1.Mechanism of Shenfu Xiongze Prescription in Regulating Autophagy Level to Intervene in Myocardial Remodeling in Rats via AMPK/mTOR Signaling Pathway
Xueqing WANG ; Wei ZHONG ; Liangliang PAN ; Caihong LI ; Man HAN ; Xiaowei YANG ; Yuanwang YU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):136-144
ObjectiveTo explore the mechanism by which the Shenfu Xiongze prescription regulates autophagy in rats with myocardial remodeling through the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway. MethodsA rat model of myocardial remodeling induced by isoprenaline (ISO) was established. Rats were divided into the blank group,the model group,the low-,medium-, and high-dose groups of Shenfu Xiongze prescription,and the captopril group, 6 rats in each group. Except for the blank group,the rat model of myocardial remodeling was established in the other groups by intraperitoneal injection of 2.5 mg·kg-1 ISO for 3 consecutive weeks. At the same time of modeling, the low-,medium-, and high-dose groups of Shenfu Xiongze prescription were administered the corresponding doses of Shenfu Xiongze prescription solution (8.4,16.8,and 33.6 g·kg-1),and the captopril group was administered captopril solution (25 mg·kg-1). As for the blank group and the model group, the same volume of normal saline was given. The treatment was continued for 3 weeks. Echocardiography was used to observe the cardiac structure and function,and the heart weight index was detected. Masson staining and hematoxylin-eosin (HE) staining were used to observe the pathological morphology changes of myocardial tissue. The levels of interleukin-6 (IL-6) and B-type natriuretic peptide (BNP) in serum were detected by enzyme-linked immunosorbent assay (ELISA). The expression of type Ⅰ collagen (Collagen Ⅰ),type Ⅲ collagen (Collagen Ⅲ),and microtubule-associated protein 1 light chain 3 (LC3) proteins in myocardial tissue was determined by immunohistochemistry. Autophagy was observed by transmission electron microscopy. The mRNA expression of Collagen Ⅰ,Collagen Ⅲ,α-smooth muscle actin (α-SMA),LC3,yeast Atg6 homolog protein (Beclin-1),AMPK,and mTOR in myocardial tissue was detected by quantitative real-time polymerase chain reaction (real-time PCR). The protein expression of Collagen Ⅰ,α-SMA,transforming growth factor-β1 (TGF-β1),LC3,Beclin-1,p62, phosphorylation(p)-AMPK,p-mTOR,AMPK,and mTOR was detected by Western blot. ResultsCompared with the normal group,rats in the model group exhibited significantly decreased values of ejection fraction (EF) and left ventricular fractional shortening (FS) (P<0.01), significantly increased values of left ventricular end-diastolic diameter (LVIDd) and left ventricular end-systolic diameter (LVIDs) (P<0.01). Additionally, the model group also showed increased degrees of inflammatory infiltration and fibrosis of myocardial tissue, significantly elevated levels of serum IL-6 and BNP (P<0.01), significantly increased mRNA and protein levels of Collagen Ⅰ,Collagen Ⅲ,α-SMA,and mTOR (P<0.01),and markedly decreased mRNA and protein levels of LC3,Beclin-1,and AMPK (P<0.05,P<0.01). Compared with the model group, the low-,medium-, and high-dose groups of Shenfu Xiongze prescription presented significantly elevated EF and FS values (P<0.01) and lowered LVIDd and LVIDs (P<0.05). In these groups, the inflammation and fibrosis were alleviated significantly. They also exhibited decreased serum levels of IL-6 and BNP (P<0.01), significantly reduced protein expression of Collagen Ⅰ, α-SMA, TGF-β1, p62, and p-mTOR (P<0.01), significantly decreased mRNA expression of Collagen Ⅰ, Collagen Ⅲ, α-SMA, and mTOR (P<0.01), and significantly increased mRNA and protein levels of LC3, Beclin-1, and AMPK (P<0.05,P<0.01). ConclusionThe Shenfu Xiongze prescription can improve the myocardial remodeling induced by ISO in rats by regulating the autophagy level,enhance cardiac function,and reduce inflammatory and fibrotic levels. This effect may be achieved through the AMPK/mTOR signaling pathway.
2.In Vitro and In Vivo Chemical Composition Analysis of Reference Sample of Jinshui Liujunjian Based on UPLC-Q-TOF-MS/MS
Xinyue YANG ; Huiyu LI ; Yaqi LOU ; Xingxing WANG ; Guifang YU ; Chenfeng ZHANG ; Zhenzhong WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):166-173
ObjectiveTo elucidate the chemical composition of the reference sample of Jinshui Liujunjian and its distribution characteristics in blood and tissues of rats. MethodsUltra performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS) was used to detect the reference sample solution, plasma, and tissue samples of Jinshui Liujunjian under positive and negative ion modes, respectively. Qualitative Analysis 10.0 software and a self-constructed database were employed for primary mass spectrum matching.Compound identification was further validated by comparing retention times, secondary mass spectral fragments, reference standards, and literature data to deduce fragmentation pathways. ResultsA total of 122 compounds were identified in the reference sample of Jinshui Liujunjian, including 47 flavonoids, 5 amino acids, 13 iridoids, 16 triterpenoid saponins, etc., of which 42 compounds were confirmed by comparison with reference substances. A total of 21 prototype components were identified in blood components; 50 prototype components were identified in different tissues, among which 13, 10, 7, 21, 11, 6, 14, and 40 prototype components were identified in the heart, liver, spleen, lung, kidney, brain, large intestine, and stomach, respectively. Among them, 7 compounds such as ferulic acid, glycyrrhizic acid, and nobiletin were exposed in the target organs of lung and kidney. ConclusionThis study elucidates the material basis of the reference samples of Jinshui Liujunjian, primarily composed of flavonoids and triterpenoid saponins, along with their in vivo distribution characteristics. These findings provide a scientific basis for establishing quality evaluation indicators and offer references for subsequent pharmacodynamic and pharmacokinetic investigations.
3.In Vitro and In Vivo Chemical Composition Analysis of Reference Sample of Jinshui Liujunjian Based on UPLC-Q-TOF-MS/MS
Xinyue YANG ; Huiyu LI ; Yaqi LOU ; Xingxing WANG ; Guifang YU ; Chenfeng ZHANG ; Zhenzhong WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):166-173
ObjectiveTo elucidate the chemical composition of the reference sample of Jinshui Liujunjian and its distribution characteristics in blood and tissues of rats. MethodsUltra performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS) was used to detect the reference sample solution, plasma, and tissue samples of Jinshui Liujunjian under positive and negative ion modes, respectively. Qualitative Analysis 10.0 software and a self-constructed database were employed for primary mass spectrum matching.Compound identification was further validated by comparing retention times, secondary mass spectral fragments, reference standards, and literature data to deduce fragmentation pathways. ResultsA total of 122 compounds were identified in the reference sample of Jinshui Liujunjian, including 47 flavonoids, 5 amino acids, 13 iridoids, 16 triterpenoid saponins, etc., of which 42 compounds were confirmed by comparison with reference substances. A total of 21 prototype components were identified in blood components; 50 prototype components were identified in different tissues, among which 13, 10, 7, 21, 11, 6, 14, and 40 prototype components were identified in the heart, liver, spleen, lung, kidney, brain, large intestine, and stomach, respectively. Among them, 7 compounds such as ferulic acid, glycyrrhizic acid, and nobiletin were exposed in the target organs of lung and kidney. ConclusionThis study elucidates the material basis of the reference samples of Jinshui Liujunjian, primarily composed of flavonoids and triterpenoid saponins, along with their in vivo distribution characteristics. These findings provide a scientific basis for establishing quality evaluation indicators and offer references for subsequent pharmacodynamic and pharmacokinetic investigations.
4.A bibliometric and visual analysis of the literature published in the journal of Organ Transplantation since its inception
Xi CAO ; Tao HUANG ; Qiwei YANG ; Lin YU ; Xiaowen WANG ; Wenfeng ZHU ; Haoqi CHEN ; Ning FAN ; Genshu WANG
Organ Transplantation 2026;17(1):133-142
Objective To systematically analyze the literature characteristics of Journal of Organ Transplantation since its inception. Methods Using the China National Knowledge Infrastructure (CNKI) academic journal full-text database as the data source, all articles published in the Journal of Organ Transplantation from January 2010 to August 2025 were retrieved. After excluding non-academic papers, a total of 1 568 research papers were included. R language 4.3.0, Bibliometrix package 3.2.1, and Citespace software were used to analyze the number of publications, publishing institutions, authors, keywords and other aspects. Results The number of publications in Journal of Organ Transplantation increased from an average of 82 articles per year in the early years after its inception to 113 articles per year in recent years, a growth of 37.8%. The geographical distribution of publishing institutions covers 32 provinces, cities and autonomous regions nationwide, mainly concentrated in the South China, East China and North China regions, and has now basically covered the central and western regions in recent years. The author collaboration network includes 45 authors distributed across 7 major collaboration clusters, forming a stable multi-level national research system centered on key university-affiliated hospitals. The high-frequency keywords are dominated by "liver transplantation" (425 times) and "kidney transplantation" (396 times). The theme evolution shows a clear three-stage characteristic: initially focusing on clinical technology application, deepening to immune mechanism exploration in the middle stage, and recently (since 2022) focusing on cutting-edge research areas such as xenotransplantation. Conclusions Journal of Organ Transplantation has witnessed the rapid development of China's organ transplantation cause, fully reflecting the research status and trends in China's organ transplantation field, and has provided an important platform for the future development and international cooperation in China's organ transplantation field.
5.Mechanism of Action of Kaixinsan in Ameliorating Alzheimer's Disease
Xiaoming HE ; Xiaotong WANG ; Dongyu MIN ; Xinxin WANG ; Meijia CHENG ; Yongming LIU ; Yetao JU ; Yali YANG ; Changbin YUAN ; Changyang YU ; Li ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):20-29
ObjectiveTo investigate the mechanism of action of Kaixinsan in the treatment of Alzheimer's disease (AD) based on network pharmacology, molecular docking, and animal experimental validation. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and the Encyclopedia of Traditional Chinese Medicine(ETCM) databases were used to obtain the active ingredients and targets of Kaixinsan. GeneCards, Online Mendelian Inheritance in Man(OMIM), TTD, PharmGKB, and DrugBank databases were used to obtain the relevant targets of AD. The intersection (common targets) of the active ingredient targets of Kaixinsan and the relevant targets of AD was taken, and the network interaction analysis of the common targets was carried out in the STRING database to construct a protein-protein interaction(PPI) network. The CytoNCA plugin within Cytoscape was used to screen out the core targets, and the Metascape platform was used to perform gene ontology(GO) functional enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis. The “drug-active ingredient-target” interaction network was constructed with the help of Cytoscape 3.8.2, and AutoDock Vina was used for molecular docking. Scopolamine (SCOP) was utilized for modeling and injected intraperitoneally once daily. Thirty-two male C57/BL6 mice were randomly divided into blank control (CON) group (0.9% NaCl, n=8), model (SCOP) group (3 mg·kg-1·d-1, n=8), positive control group (3 mg·kg-1·d-1 of SCOP+3 mg·kg-1·d-1 of Donepezil, n=8), and Kaixinsan group (3 mg·kg-1·d-1 of SCOP+6.5 g·kg-1·d-1 of Kaixinsan, n=8). Mice in each group were administered with 0.9% NaCl, Kaixinsan, or Donepezil by gavage twice a day for 14 days. Morris water maze experiment was used to observe the learning memory ability of mice. Hematoxylin-eosin (HE) staining method was used to observe the pathological changes in the CA1 area of the mouse hippocampus. Enzyme linked immunosorbent assay(ELISA) was used to determine the serum acetylcholine (ACh) and acetylcholinesterase (AChE) contents of mice. Western blot method was used to detect the protein expression levels of signal transducer and activator of transcription 3(STAT3) and nuclear transcription factor(NF)-κB p65 in the hippocampus of mice. ResultsA total of 73 active ingredients of Kaixinsan were obtained, and 578 potential targets (common targets) of Kaixinsan for the treatment of AD were screened out. Key active ingredients included kaempferol, gijugliflozin, etc.. Potential core targets were STAT3, NF-κB p65, et al. GO functional enrichment analysis obtained 3 124 biological functions, 254 cellular building blocks, and 461 molecular functions. KEGG pathway enrichment obtained 248 pathways, mainly involving cancer-related pathways, TRP pathway, cyclic adenosine monophosphate(cAMP) pathway, and NF-κB pathway. Molecular docking showed that the binding of the key active ingredients to the target targets was more stable. Morris water maze experiment indicated that Kaixinsan could improve the learning memory ability of SCOP-induced mice. HE staining and ELISA results showed that Kaixinsan had an ameliorating effect on central nerve injury in mice. Western blot test indicated that Kaixinsan had a down-regulating effect on the levels of NF-κB p65 phosphorylation and STAT3 phosphorylation in the hippocampal tissue of mice in the SCOP model. ConclusionKaixinsan can improve the cognitive impairment function in SCOP model mice and may reduce hippocampal neuronal damage and thus play a therapeutic role in the treatment of AD by regulating NF-κB p65, STAT3, and other targets involved in the NF-κB signaling pathway.
6.Efficacy and Safety of Qihuang Acupuncture Theory Combined with Opioid Analgesics in the Treatment of Moderate to Severe Cancer Pain in Lung Cancer Patients:a Randomize-Controlled Trial
Yingqi WANG ; Ruifang YU ; Jinpeng HUANG ; Guiya LIAO ; Ziyan GAN ; Zhenhu CHEN ; Xiaobing YANG ; Chunzhi TANG
Journal of Traditional Chinese Medicine 2025;66(4):358-366
ObjectiveTo observe the analgesic efficacy and safety of Qihuang acupuncture theory combined with opioid analgesics in patients with moderate to severe cancer pain due to lung cancer. MethodsPatients with moderate to severe cancer pain from lung cancer were randomly divided into Qihuang acupuncture group and control group, with 33 cases in each group. The control group was treated with long-acting opioid analgesics at maintenance doses and supplementary analgesic medications as needed. In case of breakthrough pain, short-acting opioids were used for rescue. The Qihuang acupuncture group received Qihuang acupuncture treatment in addition to the treatment used in the control group, administered once every other day, with 3 sessions constituting one treatment course. The treatment duration for both groups was 5 days. The primary outcome was the change in pain intensity, measured using the numerical rating scale (NRS) before and after treatment, and the NRS change rate was calculated. Secondary endpoints included the daily NRS change rate, the Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score, the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) score, and the 24-hour equivalent hydrocodone sustained-release tablet dose. Laboratory tests, including routine blood, urine, stool, liver function, and kidney function, were performed before and after treatment. Adverse events were recorded throughout the trial. ResultsAll patients completed the trial, and both groups showed a decrease in average NRS scores and PS scores after treatment, with the Qihuang acupuncture group showing lower average NRS scores and PS scores than the control group (P<0.05 or P<0.01). After treatment, the NRS change rate in the Qihuang acupuncture group was (0.42±0.17), significantly higher than that in the control group (0.14±0.27, P<0.01). The daily NRS change rate during treatment was also higher in the Qihuang acupuncture group compared to the control group (P<0.01). The Qihuang acupuncture group showed an increase in overall health status and functional scores in the EORTC QLQ-C30, and a decrease in symptom scores for fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, and financial difficulties. In contrast, overall health status and constipation scores in the control group increased, while scores of fatigue, nausea and vomiting, pain, and appetite loss decreased (P<0.05 or P<0.01). After treatment, the 24-hour equivalent hydrocodone sustained-release tablet dose did not show significant difference in the Qihuang acupuncture group (P>0.05), while the control group showed a significant increase in the 24-hour dose (P<0.01). No significant abnormalities were observed in laboratory tests before and after treatment in either group. During the study, the incidence of nausea and vomiting as well as constipation in the Qihuang acupuncture group was both 3.03% (1/33), while the incidence in the control group was 27.27% (9/33) and 36.36% (12/33), respectively, with the Qihuang acupuncture group showing significantly lower incidence (P<0.01). No serious adverse reactions were observed in either group. ConclusionQihuang acupuncture therapy combined with opioid analgesics is more effective than using opioids alone in relieving pain in patients with moderate to severe cancer pain due to lung cancer. It can improve the patients' physical condition and quality of life, reduce the dose of opioid analgesics, and has good safety.
7.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.
8.Translational Research of Electromagnetic Fields on Diseases Related With Bone Remodeling: Review and Prospects
Peng SHANG ; Jun-Yu LIU ; Sheng-Hang WANG ; Jian-Cheng YANG ; Zhe-Yuan ZHANG ; An-Lin LI ; Hao ZHANG ; Yu-Hong ZENG
Progress in Biochemistry and Biophysics 2025;52(2):439-455
Electromagnetic fields can regulate the fundamental biological processes involved in bone remodeling. As a non-invasive physical therapy, electromagnetic fields with specific parameters have demonstrated therapeutic effects on bone remodeling diseases, such as fractures and osteoporosis. Electromagnetic fields can be generated by the movement of charged particles or induced by varying currents. Based on whether the strength and direction of the electric field change over time, electromagnetic fields can be classified into static and time-varying fields. The treatment of bone remodeling diseases with static magnetic fields primarily focuses on fractures, often using magnetic splints to immobilize the fracture site while studying the effects of static magnetic fields on bone healing. However, there has been relatively little research on the prevention and treatment of osteoporosis using static magnetic fields. Pulsed electromagnetic fields, a type of time-varying field, have been widely used in clinical studies for treating fractures, osteoporosis, and non-union. However, current clinical applications are limited to low-frequency, and research on the relationship between frequency and biological effects remains insufficient. We believe that different types of electromagnetic fields acting on bone can induce various “secondary physical quantities”, such as magnetism, force, electricity, acoustics, and thermal energy, which can stimulate bone cells either individually or simultaneously. Bone cells possess specific electromagnetic properties, and in a static magnetic field, the presence of a magnetic field gradient can exert a certain magnetism on the bone tissue, leading to observable effects. In a time-varying magnetic field, the charged particles within the bone experience varying Lorentz forces, causing vibrations and generating acoustic effects. Additionally, as the frequency of the time-varying field increases, induced currents or potentials can be generated within the bone, leading to electrical effects. When the frequency and power exceed a certain threshold, electromagnetic energy can be converted into thermal energy, producing thermal effects. In summary, external electromagnetic fields with different characteristics can generate multiple physical quantities within biological tissues, such as magnetic, electric, mechanical, acoustic, and thermal effects. These physical quantities may also interact and couple with each other, stimulating the biological tissues in a combined or composite manner, thereby producing biological effects. This understanding is key to elucidating the electromagnetic mechanisms of how electromagnetic fields influence biological tissues. In the study of electromagnetic fields for bone remodeling diseases, attention should be paid to the biological effects of bone remodeling under different electromagnetic wave characteristics. This includes exploring innovative electromagnetic source technologies applicable to bone remodeling, identifying safe and effective electromagnetic field parameters, and combining basic research with technological invention to develop scientifically grounded, advanced key technologies for innovative electromagnetic treatment devices targeting bone remodeling diseases. In conclusion, electromagnetic fields and multiple physical factors have the potential to prevent and treat bone remodeling diseases, and have significant application prospects.
9.Mechanism of Different Dosage Forms of Kaixinsan in Improving Mitochondrial Function for Prevention and Treatment of Cognitive Disorder Based on AMPK/PGC-1α/SIRT3 Pathway
Shuyue KANG ; Yanzi YU ; Jiaqun SUN ; Wenxuan CHEN ; Yaqin YANG ; Qi WANG ; Weirong LI ; Limei YAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):15-24
ObjectiveTo explore the effects of different dosage forms of Kaixinsan (KXS) on the morphology and function of mitochondria in rat models of Alzheimer's disease (AD) and potential mechanisms of action. MethodsMale SD rats were randomly assigned to a sham group, model group, treatment groups receiving KXS decoction, powders, and granules (3.08 g·kg-1), as well as donepezil group (0.51×10-3 g·kg-1), with 10 rats in each group. AD model was created using intracerebroventricular injection of streptozocin (STZ). After 30 days of administration, behavioral assessments were conducted, and mitochondrial morphology was observed using transmission electron microscopy. Mitochondrial respiratory chain complex content was measured via enzyme-linked immunosorbent assay (ELISA). Changes in mitochondrial membrane potential were measured via JC-1 staining, and superoxide dismutase (SOD) activity and reactive oxygen species (ROS) levels were measured via biochemical assays. The mRNA expression of adenosine 5'-monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and silent information regulator 3 (SIRT3) was detected by real-time fluorescent quantitative polymerase chain reaction (Real-time PCR), and Western blot was used to examine the protein expression levels of optic atrophy protein1 (OPA1), mitochondrial fission protein 1 (FIS1), AMPK, p-AMPK, PGC-1α, and SIRT3. ResultsCompared with the sham group, rats in the model group had significantly lower recognition index, spontaneous alternation rate, escape latency, number of platform crossings, time spent in the target quadrant, and percentage of distance traveled in the target quadrant distance (P<0.05, P<0.01). Significant mitochondrial damage was observed in the hippocampal tissue, with a marked decrease in mitochondrial respiratory chain complex content (P<0.01) and reduced mitochondrial membrane potential (P<0.05). Additionally, the SOD activity was reduced, while ROS levels were elevated (P<0.01). The mRNA expression of PGC-1α and SIRT3 was significantly downregulated (P<0.01), along with decreased protein expression levels of OPA1, p-AMPK/AMPK, PGC-1α, and SIRT3, whereas FIS1 protein expression was significantly upregulated (P<0.05, P<0.01). Compared with the model group, rats in KXS-treated groups (various dosage forms) showed significant improvement in behavioral indexes (P<0.05, P<0.01), reduced hippocampal mitochondrial damage, and more organized mitochondrial cristae. Mitochondrial respiratory chain complex content was significantly increased (P<0.05, P<0.01), and mitochondrial membrane potentials were elevated (P<0.05). SOD activity was elevated, and ROS levels were significantly reduced (P<0.05, P<0.01). Furthermore, the mRNA expression of PGC-1α and SIRT3 was upregulated, with increased protein levels of OPA1, p-AMPK/AMPK, PGC-1α, and SIRT3, while FIS1 protein expression levels were significantly reduced (P<0.05, P<0.01). Across the KXS-treated groups, the granule group showed a higher spontaneous alternation rate than the decoction and powder groups (P<0.05). ConclusionKXS decoction, powders, and granules can improve the learning and memory ability of rats, with granules being the most effective. The mechanism of action may involve activation of the AMPK/PGC-1α/SIRT3 signaling pathway, improvement of the mitochondrial function, and subsequent amelioration of the brain energy metabolism disorders.
10.Mechanism of Different Dosage Forms of Kaixinsan in Improving Mitochondrial Function for Prevention and Treatment of Cognitive Disorder Based on AMPK/PGC-1α/SIRT3 Pathway
Shuyue KANG ; Yanzi YU ; Jiaqun SUN ; Wenxuan CHEN ; Yaqin YANG ; Qi WANG ; Weirong LI ; Limei YAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):15-24
ObjectiveTo explore the effects of different dosage forms of Kaixinsan (KXS) on the morphology and function of mitochondria in rat models of Alzheimer's disease (AD) and potential mechanisms of action. MethodsMale SD rats were randomly assigned to a sham group, model group, treatment groups receiving KXS decoction, powders, and granules (3.08 g·kg-1), as well as donepezil group (0.51×10-3 g·kg-1), with 10 rats in each group. AD model was created using intracerebroventricular injection of streptozocin (STZ). After 30 days of administration, behavioral assessments were conducted, and mitochondrial morphology was observed using transmission electron microscopy. Mitochondrial respiratory chain complex content was measured via enzyme-linked immunosorbent assay (ELISA). Changes in mitochondrial membrane potential were measured via JC-1 staining, and superoxide dismutase (SOD) activity and reactive oxygen species (ROS) levels were measured via biochemical assays. The mRNA expression of adenosine 5'-monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and silent information regulator 3 (SIRT3) was detected by real-time fluorescent quantitative polymerase chain reaction (Real-time PCR), and Western blot was used to examine the protein expression levels of optic atrophy protein1 (OPA1), mitochondrial fission protein 1 (FIS1), AMPK, p-AMPK, PGC-1α, and SIRT3. ResultsCompared with the sham group, rats in the model group had significantly lower recognition index, spontaneous alternation rate, escape latency, number of platform crossings, time spent in the target quadrant, and percentage of distance traveled in the target quadrant distance (P<0.05, P<0.01). Significant mitochondrial damage was observed in the hippocampal tissue, with a marked decrease in mitochondrial respiratory chain complex content (P<0.01) and reduced mitochondrial membrane potential (P<0.05). Additionally, the SOD activity was reduced, while ROS levels were elevated (P<0.01). The mRNA expression of PGC-1α and SIRT3 was significantly downregulated (P<0.01), along with decreased protein expression levels of OPA1, p-AMPK/AMPK, PGC-1α, and SIRT3, whereas FIS1 protein expression was significantly upregulated (P<0.05, P<0.01). Compared with the model group, rats in KXS-treated groups (various dosage forms) showed significant improvement in behavioral indexes (P<0.05, P<0.01), reduced hippocampal mitochondrial damage, and more organized mitochondrial cristae. Mitochondrial respiratory chain complex content was significantly increased (P<0.05, P<0.01), and mitochondrial membrane potentials were elevated (P<0.05). SOD activity was elevated, and ROS levels were significantly reduced (P<0.05, P<0.01). Furthermore, the mRNA expression of PGC-1α and SIRT3 was upregulated, with increased protein levels of OPA1, p-AMPK/AMPK, PGC-1α, and SIRT3, while FIS1 protein expression levels were significantly reduced (P<0.05, P<0.01). Across the KXS-treated groups, the granule group showed a higher spontaneous alternation rate than the decoction and powder groups (P<0.05). ConclusionKXS decoction, powders, and granules can improve the learning and memory ability of rats, with granules being the most effective. The mechanism of action may involve activation of the AMPK/PGC-1α/SIRT3 signaling pathway, improvement of the mitochondrial function, and subsequent amelioration of the brain energy metabolism disorders.

Result Analysis
Print
Save
E-mail