1.Mechanism of Zuogui Jiangtang Jieyu Prescription Against Damage to Hippocampal Synaptic Microenvironment via Suppressing GluR2/Parkin Signal-mediated Mitophagy in Rats with Diabetes-related Depression
Jian LIU ; Lin LIU ; Xiaoyuan LIN ; Wei LI ; Yuhong WANG ; Hui YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):104-112
ObjectiveTo reveal the mechanism of Zuogui Jiangtang Jieyu prescription against damage to hippocampal synaptic microenvironment via suppressing glutamate receptor 2 (GluR2)/Parkin signal-mediated mitophagy in rats with diabetes-related depression (DD). MethodsEighty male SD rats underwent adaptive feeding for 5 days before the study. Ten rats were randomly assigned to the normal group. The model of DD rats was established with the rest by 2-week high-fat diet + streptozotocin (STZ) tail intravenous injection + 28 days of chronic unpredictable mild stress (CUMS) combined with isolation. The rats were randomly divided into a normal group, a model group, a GluR2 blocker group (5 μg·kg-1), a GluR2 agonist group (10 μg·kg-1), a metformin + fluoxetine group (0.18 g·kg-1 metformin + 1.8 mg·kg-1 fluoxetine), and high- and low-dose Zuogui Jiangtang Jieyu prescription groups (20.52 and 10.26 g·kg-1, respectively). The rats in the GluR2 blocker group and the GluR2 agonist group were continuously injected with CNQX and Cl-HIBO in the dentate gyrus of the hippocampus once a week starting from stress modeling, respectively, while the metformin + fluoxetine group and the high- and low-dose Zuogui Jiangtang Jieyu prescription groups were continuously given intragastric administration for 28 d at the same time of stress modeling. Depression-like behavior was evaluated by open field and forced swimming experiments. The levels of serum insulin and adenosine triphosphate (ATP) in hippocampus were detected by biochemical analysis. The levels of 5-hydroxytryptamine (5-HT) and dopamine (DA) in hippocampus were detected by enzyme-linked immunosorbent assay (ELISA). The autophagosomes of hippocampal neurons were observed by transmission electron microscopy. The morphology and structure of dendrites and spines of hippocampal neurons were evaluated by Golgi staining. Western blot detected the expression levels of GluR2 and Parkin proteins in hippocampus. The expression levels of GluR2, Parkin, regulating synaptic membrane exocytosis protein 3 (RIMS3), and postsynaptic density protein 95 (PSD95) in the dentate gyrus of the hippocampus were detected by immunofluorescence. ResultsCompared with the normal group, the model group exhibited reduced total activity distance in the open field and increased immobility time in forced swimming (P<0.01), lowered levels of serum insulin and ATP, 5-HT, and DA in hippocampus (P<0.01), increased autophagosomes of hippocampal neurons, significantly damaged morphology and structure of dendrites and spines of hippocampal neurons, decreased expression levels of GluR2, RIMS3, and PSD95 in hippocampus, and an increased Parkin expression level (P<0.05, P<0.01). Compared with the model group, the GluR2 blocker group and the GluR2 agonist group showed aggravation and alleviation of the above abnormal changes, respectively (P<0.05, P<0.01). The above depression-like behavior was significantly improved in the high- and low-dose Zuogui Jiangtang Jieyu prescription groups to different degrees. Specifically, the two groups saw elevated levels of serum insulin and ATP, 5-HT, and DA in hippocampus (P<0.05, P<0.01), restrained increase in autophagosomes and damage to morphology and structure of dendrites and spines of hippocampal neurons, up-regulated protein expression levels of GluR2, RIMS3, and PSD95, and down-regulated Parkin expression level (P<0.05, P<0.01). ConclusionZuogui Jiangtong Jieyu prescription can ameliorate the mitophagy-mediated damage to hippocampal synaptic microenvironment in DD rats, the mechanism of which might be related to the regulation of GluR2/Parkin signaling pathway.
2.Chinese Materia Medica by Regulating Nrf2 Signaling Pathway in Prevention and Treatment of Ulcerative Colitis: A Review
Yasheng DENG ; Lanhua XI ; Yanping FAN ; Wenyue LI ; Tianwei LIANG ; Hui HUANG ; Shan LI ; Xian HUANG ; Chun YAO ; Guochu HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):321-330
Ulcerative colitis(UC) is a chronic non-specific inflammatory bowel disease characterized by inflammation and ulceration of the colonic mucosa and submucosa, and its complex pathogenesis involves immune abnormality, oxidative stress and other factors. The nuclear transcription factor E2-related factor 2(Nrf2), encoded by the Nfe212 gene, plays a central role in antioxidant responses. It not only activates various antioxidant response elements such as heme oxygenase-1(HO-1) and quinone oxidoreductase 1(NQO1), but also enhances the activity of glutathione-S-transferase(GST) and superoxide dismutase 1(SOD1), effectively eliminating reactive oxygen species(ROS) accumulated in the body, and mitigating oxidative stress-induced damage to intestinal mucosa. In addition, Nrf2 can reduce the release of inflammatory factors and infiltration of immune cells by regulating immune response, cell apoptosis and autophagy pathways, thereby alleviating intestinal inflammation and promoting the repair and regeneration of damaged mucosa. Based on this, this paper reviews the research progress of Chinese materia medica in the prevention and treatment of UC by modulating the Nrf2 signaling pathway. It deeply explores the physiological role of Nrf2, the molecular mechanism of activation, the protective effect in the pathological process of UC, and how active ingredients in Chinese materia medica regulate the Nrf2 signaling pathway through multiple pathways to exert their potential mechanisms. These studies have revealed in depth that Chinese materia medica can effectively combat oxidative stress by regulating the Nrf2 signaling pathway. It can also play a role in anti-inflammatory, promoting autophagy, inhibiting apoptosis, protecting the intestinal mucosal barrier, and promoting intestinal mucosal repair, providing new ideas and methods for the multi-faceted treatment of UC.
3.Evaluation of Effect of Tongnaoyin on Blood-brain Barrier Injury in Acute Ischemic Stroke Patients Based on Dynamic Contrast-enhanced Magnetic Resonance Imaging
Yangjingyi XIA ; Shanshan LI ; Li LI ; Xiaogang TANG ; Xintong WANG ; Qing ZHU ; Hui JIANG ; Cuiping YUAN ; Yongkang LIU ; Zhaoyao CHEN ; Wenlei LI ; Yuan ZHU ; Minghua WU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):140-146
ObjectiveTo evaluate the effects of Tongnaoyin on the blood-brain barrier status and neurological impairment in acute ischemic stroke (AIS) patients with the syndrome of phlegm-stasis blocking collaterals by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). MethodsA total of 63 patients diagnosed with AIS in the Jiangsu Province Hospital of Chinese Medicine from October 2022 to December 2023 were enrolled in this study. According to random number table method,the patients were assigned into a control group (32 cases) and an observation group (31 cases). The control group received conventional Western medical treatment,and the observation group took 200 mL Tongnaoyin after meals,twice a day from day 2 of admission on the basis of the treatment in the control group. After 7 days of treatment,the patients were examined by DCE-MRI. The baseline data for two groups of patients before treatment were compared. The National Institute of Health Stroke Scale (NIHSS) score and modified Rankin Scale (mRS) score were recorded before treatment and after 90 days of treatment for both groups. The rKtrans,rKep,and rVe values were obtained from the region of interest (ROI) of the infarct zone/mirror area and compared between the two groups. ResultsThere was no significant difference in the NIHSS or mRS score between the two groups before treatment. After 90 days of treatment,the NIHSS and mRS scores declined in both groups,and the observation group had lower scores than the control group (P<0.05). After treatment,the rKtrans and rVe in the observation group were lower than those in the control group (P<0.01). ConclusionCompared with conventional Western medical treatment alone,conventional Western medical treatment combined with Tongnaoyin accelerates the repair of the blood-brain barrier in AIS patients,thereby ameliorating neurological impairment after AIS to improve the prognosis.
4.Clinical Evidence Profile of Eleven Expensive Chinese Patent Medicines: A Scoping Analysis
Yajing LI ; Miaomiao LI ; Le ZHANG ; Wenya WANG ; Hui ZHAO ; Xing LIAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):227-238
ObjectiveThis study employed the scoping review method to systematically retrieve and analyze the basic information and clinical research evidence of expensive Chinese patent medicines (CPMs), aiming to provide a basis for future related research and clinical applications. MethodsEight Chinese and English databases were systematically searched for the clinical research evidence on expensive CPMs. ResultsEleven expensive CPMs (Angong Niuhuang Wan, Jufang Zhibao Wan, Suhexiang Wan, Pien Tze Huang, Niuhuang Qingxin Wan, Qinggong Shoutao Wan, Compound Realgar Natural Indigo Tablets, Xihuang Wan, Dingkun Wan, Babao Wan, and Guilingji Capsules) were selected. A total of 365 related studies were included in this review, comprising 331 clinical studies (of which 291 were randomized controlled trials), 30 systematic reviews and Meta-analyses, 3 expert consensus, and 1 rapid health technology assessment. Among the 11 CPMs, 2(Angong Niuhuang Wan and Jufang Zhibao Wan) had a daily price over 500 yuan. The famous and precious Chinese medicinal materials involved included Moschus (frequency of 7), Bovisc Alculus (7), and Borneol (5). The dosage forms included pills, capsules, oral liquid, tablets, and lozenges. The diseases treated by these CPMs mainly included malignant tumors, cerebrovascular diseases, gynecological diseases, and hepatobiliary system diseases. The sample sizes of the clinical studies were mainly concentrated within the range of 51-100 cases, and the main control form was CPM + basic Western medicine treatment vs. basic Western medicine treatment. The 331 clinical studies reported a total of 44 adverse events occurred, of which 36 were determined to be adverse reactions. ConclusionThe scarcity of raw materials leads to the high prices of expensive CPMs. The difficulty of conducting clinical research and the critical and severe cases treated lead to a lack of clinical research evidence with large sample sizes. The uneven distribution of existing studies, incomplete information on medicine package, and non-standard clinical research designs remain to be addressed in the future.
5.Genetic Transformation for Medicinal Plants: A Review
Haoxiyu ZHANG ; Longfei LIN ; Yuan YUAN ; Yuling LIU ; Hui LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):323-330
Medicinal plants, with diverse species, high heterozygosity, and special breeding objectives, can be hardly bred with conventional hybridization techniques. Plant genetic transformation is highly selective and can specifically change the traits of plants, serving as an important technical means for the breeding of medicinal plants. The commonly used plant genetic transformation technologies include Agrobacterium-mediated transformation and particle bombardment. Agrobacterium-mediated transformation is the most widely used method, while it is not applicable to all medicinal plants due to the high specificity. Although not specific, particle bombardment is limited in application due to the low conversion efficiency and external force damage to cells and tissue. With the rise and development of nanotechnology, the emerging nanomaterial-mediated transformation has solved the problems of the above two technologies. However, limited by its late development, the mechanism of nanomaterial-mediated introduction of genetic materials into plant cells remains unclear, and thus this technology is rarely used in medicinal plants. This article summarizes the development status of several commonly used or emerging plant genetic transformation technologies such as Agrobacterium-mediated transformation, particle bombardment, and nanomaterial-mediated transformation, as well as their application in different medicinal plants. Furthermore, this article looks forward to the development trend of genetic transformation technologies for plants and their application prospects in medicinal plants and Chinese materia medica resources, aiming to provide new technical ideas for the genetic improvement and germplasm innovation of medicinal plants and inject new impetus into the sustainable development of Chinese materia medica resources.
6.Comparison of bilateral implantation of extended depth-of-focus intraocular lens and mix-and-match implantation of extended depth-of-focus intraocular lens with a diffractive bifocal intraocular lens
Tong LI ; Zhuoya LI ; Rong GUO ; Xiaomin HU ; Hui ZHANG
International Eye Science 2025;25(3):337-343
AIM: To compare the clinical outcomes of extended depth-of-focus intraocular lenses(EDOF IOLs)using either micromonovision implantation or mixed implantation of EDOF and diffractive bifocal IOLs.METHODS: This retrospective clinical trial included 130 patients(260 eyes), who were divided into two groups. Group RR comprised 70 patients(140 eyes)bilaterally implanted with ZXR00 IOLs(Tecnis ZXR00, where one target was -0.5 D to -0.75 D and the other was 0 to -0.25 D). Group RM comprised 60 patients(120 eyes)unilaterally implanted with both ZXR00 and ZMB00 IOLs(Tecnis ZMB00, 0 to -0.25 D). Postoperative outcomes were compared after 3 mo, including visual acuity, defocus curves, stereoacuity, modulation transfer functions(MTFs), higher-order aberrations, and Visual Function-14(VF-14)questionnaire responses.RESULTS: Group RR had superior bilateral intermediate vision, while the group RM had superior bilateral near vision(both P<0.05). Group RM also exhibited superior MTFs and reduced higher-order aberrations(both P<0.05). Stereoacuity and VF-14 questionnaire results showed no statistically significant difference between groups(P>0.05).CONCLUSION: The implantation of micromonovision has significantly improved near vision. IOLs and their collocation can be customized according to individual patient needs to achieve precise treatment and provide cataract patients with high-quality vision.
7.Comparison of bilateral implantation of extended depth-of-focus intraocular lens and mix-and-match implantation of extended depth-of-focus intraocular lens with a diffractive bifocal intraocular lens
Tong LI ; Zhuoya LI ; Rong GUO ; Xiaomin HU ; Hui ZHANG
International Eye Science 2025;25(3):337-343
AIM: To compare the clinical outcomes of extended depth-of-focus intraocular lenses(EDOF IOLs)using either micromonovision implantation or mixed implantation of EDOF and diffractive bifocal IOLs.METHODS: This retrospective clinical trial included 130 patients(260 eyes), who were divided into two groups. Group RR comprised 70 patients(140 eyes)bilaterally implanted with ZXR00 IOLs(Tecnis ZXR00, where one target was -0.5 D to -0.75 D and the other was 0 to -0.25 D). Group RM comprised 60 patients(120 eyes)unilaterally implanted with both ZXR00 and ZMB00 IOLs(Tecnis ZMB00, 0 to -0.25 D). Postoperative outcomes were compared after 3 mo, including visual acuity, defocus curves, stereoacuity, modulation transfer functions(MTFs), higher-order aberrations, and Visual Function-14(VF-14)questionnaire responses.RESULTS: Group RR had superior bilateral intermediate vision, while the group RM had superior bilateral near vision(both P<0.05). Group RM also exhibited superior MTFs and reduced higher-order aberrations(both P<0.05). Stereoacuity and VF-14 questionnaire results showed no statistically significant difference between groups(P>0.05).CONCLUSION: The implantation of micromonovision has significantly improved near vision. IOLs and their collocation can be customized according to individual patient needs to achieve precise treatment and provide cataract patients with high-quality vision.
8.Effect Analysis of Different Interventions to Improve Neuroinflammation in The Treatment of Alzheimer’s Disease
Jiang-Hui SHAN ; Chao-Yang CHU ; Shi-Yu CHEN ; Zhi-Cheng LIN ; Yu-Yu ZHOU ; Tian-Yuan FANG ; Chu-Xia ZHANG ; Biao XIAO ; Kai XIE ; Qing-Juan WANG ; Zhi-Tao LIU ; Li-Ping LI
Progress in Biochemistry and Biophysics 2025;52(2):310-333
Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.
9.Effects and mechanism of paeoniflorin on oxidative stress of ulcerative colitis mice
Xin DAI ; Ying WANG ; Xinyue REN ; Dingxing FAN ; Xianzhe LI ; Jiaxuan FENG ; Shilei LOU ; Hui YAN ; Cong SUN
China Pharmacy 2025;36(4):427-433
OBJECTIVE To investigate the effects and potential mechanism of paeoniflorin on oxidative stress of ulcerative colitis (UC) mice based on adenosine monophosphate-activated protein kinase (AMPK)/nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway. METHODS Male BALB/c mice were randomly divided into control group, model group, inhibitor group (AMPK inhibitor Compound C 20 mg/kg), paeoniflorin low-, medium- and high-dose groups (paeoniflorin 12.5, 25, 50 mg/kg), high- dose of paeoniflorin+inhibitor group (paeoniflorin 50 mg/kg+Compound C 20 mg/kg), with 8 mice in each group. Except for the control group, mice in all other groups were given 4% dextran sulfate sodium solution for 5 days to establish the UC model. Subsequently, mice in each drug group were given the corresponding drug solution intragastrically or intraperitoneally, once a day, for 7 consecutive days. The changes in body weight of mice were recorded during the experiment. Twenty-four hours after the last administration, colon length, malondialdehyde (MDA) content, and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in colon tissues were measured; histopathological morphology of colon tissues, tight junctions between intestinal epithelial cells, and histopathological scoring were all observed and evaluated; the mRNA expressions of AMPK and Nrf2, as well as the protein expressions of heme oxygenase-1(HO-1), occludin and claudin-1, were all determined in colon tissue. RESULTS Compared with model group, paeoniflorin groups exhibited recovery from pathological changes such as inflammatory cell infiltration and crypt damage in the colon tissue, as well as improved tight junction damage between intestinal epithelial cells. Additionally, significant increases or upregulations were observed in body weight, colon length, activities of SOD and GSH-Px, phosphorylation level of AMPK, and protein expression of Nrf2, HO-1, occludin, claudin-1, and mRNA expressions of AMPK and Nrf2; concurrently, MDA content and histopathological scores were significantly reduced (P< 0.05 or P<0.01). In contrast, the inhibitor group showed comparable (P>0.05) or worse (P<0.05 or P<0.01) indicators compared to the model group. Conversely, the addition of AMPK inhibitor could significantly reverse the improvement of high- dose paconiflorin (P<0.01). CONCLUSIONS Paeoniflorin can repair intestinal epithelial cell damage in mice, improve tight junctions between epithelial cells, upregulate the expression of related proteins, and promote the expression and secretion of antioxidant-promoting molecules, thereby ameliorating UC; its mechanism may be associated with activating AMPK/Nrf2 antioxidant pathway.
10.Protective Effect of Shengxiantang on Myocardial Microvascular Injury in Rats with Chronic Heart Failure
Hui GAO ; Zeqi YANG ; Fan GAO ; Hongjing LI ; Aiyangzi LU ; Xingchao LIU ; Qiuhong GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):35-42
ObjectiveTo explore the protective effect of Shengxiantang on cardiac function and myocardial microvascular injury in rats with chronic heart failure (CHF). MethodsThe CHF rat model was prepared by aortic arch constriction (TAC). Of the 72 SD rats, 8 were randomly selected as the sham operation group, where the chest was opened without ligating the aortic arch. The 40 successfully modeled rats were randomly divided into the model group, the Shengxiantang low-, medium-, and high-dose groups (5.1, 10.2, 20.4 g·kg-1), and the trimetazidine group (6.3 mg·kg-1), with 8 rats in each group. Drug administration began 4 weeks after modeling. The administration groups received the corresponding drugs by gavage, while the sham operation and model groups were given the same amount of distilled water for 8 consecutive weeks. Echocardiography was used to assess cardiac function. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of nitric oxide (NO), endothelin (ET-1), vascular endothelial growth factor (VEGF), and von Willebrand factor (vWF). Ultrastructural changes of microvessels were observed by transmission electron microscopy. Immunohistochemistry was used to detect the expression levels of ATP synthase subunit (ATP5D) and F-actin in myocardial tissue. Western blot was used to detect the expression levels of occludin, claudin, vascular endothelial cadherin (VE-Cadherin), and zonula occludens-1 (ZO-1). Microvessel density was measured by immunofluorescence staining. ResultsCompared with the sham operation group, the ejection fraction (EF) and left ventricular shortening fraction (FS) in the model group were significantly decreased (P<0.01), while the left ventricular diastolic diameter (LVIDd), left ventricular systolic diameter (LVIDs), left ventricular end-diastolic posterior wall thickness (LVPWd), left ventricular end-systolic posterior wall thickness (LVPWs), left ventricular end-diastolic volume (LVVOLd), and left ventricular end-systolic volume (LVVOLs) were significantly increased (P<0.01). The levels of NO and VEGF were significantly decreased (P<0.01), while the levels of ET-1 and vWF were significantly increased (P<0.01). Under electron microscopy, the microvascular basement membrane was incomplete and the tight junctions were blurred. The expression levels of ATP5D, F-actin, occludin, claudin, ZO-1, and VE-Cadherin were significantly decreased (P<0.05, P<0.01), and the relative density of microvessels was significantly reduced (P<0.05, P<0.01). After intervention with Shengxiantang, the EF and FS of CHF rats significantly increased (P<0.01), while the LVIDd, LVIDs, LVPWd, LVPWs, LVVOLd, and LVVOLs significantly decreased (P<0.01). The levels of NO and VEGF significantly increased (P<0.01), while the levels of ET-1 and vWF significantly decreased (P<0.01). Under electron microscopy, the microvascular basement membrane was relatively complete and the tight junctions were more continuous. The expression levels of ATP5D, F-actin, occludin, claudin, ZO-1, and VE-Cadherin significantly increased (P<0.05, P<0.01), and the relative density of microvessels significantly increased (P<0.01). ConclusionShengxiantang can effectively improve the cardiac function of CHF rats, reduce microvascular endothelial injury, strengthen the connection between endothelial cells, and increase microvessel density, thereby protecting myocardial microvascular injury.

Result Analysis
Print
Save
E-mail