1.Serum Metabolomics of Simulated Weightless Rats Treated with Taikong Yangxin Pills
Xiaodi LIU ; Xuemei FAN ; Yiming WANG ; Mengjia YAN ; Yongzhi LI ; Jiaping WANG ; Junlian LIU ; Guoan LUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):147-153
ObjectiveTo study the effect of Taikong Yangxin Pills on the metabolism of simulated weightless rats based on metabolomics and discuss the metabolism mechanism. MethodsIn the simulated space capsule environment on the ground, the rat model of simulated weightlessness was established by the tail suspension method. Rats were randomly grouped as follows: out-of-capsule control, in-capsule control, model, and high (3.0 g·kg-1) and low (1.5 g·kg-1) doses of Taikong Yangxin Pills, and they were administrated with corresponding drugs by gavage for 28 days. The serum levels of endogenous metabolites in rats were determined by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). The obtained data were processed by principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) to screen for differential metabolites and potential biomarkers. MetaboAnalyst 5.0 was used for pathway enrichment analysis to explain the metabolic regulation mechanism of the drug. ResultsCompared with the out-of-capsule control group, the in-capsule control group showed elevated levels of thirteen metabolites, including 14-hydroxyhexadecanoic acid, linoleic acid, and α-linolenic acid (P<0.05), which suggested that the space capsule environment mainly affected the metabolism of α-linolenic acid and linoleic acid in the rats. Compared with the in-capsule control group, the model group showed lowered levels of fourteen metabolites, including 4-imidazolone-5-propionic acid, isocitric acid/citric acid, and L-tyrosine (P<0.05), which were recovered after the treatment with Taikong Yangxin pills (P<0.05). The pathway enrichment analysis revealed that weightlessness induced by tail suspension and drug intervention mainly involved the phenylalanine, tyrosine, and tryptophan biosynthesis, tyrosine metabolism, histidine metabolism, and citric acid cycle. ConclusionThe simulated space capsule environment and simulated weightlessness induced by tail suspension can both affect the metabolism level of rats. Taikong Yangxin pills can ameliorate the metabolic abnormality in the rat model of weightlessness by regulating various amino acids and energy metabolism-related pathways.
2.Mechanism of Ferroptosis in Regulating Chronic Heart Failure and Traditional Chinese Medicine Prevention and Treatment Based on Qi Deficiency and Stagnation: A Review
Ziyang YUAN ; Yan ZHANG ; Wei ZHANG ; Yaqin WANG ; Wenjun MAO ; Guo YANG ; Xuewei WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):248-255
Chronic heart failure (CHF) is the final stage of cardiovascular diseases. It is a complex syndrome, with dyspnea and edema as the main clinical manifestations, and it is characterized by complex disease conditions, difficult cure, and high mortality. Ferroptosis, a new type of programmed cell death, is different from other types of programmed cell death. Ferroptosis is iron-dependent, accompanied by lipid peroxide accumulation and mitochondrial shrinkage, becoming a hot research topic. Studies have confirmed that ferroptosis plays a key role in the occurrence and development of CHF. The regulation of ferroptosis may become a potential target for the treatment of CHF in the future. The theory of Qi deficiency and stagnation refers to the pathological state of original Qi deficiency and abnormal transportation and distribution of Qi, blood, and body fluid, which has guiding significance for revealing the pathogenesis evolution of some chronic diseases. We believe that Qi deficiency and stagnation is a summary of the pathogenesis of ferroptosis in CHF. Deficiency of Qi (heart Qi) is the root cause of CHF, and stagnation (phlegm turbidity and blood stasis) is the branch of this disease. The two influence each other in a vicious circle to promote the development of this disease. Traditional Chinese medicine (TCM) plays an important role in the treatment of CHF, improving the prognosis and quality of life of CHF patients. This paper explores the correlation between the theory of Qi deficiency and stagnation and the mechanism of ferroptosis in CHF. Furthermore, this paper reviews the mechanism of Chinese medicines and compound prescriptions in preventing and treating CHF by regulating ferroptosis according to the principles of replenishing Qi and dredging to remove stagnation, aiming to provide new ideas and methods for the treatment of CHF with TCM.
3.Gualou Xiebai Banxiatang in Treatment of Cardiovascular Diseases: A Review
Yalong KANG ; Bo NING ; Juanjuan TAN ; Hongfei QI ; Yan SHI ; Fang GUAN ; Haifang WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):256-267
Cardiovascular diseases (CVD),a group of common diseases in clinical practice,are witnessing a steady rise in both incidence and mortality rates,posing a challenge to public health. Gualou Xiebai Banxiatang,originating from Synopsis of the Golden Chamber (《金匮要略》),was initially used to treat severe cases of chest impediment. The formula consists of Trichosanthis Fructus,Allii Macrostemonis Bulbus,Pinelliae Rhizoma,and Baijiu. It has a wide range of clinical applications,with therapeutic effects including moving Qi to relieve depression,activating Yang to dissipate mass,and expelling phlegm to alleviate chest congestion. In recent years,clinical research has confirmed that Gualou Xiebai Banxiatang,with or without modification,used alone or in combination with Western medicine,has definite effects in the treatment of CVD such as hyperlipidemia,coronary atherosclerotic heart disease,hypertension,heart failure,and arrhythmia. It can alleviate disease symptoms and reduce the risk of re-hospitalization. Basic research indicates that the mechanisms of Gualou Xiebai Banxiatang include improving endothelial functions,exhibiting anti-inflammatory properties,countering oxidative stress,preventing apoptosis,inhibiting ventricular remodeling,regulating mitochondrial functions,improving hemorheology,and modulating autophagy and neurotransmitters. This article reviews relevant articles in recent years with focuses on the compatibility,clinical application,and mechanism of Gualou Xiebai Banxiatang. This review is expected to provide a theoretical basis for the mechanism research and clinical application of this formula in treating CVD and to offer ideas and reference for in-depth research.
4.Traditional Chinese Medicine Treats Sepsis by Regulating PI3K/Akt Pathway: A Review
Zhu LIU ; Jiawei WANG ; Jing YAN ; Jinchan PENG ; Mingyao XU ; Liqun LI ; Sheng XIE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):314-322
Sepsis is a systemic inflammatory response syndrome caused by the invasion of pathogenic microorganisms such as bacteria. In addition to the manifestations of systemic inflammatory response syndrome and primary infection lesions, critical cases often have manifestations of organ hypoperfusion. The morbidity and mortality of sepsis have remained high in recent years, which seriously affect the quality of life of the patients. The pathogenesis of sepsis is complicated, in which uncontrollable inflammation is a key mechanism. The phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway plays a key role in mediating inflammation in sepsis. The available therapies of sepsis mainly include resuscitation, anti-infection, vasoactive drugs, intensive insulin therapy, and organ support, which show limited effects of reducing the mortality. Therefore, finding new therapeutic drugs is a key problem to be solved in the clinical treatment of sepsis. In recent years, studies have shown that traditional Chinese medicine (TCM) can regulate the PI3K/Akt pathway via multiple pathways, multiple effects, and multiple targets to inhibit inflammation and curb the occurrence and development of sepsis, which has gradually become a hot spot in the prevention and treatment of sepsis. Moreover, studies have suggested that TCM has unique advantages in the treatment of sepsis. TCM can regulate the PI3K/Akt signaling pathway to inhibit inflammation, reduce oxidative stress, and control apoptosis in the prevention and treatment of sepsis. Despite the research progress, a systematic review remains to be performed regarding the TCM treatment of sepsis by regulating the PI3K/Akt signaling pathway. After reviewing relevant papers published in recent years, this study systematically summarizes the relationship between PI3K/Akt pathway and sepsis and the role of TCM in the treatment of sepsis, aiming to provide new ideas for the potential treatment of sepsis and the development of new drugs.
5.Characteristics of cardiometabolic risk in patients with different subtypes of non-alcoholic fatty liver disease
Lili GAO ; Yong WANG ; Huafang YAN ; Xiaoliang WANG ; Yunfeng WANG
Journal of Clinical Hepatology 2025;41(1):63-68
ObjectiveTo investigate the difference in the risk of cardiovascular diseases between patients with different subtypes of non-alcoholic fatty liver disease (NAFLD) from the perspective of metabolism, since cardiovascular events induced by metabolic disorders are the leading cause of death in NAFLD. MethodsThe cluster sampling method was used to conduct a multicenter cross-sectional study among three representative hospitals in Pudong New Area of Shanghai, China. A total of 37 122 sets of physical examination data from July 2022 to June 2023 were collected and stratified according to body mass index (BMI). The chi-square test was used for comparison of continuous data between groups, and a multivariable Logistic regression analysis was used to investigate the association between NAFLD subtypes and cardiometabolic risk factors. ResultsA total of 9 372 cases of NAFLD were detected, with a detection rate of 25.25%, and more than 97% of these patients were diagnosed with metabolic associated fatty liver disease (MAFLD). The subgroup analysis showed that the detection rates of lean, overweight, and obese NAFLD were 7.72%, 33.99%, and 63.56%, respectively. Compared with the patients with lean or overweight NAFLD, the patients with obese NAFLD showed a significantly higher proportion of patients with abnormalities in blood pressure, blood glucose, triglyceride (TG), high-density lipoprotein (HDL) or uric acid (all P<0.001). Among related risk factors, lean NAFLD was associated with the increase in total cholesterol (TC)(P<0.05), while overweight NAFLD and obese NAFLD were not associated with TC abnormalities (P>0.05); obese NAFLD was not associated with TG abnormalities, while lean NAFLD and overweight NAFLD were associated with TG abnormalities (both P<0.05); all types of NAFLD were associated with the abnormalities of waist-hip ratio, blood pressure, blood glucose, low-density lipoprotein, HDL, and uric acid (all P<0.05). ConclusionThe detection rates of different subtypes of NAFLD in Shanghai Pudong are close to those reported in China and globally, and the epidemiologic data of NAFLD can be used analogously for MAFLD. There are certain differences in the distribution and association of cardiometabolic risk factors between different subtypes of NAFLD, and targeted interventions should be formulated based on the metabolic characteristics of each type of NAFLD.
6.POEMS syndrome with hepatosplenomegaly as the initial manifestation: A report of two cases
Ye ZHANG ; Wenqing WANG ; Jing LI ; Qianrong BAI ; Jiayu LI ; Yan CHENG ; Miaomiao FANG ; Nana GAO ; Changxing HUANG
Journal of Clinical Hepatology 2025;41(1):127-132
POEMS syndrome is a rare condition associated with plasma cell disorders, and it often involves multiple systems and has diverse clinical manifestations. This article reports two cases of POEMS syndrome with hepatosplenomegaly as the initial manifestation. During the course of the disease, the patients presented with lower limb weakness, hepatosplenomegaly, lymph node enlargement, ascites, hypothyroidism, positive M protein, and skin hyperpigmentation, and 18F-FDG PET-CT imaging revealed bone lesions mainly characterized by osteolytic changes and plasma cell tumors. There was an increase in the serum level of vascular endothelial growth factor. The patients were finally diagnosed with POEMS syndrome, and the symptoms were relieved after immunomodulatory treatment.
7.Professor LIU Jinmin's Clinical Experience in Treating Epilepsy Based on the Method of Closing Yangming and Regaining Vital Activity
Lin ZOU ; Tianye SUN ; Mingyuan YAN ; Mi ZHAGN ; Shuai ZHAO ; Kaiyue WANG ; Lili LI ;
Journal of Traditional Chinese Medicine 2025;66(4):344-348
To summarize the clinical experience of Professor LIU Jinmin in treatment for epilepsy. It is believed that main pathogenesis of epilepsy is yangming failure to close and vital activity loss control, so a therapeutic approach focused on restoring the closure of yangming and regaining vital activity was proposed for the treatment of epilepsy. For excess syndrome, the treatment focuses on draining excess and descending qi, promoting purgation and restoring spirit. When yangming dryness-heat predominates, the approach involves unblock the bowels and regulating the spirit, descending qi and reducing fire, with modified Chengqi Decoction (承气汤) as prescription; when yangming phlegm-fire predominates, the treatment focuses on clearing heat and resolving phlegm, calming mind and suppressing fright, with modified Qingxin Wendan Decoction (清心温胆汤) as prescription; when yangming blood stasis predominates, the approach involves breaking up blood stasis and promoting purgation, eliminating stasis and awakening the mind, with Taoren Chengqi Decoction (桃核承气汤) as prescription. For deficiency syndrome, the treatment emphasizes tonifying deficiency and raising qi, strengthening the stomach and nourishing the spirit. When center qi deficiency and sinking of clear qi of the nutrients from food, the approach involves replenishing and uplifting qi while nourishing vital activity, with modified Liujunzi Decoction (六君子汤) as prescription; when yin deficiency and fluid consumption, the treatment focuses on nourishing stomach and tonifying yin, promoting fluid production and calming the spirit, with modified Maimendong Decoction (麦门冬汤) combined with Yiwei Decoction (益胃汤) as prescriptions. In clinical situations of deficiency-excess complex, it is essential to distinguish the primary condition from the secondary, applying both supplementing and draining methods flexibly to achieve optimal treatment.
8.Mechanism of Xuefu Zhuyutang in Intervening in Ferroptosis in Rats with Coronary Heart Disease with Blood Stasis Syndrome Based on ACSL4 Signalling Pathway
Yi LIU ; Yang YANG ; Chang SU ; Peng TIAN ; Mingyun WANG ; Ruqian ZHONG ; Xuejiao XIE ; Qing YAN ; Qinghua PENG ; Qiuyan ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):27-38
ObjectiveTo investigate the mechanism of ferroptosis mediated by long-chain acyl-CoA synthetase 4 (ACSL4) signalling pathway in rats with coronary heart disease with blood stasis syndrome and the intervention effect of Xuefu Zhuyutang. MethodsSPF male SD rats were randomly divided into normal group, sham-operation group, model group, trimetazidine group (5.4 mg·kg-1), low-, medium-, and high-dose group (3.51, 7.02,14.04 g·kg-1) of Xuefu Zhuyutang. The coronary artery left anterior descending ligation method was used to prepare a model of coronary heart disease with blood stasis syndrome, and continuous treatment for 7 d was conducted, while the sham-operation group was only threaded and not ligated. The general macroscopic symptoms of the rats were observed, and indicators such as electrocardiogram, echocardiography, and blood rheology were detected. The pathological morphology of myocardial tissue was observed by hematoxylin-eosin (HE) staining, and the changes in mitochondria in myocardial tissue were observed by transmission electron microscopy. The level of iron deposition in myocardial tissue was observed by Prussian blue staining. The levels of 12-hydroxyeicosatetraenoic acid (12-HETE) and 15-HETE were detected in serum by enzyme-linked immunosorbent assay. A biochemical colourimetric assay was used to detect the levels of Fe2+, lipid peroxidation (LPO), glutathione (GSH), and T-GSH/glutathione disulfide (GSSG) in myocardial tissue. DCFH-DA fluorescence quantitative assay was employed to detect the levels of reactive oxygen species (ROS). Western blot and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was adopted to detect the protein and mRNA expressions of glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), ACSL4, and ly-sophosphatidylcholine acyltransferase3 (LPCAT3) in myocardial tissue. ResultsCompared with those in the normal group, the rats in the model group were poor in general macroscopic symptoms. The electrocardiogram showed widened QRS wave amplitude and increased voltage, bow-back elevation of the ST segments, elevated T waves, J-point elevation, and accelerated heart rate. Echocardiography showed a significant reduction in left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) (P<0.01). Blood rheology showed that the viscosity of the whole blood (low, medium, and high rate of shear) was significantly increased (P<0.01). HE staining showed an abnormal structure of myocardial tissue. There was a large area of myocardial necrosis and inflammatory cell infiltration and a large number of connective tissue between myocardial fibers. Transmission electron microscopy showed that the mitochondria were severely atrophy or swelling. The cristae were reduced or even broken, and the matrix was flocculent or even vacuolated. Prussian blue staining showed that there were a large number of iron-containing particles, and the iron deposition was obvious. The content of 12-HETE and 15-HETE in the serum was significantly increased (P<0.01). The content of Fe2+, LPO, and ROS in myocardial tissue was significantly increased (P<0.01). The content of GSH was significantly decreased (P<0.01), and T-GSH/GSSG was decreased (P<0.01). The protein and mRNA expressions of GPX4 and FTH1 in myocardial tissue were both significantly decreased (P<0.05, P<0.01), while those of ACSL4 and LPCAT3 increased significantly (P<0.01). Compared with the model group, the general macroscopic symptoms and electrocardiogram results of rats in low-, medium- and high-dose groups of Xuefu Zhuyutang were alleviated, and the differences in LVEF/LVFS ratios were all significantly increased (P<0.05, P<0.01). The differences in whole-blood viscosity (low, medium, and high rate of shear) were all significantly decreased (P<0.01). The results of HE staining and transmission electron microscopy showed that the morphology, structure, and mitochondria of cardiomyocytes were improved. The content of 12-HETE and 15-HETE in serum was reduced to different degrees in low-, medium-, and high-dose groups of Xuefu Zhuyutang (P<0.05, P<0.01). The content of Fe2+, LPO, and ROS was significantly reduced in the medium- and high-dose groups of Xuefu Zhuyutang (P<0.05, P<0.01), and the content of GSH and T-GSH/GSSG was significantly increased (P<0.05, P<0.01). The protein and mRNA expressions of GPX4 and FTH1 were significantly increased to varying degrees in the medium- and high-dose groups of Xuefu Zhuyutang (P<0.05, P<0.01), and ACSL4 and LPCAT3 were decreased to different degrees in the low-, medium-, and high-dose groups of Xuefu Zhuyutang (P<0.05, P<0.01). ConclusionXuefu Zhuyutang can regulate iron metabolism and anti-lipid oxidation reaction to mediate ferroptosis through the ACSL4 signalling pathway, thus exerting a protective effect on rats with coronary heart disease with blood stasis syndrome.
9.UPLC-Q-TOF-MS Reveals Mechanisms of Modified Qing'e Formula in Delaying Skin Photoaging and Regulating Circadian Rhythm
Wanyu YANG ; Xiujun ZHANG ; Yan WANG ; Chunjing SONG ; Haoming MA ; Lifeng WANG ; Nan LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):88-97
ObjectiveTo reveal the active substances and mechanisms of modified Qing'e formula (MQEF) in delaying skin photoaging by ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-TOF-MS),network pharmacology, and cell experiments. MethodsUPLC-Q-TOF-MS and a literature review were employed to analyze the transdermally absorbed components in mice after the topical application of MQEF. The potential targets of MQEF in treating skin photoaging were retrieved from databases.The compound-potential target network and protein-protein interaction network were constructed to screen the key components and core targets. A photoaging cell model was established by irradiating HaCaT cells with medium-wave ultraviolet B (UVB). The safe doses of bakuchiol (BAK) and salvianolic acid B (SAB) for treating HaCaT cells and the effects of BAK and SAB on the viability of cells exposed to UVB irradiation were determined by the cell counting kit-8 (CCK-8) method.The reactive oxygen species (ROS) fluorescent probe was used to measure the ROS production in the cells treated with BAK and SAB.The expression levels of genes related to oxidative stress,inflammation,collagen metabolism,and circadian rhythm clock were measured by Real-time PCR. ResultsA total of 24 transdermally absorbed components of MQEF were identified,which acted on 367 potential targets,and 417 targets related to skin photoaging were screened out,among which 47 common targets were predicted as the targets of MQEF in treating skin photoaging. MQEF exerted the anti-photoaging effect via key components such as BAK and SAB,which acted on core proteins such as serine/threonine kinase 1 (Akt1) and mitogen-activated protein kinase 3 (MAPK3) and intervened in core pathways such as the tumor necrosis factor (TNF) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathways.Compared with the model group,the administration of BAK and SAB increased the survival rate of HaCaT cells (P<0.01),down-regulated the mRNA levels of cyclooxygenase-2 (COX-2),interleukin-6 (IL-6),tumor necrosis factor-α (TNF-α),matrix metalloproteinase-1 (MMP-1),and matrix metalloproteinase-9 (MMP-9) (P<0.01),and up-regulated the mRNA levels of heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO-1) (P<0.05,P<0.01) in photoaged HaCaT cells.In addition,it eliminated excess ROS production induced by UVB and up-regulated the mRNA levels of brain and muscle ARNT-like 1 (BMAL1) and circadian locomotor output cycles kaput (CLOCK) associated with circadian clock (P<0.05,P<0.01). ConclusionMQEF delays skin photoaging through the coordinated effects of various components,multiple targets,and diverse pathways.The key components BAK and SAB in MQEF exhibit anti-photoaging properties,which involve inhibiting oxidative stress,preventing collagen degradation,mitigating inflammation,and maintaining normal skin circadian rhythms by regulating clock gene expression.
10.Processing History and Modern Research of Jianghuanglian: A Review
Ying LI ; Yun WANG ; Zhe JIA ; Lin YAN ; Min JIN ; Cun ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):275-282
Jianghuanglian is one of the representative processed products of Coptidis Rhizoma for treating cold syndrome with drugs of heat nature, and ginger is used to restrict the bitter cold of Coptidis Rhizoma, which can be traced back to Bojifang, and it is suitable for stagnation of damp-heat in middle-jiao, cold-heat mutual knots and other symptoms. Jianghuanglian retains the alkaloids, phenylpropanoids and flavonoids of Coptidis Rhizoma, and also introduces gingerol components such as 6-gingerol in ginger, which has pharmacological activities such as anti-inflammatory, antibacterial, anti-tumor, and improving gastrointestinal function. The 2020 edition of Chinese Pharmacopoeia and many local processing specifications have included the traditional processing process and quality standards of Jianghuanglian, but the specific process parameters and quality standards are incomplete, which limits the production and clinical application of this processed product. By summarizing the processing history, process research, quality evaluation, pharmacodynamic and medicinal property changes and application of Jianghuanglian in the past 20 years, there are differences in the processing methods and standards in various provinces and cities, which are mainly reflected in the preparation method, dosage, processing process and quantitative standards of ginger juice. In addition, there are also certain differences in the changes of the main components of Jianghuanglian prepared from ginger or dried ginger, as well as their efficacy and medicinal properties. The research on the processing process of Jianghuanglian plays an important role in improving its quality standards, and this review can provide a reference for improving the quality evaluation system of Jianghuanglian.

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