1.Epidemiological characteristics and disease burden of liver cancer in Guangdong Province
Ying ZHANG ; Yixuan CHEN ; Rong CAO ; Yue GAO ; Yutong HAN ; Ye WANG ; Ruilin MENG ; Xueyan ZHENG ; Yu LIAO ; Zhuanping ZENG
Journal of Public Health and Preventive Medicine 2026;37(1):68-72
Objective To analyze the epidemiological characteristics and disease burden of liver cancer in Guangdong Province in 2020, and to provide a scientific foundation for the development of regionalized prevention and control strategies for liver cancer. Methods According to the cancer registry data of Guangdong Province, the incidence, mortality and age-standardized rate by Chinese standard population in 2020 were calculated to analyze the epidemiological characteristics of liver cancer. The disability adjusted life years (DALYs), year of life loss (YLL), year of lived with disability (YLD), and cause-eliminated life expectancy were used to assess the disease burden of liver cancer. Results In 2020, the crude incidence rate and the age-standardized incidence rate of liver cancer in Guangdong Province were 27.79/100 000 and 20.84/100 000,respectively, and the crude mortality rate and the age-standardized mortality rate of liver cancer were 25.49/100,000 and 17.64/100 000, respectively. The total DALY and DALY rate of liver cancer in Guangdong Province were 515 311 person-years and 513.83/100 000, respectively. After eliminating the causes of death from liver cancer, the life expectancy in Guangdong Province increased from 84.60 years to 84.99 years. All indicators consistently demonstrated that the burden of liver cancer was higher in males than that in females, and the burden of liver cancer was higher in rural areas than that in urban areas. Conclusion Liver cancer in Guangdong Province exhibits a high incidence, mortality and disease burden level in 2020. There are obvious differences of gender, age and region in cancer burden. It is necessary to strengthen liver cancer screening and diagnosis and treatment in men, the elderly and those in rural areas to reduce the burden of liver cancer gradually in Guangdong Province.
2.Effects of Modified Buyang Huanwu Tang on Mice with Cerebral Ischemia-reperfusion Injury by Regulating PINK1/Parkin Signaling Pathway-mediated Mitochondrial Autophagy
Li GUO ; Hengwen CHEN ; Cun ZHAN ; Zhenzhen YING ; Zuomin WU ; Shaoju JIN ; Shangmei CAO ; Shengming HUANG ; Jin WANG ; Xiaotao YU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(11):34-43
ObjectiveTo investigate the effects of modified Buyang Huanwu Tang on cerebral ischemia-reperfusion injury (CI/RI) in mice via the PTEN-induced putative kinase 1/E3 ubiquitin ligase (PINK1/Parkin) signaling pathway-mediated mitophagy, and to explore the underlying mechanism by which modified Buyang Huanwu Tang improves CI/RI. MethodsSeventy-two male C57BL/6J mice were randomly divided into six groups (n = 12 per group): Sham-operated group, middle cerebral artery occlusion/reperfusion (MCAO/R) model group, low-, medium-, and high-dose modified Buyang Huanwu Tang groups (8.84, 17.68, 35.36 g·kg-1·d-1), and an aspirin group (13.00 mg·kg-1·d-1). Neurological deficit scores were assessed using the Zea-Longa method. Cerebral infarct volume ratio was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Histopathological changes and neuronal injury in brain tissues were observed using hematoxylin-eosin (HE) staining and Nissl staining. Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Mitochondrial ultrastructure in brain tissue was observed by transmission electron microscopy (TEM). Serum levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were determined by enzyme-linked immunosorbent assay (ELISA). The mRNA and protein expression levels of PINK1, Parkin, microtubule-associated protein 1 light chain 3B (LC3B, LC3Ⅱ/Ⅰ), and p62 in brain tissues were detected by real-time quantitative reverse transcription PCR (Real-time PCR) and Western blot, respectively. ResultsCompared with the sham-operated group, the MCAO/R model group showed significantly increased neurological deficit scores and cerebral infarct volume ratios (P<0.01). Severe cortical injury on the infarct side was observed, characterized by decreased neuronal density, cytoplasmic vacuolation, nuclear pyknosis, a marked reduction in Nissl bodies, dissolution of Nissl bodies in the cytoplasm of some pyramidal neurons, and blurred cellular boundaries. The number of TUNEL-positive cells increased significantly (P<0.01). Mitochondria exhibited cristae membrane rupture and matrix vacuolation, with rupture of the outer mitochondrial membrane and formation of autophagosomes, the number of which increased significantly. Serum SOD activity decreased significantly (P<0.01), while MDA content increased significantly (P<0.01). In infarcted brain tissues of model mice, the relative mRNA expression and protein levels of PINK1, Parkin and LC3B were significantly increased (P<0.05, P<0.01), whereas p62 mRNA and protein expression were significantly decreased (P<0.05, P<0.01), showing statistical significance. Compared with the model group, all treatment groups showed significantly decreased neurological deficit scores and cerebral infarct volume ratios (P<0.01). Neuronal density increased significantly, cytoplasmic vacuolation was alleviated, nuclear morphology tended to be more regular and clearer, Nissl body density increased significantly with reduced dissolution and improved contour clarity. The mitochondrial cristae structure was partially restored, with some mitochondria showing autophagosome encapsulation, and the degree of mitochondrial damage was alleviated. Serum SOD activity increased significantly (P<0.01), while MDA content decreased significantly. The mRNA and protein expression levels of PINK1, Parkin, and LC3Ⅱ/Ⅰ were significantly increased (P<0.05, P<0.01), while p62 mRNA and protein expression in the low- and medium-dose modified Buyang Huanwu Tang groups were significantly decreased (P<0.05, P<0.01), showing statistical significance. ConclusionModified Buyang Huanwu Tang can upregulate the protein expression levels of PINK1, Parkin, and LC3Ⅱ/Ⅰ and downregulate p62 protein expression, suggesting that it may improve CI/RI by regulating the expression of proteins related to the PINK1/Parkin signaling pathway. Regulation of the mitophagy pathway may be one of the mechanisms by which modified Buyang Huanwu Tang alleviates CI/RI in mice.
3.Empirical study of input, output, outcome and impact of community-based rehabilitation stations
Xiayao CHEN ; Ying DONG ; Xue DONG ; Zhongxiang MI ; Jun CHENG ; Aimin ZHANG ; Didi LU ; Jun WANG ; Jude LIU ; Qianmo AN ; Hui GUO ; Xiaochen LIU ; Zefeng YU
Chinese Journal of Rehabilitation Theory and Practice 2026;32(1):83-89
ObjectiveTo investigate the present situation of input, output, outcome and impact of all registered community-based rehabilitation stations in Inner Mongolia in China, and analyze how the input predict the output, outcome and impact. MethodsFrom March 1st to April 30th, 2025, a questionnaire survey was conducted on all registered community-based rehabilitation stations in Inner Mongolia, covering four dimensions: input, output, outcome and impact. A total of 1 365 questionnaires were distributed. The input included four items: laws and policies, human resources, equipment and facilities, and rehabilitation information management. The output included two items: technical paths and benefits/effectiveness. The outcome included three items: coverage rates, rehabilitation interventions and functional results. The impact included two items: health and sustainability. Each item contained several questions, all of which were described in a positive way. Each question was scored from one to five. A lower score indicated that the situation of the community-based rehabilitation station was more in line with the content described in the question. Regression analysis was performed using the total score of each item of input dimension as independent variables, and the total scores of the output, outcome and impact dimensions as dependent variables. ResultsA total of 1 262 valid questionnaires were collected. The mean values of input, output, outcome and impact of community-based rehabilitation stations were 1.827 to 1.904, with coefficient of variation of 45.892% to 49.239%. The regression analysis showed that, rehabilitation information management, human resources, and laws and policies significantly predicted the output dimension (R² = 0.910, P < 0.001). Meanwhile, all four items in the input dimension predicted both the outcome (R² = 0.850, P < 0.001) and impact dimensions (R² = 0.833, P < 0.001). ConclusionInput, output, outcome and impact of the community-based rehabilitation stations in Inner Mongolia were generally in line with the content of the questions, although some imbalances were observed. Additionally, the input of community-based rehabilitation stations could significantly predict their output, outcome and impact.
4.Effect of Different Time Interventions of Yangxin Tongmai Formula (养心通脉方) on DNA Methylation in Rat Models of Premature Coronary Heart Disease with Blood Stasis Syndrome
Xing CHEN ; Zixuan YU ; Shumeng ZHANG ; Yanjuan LIU ; Shuangyou DENG ; Ying WANG ; Lingli CHEN ; Jie LI
Journal of Traditional Chinese Medicine 2025;66(11):1165-1173
ObjectiveTo observe the effect of Yangxin Tongmai Formula (养心通脉方) by midnight-noon ebb-flow administration method for rat models of premature coronary heart disease (PCHD) with blood stasis syndrome, and to explore the possible mechanism of action from the perspective of DNA methylation differential gene expression. MethodsThere were 3 SD rats in each of the blank group, model group and Yangxin Tongmai Formula group, and the rats in the model group and Yangxin Tongmai Formula group were fed with high-fat chow plus vitamin D3 by gavage plus isoproterenol hydrochloride by subcutaneous injection to construct rat models of PCHD with blood stasis syndrome. After successful modelling, rats in Yangxin Tongmai Formula group were gavaged with 18 g/(kg‧d) of Yangxin Tongmai Formula, and rats in blank group and the model group were gavaged with 4 ml/(kg‧d) of 0.9% NaCl solution, and serum samples of rats in each group were collected for DNA methylation sequencing after 3 weeks to screen for the relevant DNA methylation differentiation genes. In addition, rats with successful modelling of PCHD with blood stasis were randomly divided into model group, Yangxin Tongmai Formula with midnight-noon ebb-flow administration method group [18 g/(kg‧d) of Yangxin Tongmai Formula was gavaged twice in the heart channel period (12:00) and pericardium channel period (20:00)], the Yangxin Tongmai Formula control group [18 g/(kg‧d) of Yangxin Tongmai Formula was gavaged twice at 8:00 and 18:00] and the Atorvastatin Calcium group [atorvastatin calcium tablets solution 1.8 mg/(kg‧d) at the same intervention time as that in Yangxin Tongmai Formula control group], and set up a blank group of 8 rats in each group. The model group and blank group were gavaged with 0.9% NaCl solution 4 ml/(kg‧d) for the same time as the Yangxin Tongmai Formula control group. After 3 weeks of gavage, the blood lipids [including total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL)] levels of rats in each group were detected; the HE staining of myocardial tissues and thoracic aorta was used to observe the pathomorphological changes; the levels of serum inflammation indexes [tumour necrosis factor alpha (TNF-alpha), lipopolysaccharide (LPS), and interleukin 10 (IL-10)] were detected; immunoprecipitation-realtime fluorescence quantitative PCR was used to detect the relative expression of cardiac tissue screening differential genes. ResultsThe genes screened for differentially methylated regions were calmodulin 2 (Calm2), calcium voltage-gated channel subunit α1s (Cacna1s), and phospholipase Cβ1 (Plcb1). Compared with the blank group, rats in the model group showed elevated levels of TC, LDL, TNF-α and LPS, and decreased levels of HDL and IL-10 (P<0.05 or P<0.01); HE staining showed obvious swelling of myocardial fibres, accompanied by a large number of inflammatory cell infiltration, and thickening of the inner wall of the aortic vessels with internal wall damage, which was visible as a large number of lipid cholesterol crystals and obvious inflammatory cell infiltration. Compared with the model group, the TC, LDL, TNF-α and LPS contents of rats in the Yangxin Tongmai Formula with midnight-noon ebb-flow administration method group, the Yangxin Tongmai Formula control group, and the atorvastatin calcium group all reduced, and the contents of HDL and IL-10 all elevated (P<0.05), with the improvement of myocardial tissue damage and the reduction of inflammatory infiltration, and the improvement of the damage of the inner lining of the thoracic aorta and the reduction of lipid infiltration. Compared with Yangxin Tongmai Formula control group, LDL, TNF-α and LPS contents reduced, and IL-10 contents increased in the midnight-noon ebb-flow administration method group (P<0.05). Compared with the model group, the relative expression of Calm2 and Plcb1 genes decreased and the relative expression of Cacna1s gene increased in Yangxin Tongmai Formula control group and the midnight-noon ebb-flow administration method group (P<0.05); compared with the Yangxin Tongmai Formula control group, the relative expression of Calm2 gene decreased and the relative expression of Cacna1s gene increased in the midnight-noon ebb-flow administration method group (P<0.05). ConclusionThe intervention of Yangxin Tongmai Formula in the heart channel period (12:00) and pericardium channel period (20:00) was more effective in improving the blood lipid level, inhibiting inflammation, and improving myocardial tissue damage in rats of PCHD with blood stasis syndrome, and Calm2 and Cacna1s genes may be the key targets of Yangxin Tongmai Formula in intervening the blood stasis syndrome of PCHD.
5.Exploration and application of pyrolysis in production of fuel gas from traditional Chinese medicine solid waste under "dual carbon" goals.
Ying-Lei LU ; Xu LONG ; Ke-Ying WANG ; Jing-Li LIU ; Yan-Lei ZHANG ; Yu-Ping TANG
China Journal of Chinese Materia Medica 2025;50(6):1437-1448
Traditional Chinese medicine(TCM) solid waste is characterized by widespread availability, renewability, and substantial production volume. In the context of the "dual carbon" goals, the pyrolysis of TCM solid waste for producing fuel gas for recycling in pharmaceutical production has emerged as a crucial strategy for optimizing the energy structure in the TCM industry and developing renewable energy. This paper comprehensively reviews both internal and external factors that influence the pyrolysis of TCM solid waste. Internal factors encompass moisture content, particle size, ash content, and the morphology of the raw materials, while external factors include pyrolysis conditions, equivalence ratios, types of gasifiers, and gasifying agents. Furthermore, this paper details the challenges associated with the pyrolysis of TCM solid waste, such as the dispersion of feedstocks, the diversity of resources, the complexity of the pyrolysis process, and the variations in gasifier performance. Finally, this paper proposes measures to address these challenges. This paper aims to provide insights into the development of a circular economy for TCM resources and the advancement of low-carbon energy utilization in the TCM industry.
Pyrolysis
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Carbon/chemistry*
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Medicine, Chinese Traditional
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Solid Waste/analysis*
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Drugs, Chinese Herbal/chemistry*
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Gases/chemistry*
6.Differences in growth and secondary metabolite accumulation of Panax quinquefolius between understory and field planting in Shandong, China.
Yue WANG ; Xin-Ying MAO ; Yu DING ; Hong-Xia YU ; Zhi-Fang RAN ; Xiao-Li CHEN ; Jie ZHOU
China Journal of Chinese Materia Medica 2025;50(6):1524-1533
In order to compare the differences in growth and secondary metabolite accumulation of Panax quinquefolius between understory and field planting, growth indexes, photosynthetic characteristics, soil enzyme activities, secondary metabolite contents, and antioxidant activities of P. quinquefolius under different planting modes were examined and compared, and One-way analysis of variance(ANOVA) and correlation analyses were carried out by using the software SPSS 25.0 and GraphPad Prism 9.5. The Origin 2021 software was used for plotting. The results showed that compared with those under field planting, the plant height, leaf length, leaf width, photosynthetic rate, and chlorophyll content of P. quinquefolius under understory planting were significantly reduced, and arbuscular mycorrhizal fungi(AMF) infestation rate and infestation intensity, ginsenoside content, and antioxidant activity were significantly increased. The activities of inter-root soil urease, sucrase, and catalase increased, while the activities of non-inter-root soil urease and alkaline phosphatase increased. Correlation analyses showed that the plant height and leaf length of P. quinquefolius plant were significantly positively correlated with net photosynthetic rate, transpiration rate, chlorophyll content, and electron transfer rate(P<0.05), while ginsenoside content was significantly negatively correlated with net photosynthetic rate, chlorophyll content, and electron transfer rate(P<0.05) and significantly positively correlated with AMF infestation rate and infestation intensity(P<0.05). In addition, ginsenoside content was significantly positively correlated with the activities of inter-root soil sucrase, urease, and catalase(P<0.05). This study provides basic data for revealing the mechanism of secondary metabolite accumulation in P. quinquefolius under understory planting and for exploring and practicing the ecological mode of P. quinquefolius under understory planting.
Panax/microbiology*
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China
;
Secondary Metabolism
;
Soil/chemistry*
;
Photosynthesis
;
Plant Leaves/metabolism*
;
Chlorophyll/metabolism*
;
Mycorrhizae
7.Medicinal properties and mechanisms of p-cymene with mild and warm nature based on deficiency-cold and deficiency-heat syndrome models.
Xiao-Fang WU ; Yi LI ; Xing-Yu ZHAO ; Lin-Ze LI ; Qi ZHANG ; Yin-Ming ZHAO ; Ying-Li ZHU ; Chun WANG ; Jian-Jun ZHANG ; Lin-Yuan WANG
China Journal of Chinese Materia Medica 2025;50(8):2032-2040
This paper aims to study the effect of p-cymene on mice with deficiency-cold syndrome induced by hydrocortisone and deficiency-heat syndrome induced by dexamethasone and explore the medicinal properties and mechanism of p-cymene with mild and warm nature based on the dominant characteristics of the two-way applicable conditions of mild drugs. A total of 80 KM mice were randomly divided into blank group, deficiency-cold syndrome model group, deficiency-cold syndrome + ginseng group, and deficiency-cold syndrome + low-dose and high-dose p-cymene groups, as well as blank group, deficiency-heat syndrome model group, deficiency-heat syndrome + American ginseng group, and deficiency-heat syndrome + low-dose and high-dose p-cymene groups. Hydrocortisone and dexamethasone solution were intragastrically administered for 14 consecutive days to prepare deficiency-cold syndrome and deficiency-heat syndrome models. Except for the blank group and the model group intragastrically administered with normal saline, the other groups were intragastrically administrated with drugs for 14 days. The levels of cyclic adenosine monophosphate(cAMP), cyclic guanosine monophosphate(cGMP), triiodothyronine(T3), thyroxine(T4), total cholesterol(TC), triglyceride(TG), immunoglobin G(IgG), and immunoglobin M(IgM) in serum, as well as the activity of Na~+-K~+-ATPase in liver tissue were detected. The expression of transient receptor potential melastatin 8(TRPM8), transient receptor potential vanilloid 1(TRPV1), and uncoupling protein 1(UCP1) in brown adipose tissue of deficiency-cold syndrome model after intervention with p-cymene was studied. The results showed that p-cymene could effectively improve the levels of cAMP, cAMP/cGMP, TC, IgM, and IgG in serum and the activity of Na~+-K~+-ATPase in liver tissue of mice with deficiency-cold syndrome and reduce the content of cGMP. The effects on T3, T4, and TG were not statistically significant. At the same time, p-cymene could reduce the levels of cAMP, cAMP/cGMP, and T4 in serum and the activity of Na~+-K~+-ATPase in liver tissue of mice with deficiency-cold syndrome and increase the levels of cGMP, IgM, and IgG, and it had no effect on T3, TC, and TG. In addition, p-cymene could up-regulate the expression of TRPV1 and UCP1 in brown fat of mice with deficiency-cold syndrome and down-regulate the expression of TRPM8. In summary, p-cymene could significantly regulate the syndrome indexes of mice with deficiency-cold syndrome, and some indexes of mice with deficiency-heat syndrome could be improved, but the effects on lipid metabolism and energy metabolism indexes were not obvious, indicating that the regulation effect of p-cymene on deficiency-cold syndrome model was more prominent and that the medicinal properties of p-cymene were mild and warm. The regulation of TRPV1/TRPM8/UCP1 channel expression may be the molecular biological mechanism of p-cymene with mild and warm nature affecting the energy metabolism of the body.
Animals
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Cymenes
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Mice
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Drugs, Chinese Herbal/administration & dosage*
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Male
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Disease Models, Animal
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Humans
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Cyclic AMP/metabolism*
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Monoterpenes/administration & dosage*
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Liver/metabolism*
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Cyclic GMP/metabolism*
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TRPV Cation Channels/genetics*
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Uncoupling Protein 1/genetics*
8.Mechanism of Maxiong Powder in inhibiting Epac1-Piezo2 signaling pathway in medial habenular nucleus-interpeduncular nucleus of rats with neuropathic pain.
Xin-Yuan WANG ; Zhi CHEN ; Ying LIU ; Jian SUN ; Ru-Jie LI ; Zhi-Guo WANG ; Mei-Yu ZHANG
China Journal of Chinese Materia Medica 2025;50(10):2719-2729
Central sensitization(CS) is an important factor in inducing neuropathic pain(NPP), and the association between signal transduction protein 1(Epac1) and piezoelectric type mechanosensitive ion channel component 2(Piezo2) is a new and significant pathway for initiating CS. This study whether the central analgesic effect of Maxiong Powder is achieved through the synchronized regulation of the Epac1-Piezo2 signaling pathway in the medial habenular nucleus(MHb) and interpeduncular nucleus(IPN) of the brain. Dynamic in vivo microdialysis, combined with high-performance liquid chromatography-fluorescence detection(HPLC-RFC), behavioral assessments, immunohistochemistry, Western blot, and quantitative reverse transcription PCR, were employed in rats with partial sciatic nerve injury(SNI) to investigate the distribution and expression of Epac1 and Piezo2 proteins and genes in the MHb and IPN regions, and the changes in the extracellular levels of glutamate(Glu), aspartic acid(Asp), and glycine(Gly). Compared with the sham group, rats in the SNI group showed significantly reduced analgesic activity, a significant increase in cold pain sensitivity scores, and elevated Glu levels in the MHb and IPN regions. Additionally, the number of Piezo2-positive cells in these regions, as well as the expression levels of Epac1 and Piezo2 proteins and genes, were significantly increased. Compared with the SNI group, after Maxiong Powder administration, the analgesic activity in rats significantly increased, and cold pain sensitivity scores were significantly reduced. Maxiong Powder also significantly decreased the Glu content in the MHb and IPN regions and the Gly content in the MHb region, while significantly increasing the Asp content in both regions. Furthermore, Maxiong Powder significantly reduced the number of Piezo2-positive cells and lowered the protein and gene expression levels of Epac1 and Piezo2 in both brain regions. The central analgesic effect of Maxiong Powder may be related to its inhibition of Glu and Gly release in the extracellular fluid of the MHb and IPN regions, the increase of Asp levels in these regions, and the regulation of the Epac1-Piezo2 pathway through the reduction of Epac1 and Piezo2 protein and gene expression. These results provide partial scientific evidence for the clinical analgesic efficacy of Maxiong Powder and offer new ideas and approaches for the clinical treatment of NPP.
Animals
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Neuralgia/genetics*
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Rats
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Signal Transduction/drug effects*
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Male
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Rats, Sprague-Dawley
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Guanine Nucleotide Exchange Factors/genetics*
;
Drugs, Chinese Herbal/administration & dosage*
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Habenula/drug effects*
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Ion Channels/genetics*
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Humans
9.Mechanism related to bile acids metabolism of liver injury induced by long-term administration of emodin.
Jing-Zhuo TIAN ; Lian-Mei WANG ; Yan YI ; Zhong XIAN ; Nuo DENG ; Yong ZHAO ; Chun-Ying LI ; Yu-Shi ZHANG ; Su-Yan LIU ; Jia-Yin HAN ; Chen PAN ; Chen-Yue LIU ; Jing MENG ; Ai-Hua LIANG
China Journal of Chinese Materia Medica 2025;50(11):3079-3087
Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage*
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Bile Acids and Salts/metabolism*
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Animals
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Male
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Liver/injuries*
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Chemical and Drug Induced Liver Injury/genetics*
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Drugs, Chinese Herbal/adverse effects*
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Humans
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Rats, Sprague-Dawley
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Mice
;
Rats
10.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*
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Benzhydryl Compounds/administration & dosage*
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Glucosides/administration & dosage*
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Abelmoschus/chemistry*
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Male
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Homeostasis/drug effects*
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Flavones/administration & dosage*
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Rats, Sprague-Dawley
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Diabetic Nephropathies/physiopathology*
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Drugs, Chinese Herbal/administration & dosage*
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DNA-Binding Proteins/genetics*
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Humans
;
Apoptosis/drug effects*


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