1.Effect of Stasis-dispelling and Detoxifying Therapy on Clinical Efficacy and JNK Signaling Pathway-related Protein Expression in Endometriosis Patients with Syndrome of Kidney Deficiency and Blood Stasis
Tingting WANG ; Zhaokang QI ; Jinxin REN ; Shuai ZHAO ; Chunxiao WEI ; Yi YU ; Fang LIAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):120-129
ObjectiveTo observe the clinical efficacy of the stasis-dispelling and detoxifying therapy in endometriosis (EMs) patients with the syndrome of kidney deficiency and blood stasis and the effects of this therapy on the expression levels of proteins related to the c-Jun N-terminal kinase (JNK) signaling pathway. MethodsA total of 72 patients with EMs due to kidney deficiency and blood stasis who met the criteria at the Integrated Traditional Chinese and Western Medicine Center for Reproduction and Genetics of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from March 2024 to February 2025 were selected and randomized into a treatment group and a control group, with 36 patients in each group. Another 36 patients undergoing in vitro fertilization-embryo transfer (IVF-ET) due to male factors alone were selected as the blank group. The treatment group took the Zishen Quyu Jiedu formula orally, while the control group and the blank group took placebos. The treatment course encompassed the cycle before ovarian stimulation and the oocyte retrieval cycle. The TCM syndrome score of kidney deficiency and blood stasis, as well as the serum level of cancer antigen 125 (CA125), were evaluated at the time of enrollment (before treatment) and on the trigger day (after treatment). Serum levels of sex hormones were measured on day 2 of the menstrual cycle. On the trigger day, the duration and dosage of gonadotropin (Gn) administration and the serum levels of hormones on the day of human chorionic gonadotropin (HCG) injection were assessed. Embryo outcomes were evaluated 3 days after oocyte retrieval, and clinical pregnancy rates were assessed 28 days after embryo transfer. The baseline data of three groups were observed. The TCM syndrome scores and serum CA125 levels before and after treatment were compared between the treatment and control groups. The baseline endocrine levels, Gn days, Gn dosage, hormone levels on the day of HCG administration, number of oocytes retrieved, number of 2 pronucleus (2PN) fertilizations, number of available embryos, high-quality embryo rate, and clinical pregnancy rate were also assessed in all three groups. Six patients from each group were selected for determination of the protein levels of JNK, c-Jun, and nuclear receptor subfamily 4 group A member 2 (NR4A2) in ovarian granulosa cells (GCs) on the day of oocyte retrieval by Western blot. Results(1) There were no statistically significant differences in the baseline data among three groups, indicating comparability. (2) Compared with the baseline within the same group, the treatment group showed a decrease in the syndrome score of kidney deficiency and blood stasis after treatment. After treatment, serum CA125 levels decreased in both groups (P<0.05), with a more substantial reduction in the treatment group, resulting in a difference between the two groups (P<0.05). (3) There were no significant differences among three groups in terms of baseline serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and progesterone (P), as well as the duration and dosage of Gn administration and the serum levels of LH, E2, and P on the day of HCG administration. (4) For embryo outcomes, the number of oocytes retrieved, 2PN fertilizations, available embryos, and high-quality embryo rates in the treatment group and the blank group were higher than those in the control group (P<0.05), and the treatment group and the blank group had similar 2PN fertilizations. (5) There were differences in clinical pregnancy rate among three groups (P<0.05), and the treatment group had higher pregnancy rate than the control and blank groups. (6) The protein levels of JNK, c-Jun, and NR4A2 in the GCs of the treatment group were lower than those in the control group (P<0.01) and close to those in the blank group (P<0.01). (7) No obvious adverse reactions were observed in any of the subjects during the clinical observation process. ConclusionZishen Quyu Jiedu formula can ameliorate the clinical symptoms of patients with EMs due to kidney deficiency and blood stasis, reduce the serum CA125 level, increase the number of oocytes retrieved, 2PN fertilizations, available embryos, and high-quality embryo rate, and improve pregnancy outcomes. The mechanism may involve downregulating the levels of JNK, c-Jun, and NR4A2 to reduce the apoptosis of ovarian GCs and improve the ovarian function in the patients.
2.Effect of Stasis-dispelling and Detoxifying Therapy on Clinical Efficacy and JNK Signaling Pathway-related Protein Expression in Endometriosis Patients with Syndrome of Kidney Deficiency and Blood Stasis
Tingting WANG ; Zhaokang QI ; Jinxin REN ; Shuai ZHAO ; Chunxiao WEI ; Yi YU ; Fang LIAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):120-129
ObjectiveTo observe the clinical efficacy of the stasis-dispelling and detoxifying therapy in endometriosis (EMs) patients with the syndrome of kidney deficiency and blood stasis and the effects of this therapy on the expression levels of proteins related to the c-Jun N-terminal kinase (JNK) signaling pathway. MethodsA total of 72 patients with EMs due to kidney deficiency and blood stasis who met the criteria at the Integrated Traditional Chinese and Western Medicine Center for Reproduction and Genetics of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from March 2024 to February 2025 were selected and randomized into a treatment group and a control group, with 36 patients in each group. Another 36 patients undergoing in vitro fertilization-embryo transfer (IVF-ET) due to male factors alone were selected as the blank group. The treatment group took the Zishen Quyu Jiedu formula orally, while the control group and the blank group took placebos. The treatment course encompassed the cycle before ovarian stimulation and the oocyte retrieval cycle. The TCM syndrome score of kidney deficiency and blood stasis, as well as the serum level of cancer antigen 125 (CA125), were evaluated at the time of enrollment (before treatment) and on the trigger day (after treatment). Serum levels of sex hormones were measured on day 2 of the menstrual cycle. On the trigger day, the duration and dosage of gonadotropin (Gn) administration and the serum levels of hormones on the day of human chorionic gonadotropin (HCG) injection were assessed. Embryo outcomes were evaluated 3 days after oocyte retrieval, and clinical pregnancy rates were assessed 28 days after embryo transfer. The baseline data of three groups were observed. The TCM syndrome scores and serum CA125 levels before and after treatment were compared between the treatment and control groups. The baseline endocrine levels, Gn days, Gn dosage, hormone levels on the day of HCG administration, number of oocytes retrieved, number of 2 pronucleus (2PN) fertilizations, number of available embryos, high-quality embryo rate, and clinical pregnancy rate were also assessed in all three groups. Six patients from each group were selected for determination of the protein levels of JNK, c-Jun, and nuclear receptor subfamily 4 group A member 2 (NR4A2) in ovarian granulosa cells (GCs) on the day of oocyte retrieval by Western blot. Results(1) There were no statistically significant differences in the baseline data among three groups, indicating comparability. (2) Compared with the baseline within the same group, the treatment group showed a decrease in the syndrome score of kidney deficiency and blood stasis after treatment. After treatment, serum CA125 levels decreased in both groups (P<0.05), with a more substantial reduction in the treatment group, resulting in a difference between the two groups (P<0.05). (3) There were no significant differences among three groups in terms of baseline serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and progesterone (P), as well as the duration and dosage of Gn administration and the serum levels of LH, E2, and P on the day of HCG administration. (4) For embryo outcomes, the number of oocytes retrieved, 2PN fertilizations, available embryos, and high-quality embryo rates in the treatment group and the blank group were higher than those in the control group (P<0.05), and the treatment group and the blank group had similar 2PN fertilizations. (5) There were differences in clinical pregnancy rate among three groups (P<0.05), and the treatment group had higher pregnancy rate than the control and blank groups. (6) The protein levels of JNK, c-Jun, and NR4A2 in the GCs of the treatment group were lower than those in the control group (P<0.01) and close to those in the blank group (P<0.01). (7) No obvious adverse reactions were observed in any of the subjects during the clinical observation process. ConclusionZishen Quyu Jiedu formula can ameliorate the clinical symptoms of patients with EMs due to kidney deficiency and blood stasis, reduce the serum CA125 level, increase the number of oocytes retrieved, 2PN fertilizations, available embryos, and high-quality embryo rate, and improve pregnancy outcomes. The mechanism may involve downregulating the levels of JNK, c-Jun, and NR4A2 to reduce the apoptosis of ovarian GCs and improve the ovarian function in the patients.
3.Spicy food consumption and risk of vascular disease: Evidence from a large-scale Chinese prospective cohort of 0.5 million people.
Dongfang YOU ; Dianjianyi SUN ; Ziyu ZHAO ; Mingyu SONG ; Lulu PAN ; Yaqian WU ; Yingdan TANG ; Mengyi LU ; Fang SHAO ; Sipeng SHEN ; Jianling BAI ; Honggang YI ; Ruyang ZHANG ; Yongyue WEI ; Hongxia MA ; Hongyang XU ; Canqing YU ; Jun LV ; Pei PEI ; Ling YANG ; Yiping CHEN ; Zhengming CHEN ; Hongbing SHEN ; Feng CHEN ; Yang ZHAO ; Liming LI
Chinese Medical Journal 2025;138(14):1696-1704
BACKGROUND:
Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association.
METHODS:
This study was performed using the large-scale China Kadoorie Biobank (CKB) prospective cohort of 486,335 participants. The primary outcomes were vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease. A Cox proportional hazards regression model was used to assess the association between spicy food consumption and incident vascular diseases. Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics. In addition, the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease were also evaluated, and sensitivity analyses were performed to assess the reliability of the association results.
RESULTS:
During a median follow-up time of 12.1 years, a total of 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Participants who consumed spicy food 1-2 days/week (hazard ratio [HR] = 0.95, 95% confidence interval [95% CI] = [0.93, 0.97], P <0.001), 3-5 days/week (HR = 0.96, 95% CI = [0.94, 0.99], P = 0.003), and 6-7 days/week (HR = 0.97, 95% CI = [0.95, 0.99], P = 0.002) had a significantly lower risk of vascular disease than those who consumed spicy food less than once a week ( Ptrend <0.001), especially in those who were younger and living in rural areas. Notably, the disease-based subgroup analysis indicated that the inverse associations remained in IHD ( Ptrend = 0.011) and MCEs ( Ptrend = 0.002) risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD ( Pinteraction = 0.037).
CONCLUSIONS
Our findings support an inverse association between spicy food consumption and vascular disease in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases.
Humans
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Male
;
Female
;
Prospective Studies
;
Middle Aged
;
Aged
;
Vascular Diseases/etiology*
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Risk Factors
;
China/epidemiology*
;
Adult
;
Proportional Hazards Models
;
Cerebrovascular Disorders/epidemiology*
;
East Asian People
4.Research progress on the mechanisms of Tau phosphorylation and its kinases in hypoxic-ischemic brain damage.
Qi-Yi HUANG ; You XIANG ; Jia-Hang TANG ; Li-Jia CHEN ; Kun-Lin LI ; Wei-Fang ZHAO ; Qian WANG
Acta Physiologica Sinica 2025;77(1):139-150
Hypoxic-ischemic brain damage (HIBD) is one of the main causes of disability in middle-aged and elderly people, as well as high mortality rates and long-term physical impairments in newborns. The pathological manifestations of HIBD include neuronal damage and loss of myelin sheaths. Tau protein is an important microtubule-associated protein in brain, exists in neurons and oligodendrocytes, and regulates various cellular activities such as cell differentiation and maturation, axonal transport, and maintenance of cellular cytoskeleton structure. Phosphorylation is a common chemical modification of Tau. In physiological condition, it maintains normal cell cytoskeleton and biological functions by regulating Tau structure and function. In pathological conditions, it leads to abnormal Tau phosphorylation and influences its structure and functions, resulting in Tauopathies. Studies have shown that brain hypoxia-ischemia could cause abnormal alteration in Tau phosphorylation, then participating in the pathological process of HIBD. Meanwhile, brain hypoxia-ischemia can induce oxidative stress and inflammation, and multiple Tau protein kinases are activated and involved in Tau abnormal phosphorylation. Therefore, exploring specific molecular mechanisms by which HIBD activates Tau protein kinases, and elucidating their relationship with abnormal Tau phosphorylation are crucial for future researches on HIBD related treatments. This review aims to focus on the mechanisms of the role of Tau phosphorylation in HIBD, and the potential relationships between Tau protein kinases and Tau phosphorylation, providing a basis for intervention and treatment of HIBD.
Humans
;
tau Proteins/physiology*
;
Phosphorylation
;
Hypoxia-Ischemia, Brain/physiopathology*
;
Animals
;
Oxidative Stress
5.Medication rules and mechanisms of treating chronic renal failure by Jinling medical school based on data mining, network pharmacology, and experimental validation.
Jin-Long WANG ; Wei WU ; Yi-Gang WAN ; Qi-Jun FANG ; Yu WANG ; Ya-Jing LI ; Fee-Lan CHONG ; Sen-Lin MU ; Chu-Bo HUANG ; Huang HUANG
China Journal of Chinese Materia Medica 2025;50(6):1637-1649
This study aims to explore the medication rules and mechanisms of treating chronic renal failure(CRF) by Jinling medical school based on data mining, network pharmacology, and experimental validation systematically and deeply. Firstly, the study selected the papers published by the inherited clinicians in Jinling medical school in Chinese journals using the subject headings named "traditional Chinese medicine(TCM) + chronic renal failure", "TCM + chronic renal inefficiency", or "TCM + consumptive disease" in China National Knowledge Infrastructure, Wanfang, and VIP Chinese Science and Technology Periodical Database and screened TCM formulas for treating CRF according to inclusion and exclusion criteria. The study analyzed the frequency of use of single TCM and the four properties, five tastes, channel tropism, and efficacy of TCM used with high frequency and performed association rule and clustering analysis, respectively. As a result, a total of 215 TCM formulas and 235 different single TCM were screened, respectively. The TCM used with high frequency included Astragali Radix, Rhei Radix et Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Poria, and Atractylodis Macrocephalae Rhizoma(top 5). The single TCM characterized by "cold properties, sweet flavor, and restoring spleen channel" and the TCM with the efficacy of tonifying deficiency had the highest frequency of use, respectively. Then, the TCM with the rules of "blood-activating and stasis-removing" and "diuretic and dampness-penetrating" appeared. In addition, the core combination of TCM [(Hexin Formula, HXF)] included "Astragali Radix, Rhei Radix et Rhizoma, Poria, Salviae Miltiorrhizae Radix, and Angelicae Sinensis Radix". The network pharmacology analysis showed that HXF had 91 active compounds and 250 corresponding protein targets including prostaglandin-endoperoxide synthase 2(PTGS2), PTGS1, sodium voltage-gated channel alpha subunit 5(SCN5A), cholinergic receptor muscarinic 1(CHRM1), and heat shock protein 90 alpha family class A member 1(HSP90AA1)(top 5). Gene Ontology(GO) function analysis revealed that the core targets of HXF predominantly affected biological processes, cellular components, and molecular functions such as positive regulation of transcription by ribonucleic acid polymerase Ⅱ and DNA template transcription, formation of cytosol, nucleus, and plasma membrane, and identical protein binding and enzyme binding. Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis revealed that CRF-related genes were involved in a variety of signaling pathways and cellular metabolic pathways, primarily involving "phosphatidylinositol 3-kinase(PI3K)-protein kinase B(Akt) pathway" and "advanced glycation end products-receptor for advanced glycation end products". Molecular docking results showed that the active components in HXF such as isomucronulatol 7-O-glucoside, betulinic acid, sitosterol, and przewaquinone B might be crucial in the treatment of CRF. Finally, a modified rat model with renal failure induced by adenine was used, and the in vivo experimental confirmation was performed based on the above-mentioned predictions. The results verify that HXF can regulate mitochondrial autophagy in the kidneys and the PI3K-Akt-mammalian target of rapamycin(mTOR) signaling pathway activation at upstream, so as to alleviate renal tubulointerstitial fibrosis and then delay the progression of CRF.
Data Mining
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Drugs, Chinese Herbal/chemistry*
;
Network Pharmacology
;
Humans
;
Kidney Failure, Chronic/metabolism*
;
Medicine, Chinese Traditional
;
China
6.Mechanism of Jiming Powder in improving mitophagy for treatment of myocardial infarction based on PINK1-Parkin pathway.
Xin-Yi FAN ; Xiao-Qi WEI ; Wang-Jing CHAI ; Kuo GAO ; Fang-He LI ; Xue YU ; Shu-Zhen GUO
China Journal of Chinese Materia Medica 2025;50(12):3346-3355
In the present study, a mouse model of coronary artery ligation was employed to evaluate the effects of Jiming Powder on mitophagy in the mouse model of myocardial infarction and elucidate its underlying mechanisms. A mouse model of myocardial infarction post heart failure was constructed by ligating the left anterior descending branch of the coronary artery. The therapeutic efficacy of Jiming Powder was assessed from multiple perspectives, including ultrasonographic imaging, hematoxylin-eosin(HE) staining, Masson staining, and serum cardiac enzyme profiling. Dihydroethidium(DHE) staining was employed to evaluate the oxidative stress levels in the hearts of mice from each group. Mitophagy levels were assessed by scanning electron microscopy and immunofluorescence co-localization. Western blot was employed to determine the levels of key proteins involved in mitophagy, including Bcl-2-interacting protein beclin 1(BECN1), sequestosome 1(SQSTM1), microtubule-associated protein 1 light chain 3 beta(LC3B), PTEN-induced putative kinase 1(PINK1), phospho-Parkinson disease protein(p-Parkin), and Parkinson disease protein(Parkin). The results demonstrated that compared with the model group, high and low doses of Jiming Powder significantly reduced the left ventricular internal diameter in systole(LVIDs) and left ventricular internal diameter in diastole(LVIDd) and markedly improved the left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), effectively improving the cardiac function in post-myocardial infarction mice. Jiming Powder effectively reduced the levels of myocardial injury markers such as creatine kinase(CK), creatine kinase isoenzyme(CK-MB), and lactate dehydrogenase(LDH), thereby protecting ischemic myocardium. HE staining revealed that Jiming Powder attenuated inflammatory cell infiltration after myocardial infarction. Masson staining indicated that Jiming Powder effectively inhibited ventricular remodeling. Western blot results showed that Jiming Powder activated the PINK1-Parkin pathway, up-regulated the protein level of BECN1, down-regulated the protein level of SQSTM1, and increased the LC3Ⅱ/LC3Ⅰ ratio to promote mitophagy. In conclusion, Jiming Powder exerts therapeutic effects on myocardial infarction by inhibiting ventricular remodeling. The findings pave the way for subsequent pharmacological studies on the active components of Jiming Powder.
Animals
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Myocardial Infarction/physiopathology*
;
Mitophagy/drug effects*
;
Mice
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Drugs, Chinese Herbal/administration & dosage*
;
Protein Kinases/genetics*
;
Male
;
Ubiquitin-Protein Ligases/genetics*
;
Humans
;
Disease Models, Animal
;
Mice, Inbred C57BL
;
Signal Transduction/drug effects*
7.Effect and mechanism of Bufei Decoction on improving Klebsiella pneumoniae pneumonia in rats by regulating IL-17 signaling pathway.
Li-Na HUANG ; Zheng-Ying QIU ; Xiang-Yi PAN ; Chen LIU ; Si-Fan LI ; Shao-Guang GE ; Xiong-Wei SHI ; Hao CAO ; Rui-Hua XIN ; Fang-di HU
China Journal of Chinese Materia Medica 2025;50(11):3097-3107
Based on the interleukin-17(IL-17) signaling pathway, this study explores the effect and mechanism of Bufei Decoction on Klebsiella pneumoniae pneumonia in rats. SD rats were randomly divided into the control group, model group, Bufei Decoction low-dose group(6.68 g·kg~(-1)·d~(-1)), Bufei Decoction high-dose group(13.36 g·kg~(-1)·d~(-1)), and dexamethasone group(1.04 mg·kg~(-1)·d~(-1)), with 10 rats in each group. A pneumonia model was established by tracheal drip injection of K. pneumoniae. After successful model establishment, the improvement in lung tissue damage was observed following drug administration. Core targets and signaling pathways were screened using transcriptomics techniques. Real-time fluorescence quantitative polymerase chain reaction was used to detect the mRNA expression of core targets interleukin-6(IL-6), interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and chemokine CXC ligand 6(CXCL6). Western blot was used to assess key proteins in the IL-17 signaling pathway, including interleukin-17A(IL-17A), nuclear transcription factor-κB activator 1(Act1), tumor necrosis factor receptor-associated factor 6(TRAF6), and downstream phosphorylated p38 mitogen-activated protein kinase(p-p38 MAPK), and phosphorylated nuclear factor-κB p65(p-NF-κB p65). Apoptosis of lung tissue cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling(TUNEL). The results showed that, compared with the control group, the model group exhibited significant pathological damage in lung tissue. The mRNA expression of IL-6, IL-1β, TNF-α, and CXCL6, as well as the protein levels of IL-17A, Act1, TRAF6, p-p38 MAPK/p38 MAPK, and p-NF-κB p65/NF-κB p65, were significantly increased, and the number of apoptotic cells was notably higher, indicating successful model establishment. Compared with the model group, both low-and high-dose groups of Bufei Decoction showed reduced pathological damage in lung tissue. The mRNA expression levels of IL-6, IL-1β, TNF-α, and CXCL6, and the protein levels of IL-17A, Act1, TRAF6, p-p38 MAPK/p38 MAPK, and p-NF-κB p65/NF-κB p65, were significantly decreased, with a significant reduction in apoptotic cells in the high-dose group. In conclusion, Bufei Decoction can effectively improve lung tissue damage and reduce inflammation in rats with K. pneumoniae. The mechanism may involve the regulation of the IL-17 signaling pathway and the reduction of apoptosis.
Animals
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Interleukin-17/metabolism*
;
Drugs, Chinese Herbal/administration & dosage*
;
Rats, Sprague-Dawley
;
Signal Transduction/drug effects*
;
Rats
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Male
;
Klebsiella pneumoniae/physiology*
;
Klebsiella Infections/immunology*
;
Humans
;
Lung/drug effects*
8.Mechanism of Jiming Powder in inhibiting ferroptosis in treatment of myocardial infarction based on NRF2/HO-1/GPX4 pathway.
Xin-Yi FAN ; Xiao-Qi WEI ; Wang-Jing CHAI ; Fang-He LI ; Kuo GAO ; Xue YU ; Shu-Zhen GUO
China Journal of Chinese Materia Medica 2025;50(11):3108-3116
This study employed a mouse model of coronary artery ligation to assess the effect and mechanism of Jiming Powder on mitochondrial autophagy in mice with myocardial infarction. The mouse model of heart failure post-myocardial infarction was established by ligating the left anterior descending coronary artery. The pharmacological efficacy of Jiming Powder was evaluated through echocardiographic imaging, hematoxylin-eosin(HE) staining, and Masson staining. The levels of malondialdehyde(MDA), Fe~(2+), reduced glutathione(GSH), and superoxide dismutase(SOD) in heart tissues, as well as MDA immunofluorescence of heart tissues, were measured to assess lipid peroxidation and Fe~(2+) levels in the hearts of mice in different groups. Ferroptosis levels in the groups were evaluated using scanning electron microscopy and Prussian blue staining. Western blot analysis was conducted to detect the levels of key ferroptosis-related proteins, including nuclear factor erythroid 2-related factor 2(NRF2), ferritin heavy chain(FTH), glutathione peroxidase 4(GPX4), solute carrier family 7 member 11(SLC7A11), heme oxygenase 1(HO-1), and Kelch-like ECH-associated protein 1(KEAP1). The results showed that compared with the model group, both the high-and low-dose Jiming Powder groups exhibited significantly reduced left ventricular internal diameter in systole(LVIDs) and left ventricular internal diameter in diastole(LVIDd), while the left ventricular ejection fraction(EF) and left ventricular fractional shortening(FS) were significantly improved, effectively enhancing cardiac function in mice post-myocardial infarction. HE staining revealed that Jiming Powder attenuated myocardial inflammatory cell infiltration post-infarction, and Masson staining indicated that Jiming Powder effectively reduced fibrosis in the infarct margin area. Treatment with Jiming Powder reduced the levels of MDA and Fe~(2+), indicators of lipid peroxidation post-myocardial infarction, while increasing GSH and SOD levels, thus protecting ischemic myocardium. Western blot results demonstrated that Jiming Powder reduced KEAP1 protein accumulation, activated the NRF2/HO-1/GPX4 pathway, and up-regulated the protein expression of FTH and SLC7A11, exerting an inhibitory effect on ferroptosis. This study reveals that Jiming Powder exerts a therapeutic effect on myocardial infarction by inhibiting ferroptosis through the NRF2/HO-1/GPX4 pathway, providing a foundation for subsequent research on the pharmacological effects of Jiming Powder.
Animals
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Ferroptosis/drug effects*
;
Myocardial Infarction/physiopathology*
;
NF-E2-Related Factor 2/genetics*
;
Mice
;
Drugs, Chinese Herbal/administration & dosage*
;
Male
;
Heme Oxygenase-1/genetics*
;
Phospholipid Hydroperoxide Glutathione Peroxidase/genetics*
;
Humans
;
Mice, Inbred C57BL
;
Signal Transduction/drug effects*
;
Disease Models, Animal
9.Effects and mechanisms of total flavones of Abelmoschus manihot combined with empagliflozin in attenuating diabetic tubulopathy through multiple targets based on mitochondrial homeostasis and ZBP1-mediated PANoptosis.
Si-Yu CHA ; Meng WANG ; Yi-Gang WAN ; Si-Ping DING ; Yu WANG ; Shi-Yu SHEN ; Wei WU ; Ying-Lu LIU ; Qi-Jun FANG ; Yue TU ; Hai-Tao TANG
China Journal of Chinese Materia Medica 2025;50(13):3738-3753
This study aimed to explore the mechanisms and molecular targets of total flavones of Abelmoschus manihot(TFA) plus empagliflozin(EM) in attenuating diabetic tubulopathy(DT) by targeting mitochondrial homeostasis and pyroptosis-apoptosis-necroptosis(PANoptosis). In the in vivo study, the authors established the DT rat models through a combination of uninephrectomy, administration of streptozotocin via intraperitoneal injections, and exposure to a high-fat diet. Following modeling successfully, the DT rat models received either TFA, EM, TFA+EM, or saline(as a vehicle) by gavage for eight weeks, respectively. In the in vitro study, the authors subjected the NRK52E cells with or without knock-down Z-DNA binding protein 1(ZBP1) to a high-glucose(HG) environment and various treatments including TFA, EM, and TFA+EM. In the in vivo and in vitro studies, The authors investigated the relative characteristics of renal tubular injury and renal tubular epithelial cells damage induced by reactive oxygen species(ROS), analyzed the relative characteristics of renal tubular PANoptosis and ZBP1-mediatted PANoptosis in renal tubular epithelial cells, and compared the relative characteristics of the protein expression levels of marked molecules of mitochondrial fission in the kidneys and mitochondrial homeostasis in renal tubular epithelial cells, respectively. Furthermore, in the network pharmacology study, the authors predicted and screened targets of TFA and EM using HERB and SwissTargetPrediction databases; The screened chemical constituents and targets of TFA and EM were constructed the relative network using Cytoscape 3.7.2 network graphics software; The relative targets of DT were integrated using OMIM and GeneCards databases; The intersecting targets of TFA, EM, and DT were enriched and analyzed signaling pathways by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG) software using DAVID database. In vivo study results showed that TFA+EM could improve renal tubular injury, the protein expression levels and characteristics of key signaling molecules in PANoptosis pathway in the kidneys, and the protein expression levels of marked molecules of mitochondrial fission in the kidneys. And that, the ameliorative effects in vivo of TFA+EM were both superior to TFA or EM. Network pharmacology study results showed that TFA+EM treated DT by regulating the PANoptosis signaling pathway. In vitro study results showed that TFA+EM could improve ROS-induced cell injury, ZBP1-mediatted PANoptosis, and mitochondrial homeostasis in renal tubular epithelial cells under a state of HG, including the protein expression levels of marked molecules of mitochondrial fission, mitochondrial ultrastructure, and membrane potential level. And that, the ameliorative effects in vitro of TFA+EM were both superior to TFA or EM. More importantly, using the NRK52E cells with knock-down ZBP1, the authors found that, indeed, ZBP1 was mediated PANoptosis in renal tubular epithelial cells as an upstream factor. In addition, TFA+EM could regulate the protein expression levels of marked signaling molecules of PANoptosis by targeting ZBP1. In summary, this study clarified that TFA+EM, different from TFA or EM, could attenuate DT with multiple targets by ameliorating mitochondrial homeostasis and inhibiting ZBP1-mediated PANoptosis. These findings provide the clear pharmacological evidence for the clinical treatment of DT with a novel strategy of TFA+EM, which is named "coordinated traditional Chinese and western medicine".
Animals
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Rats
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Mitochondria/metabolism*
;
Benzhydryl Compounds/administration & dosage*
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Glucosides/administration & dosage*
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Abelmoschus/chemistry*
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Male
;
Homeostasis/drug effects*
;
Flavones/administration & dosage*
;
Rats, Sprague-Dawley
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Diabetic Nephropathies/physiopathology*
;
Drugs, Chinese Herbal/administration & dosage*
;
DNA-Binding Proteins/genetics*
;
Humans
;
Apoptosis/drug effects*
10.Lumbar temperature change after acupuncture or moxibustion at Weizhong (BL40) or Chize (LU5) in healthy adults: A randomized controlled trial.
Si-Yi ZHENG ; Xiao-Ying WANG ; Li-Nan LIN ; Shan LIU ; Xiao-Xiao HUANG ; Yi-Yue LIU ; Xiao-Shuai YU ; Wei PAN ; Jian-Qiao FANG ; Yi LIANG
Journal of Integrative Medicine 2025;23(2):145-151
BACKGROUND:
There is a gap in understanding the effects of different acupoints and treatment methods (acupuncture and moxibustion) on microcirculatory changes in the lumbar region.
OBJECTIVE:
This study aimed to assess the thermal effects of acupuncture at Weizhong (BL40), with acupuncture at Chize (LU5) and moxibustion at both acupoints as control interventions.
DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS:
In this randomized controlled trial, 140 healthy participants were equally divided into four groups: acupuncture at BL40 (Acu-BL40), acupuncture at LU5 (Acu-LU5), moxibustion at BL40 (Mox-BL40) and moxibustion at LU5 (Mox-LU5). Participants underwent a 30-minute session of their assigned treatment. Infrared thermal imaging was used to collect temperature data on the areas of interest for analysis.
MAIN OUTCOME MEASURES:
The primary measure was the change in average temperature of the observed area after the intervention. The secondary measures included periodic temperature changes every 5 min and the temperature changes of the Governor Vessel and Bladder Meridian in the observed area after the intervention.
RESULTS:
Significant interactions were observed between treatments and acupoints affecting temperature (P < 0.001). The Acu-BL40 group showed a notably higher increase in mean temperature after 30 min compared to the Acu-LU5 and Mox-BL40 groups, with increases of 0.29 (95% confidence interval [CI] = 0.17 to 0.41) and 0.24 (95% CI = 0.08 to 0.41) °C, respectively.
CONCLUSION:
Acupuncture at BL40 acupoint can significantly increase the mean temperature in the observed area, highlighting the specific thermal effect of acupuncture compared to moxibustion in the lumbar area. This suggests a potential therapeutic benefit of acupuncture at BL40 for managing lumbar conditions.
TRIAL REGISTRATION
ClinicalTrials.gov (NCT05665426). Please cite this article as: Zheng SY, Wang XY, Lin LN, Liu S, Huang XX, Liu YY, Yu XS, Pan W, Fang JQ, Liang Y. Lumbar temperature change after acupuncture or moxibustion at Weizhong (BL40) or Chize (LU5) in healthy adults: A randomized controlled trial. J Integr Med. 2025; 23(2): 145-151.
Adult
;
Female
;
Humans
;
Male
;
Young Adult
;
Acupuncture Points
;
Acupuncture Therapy
;
Body Temperature
;
Healthy Volunteers
;
Lumbosacral Region/physiology*
;
Moxibustion
;
Adolescent

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