compared. ResultsThere were significant differences in the length of hospital stay (Z=-5.35, P<0.05) and total hospitalization expenses (Z=-6.79, P<0.05) between the CLABSI and non-CLABSI group. Total hospitalization expenses showed significant differences among patients with different lengths of hospital stay (H=43.01, P<0.05), with much higher median one in those with 60 or more days of hospital stay than other patients. Greater differences of median total hospitalization expenses were found in males than in females (Z=-3.98, P<0.05), as well as in patients aged 60-80 years than in patients of other ages (Z=-5.79, P<0.05). ConclusionsThe occurrence of CLABSI significantly increases the ICU patients’ length of hospital stay and hospitalization expenses. There are differences in the costs of different hand hygiene methods and differing approaches to environmental cleaning and disinfection, but these costs are acceptable compared to the incremental costs directly attributable to CLABSI. Therefore, medical institutions should attach importance to the investment in prevention and control of nosocomial infections such as hand hygiene and environmental cleaning and disinfection, formulate practical, reasonable and feasible plans, and ensure their implementation, in order to avoid nosocomial infections, improve the medical quality, effectively control patients’ length of hospital stay and hospitalization costs, and strive to maintain patient safety.
4.Long-term safety and effectiveness of withdrawal of HBIG and/or nucleos(t)ide analogues in recipients undergoing hepatitis B immune reconstitution after liver transplantation
Feng WU ; Binwei DUAN ; Yabo OUYANG ; Jing ZHANG ; Yu CAO ; Guangming LI
Organ Transplantation 2024;15(3):435-442
Objective To investigate the long-term safety and effectiveness of withdrawal of hepatitis B immuneglobulin (HBIG) and/or nucleos(t)ide analogues (NAs) to prevent hepatitis B virus (HBV) reinfection in liver transplant recipients with hepatitis B-related diseases after successful vaccination. Methods Baseline data of 76 liver transplant recipients undergoing hepatitis B immune reconstitution after receiving hepatitis B vaccines were retrospectively analyzed. The vaccination and response, the follow-up results of respondents with HBIG and/or NAs withdrawal, and the reinfection of HBV after withdrawal of HBIG and/or NAs were analyzed. Results The time interval from liver transplantation to hepatitis B vaccination was 26 (20, 40) months. The time interval from vaccination to response was 15 (8,27) months. Initially, 76 recipients withdrew HBIG, and 36 recipients withdrew HBIG and NAs. During the follow-up, 12 of 76 recipients who withdrew HBIG resumed use of HBIG, and 16 of 36 recipients who withdrew HBIG and NAs resumed use of NAs. The withdrawal time of HBIG and NAs was 135 (98,150) and 133 (34,149) months, respectively. Sixteen respondents did not receive booster, and 36 respondents received boosters on a regular basis. The time interval between the first booster and HBIG withdrawal was 44 (11,87) months. No significant differences were observed in baseline data between the respondents with and without boosters (all P>0.05). During the follow-up, 9 recipients were lost to follow-up, 5 were re-infected with HBV, 3 died, and 1 recipient developed graft loss and underwent secondary liver transplantation. Among 5 recipients re-infected with HBV, 4 cases had virus mutation. Significant differences were found between re-infected and uninfected patients regarding withdrawal of NAs and hepatitis B e antigen (HBeAg) positive before transplantation (both P<0.05). Conclusions Long-term withdrawal of HBIG is feasible and safe for recipients with successful hepatitis B immune reconstitution after liver transplantation for hepatitis B-related diseases. Nevertheless, whether antiviral drugs can be simultaneously withdrawn remains to be validated.
5.Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients (version 2024)
Yao LU ; Yang LI ; Leiying ZHANG ; Hao TANG ; Huidan JING ; Yaoli WANG ; Xiangzhi JIA ; Li BA ; Maohong BIAN ; Dan CAI ; Hui CAI ; Xiaohong CAI ; Zhanshan ZHA ; Bingyu CHEN ; Daqing CHEN ; Feng CHEN ; Guoan CHEN ; Haiming CHEN ; Jing CHEN ; Min CHEN ; Qing CHEN ; Shu CHEN ; Xi CHEN ; Jinfeng CHENG ; Xiaoling CHU ; Hongwang CUI ; Xin CUI ; Zhen DA ; Ying DAI ; Surong DENG ; Weiqun DONG ; Weimin FAN ; Ke FENG ; Danhui FU ; Yongshui FU ; Qi FU ; Xuemei FU ; Jia GAN ; Xinyu GAN ; Wei GAO ; Huaizheng GONG ; Rong GUI ; Geng GUO ; Ning HAN ; Yiwen HAO ; Wubing HE ; Qiang HONG ; Ruiqin HOU ; Wei HOU ; Jie HU ; Peiyang HU ; Xi HU ; Xiaoyu HU ; Guangbin HUANG ; Jie HUANG ; Xiangyan HUANG ; Yuanshuai HUANG ; Shouyong HUN ; Xuebing JIANG ; Ping JIN ; Dong LAI ; Aiping LE ; Hongmei LI ; Bijuan LI ; Cuiying LI ; Daihong LI ; Haihong LI ; He LI ; Hui LI ; Jianping LI ; Ning LI ; Xiying LI ; Xiangmin LI ; Xiaofei LI ; Xiaojuan LI ; Zhiqiang LI ; Zhongjun LI ; Zunyan LI ; Huaqin LIANG ; Xiaohua LIANG ; Dongfa LIAO ; Qun LIAO ; Yan LIAO ; Jiajin LIN ; Chunxia LIU ; Fenghua LIU ; Peixian LIU ; Tiemei LIU ; Xiaoxin LIU ; Zhiwei LIU ; Zhongdi LIU ; Hua LU ; Jianfeng LUAN ; Jianjun LUO ; Qun LUO ; Dingfeng LYU ; Qi LYU ; Xianping LYU ; Aijun MA ; Liqiang MA ; Shuxuan MA ; Xainjun MA ; Xiaogang MA ; Xiaoli MA ; Guoqing MAO ; Shijie MU ; Shaolin NIE ; Shujuan OUYANG ; Xilin OUYANG ; Chunqiu PAN ; Jian PAN ; Xiaohua PAN ; Lei PENG ; Tao PENG ; Baohua QIAN ; Shu QIAO ; Li QIN ; Ying REN ; Zhaoqi REN ; Ruiming RONG ; Changshan SU ; Mingwei SUN ; Wenwu SUN ; Zhenwei SUN ; Haiping TANG ; Xiaofeng TANG ; Changjiu TANG ; Cuihua TAO ; Zhibin TIAN ; Juan WANG ; Baoyan WANG ; Chunyan WANG ; Gefei WANG ; Haiyan WANG ; Hongjie WANG ; Peng WANG ; Pengli WANG ; Qiushi WANG ; Xiaoning WANG ; Xinhua WANG ; Xuefeng WANG ; Yong WANG ; Yongjun WANG ; Yuanjie WANG ; Zhihua WANG ; Shaojun WEI ; Yaming WEI ; Jianbo WEN ; Jun WEN ; Jiang WU ; Jufeng WU ; Aijun XIA ; Fei XIA ; Rong XIA ; Jue XIE ; Yanchao XING ; Yan XIONG ; Feng XU ; Yongzhu XU ; Yongan XU ; Yonghe YAN ; Beizhan YAN ; Jiang YANG ; Jiangcun YANG ; Jun YANG ; Xinwen YANG ; Yongyi YANG ; Chunyan YAO ; Mingliang YE ; Changlin YIN ; Ming YIN ; Wen YIN ; Lianling YU ; Shuhong YU ; Zebo YU ; Yigang YU ; Anyong YU ; Hong YUAN ; Yi YUAN ; Chan ZHANG ; Jinjun ZHANG ; Jun ZHANG ; Kai ZHANG ; Leibing ZHANG ; Quan ZHANG ; Rongjiang ZHANG ; Sanming ZHANG ; Shengji ZHANG ; Shuo ZHANG ; Wei ZHANG ; Weidong ZHANG ; Xi ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Xiaojun ZHANG ; Guoqing ZHAO ; Jianpeng ZHAO ; Shuming ZHAO ; Beibei ZHENG ; Shangen ZHENG ; Huayou ZHOU ; Jicheng ZHOU ; Lihong ZHOU ; Mou ZHOU ; Xiaoyu ZHOU ; Xuelian ZHOU ; Yuan ZHOU ; Zheng ZHOU ; Zuhuang ZHOU ; Haiyan ZHU ; Peiyuan ZHU ; Changju ZHU ; Lili ZHU ; Zhengguo WANG ; Jianxin JIANG ; Deqing WANG ; Jiongcai LAN ; Quanli WANG ; Yang YU ; Lianyang ZHANG ; Aiqing WEN
Chinese Journal of Trauma 2024;40(10):865-881
Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.
6.Anemoside B4 regulates fatty acid metabolism reprogramming in mice with colitis-associated cancer.
Xin YANG ; Jing JIA ; Xin-Xu XIE ; Meng-Qiang WAN ; Yu-Lin FENG ; Ying-Ying LUO ; Hui OUYANG ; Jun YU
China Journal of Chinese Materia Medica 2023;48(9):2325-2333
The study aimed to investigate the effect of anemoside B4(B4) on fatty acid metabolism in mice with colitis-associated cancer(CAC). The CAC model was established by azoxymethane(AOM)/dextran sodium sulfate(DSS) in mice. Mice were randomly divided into a normal group, a model group, and low-, medium-, and high-dose anemoside B4 groups. After the experiment, the length of the mouse colon and the size of the tumor were measured, and the pathological alterations in the mouse colon were observed using hematoxylin-eosin(HE) staining. The slices of the colon tumor were obtained for spatial metabolome analysis to analyze the distribution of fatty acid metabolism-related substances in the tumor. The mRNA levels of SREBP-1, FAS, ACCα, SCD-1, PPARα, ACOX, UCP-2, and CPT-1 were determined by real-time quantitative PCR(RT-qPCR). The results revealed that the model group showed decreased body weight(P<0.05) and colon length(P<0.001), increased number of tumors, and increased pathological score(P<0.01). Spatial metabolome analysis revealed that the content of fatty acids and their derivatives, carnitine, and phospholipid in the colon tumor was increased. RT-qPCR results indicated that fatty acid de novo synthesis and β-oxidation-related genes, such as SREBP-1, FASN, ACCα, SCD-1, ACOX, UCP-2, and CPT-1 mRNA expression levels increased considerably(P<0.05, P<0.001). After anemoside B4 administration, the colon length increased(P<0.01), and the number of tumors decreased in the high-dose anemoside B4 group(P<0.05). Additionally, spatial metabolome analysis showed that anemoside B4 could decrease the content of fatty acids and their derivatives, carnitine, and phospholipids in colon tumors. Meanwhile, anemoside B4 could also down-regulate the expression of FASN, ACCα, SCD-1, PPARα, ACOX, UCP-2, and CPT-1 in the colon(P<0.05, P<0.01, P<0.001). The findings of this study show that anemoside B4 may inhibit CAC via regulating fatty acid metabolism reprogramming.
Mice
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Animals
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Sterol Regulatory Element Binding Protein 1
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Colitis-Associated Neoplasms
;
PPAR alpha/genetics*
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Colonic Neoplasms/genetics*
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Colon
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Azoxymethane
;
RNA, Messenger
;
Dextran Sulfate
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Colitis/drug therapy*
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Mice, Inbred C57BL
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Disease Models, Animal
7.Analysis of Chemical Constituents in Puerariae Lobatae Radix Dispensing Granules by UPLC-Q-TOF-MS/MS
Meiqing CHEN ; Weifeng ZHU ; Yongmei GUAN ; Yulin FENG ; Yanli ZHANG ; Xiucun JING ; Wanqian PENG ; Hui OUYANG ; Qiong LI
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(19):176-186
ObjectiveA rapid method for identification of chemical constituents in Puerariae Lobatae Radix dispensing granules was established in order to clarify the material basis. MethodThe chemical constituents of Puerariae Lobatae Radix dispensing granules was qualitatively analyzed by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) under positive and negative ion modes, and the chromatographic conditions were on an ACQUITY UPLC HSS T3 column(2.1 mm×100 mm, 1.8 μm) with 0.1% formic acid aqueous solution(A)-0.1% formic acid acetonitrile solution(B) as mobile phase for gradient elution(0-4 min, 5%-10%B; 4-10 min, 10%-15%B; 10-20 min, 15%-16%B; 20-27 min, 16%-31%B; 27-33 min, 31%-59%B; 33-42 min, 59%-95%B; 42-42.1 min, 95%-5%B; 42.1-45 min, 5%B), the flow rate was 0.35 mL·min-1, the column temperature was 40 ℃, the injection volume was 5 μL, and electrospray ionization(ESI) was selected. Then these chemical constituents were comprehensively identified based on PeakView 1.2, PubChem, ChemicalBook, ChemSpider, comparative control profiles and literature information. ResultA total of 128 chemical constituents were identified from the dispensing granules, including 60 flavonoids, 26 organic acids, 7 glycosides, 6 coumarins, 3 nucleosides and 26 other compounds. By focusing on the cleavage patterns of flavonoids, organic acids, glycosides, coumarins, nucleosides and other compounds, 12 compounds that have not been reported in Puerariae Lobatae Radix species were identified from the dispensing granules. ConclusionThe established method can systematically and rapidly identify the chemical constituents in Puerariae Lobatae Radix dispensing granules, and cleared it composition is mainly flavonoids and organic acids. Laying a foundation for the study of the material basis, mechanism of action and clinical application of the dispensing granules.
8.Reverse partial pulmonary resection: a new surgical approach for pediatric pulmonary cysts.
Libo YANG ; Haishen ZHOU ; Xuejun OUYANG ; Fuwei ZHANG ; Jing FENG ; Jiaqing ZHANG
Journal of Southern Medical University 2023;43(4):649-653
OBJECTIVE:
To evaluate the safety and efficacy of reverse partial lung resection for treatment of pediatric pulmonary cysts combined with lung abscesses or thoracic abscess.
METHODS:
We retrospectively analyzed the clinical data of children undergoing reverse partial lung resection for complex pulmonary cysts in our hospital between June, 2020 and June, 2021.During the surgery, the patients lay in a lateral position, and a 3-5 cm intercostal incision was made at the center of the lesion, through which the pleura was incised and the fluid or necrotic tissues were removed.The anesthesiologist was instructed to aspirate the sputum in the trachea to prevent entry of the necrotic tissues in the trachea.The cystic lung tissue was separated till reaching normal lung tissue on the hilar side.The proximal end of the striated tissue in the lesion was first double ligated with No.4 silk thread, the distal end was disconnected, and the proximal end was reinforced with continuous sutures with 4-0 Prolene thread.The compromised lung tissues were separated, and the thoracic cavity was thoroughly flushed followed by pulmonary inflation, air leakage management and incision suture.
RESULTS:
Sixteen children aged from 3 day to 2 years underwent the surgery, including 3 with simple pulmonary cysts, 11 with pulmonary cysts combined with pulmonary or thoracic abscess, 1 with pulmonary cysts combined with tension pneumothorax and left upper lung bronchial defect, and 1 with pulmonary herpes combined with brain tissue heterotaxy.All the operations were completed smoothly, with a mean operation time of 129 min, an mean hospital stay of 11 days, and a mean drainage removal time of 7 days.All the children recovered well after the operation, and 11 of them had mild air leakage.None of the children had serious complications or residual lesions or experienced recurrence of infection after the operation.
CONCLUSION
Reverse partial lung resection is safe and less invasive for treatment of complex pediatric pulmonary cysts complicated by infections.
Humans
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Child
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Abscess
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Retrospective Studies
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Lung/surgery*
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Cysts/surgery*
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Bronchi
9.Baimai Ointment relieves chronic pain induced by chronic compression of dorsal root ganglion in rats by regulating neuroactive ligand-receptor interaction and HIF-1 signaling pathway.
Fang-Ting ZHOU ; Ying ZONG ; Wu-Qiong HOU ; Sen-Sen LI ; Fei YANG ; Li-Ting XU ; Xia MAO ; Yu-Dong LIU ; Xiao-Hui SU ; Hong-Ye WAN ; Jing-Feng OUYANG ; Qiu-Yan GUO ; Wei-Jie LI ; Zhen WANG ; Chao WANG ; Na LIN
China Journal of Chinese Materia Medica 2023;48(23):6457-6474
The Baimai Ointment with the effect of relaxing sinew and activating collaterals demonstrates a definite effect on Baimai disease with pain, spasm, stiffness and other symptoms, while the pharmacodynamic characteristics and mechanism of this agent remain unclear. In this study, a rat model of chronic compression of L4 dorsal root ganglion(CCD) was established by lumbar disc herniation, and the efficacy and mechanism of Baimai Ointment in the treatment of CCD were preliminarily explored by behavioral tests, side effect evaluation, network analysis, antagonist and molecular biology verification. The pharmacodynamic experiment indicated that Baimai Ointment significantly improved the pain thresholds(mechanical pain, thermal pain, and cold pain) and gait behavior of CCD model rats without causing tolerance or obvious toxic and side effects. Baimai Ointment inhibited the second-phase nociceptive response of mice in the formalin test, increased the hot plate threshold of normal mice, and down-regulated the expression of inflammatory cytokines in the spinal cord. Network analysis showed that Baimai Ointment had synergistic effect in the treatment of CCD and was related to descending inhibition/facilitation system and neuroinflammation. Furthermore, behavioral tests, Western blot, and immunofluorescence assay revealed that the pain-relieving effect of Baimai Ointment on CCD may be related to the regulation of the interaction between neuroactive ligand and receptors(neuroligands) such as CHRNA7, ADRA2A, and ADRB2, and the down-regulation of the expression of NOS2/pERK/PI3K, the core regulatory element of HIF-1 signaling pathway in spinal microglia. The findings preliminarily reveal the mechanism of relaxing sinew and activating collaterals of Baimai Ointment in the treatment of Baimai disease, providing a reference for the rational drug use and further research of this agent.
Rats
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Mice
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Animals
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Chronic Pain/metabolism*
;
Rats, Sprague-Dawley
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Ganglia, Spinal/metabolism*
;
Ligands
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Signal Transduction
;
Hyperalgesia/metabolism*
;
Drugs, Chinese Herbal
10.Neurorotective Effect of Chaihu Jia Longgu Mulitang on Parkinson's Disease with Depression Model Rats and Its Mechanism Based on AMPK/mTOR Signaling Pathway
Wei LIU ; Jun-ling CAO ; Zhi-wei JING ; Tuo-tuo CUI ; Meng-xia YIN ; Xin LIU ; Jing-feng OUYANG
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(8):21-29
ObjectiveTo observe the protective effect of Chaihu Jia Longgu Mulitang (CLMT) on dopaminergic neurons in Parkinson's disease with depression (PDD) model rats, and to explore the mechanism based on adenosine monophosphate-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) signaling pathway. MethodAmong the 80 male SD rats, 10 were randomly selected as normal group and the rest were treated with long-term low-dose subcutaneous injection of rotenone in the neck and back combined with chronic unpredictable mild stress (CUMS) to establish PDD rat model. The successfully modeled PDD rats were randomly divided into model group, western medicine group (madopar 0.032 g·kg-1+fluoxetine hydrochloride 0.002 g·kg-1), CLMT low-dose, medium-dose and high-dose groups (5, 10 and 20 g·kg-1), 10 rats in each group. Normal group and model group were administrated with the same amount of normal saline by gavage for 4 consecutive weeks. Behavioral changes of rats in each group were evaluated by open field test and pole climbing test. The content of dopamine (DA) and 5-hydroxytryptamine (5-HT) in cerebrospinal fluid was determined by high performance liquid chromatography (HPCL). The pathological changes of dopaminergic neurons in substantia nigra of rats were observed by hematoxylin-eosin (HE) staining. The positive expression of tyrosine hydroxylase (TH) and expression of α-synuclein in substantia nigra were detected by immunohistochemistry (IHC) and immunofluorescence (IF), repsectively. The protein expression of microtubule-associated protein 1 light chain 3 (LC3), adenosine monophosphate-activated protein kinase (AMPK), phosphorylated AMPK (p-AMPK), mammalian target of rapamycin (mTOR) and phosphorylated mTOR (p-mTOR) was detected by Western blot. ResultCompared with the conditions in normal group, the total horizontal distance and the activity time in the central region in open field test and the content of DA and 5-HT in cerebrospinal fluid were decreased (P<0.05, P<0.01), and the time of pole climbing was shortened (P<0.01), with increased score (P<0.01) in model group. Compared with model group, CLMT high-dose group and western medicine group increased the total horizontal distance and activity time in the central region and the content of DA and 5-HT (P<0.05, P<0.01), and extended the time of climbing pole (P<0.05), with decreased score (P<0.05, P<0.01). Compared with those in normal group, the number of dopaminergic neurons in the substantia nigra was reduced, with narrowed and loosely arranged cell body. The fluorescence expression of α-synuclein was enhanced (P<0.01), and the positive expression of TH was decreased (P<0.01) in model group. Compared with model group, CLMT high-dose group and western medicine group showed elevated number of dopaminergic neurons in the substantia nigra, with enlarged cell body, and decreased fluorescence expression of α-synuclein, and enhanced the positive expression of TH (P<0.05, P<0.01). Compared with normal group, model group had lowered expression of LC3Ⅱ/Ⅰ, p-AMPK/AMPK in striatum (P<0.05, P<0.01) and increased expression of p-mTOR/mTOR (P<0.01). Compared with those in model group, LC3Ⅱ/Ⅰ and p-AMPK/AMPK expression were increased (P<0.05, P<0.01) and p-mTOR /mTOR expression was decreased (P<0.01) in CLMT high-dose group and western medicine group. ConclusionCLMT exerts a neuroprotective effect by inhibiting rotenone neurotoxicity. It enhances the level of DA, and thus improves the depression condition in rats with Parkinson's disease. The underlying mechanism may be related to the regulation of AMPK/mTOR signaling pathway, activation of autophagy, and promotion of degrading α-synuclein.

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