1.Yishen Huashi Granules Protect Kidneys of db/db Mice via p38 MAPK Signaling Pathway
Kaidong ZHOU ; Sitong WANG ; Ge JIN ; Yanmo CAI ; Xin ZHOU ; Yunhua LIU ; Xinxue ZHANG ; Min ZHANG ; Zongjiang ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):58-68
ObjectiveTo explore the mechanism of Yishen Huashi granules in alleviating renal tubular epithelial cell injury and relieving diabetic kidney disease by regulating the mitogen-activated protein kinase (MAPK) signaling pathway. MethodsThe db/db mice of 12 weeks old were randomly assigned into model , dapagliflozin (1.6 mg·kg-1), and Yishen Huashi granules (4.7 g·kg-1), and db/m mice were used as the control group. The general conditions of mice were observed, and fasting blood glucose and 24-h urinary protein and albumin-to-creatinine ratio (ACR) were measured at weeks 0 and 12 of administration. After 12 weeks of treatment, the levels of serum creatinine (SCr), blood urea (UREA), triglycerides (TG), total cholesterol (TC), and low density lipoprotein (LDL) were measured. The pathological changes in the renal tissue were observed by hematoxylin-eosin (HE) staining, Periodic acid-Schiff (PAS) staining, Mallory staining, and transmission electron microscopy. Real-time PCR was employed to determine the mRNA levels of monocyte chemotactic protein-1 (MCP-1) and CC chemokine receptor-2 (CCR2) in the renal tissue of mice. The immunohistochemical assay was employed to examine the expression of p38, phospho-p38 (p-p38), MCP-1, and CCR2 in the renal tissue of mice. Western blotting was employed to measure the protein levels of p-p38, p38, MCP-1, and CCR2 in the renal tissue of mice.HK-2 cells cultured in vitro were grouped as follows: negative control, high glucose(30 mmol·L-1), Yishen Huashi granule-containing serum, and SB203580. After 48 h of cell culture in each group, RNA were extracted and the levels of MCP-1, and CCR2 mRNA were determined by Real-time PCR,proteins were extracted and the levels of p38, p-p38, MCP-1, and CCR2 were determined by Western blot. ResultsThe in vivo experiments showed that before treatment, other groups had higher body weight, blood glucose level, 24 h urinary protein, and ACR than the control group (P<0.05,P<0.01). After 12 weeks of treatment, compared with the model group, the Yishen Huashi granules group showed improved general conditions, a decreasing trend in body weight, lowered levels of blood glucose, 24-h urinary protein, and ACR (P<0.01), reduced SCr and UREA (P<0.01), and declined levels of TC, TG, and LDL (P<0.05,P<0.01). Compared with the model group, the Yishen Huashi granules group showed alleviated damage and interstitial fibrosis in the renal tissue as well as reductions in glomerular foot process fusion and basement membrane thickening. Moreover, the Yishen Huashi granules group showed down-regulated mRNA levels of MCP-1 and CCR2 (P<0.01), reduced positive expression of p-p38, MCP-1, and CCR2 (P<0.01), and down-regulated protein levels of p-p38/p38, MCP-1, and CCR2 (P<0.05) in the renal tissue. The cell experiment showed that compared with the high glucose group, the Yishen Huashi granule-containing serum group showcased down-regulated mRNA levels of MCP-1 and CCR2 (P<0.01) and down-regulated protein levels of p-p38/p38, MCP-1, and CCR2(P<0.05,P<0.01). ConclusionYishen Huashi granules can regulate glucose-lipid metabolism, reduce 24 h urinary protein and ACR, improve the renal function, alleviate the renal tubule injury caused by high glucose, and protect renal tubule epithelial cells in db/db mice by reducing MCP-1/CCR2 activation via the p38 MAPK signaling pathway.
2.Differentiation and Treatment of Lipid Turbidity Disease Based on Theory of "Spleen Ascending and Stomach Descending"
Yun HUANG ; Wenyu ZHU ; Wei SONG ; Xiaobo ZHANG ; Xin ZHOU ; Lele YANG ; Tao SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):244-252
Lipid turbidity disease is a metabolic disease featuring lipid metabolism disorders caused by many factors such as social environment, diet, and lifestyle, which is closely related to many diseases in modern medicine, such as hyperlipidemia, obesity, fatty liver, atherosclerosis, metabolic syndrome, and cardiovascular and cerebrovascular diseases, with a wide range of influence and far-reaching harm. According to the Huangdi Neijing, lipid turbidity disease reflects the pathological change of the body's physiologic grease. Grease is the thick part of body fluids, which has the function of nourishing, and it is the initial state and source of important substances in the human body such as brain, marrow, essence, and blood. Once the grease of the human body is abnormal, it can lead to lipid turbidity disease. The Huangdi Neijing also points out the physiological relationship between the transportation and transformation of body fluids and the rise and fall of the spleen and stomach, which can deduce the pathological relationship between the occurrence of lipid turbidity disease and the abnormal rise and fall of the spleen and stomach functions. Lipid turbidity disease is caused by overconsumption of fatty and sweet foods or insufficient spleen and stomach endowments, leading to disorders of the function of promoting clear and reducing turbidity in the spleen and stomach. This leads to the transformation of thick grease in body fluids into lipid turbidity, which accumulates in the body's meridians, blood vessels, skin pores, and organs, forming various forms of metabolic diseases. The research team believed that the pathological basis of lipid turbidity disease was the abnormal rise and fall of the spleen and stomach and the obstruction of the transfer of grease. According to the different locations where lipid turbidity stays, it was divided into four common pathogenesis types: ''inability to distinguish between the clear and turbid, turbid stagnation in the Ying blood'', ''spleen not rising clear, turbid accumulation in the vessels'', ''spleen dysfunction, lipid retention in the pores'', ''spleen failure to transportation and transformation, and grease accumulation in the liver''. According to the pathogenesis, it could be divided into four common syndromes, namely, turbid stagnation in the Ying blood, turbid accumulation in the vessels, lipid retention in the pores, and grease accumulation in the liver, and the corresponding prescriptions were given for syndrome differentiation and treatment, so as to guide clinical differentiation and treatment of the lipid turbidity disease.
3.Mediating effect of frailty on social isolation and cognitive function among the elderly
JIANG Meiting ; YANG Wenfei ; ZHANG Xiang ; CAI Xin ; GUAN Aijun ; ZENG Dongyang
Journal of Preventive Medicine 2025;37(1):17-20
Objective:
To examine the mediating effect of frailty on social isolation and cognitive function among the elderly.
Methods:
Demographic information, smoking, alcohol consumption and cognitive function of the elderly at ages of 60 years and older were collected from the China Health and Retirement Longitudinal Study 2020. Social isolation and frailty were evaluated using social isolation index and frailty index, respectively. The mediating effect of frailty on social isolation and cognitive function was analyzed using the Process program, and the significance of the mediating role was tested using the Bootstrap test.
Results:
A total of 2 822 individuals were enrolled, including 1 483 males (52.55%) and 1 339 females (47.45%). There were 2 497 (88.48%) and 325 (11.52%) individuals at ages of 60-<75 years and ≥75 years, respectively. The median cognitive function score was 14 (interquartile range, 16) points. There were 432 cases with social isolation (15.31%), with a median social isolation index of 10 (interquartile range, 5) points. The median frailty index was 0.11 (interquartile range, 0.15). There were 1 111 individuals without frailty, accounting for 39.37%; 1 214 individuals with pre-frailty, accounting for 43.02%; and 497 individuals with frailty, accounting for 17.61%. Mediating effect analysis showed that social isolation affected cognitive function directly and negatively with the effect value of -0.773 (95%CI: -0.899 to -0.647), and also affected cognitive function by frailty indirectly and negatively with the effect value of -0.147 (95%CI: -0.188 to -0.110), with the mediating effect contributed 15.98% of the total effect.
Conclusion
Frailty can directly or indirectly affect cognitive function among elderly through social isolation.
4.Effect of Folic Acid-modified Crebanine Polyethylene Glycol-polylactic Acid Hydroxyacetic Acid Copolymer Nanoparticles Combined with Ultrasonic Irradiation on Subcutaneous Tumor Growth of Liver Cancer in Mice
Rui PAN ; Junze TANG ; Hailiang ZHANG ; Kun YU ; Xiaoyu ZHAO ; Xin CHENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):217-225
ObjectiveTo investigate the effect of folic acid-modified crebanine polyethylene glycol-polylactic acid hydroxyacetic acid copolymer(PEG-PLGA) nanoparticles(FA-Cre@PEG-PLGA NPs, hereinafter referred to as NPs) combined with ultrasonic irradiation on subcutaneous tumor of liver cancer in Kunming(KM) mice. MethodsEighty-four healthy male KM mice were utilized to establish a subcutaneous tumor model of mouse hepatocellular carcinoma with H22 cells, then mice were randomly divided into model group, placebo group, hydroxycamptothecin group(8 mg∙kg-1), low, medium and high dose crebanine raw material groups(2, 2.5, 3 mg∙kg-1, hereinafter referred to as the low, medium and high dose crebanine groups, respectively), low, medium and high dose NPs groups(2, 2.5, 3 mg∙kg-1), and low, medium and high dose NPs combined with ultrasonic irradiation groups(2, 2.5, 3 mg∙kg-1, hereinafter referred to as the low, medium and high dose combination groups, respectively). The corresponding doses of drugs were administered via tail vein injection, the model group received no treatment, while the placebo group was injected with an equivalent amount of normal saline. Dosing was conducted for a total of 10 times on alternate days. The body mass of the mice was monitored, and parameters such as body mass change rate, thymus index, spleen index, tumor volume, tumor weight, relative tumor growth rate(T/C), and tumor inhibition rate(TGI) were calculated. Pathological changes in liver and kidney tissues as well as the tumor were observed by hematoxylin-eosin(HE) staining. Additionally, the levels of aspartate aminotransferase(AST), alanine aminotransferase(ALT), blood urea nitrogen(BUN) and creatinine(CREA) in serum of mice were detected by biochemical method. Furthermore, the effect of ultrasound on the distribution of NPs in subcutaneous tumors of mouse hepatocellular carcinoma was observed by in vivo imaging technique. ResultsAmong different treatment methods, the combination of NPs and ultrasound irradiation had the best therapeutic effect. Compared with the model group, the body mass growth rates of mice in the medium and high combination groups decreased, while the thymus index and spleen index increased, but there was no statistically significant difference in serum AST, ALT, BUN and CREA levels, indicating that NPs combined with ultrasound irradiation had little effect on the normal physiological state of the body, oth groups had TGI>40% and T/C<60%, indicating a clear anti-tumor effect. Pathological analysis showed that compared with the NPs groups, the combination groups exhibited varying degrees of necrosis in tumor cells, accompanied by less damage to the liver and kidneys. In vivo imaging of small animals showed that compared with the high dose NPs group, the high dose combination group had stronger tumor targeting ability(P<0.01). ConclusionNPs combined with ultrasonic irradiation can not only effectively targeted the drug to the tumor site, inhibit the subcutaneous tumor growth of mouse liver cancer, but also decrease damage to liver and kidney tissues.
5.Analysis of Changes on Volatile Components of Ligusticum sinense cv. Chaxiong Rhizome Before and After Wine Processing Based on Electronic Nose and HS-GC-MS
Wen ZHANG ; Peng ZHENG ; Jiangshan ZHANG ; Xiaolin XIAO ; Zaodan WU ; Li XIN ; Wenhui GONG ; Jinlian ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):173-181
ObjectiveBy comparing the composition and content of volatile components in raw products, wine-washed products and wine-fried products of Ligusticum sinense cv. Chaxiong rhizome(LSCR), to investigate the influence of wine processing on the volatile components of LSCR, in order to provide a basis for the development of quality standards for LSCR and its processed products. MethodsElectronic nose was used to identify the odors of LSCR, wine-washed and wine-fried LSCR, and their volatile components were detected by headspace gas chromatography-mass spectrometry(HS-GC-MS), and the relative mass fractions of these components were determined by peak area normalization method. Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were performed on the obtained sample data by SIMCA 14.1 software, and the differential components of LSCR, wine-washed and wine-fried LSCR were screened according to the variable importance in the projection(VIP) value>1. Pearson correlation analysis was used to explore the relationship between volatile differential flavor components and electronic nose sensors. ResultsElectronic nose detection results showed that there were significant differences in the odors of LSCR, wine-washed and wine-fried LSCR, mainly reflected in the sensors S2, S4, S5, S6, S11, S12, S13. And a total of 62 compounds were identified from LSCR and its wine-processed products, among which 46, 50 and 51 compounds were identified from LSCR, wine-fried and wine-washed LSCR, respectively. There were 21 differential components between the raw products and wine-fried products, of which 10 components were increased and 11 were decreased after processing. There were 20 differential components between the raw products and wine-washed products, of which 11 constituents increased and 9 decreased after processing. There were 17 differential components between the wine-wash products and wine-fried products. Compared with the wine-washed products, the contents of 13 components in the wine-fried products increased, and the contents of 4 components decreased. The increasing trend of the content of phthalides in the wine-washed products was more obvious than that in the wine-fried products, but the content of total volatile components was higher in the wine-fried products than the wine-washed products. Correlation analysis showed that there were different degrees of correlation between the 7 differential sensors of electronic nose and 24 differential volatile components, mainly phthalides and olefins. ConclusionThe odor and the content of volatile components in LSCR changed obviously after wine processing, and n-butylphthalide, Z-butylidenephthalide and E-ligustilide can be used as the candidate differential markers of volatile components in LSCR before and after wine processing.
6.Effect of "Fahan" on Metabolites of Blumea balsamifera Analyzed by Non-targeted Metabolomics
Jiayuan CAO ; Xin XU ; Xiangsheng ZHANG ; Bingnan LIU ; Yongyao WEI ; Ke ZHONG ; Yuxin PANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):200-207
ObjectiveTo characterize the changes of metabolites of Blumea balsamifera in the process of sweating by non-targeted metabolomics, and to investigate the influence of sweating processing on the constituents of B. balsamifera. MethodsUltra performance liquid chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) metabolomics was used to identify the metabolites in no sweating group(F1), sweating 2 d group(F2) and sweating 4 d group(F3), the differences of metabolites between the groups were compared by principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA), and differential metabolites were screened according to the variable importance in the projection(VIP) value>1 and P<0.05, and the pathway enrichment of the differential metabolites was analyzed by Kyoto Encyclopedia of Genes and Genomes(KEGG). ResultsThe results of PCA and OPLS-DA showed a clear distinction between the three groups of samples, indicating significant differences in the compositions of the three groups of samples. A total of 433 differential metabolites were screened between the F1 and F2, with 154 up-regulated and 279 down-regulated, the significant up-regulated metabolites were tangeritin, 5-O-demethylnobiletin and so on, while the metabolites with significant down-regulation included alternariol, fortunellin, etc. A total of 379 differential metabolites were screened between the F2 and F3, with 150 up-regulated and 229 down-regulated, the significant up-regulated metabolites were isoimperatorin, helianyl octanoate and so on, and the significant down-regulated metabolites were hovenoside I, goyasaponin Ⅲ, etc. KEGG pathway enrichment analysis showed that tyrosine metabolism, isoquinoline alkaloid biosynthesis, phenylalanine, tyrosine and tryptophan biosynthesis, tryptophan metabolism, valine, leucine and isoleucine biosynthesis, pantothenate and coenzyme A biosynthesis may be the key pathways affecting metabolite differences of B. balsamifera after sweating treatment. ConclusionSweating can reduce the content of endophytic mycotoxins in B. balsamifera and has a great impact on the synthesis and metabolic pathways of total flavonoids and auxin. This study can provide a reference for the process research on the sweating conditions of B. balsamifera.
7.Immunity-inflammation Mechanism of Viral Pneumonia and Traditional Chinese Medicine Treatment Based on Theory of Healthy Qi and Pathogenic Qi
Zheyu LUAN ; Hanxiao WANG ; Xin PENG ; Yihao ZHANG ; Yunhui LI ; Jihong FENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):239-247
Viral pneumonia is an infectious disease caused by virus invading the lung parenchyma and interstitial tissue and causing lung inflammation, with the incidence rising year by year. Traditional Chinese medicine (TCM) can treat viral pneumonia in a multi-component, multi-target, and holistic manner by targeting the core pathogenesis of pneumonia caused by different respiratory viruses, demonstrating minimal side effects and significant advantages. According to the theory of healthy Qi and pathogenic Qi in TCM, the struggle between healthy Qi and pathogenic Qi and the imbalance between immunity and inflammation run through the entire process of viral pneumonia, and the immunity-inflammation status at different stages of the disease reflects different relationships between healthy Qi and pathogenic Qi. Immune dysfunction leads to the deficiency of healthy Qi, causing viral infections. The struggle between healthy Qi and pathogenic Qi causes immunity-inflammation imbalance, leading to the onset of viral pneumonia. Inflammatory damage causes persistent accumulation of phlegm and stasis, leading to the progression of viral pneumonia. The cytokine storm causes immunodepletion, leading to the excess of pathogenic Qi and diminution of healthy Qi and the deterioration of viral pneumonia. After the recovery from viral pneumonia, there is a long-term imbalance between immunity and micro-inflammation, which results in healthy Qi deficiency and pathogenic Qi lingering. Healthy Qi deficiency and pathogenic Qi excess act as common core causes of pneumonia caused by different respiratory viruses. Clinical treatment should emphasize both replenishing healthy Qi and eliminating pathogenic Qi, helping to restore the balance between healthy Qi and pathogenic Qi as well as between immunity and inflammation, thus promoting the recovery of patients from viral pneumonia. According to the TCM theory of healthy Qi and pathogenic Qi, this article summarizes the immunity-inflammation mechanisms at different stages of viral pneumonia, and explores the application of the method of replenishing healthy Qi and eliminating pathogenic Qi in viral pneumonia. The aim is to probe into the scientific connotation of the TCM theory of healthy Qi and pathogenic Qi in viral pneumonia and provide ideas for the clinical application of the method of replenishing healthy Qi and eliminating pathogenic Qi to assist in the treatment of viral pneumonia.
8.Research progress on the mechanism and clinical application of the effective ingredients from Sijunzi decoction in the treatment of gastric cancer
Hongwei ZHANG ; Wenfei DANG ; Xin SUO ; Ru ZHANG ; Yan ZHANG ; Ziming JIN ; Xia DOU
China Pharmacy 2025;36(5):624-629
Gastric cancer is a common malignant tumor of the digestive tract and can be classified as “fullness of the stomach”, “epigastric pain”, “noise” and other categories in the field of traditional Chinese medicine. Sijunzi decoction is composed of Panax ginseng, Poria cocos, Atractylodes macrocephala, and honey-fried Glycyrrhiza uralensis, and it has the effect of tonifying qi and strengthening the spleen. This article summarizes the active ingredients, mechanism of action, and clinical application research progress of Sijunzi decoction in treating gastric cancer. The results show that the main active ingredients of Sijunzi decoction include ginsenosides, atractylenolide, pachymic acid, glycyrrhizic acid, etc.; Sijunzi decoction and its effective ingredients can play an anti-gastric cancer role by inhibiting the proliferation of gastric cancer cell, inducing apoptosis of gastric cancer cell, enhancing gastric cancer cell chemotherapy sensitivity, and inhibiting invasion and metastasis of gastric cancer cell. In addition, Sijunzi decoction can enhance the efficacy of chemotherapy drugs, strengthen the immune function of the body and lower serum cancer marker levels during the clinical treatment of gastric cancer.
9.Clinical Diseases Responding Specially to TCM Treatment: Psoriasis
Liu LIU ; Xiaoying SUN ; Mei MO ; Yaqiong ZHOU ; Bin LI ; Xiaoxiao ZHANG ; Xin LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):260-268
Psoriasis is a common chronic inflammatory systemic disease in dermatology. Its high prevalence, recurrence rate, and numerous comorbidities impose a significant physical and mental burden on patients. With the continuous advancement of modern medicine, the emergence of biological agents has improved clinical efficacy, making it possible to overcome psoriasis, in addition to classical treatments. However, in clinical practice, adverse reactions, drug resistance, recurrence rates, and immune drift cannot be ignored. Traditional Chinese medicine (TCM) has a history of thousands of years in treating psoriasis, demonstrating good efficacy, high safety, and a low recurrence rate, but a standardized management system is lacking. Therefore, the 25th Clinical Diseases Responding Specially to TCM Treatment Series (Psoriasis) Youth Salon, hosted by the Chinese Association of Chinese Medicine and organized by the Youth Committee of the Chinese Association of Chinese Medicine, invited 29 experts and scholars from TCM, Western medicine, and interdisciplinary fields to actively discuss the "Advantages, Challenges, and Clinical Transformation of TCM and Western Medicine in the Diagnosis and Treatment of Psoriasis". The experts at the meeting concluded that the advantages of TCM in the treatment of psoriasis are as follows. Firstly, in the TCM-led treatment plan, TCM's understanding of psoriasis follows the principle of combining the differentiation of disease and syndrome. This approach distinguishes the basic contradiction from the current main contradiction and enables a clear grasp of the dynamic process of psoriasis development. Based on the system of syndrome differentiation and treatment, TCM intervention is applied to address the current main contradiction, and the optimal TCM treatment plan is formulated by combining internal and external treatments. Adhering to the principle of "what is visible outside must be addressed inside", TCM can prevent and treat psoriasis comorbidities early by differentiating syndrome types. Secondly, in the integrated TCM and Western medicine treatment plan, the combination of both methods not only enhances efficacy but also reduces the adverse reactions of immunosuppressants and biological agents, lowering the recurrence rate. This conference provides a reference for the diagnosis and treatment of psoriasis using TCM and integrated TCM and Western medicine, opening up new ideas for clinical and basic research and guiding future research directions.
10.Mechanism of Xinnao shutong capsule alleviating cerebral ischemia-reperfusion injury in rats by regulating ferroptosis
Huani LI ; Changhe LIU ; Xiaoyan GUO ; Xin ZHONG ; Wei ZHANG ; Wenjing GE
China Pharmacy 2025;36(3):306-311
OBJECTIVE To study the mechanism of Xinnao shutong capsule alleviating cerebral ischemia reperfusion injury (CIRI) in rats by regulating the ferroptosis pathway. METHODS SD rats were randomly divided into sham operation group, model group, Xinnao shutong low-dose, high-dose group (220, 440 mg/kg), Ginkgo biloba leaves extract group (positive control, 150 mg/kg). Each group of rats was orally administered with the corresponding medication/normal saline for 7 consecutive days. Transient occlusion of the middle cerebral artery was adopted to induce the CIRI model; the samples were taken 24 h after the operation; the cerebral infarction area of rats was detected, and the cerebral infarction rate was calculated. The pathological changes of brain tissues were observed, and the levels of lipid peroxide (LPO), malondialdehyde (MDA) and glutathione (GSH) in cerebral tissue were detected; mRNA and protein expressions of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase 1(HO-1) and glutathione peroxidase 4 (GPX4) were all detected in cerebral tissue of rats. RESULTS Compared with model group, the cerebral infarction rate, the content of total iron in cerebral tissue and serum level of LPO (except for Ginkgo biloba leaves extract group and Xinnao shutong low-dose group) were all decreased significantly in G. biloba leaves extract group and Xinnao shutong groups (P<0.05 or P<0.01); the serum level of GSH, the protein and mRNA expressions of Nrf2, HO-1 and GPX4 were all increased significantly (P<0.05 or P<0.01). The pathological damage to brain tissue was reduced, the number of nerve cells increased, the edema was alleviated, and the nuclear membrane was flattened. CONCLUSIONS Xinnao shutong capsule can inhibit ferroptosis and reduce CIRI, the mechanism of which may be associated with the activation of the Nrf2/HO-1/GPX4 signaling pathway.


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