1.Mechanistic of Yueju Wan volatile oil in inhibiting inflammation for antidepressant effects by regulating AGE/PI3K/Akt pathway.
Tan-Lu CHU ; Ze-Jun GUO ; Wei ZHANG ; Ling-Feng WANG ; Shu-Rui LYU ; Wan-Yu GUO ; Xiao-Ming ZHONG ; Feng-Mei QIU ; Zhen HUANG
China Journal of Chinese Materia Medica 2025;50(11):3147-3158
The antidepressant activity and molecular mechanisms of Yueju Wan volatile oil were investigated. The Yueju Wan volatile oil was extracted by using supercritical CO_2. Gas chromatography-mass spectrometry(GC-MS) combined with network pharmacology identified 28 chemical constituents in Yueju Wan volatile oil, primarily terpenes and lactones. A total of 123 overlapping targets were associated with depression, including core targets of interleukin-1β(IL-1β), signal transducer and activator of transcription 3(STAT3), and caspase-3(CASP3). These targets were mainly involved in the prolactin, advanced glycation end products/receptor(AGE/RAGE), and phosphoinositide 3-kinase/protein kinase B(PI3K/Akt) signaling pathways. A reserpine-induced depression mouse model was established to evaluate the therapeutic effects and mechanisms of Yueju Wan volatile oil. The effects of Yueju Wan volatile oil on depression-like behavior in mice were evaluated by analyzing body mass, body temperature index, tail suspension immobility time, forced swimming immobility time, and sucrose preference. Hematoxylin-eosin(HE) staining revealed neuronal protection of Yueju Wan volatile oil in the brain of mice. Enzyme-linked immunosorbent assay(ELISA) and Western blot were employed to detect the protein expression of AGEs, IL-1β, phosphorylated PI3K(p-PI3K), Akt, phosphorylated Akt(p-Akt), nuclear factor κB(NF-κB), and brain-derived neurotrophic factor(BDNF). Behavioral evaluation showed that Yueju Wan volatile oil could effectively control the decline of body mass and body temperature of depressed mice, reduce tail suspension and swimming immobility time, and enhance their preference for sucrose. Histopathological examination showed that Yueju Wan volatile oil could alleviate the neuronal damage in CA1 and dentate gyrus(DG) of the hippocampus of mice. ELISA and Western blot results showed that Yueju Wan volatile oil could significantly increase the protein expression levels of PI3K, Akt, and BDNF and significantly decrease the protein expression levels of AGEs, IL-1β, p-PI3K, p-Akt, and NF-κB in the hippocampus of mice. Furthermore, the p-PI3K/PI3K and p-Akt/Akt ratios were significantly decreased at medium and high doses. These findings suggest that the aromatherapy of Yueju Wan volatile oil can significantly improve reserpine-induced depression-like behavior in mice, which may be related to reducing the expression of neuronal membrane protein AGEs, reducing the phosphorylation levels of PI3K and Akt, inhibiting NF-κB entry into the nucleus, and alleviating the release of pro-inflammatory factors and nerve injury.
Animals
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Antidepressive Agents/chemistry*
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Mice
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Proto-Oncogene Proteins c-akt/immunology*
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Phosphatidylinositol 3-Kinases/immunology*
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Oils, Volatile/chemistry*
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Male
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Drugs, Chinese Herbal/chemistry*
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Signal Transduction/drug effects*
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Depression/metabolism*
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Glycation End Products, Advanced/immunology*
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Humans
2.In vitro cultured calculus bovis alleviates cerebral ischemia/reperfusion injury through regulating microglial polarization and inhibiting NLRP3.
Tanlu CHU ; Wei ZHANG ; Jingwen CHEN ; Zeyue PAN ; Lingfeng WANG ; Xiaoming ZHONG ; Fengmei QIU ; Zhen HUANG
Journal of Zhejiang University. Medical sciences 2025;54(3):360-371
OBJECTIVES:
To investigate the effect of in vitro cultured calculus bovis (ICCB) on cerebral ischemia/reperfusion injury (CIRI) and its mechanism.
METHODS:
A CIRI rat model and a cell model were induced by middle cerebral artery occlusion (MCAO) in Sprague Dawley rats and oxygen glucose deprivation/reperfusion (OGD/R) in BV2 cells, respectively. The CIRI rat model was evaluated using the modified neurological severity score (mNSS), brain water content, and cerebral infarction volume after 1.5 h of ischemia followed by 72 h of reperfusion. Histopathological changes in the cortex and hippocampal CA1 region were observed with hematoxylin and eosin staining. Microglial polarization and NOD-like receptor thermal protein domain associated protein (NLRP) 3 inflammasome expression in the cortex were examined by immunofluorescence. BV2 cell viability was measured via MTT assay after treatment with ICCB and Nigericin. The expressions of NLRP3, ASC, caspase-1 proteins and inflammatory cytokines were detected with Western blotting in OGD/R treated BV2 cells (0.5 h OGD+24 h reperfusion) and in cells pretreated with Nigericin for 24 h.
RESULTS:
ICCB treatment significantly improved neurological function, reduced cerebral infarct volume and brain water content, and mitigated pathological damage in the cortical and hippocampal CA1 regions of rats subjected to CIRI (all P<0.05). ICCB promoted the transition of cortical microglia from M1 to M2 phenotypes and suppressed NLRP3 activation in microglial cells (all P<0.01). ICCB significantly down-regulated the expression of NLRP3, ASC, and caspase-1 proteins, and reduced the secretion of IL-18 and IL-1β in BV2 cells of OGD/R model (all P<0.01). In addition, Nigericin significantly reversed the salvage effect of ICCB on model cells (both P<0.01) and the modulation of inflammatory cytokines (P<0.05).
CONCLUSIONS
ICCB exerts a protective effect against CIRI by mitigating neuroinflammation, through the reduction of M1 microglial polarization, promotion of M2 conversion, and suppression of the NLRP3/ASC/caspase-1 signaling pathway.
Animals
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Rats, Sprague-Dawley
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Reperfusion Injury/prevention & control*
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Microglia/metabolism*
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Rats
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NLR Family, Pyrin Domain-Containing 3 Protein
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Brain Ischemia/metabolism*
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Male
4.Strychni Semen and its active compounds promote axon regeneration following peripheral nerve injury by suppressing myeloperoxidase in the dorsal root ganglia.
Yan ZHANG ; Xin-Yue ZHAO ; Meng-Ting LIU ; Zhu-Chen ZHOU ; Hui-Bin CHENG ; Xu-Hong JIANG ; Yan-Rong ZHENG ; Zhong CHEN
Journal of Integrative Medicine 2025;23(2):169-181
OBJECTIVE:
Treating peripheral nerve injury (PNI) presents a clinical challenge due to limited axon regeneration. Strychni Semen, a traditional Chinese medicine, is clinically used for numbness and hemiplegia. However, its role in promoting functional recovery after PNI and the related mechanisms have not yet been systematically studied.
METHODS:
A mouse model of sciatic nerve crush (SNC) injury was established and the mice received drug treatment via intragastric gavage, followed by behavioral assessments (adhesive removal test, hot-plate test and Von Frey test). Transcriptomic analyses were performed to examine gene expression in the dorsal root ganglia (DRGs) from the third to the sixth lumbar vertebrae, so as to identify the significantly differentially expressed genes. Immunofluorescence staining was used to assess the expression levels of superior cervical ganglia neural-specific 10 protein (SCG10). The ultra-trace protein detection technique was used to evaluate changes in gene expression levels.
RESULTS:
Strychni Semen and its active compounds (brucine and strychnine) improved functional recovery in mice following SNC injury. Transcriptomic data indicated that Strychni Semen and its active compounds initiated transcriptional reprogramming that impacted cellular morphology and extracellular matrix remodeling in DRGs after SNC, suggesting potential roles in promoting axon regeneration. Imaging data further confirmed that Strychni Semen and its active compounds facilitated axon regrowth in SNC-injured mice. By integrating protein-protein interaction predictions, ultra-trace protein detection, and molecular docking analysis, we identified myeloperoxidase as a potentially critical factor in the axon regenerative effects conferred by Strychni Semen and its active compounds.
CONCLUSION
Strychni Semen and its active compounds enhance sensory function by promoting axonal regeneration after PNI. These findings establish a foundation for the future applications of Strychni Semen and highlight novel therapeutic strategies and drug targets for axon regeneration. Please cite this article as: Zhang Y, Zhao XY, Liu MT, Zhou ZC, Cheng HB, Jiang XH, Zheng YR, Chen Z. Strychni Semen and its active compounds promote axon regeneration following peripheral nerve injury by suppressing myeloperoxidase in the dorsal root ganglia. J Integr Med. 2025; 23(2): 169-181.
Animals
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Nerve Regeneration/drug effects*
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Mice
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Peripheral Nerve Injuries/physiopathology*
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Male
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Ganglia, Spinal/enzymology*
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Axons/physiology*
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Peroxidase/antagonists & inhibitors*
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Mice, Inbred C57BL
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Drugs, Chinese Herbal/pharmacology*
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Disease Models, Animal
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Strychnine/pharmacology*
5.Silencing GmWRKY33B genes leads to reduced disease resistance in soybean.
Chenli ZHONG ; Wenxu WANG ; Lina LIAO ; Jianzhong LIU
Chinese Journal of Biotechnology 2024;40(1):163-176
The WRKYs are a group of plant-specific transcription factors that play important roles in defense responses. In this study, we silenced 2 GmWRKY33B homologous genes using a bean pod mosaic virus (BPMV) vector carrying a single fragment from the conserved region of the GmWRKY33B genes. Silencing GmWRKY33B did not result in morphological changes. However, significantly reduced resistances to Pseudomonas syringae pv. glycinea (Psg) and soybean mosaic virus (SMV) were observed in the GmWRKY33B-silenced plants, indicating a positive role of the GmWRKY33B genes in disease resistance. Kinase assay showed that silencing the GmWRKY33B genes significantly reduced the activation of GmMPK6, but not GmMPK3, in response to flg22 treatment. Reverse transcriptase PCR (RT-PCR) analysis of the genes encoding prenyltransferases (PTs), which are the key enzymes in the biosynthesis of glyceollin, showed that the Psg-induced expression of these genes was significantly reduced in the GmWRKY33B-silenced plants compared with the BPMV-0 empty vector plants, which correlated with the presence of the W-boxes in the promoter regions of these genes. Taken together, our results suggest that GmWRKY33Bs are involved in soybean immunity through regulating the activation of the kinase activity of GmMPK6 as well as through regulating the expression of the key genes encoding the biosynthesis of glyceollins.
Glycine max/genetics*
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Disease Resistance/genetics*
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Biological Assay
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Dimethylallyltranstransferase
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Gene Silencing
6.Surveillance of the population density of adult Aedes albopictus in Guangdong Province from 2018 to 2023
Ruipeng LU ; Mingji CHENG ; Ao LUO ; Yating CHEN ; Min LUO ; Jinhua DUAN ; Zongjing CHEN ; Yuwen ZHONG ; Shengjun HU ; Hui DENG
Chinese Journal of Schistosomiasis Control 2024;36(6):591-597
Objective To investigate the fluctuations in the population density of Aedes albopictus and changes in the population density of Ae. albopictus in different geographical areas and different breeding habitats in Guangdong Province from 2018 to 2023, so as to provide insights into prevention and control of mosquito-borne infectious diseases in the province. Methods Ae. albopictus surveillance sites were assigned in 1 609 townships (streets) from 121 districts (counties) of 21 cities in Guangdong Province during the period between March and November from 2018 to 2023. The surveillance of the population density of Ae. albopictus was performed once a month in each surveillance site, and once a month in specific settings in cities where dengue were highly prevalent in Guangdong Province from December to February of the next year during the period from 2018 through 2023. Four streets (villages) were selected in each surveillance site according to the geographic orientation, and mosquito ovitraps were assigned in gardens, rooftops or public green belts at residential areas, parks, hospitals and construction sites. All mosquito ovitraps were collected, and the mosquito ovitrap index (MOI) was calculated. The population density of Ae. albopictus was classified into four grades in each surveillance site according to MOI, including no risk, low risk, medium risk and high risk. The risk classification of the Ae. albopictus density was analyzed in each surveillance site each year from 2018 to 2023, and the population density of Ae. albopictus was analyzed at different months and in different geographical areas and breeding habitats. Results A total of 118 241 Ae. albopictus surveillance sites were assigned in 21 cities of Guangdong Province from 2018 to 2023, and there were 68.26% of the surveillance sites with the population density of Ae. albopictus that met the requirements for dengue prevention and control, among which low, medium and high risk surveillance sites accounted for 23.61%, 6.67% and 1.47%. The risk classification of the Ae. albopictus density increased rapidly in Guangdong Province since April to May each year from 2018 to 2023, and then gradually reduced since September to October, with the peak during the period between May and July. The mean MOI was 4.21 at each surveillance site in Guangdong Province during the period from 2018 to 2023, with 4.69, 4.80, 4.38, 3.82, 3.38, and 4.33 from 2018 to 2023, respectively. The MOI was 4.35, 4.43, 3.53 and 3.58 in the Pearl River Delta region, and eastern, western, and northern Guangdong Province, respectively, and was 4.18, 5.44, 4.75, 3.24, 4.27 and 3.70 in residential areas, parks, construction sites, hospitals, waste collection stations, and other breeding habitats, respectively. Conclusions The population density of adult Ae. albopictus peaked in Guangdong Province during the period between May and July from 2018 to 2023, with a high density of Ae. albopictus in the Pearl River Delta region and eastern Guangdong Province. Targeted Ae. albopictus control measures are recommended to be implemented prior to the peak of the Ae. albopictus population density to reduce the development of mosquito-borne infectious diseases.
7.Influencing factors and path analysis of community nursing needs among patients with middle and advanced Parkinson ′s disease
Qin LI ; Xueli WAN ; Jinhua FENG ; Ling JIANG ; Wanshuang YIN ; Yulu ZHONG ; Caiping SONG
Chinese Journal of Practical Nursing 2024;40(22):1689-1698
Objective:To investigate the current situation of community nursing needs of patients with middle and advanced Parkinson ′s disease, analyze the factors affecting the demand, and further explore the possible pathways of action between the factors, so as to provide the basis for formulating targeted community intervention measures in a more comprehensive way. Methods:A cross-sectional survey of 242 patients with middle and advanced Parkinson ′s disease from the Second Hospital Affiliated to the Army Medical University from November 2022 to January 2023 were selected by convenience sampling method, and the Community Care Need Scale, General Data Questionnaire, Readiness for Hospital Discharge Scale, Medical Coping Modes Questionnaire and the Self-management Effectiveness Questionnaire of Parkinson ′s disease patients were used. SPSS 26.0 was used to analyze the data, and investigated the relationship between readiness for hospital discharge, self-management efficacy, active coping styles, and community nursing needs. Results:A total of 234 valid questionnaires were collected, including 108 males and 126 females, aged 39-93 (67.25±8.93) years. The average score of all dimensions from high to low was: disease treatment dimension (4.16±0.42), daily care dimension (4.05±0.97), fall prevention dimension (4.04±0.80), extended care dimension (3.95±0.65), emotional support dimension (3.77±0.65) and self function (3.75±0.72). Univariate analysis indicated that there were statistically significant differences in community nursing needs scores among middle and advanced Parkinson ′s disease patients with different educational level and different family income ( F=5.11, 3.05, both P<0.05). Readiness for hospital discharge, self-management efficacy and positive coping style were negatively correlated with community nursing needs of patients with middle and advanced Parkinson′s disease ( r=-0.567, -0.412, -0.398, all P<0.01), and self-management efficacy and positive coping style played a partial mediating role between readiness for hospital discharge and community nursing needs. Conclusions:There is a wide range of community nursing needs that patients with middle and advanced Parkinson ′s disease, and patients with primary school and below, high school and above, and low family income are higher. It is suggested that the community disease management process should focus on this group of people. Medical institutions should help patients with middle and advanced Parkinson ′s disease improve their ability to manage the disease by improving discharge preparation services, so that they can smoothly transition from hospital to home, thereby reducing the needs for community nursing.
8.The spatial-temporal characteristics of hand-foot-mouth disease in Minhang District of Shanghai, 2009‒2020
Yating WANG ; Wei ZHONG ; Jinhua PAN ; Zhaowen ZHANG ; Jingjing ZHANG ; Jing LYU ; Biyun JIA ; Zhouyun WANG ; Wanli CHEN ; Xuanzhao ZHANG ; Hualin SU ; Minhui ZHU ; Zhiyin XU
Shanghai Journal of Preventive Medicine 2022;34(5):441-445
ObjectiveThis study aimed to understand the epidemiological characteristics of hand-foot-mouth disease (HFMD) in Minhang District, Shanghai from 2009 to 2020, and provide a scientific basis for the prevention and control of HFMD. MethodsThe case information of HFMD was collected from the National Notifiable Infectious Diseases Reporting System of Chinese Center for Disease Control and Prevention. We used descriptive epidemiological methods to analyze the population characteristics, temporal and spatial distribution of HFMD, the pathogen composition of the case and its changing trend. ResultsFrom 2009 to 2020, a total of 66,198 cases of HFMD were reported in Minhang District, Shanghai, including 377 severe cases (severe case rate 0.57%) and 3 deaths (severs case fatality rate 0.80%). There were more cases of HFMD in boys than in girls (1.5∶1). HFMD patients aged under 5 years predominated, accounting for 88.91% of all cases. Majority of the cases (91.42%) were in scattered children (55.80%) and children in kindergartens (35.62%). The incidence showed a cyclical trend, with low incidence years and high incidence years appearing alternately. The peak period was from April to July, and sometimes there were small peaks during October to December. A total of 12 years time-space scanning analysis revealed 3 clusters. The cluster centers were located in Wujing Town, Huacao Town and Xinzhuang Town, respectively. The proportion of EV71 in common cases was generally decreasing, and reduced to zero in 2019. The proportion of CoxA6 had increased year by year, and reached 75.00% in 2020. CoxA6 became the dominant pathogen in recent years. The number of severe cases had decreased year by year since 2010, and the dominant pathogen was EV71 (90.03% on average) in severe cases. ConclusionThe incidence of HFMD in Minhang District of Shanghai has a downward trend from 2014. The dominant pathogen changes from EV71 to CoxA6, and the dominant pathogen in severe cases is EV71. The discovered temporal and spatial clustering pattern is helpful for in-depth understanding of the distribution and epidemic trend of HFMD in Minhang District, and provides a scientific basis for epidemic prevention and control.
9.Effects of duodenal papillary morphology on selective biliary cannulation
Jie YANG ; Jinhua ZHANG ; Xiangping DING ; Zhong GUO ; Haiwen MA ; Wanjun MA ; Weilin MA
Chinese Journal of Digestive Endoscopy 2022;39(6):453-458
Objective:To study the effect of duodenal papillary morphology on selective biliary cannulation (SBC).Methods:Data of 912 patients with biliopancreatic diseases treated with endoscopic retrograde cholangiopancreatography (ERCP) at the Department of Gastroenterology, Affiliated Hospital of Northwest Minzu University from January 2018 to January 2020 were retrospectively analyzed. Duodenal papillary morphology of patients was classified into 4 types by using Haraldsson's endoscopic classification. The success rate of SBC, the pre-incision rate, the difficult intubation rate and the incidence of post-ERCP pancreatitis (PEP) of different papillary types were analyzed.Results:A total of 912 patients were enrolled in this study, and 86.95% (793/912) duodenal papilla conformed to one type of the classification, of which 77.18% (612/793) were regular type (type Ⅰ), 10.21% (81/793) small nipple type (type Ⅱ), 8.58% (68/793) protruding or drooping type (type Ⅲ), and 4.04% (32/793) wrinkled or ridged type (type Ⅳ). The success rates of SBC in four types of duodenal papilla were 98.86% (605/612), 90.12% (73/81), 88.24% (60/68) and 96.60% (28/32) respectively. The success rate of SBC of type Ⅰ was higher than those of type Ⅱ-Ⅳ (all P<0.008) and there was no significant difference between those of type Ⅱ and type Ⅲ ( P> 0.008). The pre-incision rate in the four types of duodenal papilla were 7.84% (48/612), 32.10% (26/81), 50.00% (34/68) and 25.00% (8/32) respectively. The pre-incision rate of type Ⅰ was lower than those of type Ⅱ-Ⅳ (all P<0.008), and there was no significant difference between those of type Ⅱ and type Ⅲ ( P>0.008). The difficult intubation rate in the four types of duodenal papilla were 12.42% (76/612), 39.51% (32/81), 58.82% (40/68) and 28.12% (9/32) respectively .The difficult intubation rate of type Ⅰ was lower than those of type Ⅱ and type Ⅲ (both P<0.001), and that of type Ⅲ was higher than that of type Ⅳ ( P=0.004) . There was no significant difference between those of type Ⅰ and type Ⅳ or type Ⅱ and type Ⅲ (both P>0.008). The incidences of PEP of the four types were 2.61% (16/612), 12.35% (10/81), 5.88% (4/68) and 6.25% (2/32) respectively. The incidences of PEP of type Ⅱ was higher than that of type Ⅰ ( P<0.001) , and there was no significant difference between those of type Ⅰ and type Ⅳ or type Ⅱ and type Ⅲ (both P>0.008). Conclusion:SBC is affected by duodenal papilla morphology, easiest for type Ⅰ and hard for type Ⅱ and Ⅲ. Attention should be paid to risk of PEP in SBC of type Ⅱ.
10. Fufang Danshen dripping pills protect vascular smooth muscle cells by reducing endoplasmic reticulum stress and autophagy through regulating IRE1-TRAF2-ASK1 -JNK pathway
Xing-Xing LI ; Jun LIU ; Zhong-Cheng XU ; Yang DONG ; Jin ZOU
Chinese Pharmacological Bulletin 2022;38(5):776-793
Aim To investigate the molecular mechanism of the protection of vascular smooth muscle cells by the regulation of endoplasmic reticulum stress and autophagy by Fufang Danshen dripping pills.Methods Fifty patients with atherosclerosis were randomly divided into two groups; one group received normal treatment,while the other group was added Fufang Danshen dripping pills,and the clinical efficacy was observed.Vascular smooth muscle cells were divided into control,ox LDL model,Fufang Danshen dripping pill group,Fufang Danshen dripping pill+endoplasmic reticulum stress inhibitor group,and Fufang Danshen dripping pill+endoplasmic reticulum stress inducer group.Proliferation was detected,and vasodilator function factors and oxidative stress were measured in each group,ER stress marker proteins,autophagy marker proteins and apoptosis related protein expression were detected,and activation of the IRE1-TRAF2-ASK1-JNK signaling pathway was detected.Results Compared with control group,various indicators of cells in ox-LDL model group showed that they were under ER stress,high oxidative stress,high autophagy status,and the IRE1-TRAF2-ASK1-JNK pathway was found to be over activated.However,compared with ox LDL model group,the above indicators in Fufang Danshen dripping pill group and Fufang Danshen dripping pill+endoplasmic reticulum stress inhibitor group were significantly better,the IRE1-TRAF2-ASK1-JNK pathway was over activated,and the endoplasmic reticulum stress inhibitor was more obvious,and Fufang Danshen dripping pill+endoplasmic reticulum stress inducer group significantly reversed the improved effects of Fufang Danshen dripping pills.Conclusions Fufang Danshen dripping pills protect vascular smooth muscle cells by inhibiting excessive activation of the IRE1-TRAF2-ASK1-JNK pathway,decreasing endoplasmic reticulum stress,maintaining proper autophagy,and inhibiting abnormal cell proliferation and apoptosis.

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