1.Interpretation of Middle-regulating Formulas Based on Fuxing Jue
Junqiao AN ; Yixin MA ; Dongmei LI ; Qingyong HE
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):265-272
The Dunhuang manuscript Fuxing Jue takes the "Tangye Jingfa Tu" as the core of its theory on prescription and compatibility. Its medication principles mainly include the "five elements principle of tonifying and purging" and the "five elements principle of elimination and transformation". Based on the differentiation of deficiency and excess in the five Zang organs, it flexibly applies medicinal properties, usage, and flavor transformation for tonifying and purging, forming its unique method of medication and compatibility. In Taiyin disease, "fullness syndrome" often occurs together with "diarrhea", and these two conditions also serve as the primary indications for the middle-regulating formulas. Among them, Lizhong Wan (Tang) mainly address Taiyin deficiency. The three Xiexin Tang (Banxia Xiexin Tang, Gancao Xiexin Tang, Shengjiang Xiexin Tang) address Taiyin deficiency accompanied by pathogenic excess. The Sini Tangand Tongmai Sini Tang primarily treat dysfunction of the liver, spleen, and kidney with impaired opening and closing of Taiyin, manifesting as diarrhea. The medicinal flavors of middle-regulating formulas are pungent, sweet, and bitter, acting directly on the spleen of Taiyin. The pungent flavor induces purging of the spleen, sweet flavor tonifies the spleen, and bitter flavor eliminates lumps. When the constituent medicinal units of middle-regulating formulas are unified, the ratio of pungent to sweet flavors reflects the tonic and purgative strength of the formula. In addition, the two decoction methods, "short-term decoction to extract Qi" and "long-term decoction to extract flavor", also influence the formula's tonifying and purgative effects. Based on the composition of flavors and special decoction methods, this article discusses the differences in the use of middle-regulating formulas for treating "“fullness syndrome" versus "diarrhea". Dysfunction of the spleen can give rise to various diseases. Therefore, middle-regulating formulas are not limited to treating "deficiency, cold, and dampness" syndromes. Later generations of physicians further modified Lizhong Tang to treat "excess, heat, and dryness" syndromes, laying a solid foundation for more flexible and effective clinical application of middle-regulating formulas.
2.Interpretation of Middle-regulating Formulas Based on Fuxing Jue
Junqiao AN ; Yixin MA ; Dongmei LI ; Qingyong HE
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):265-272
The Dunhuang manuscript Fuxing Jue takes the "Tangye Jingfa Tu" as the core of its theory on prescription and compatibility. Its medication principles mainly include the "five elements principle of tonifying and purging" and the "five elements principle of elimination and transformation". Based on the differentiation of deficiency and excess in the five Zang organs, it flexibly applies medicinal properties, usage, and flavor transformation for tonifying and purging, forming its unique method of medication and compatibility. In Taiyin disease, "fullness syndrome" often occurs together with "diarrhea", and these two conditions also serve as the primary indications for the middle-regulating formulas. Among them, Lizhong Wan (Tang) mainly address Taiyin deficiency. The three Xiexin Tang (Banxia Xiexin Tang, Gancao Xiexin Tang, Shengjiang Xiexin Tang) address Taiyin deficiency accompanied by pathogenic excess. The Sini Tangand Tongmai Sini Tang primarily treat dysfunction of the liver, spleen, and kidney with impaired opening and closing of Taiyin, manifesting as diarrhea. The medicinal flavors of middle-regulating formulas are pungent, sweet, and bitter, acting directly on the spleen of Taiyin. The pungent flavor induces purging of the spleen, sweet flavor tonifies the spleen, and bitter flavor eliminates lumps. When the constituent medicinal units of middle-regulating formulas are unified, the ratio of pungent to sweet flavors reflects the tonic and purgative strength of the formula. In addition, the two decoction methods, "short-term decoction to extract Qi" and "long-term decoction to extract flavor", also influence the formula's tonifying and purgative effects. Based on the composition of flavors and special decoction methods, this article discusses the differences in the use of middle-regulating formulas for treating "“fullness syndrome" versus "diarrhea". Dysfunction of the spleen can give rise to various diseases. Therefore, middle-regulating formulas are not limited to treating "deficiency, cold, and dampness" syndromes. Later generations of physicians further modified Lizhong Tang to treat "excess, heat, and dryness" syndromes, laying a solid foundation for more flexible and effective clinical application of middle-regulating formulas.
3.Treatment Principles and Paradigm of Diabetic Microvascular Complications Responding Specifically to Traditional Chinese Medicine
Anzhu WANG ; Xing HANG ; Lili ZHANG ; Xiaorong ZHU ; Dantao PENG ; Ying FAN ; Min ZHANG ; Wenliang LYU ; Guoliang ZHANG ; Xiai WU ; Jia MI ; Jiaxing TIAN ; Wei ZHANG ; Han WANG ; Yuan XU ; .LI PINGPING ; Zhenyu WANG ; Ying ZHANG ; Dongmei SUN ; Yi HE ; Mei MO ; Xiaoxiao ZHANG ; Linhua ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):272-279
To explore the advantages of traditional Chinese medicine (TCM) and integrative TCM-Western medicine approaches in the treatment of diabetic microvascular complications (DMC), refine key pathophysiological insights and treatment principles, and promote academic innovation and strategic research planning in the prevention and treatment of DMC. The 38th session of the Expert Salon on Diseases Responding Specifically to Traditional Chinese Medicine, hosted by the China Association of Chinese Medicine, was held in Beijing, 2024. Experts in TCM, Western medicine, and interdisciplinary fields convened to conduct a systematic discussion on the pathogenesis, diagnostic and treatment challenges, and mechanism research related to DMC, ultimately forming a consensus on key directions. Four major research recommendations were proposed. The first is addressing clinical bottlenecks in the prevention and control of DMC by optimizing TCM-based evidence evaluation systems. The second is refining TCM core pathogenesis across DMC stages and establishing corresponding "disease-pattern-time" framework. The third is innovating mechanism research strategies to facilitate a shift from holistic regulation to targeted intervention in TCM. The fourth is advancing interdisciplinary collaboration to enhance the role of TCM in new drug development, research prioritization, and guideline formulation. TCM and integrative approaches offer distinct advantages in managing DMC. With a focus on the diseases responding specifically to TCM, strengthening evidence-based support and mechanism interpretation and promoting the integration of clinical care and research innovation will provide strong momentum for the modernization of TCM and the advancement of national health strategies.
4.Intervention Strategies for Heart Failure with Preserved Ejection Fraction Using Combined Classical Formulas Based on the Theory of "Disease of Both Blood and Water"
Yuzhi JIA ; Qingyong HE ; Jie WANG ; Xin ZHAO ; Ziyi WANG ; Dongmei LI ; Junqiao AN
Journal of Traditional Chinese Medicine 2026;67(4):370-374
Based on the theory of "disease of both blood and water" in Essentials from the Golden Cabinet (《金匮要略》), and in combination with the dynamic syndrome evolution of heart failure with preserved ejection fraction (HFpEF), this paper systematically clarifies the pathomechanism of HFpEF, characterized by yang deficiency as the root, blood stasis as the pivotal factor and water retention as the manifestation. Accordingly, the therapeutic principles have been proposed, which are warming yang and banking up original qi to consolidate the root, activating blood and unblocking collaterals to smooth the mechanism, and promoting urination and regulating pivot to remove the branch. On this basis, a compound formula structure of "one monarch, one minister and one assistant" is established, forming an integrated intervention strategy that synergistically combines the three methods of warming yang, activating blood, and promoting urination through combined classical formulas. Zhenwu Decoction (真武汤), which warms yang and dissolves rheum, is used to consolidate the root and directly target the source of yang deficiency, serving as the monarch; Guizhi Fuling Pills (桂枝茯苓丸), which activates blood, promotes urination and unblocks the pivot, assists in interrupting the binding of blood stasis and water retention, serving as the minister; Tingli Dazao Xiefei Decoction (葶苈大枣泻肺汤), which regulates qi, disperses retained fluids, and eliminates the manifestation, alleviates acute water-retention symptoms, serving as the assistant. This compound formula is warming without being drying, diuretic without being drastic, and dispels stasis without consuming blood, thereby achieving the therapeutic effects of warming yang, activating blood, and promoting urination.
5.Feasibility and prognostic value of estimated plasma volume status in assessing volume status during early fluid resuscitation in patients with sepsis.
Xiaodong LIU ; Fei WANG ; Wangbin XU ; Man YANG ; Xiao YANG ; Dongmei DAI ; Leyun XIAO-LI ; Xinghui GUAN ; Xiaoyang SU ; Yuemeng CUI ; Lei CAI
Chinese Critical Care Medicine 2025;37(7):620-627
OBJECTIVE:
To investigate the feasibility and prognostic implications of assessing volume status during early fluid resuscitation in septic patients based on estimated plasma volume status (ePVS).
METHODS:
A prospective study was conducted. Patients with sepsis admitted to intensive care unit (ICU) of the First Affiliated Hospital of Kunming Medical University from March to December in 2023 were enrolled. The general information and laboratory indicators at ICU admission were recorded, and ePVS, sequential organ failure assessment (SOFA) score, acute physiology and chronic health status evaluation II (APACHE II) score were calculated. The vital signs, arterial blood gas analysis and volume status related indicators before liquid resuscitation (T0h) and 3 hours (T3h) and 6 hours (T6h) of fluid resuscitation were recorded. The diameter and variability of the inferior vena cava (IVC) were measured by ultrasound, and ePVS, percentage change value of estimated plasma volume status (ΔePVS%), difference in central venous-to-arterial partial pressure of carbon dioxide (Pcv-aCO2), and lactate clearance rate (LCR) were calculated. Patients were divided into sepsis group and septic shock group based on the diagnosis at ICU admission, and septic patients were subdivided into survival group and death group based on their 28-day survival status. The differences in clinical data between the groups were compared. The correlation between ePVS or ΔePVS% and volume status related indicators during early liquid resuscitation was analyzed by Spearman rank sum correlation test. The predictive value of each variable for 28-day survival in patients with sepsis was analyzed by receiver operator characteristic curve (ROC curve), and 28-day death risk factors were analyzed by Logistic regression method.
RESULTS:
Fifty-four septic patients were enrolled in the final analysis, including 17 with sepsis and 37 with septic shock; 34 survived at 28 days and 20 died, with a 28-day survival rate of 63.0%. Compared with the sepsis group, the septic shock group had a lower venous ePVS at ICU admission [dL/g: 4.96 (3.67, 7.15) vs. 7.55 (4.36, 10.07), P < 0.05]. Compared with the death group, the survival group had higher T6h arterial and venous ΔePVS%, and albumin [Alb; T6h arterial ΔePVS% (%): 11.57% (-1.82%, 31.35%) vs. 0.48% (-5.67%, 6.02%), T6h venous ΔePVS%: 9.62% (3.59%, 25.75%) vs. 1.52% (-9.65%, 7.72%), Alb (g/L): 27.57±4.15 vs. 23.77±6.97, all P < 0.05], lower SOFA score, APACHE II score, AST, T0h Lac, and T3h and T6h norepinephrine dosage [SOFA score: 9.00 (8.00, 10.00) vs. 11.50 (9.25, 14.50), APACHE II score: 18.00 (14.75, 21.25) vs. 25.50 (21.00, 30.00), AST (U/L): 34.09 (23.20, 56.64) vs. 79.24 (25.34, 196.59), T0h Lac (mmol/L): 1.75 (1.40, 2.93) vs. 3.25 (2.33, 5.30), norepinephrine dosage (mg): 0.98 (< 0.01, 3.10) vs. 4.60 (1.05, 8.55) at T3h, 1.82 (0.38, 5.30) vs. 8.20 (2.80, 17.73) at T6h, all P < 0.05]. While there were no significantly differences in other basic data and ePVS at all of the time points before and after resuscitation between the two groups. Correlation analysis showed that T6h venous ePVS was significantly positively correlated with T6h IVC variability in septic patients (r = 0.360, P < 0.05), T0h arterial ePVS was significantly negatively correlated with T3h and T6h liquid intake volume (r1 = -0.367, r2 = -0.280, both P < 0.05), and venous ePVS at ICU admission was significantly positively correlated with NT-proBNP at ICU admission (r = 0.409, P < 0.05). T6h venous ΔePVS% was significantly positively correlated with T3h liquid intake volume and T6h LCR (r1 = 0.286, r2 = 0.286, both P < 0.05), and significantly negatively correlated with T6h urine volume and T6h change value of Pcv-aCO2 (ΔPcv-aCO2; r1 = -0.321, r2 = -0.371, both P < 0.05). ROC curve analysis showed that the area under the ROC curve (AUC) of T6h venous ΔePVS% for predicting 28-day survival in septic patients was 0.726 [95% confidence interval (95%CI) was 0.578-0.875, P = 0.006], with a sensitivity of 82.4%, a specificity of 60.0%, and an optimal cut-off value of 3.09%. Binary multifactorial Logistic regression analysis showed that an increase in T6h venous ΔePVS% was a protective factor for 28-day death in patients with sepsis on early fluid resuscitation [odds ratio (OR) = 0.900, 95%CI was 0.834-0.972, P = 0.007].
CONCLUSIONS
ePVS may have potential for assessing the volume status of septic patients during early fluid resuscitation. The ΔePVS% during early fluid resuscitation may help to identify septic patients with a poor prognosis.
Humans
;
Prognosis
;
Fluid Therapy
;
Sepsis/physiopathology*
;
Prospective Studies
;
Plasma Volume
;
Intensive Care Units
;
Resuscitation
;
Male
;
Female
;
Middle Aged
;
Shock, Septic/therapy*
6.Research advances in the application of artificial intelligence in transfusion medicine
Xinxin YANG ; Shilan XU ; Bing HAN ; Lixin WANG ; Fu CHENG ; Dongmei YANG ; Bin TAN ; Li QIN ; Chunxia CHEN
Chinese Journal of Blood Transfusion 2025;38(11):1502-1513
Objective: To review the current development of artificial intelligence (AI) technology in the field of transfusion medicine. Methods: A systematic search was conducted in the Clarivate Web of Science Database from inception to December 2024 for literature related to AI and transfusion. A total of 4 775 publications were identified. Based on inclusion and exclusion criteria, 133 original studies were ultimately included and analyzed using a narrative synthesis approach. Results: Research on AI in transfusion has surged since 2020 (accounting for 77% of all publications), with China ranking second globally in publication volume. Among the included studies, 69.2% focused on predicting individual transfusion needs, followed by inventory management (8.3%), diagnosis and prediction of adverse transfusion reactions (6.0%), factors influencing transfusion outcomes (5.3%), blood group identification (5.3%), blood quality testing (4.5%), and precise blood volume measurement (1.5%). Additionally, 4.5% of the studies were published in journals with an impact factor greater than 10; 19.5% developed software or applications; 31.5% were multi-center studies; 48.1% utilized decision tree methods, while 31.5% employed neural network approaches; and 14.2% conducted external validation of the algorithms. Conclusion: AI demonstrates significant potential in transfusion risk prediction, decision support, and blood management. However, challenges remain, including limited model generalizability, insufficient algorithm interpretability, and barriers to clinical translation. The deep integration of AI with transfusion medicine will accelerate the advent of precision transfusion era, maximizing blood resource utilization, reducing waste, and ensuring transfusion safety.
7.Erythrocytapheresis for the treatment of high-altitude polycythemia
Wenchun LONG ; Dongmei WAN ; Wuyi FAN ; Xuexue LI ; Yan YE ; Zengmei SUN ; Tingting LI ; Zeng HE ; Xueping SUN
Chinese Journal of Blood Transfusion 2025;38(12):1695-1701
Objective: To investigate the efficacy and incidence of adverse reactions of therapeutic erythrocytapheresis in high altitude polycythemia (HAPC) population. Methods: A retrospective study was conducted on 243 HAPC patients who were either native residents or long-term workers in Xizang and underwent therapeutic erythrocytapheresis in the Chengdu Office Hospital of the People's Government of Xizang Autonomous Region from 2021 to 2023. A comparative study was carried out on the changes in blood routine, vital signs, skin color, serum iron metabolism data, and the incidence of adverse reactions before and after the procedure. Results: After erythrocytapheresis, significant decreases were observed in red blood cell (RBC) count (7.06±0.89×10
vs 6.08±0.93×10
/L, P<0.001], hemoglobin (HGB, 211.59±17.99 vs 182.76±19.83 g/L, P<0.001), hematocrit (Hct) [(65.30±6.45)% vs (55.56±8.12)%, P<0.001], serum iron (14.46±4.38 vs 11.77±3.78 μmol/L, P=0.003), total iron-binding capacity (126.62±4.47 vs 123.73±3.77 μmol/L, P=0.002), transferrin (1.88±0.41 vs 1.77±0.12 g/L, P=0.023), transferrin saturation [(11.32±3.11)% vs (9.43±2.78)%, P=0.004], serum ferritin (832.4±295.6 vs 665.3±249.2 ng/mL, P<0.001), systolic blood pressure (123.86±14.43 vs 118.51±13.68 mmHg, P<0.001) and diastolic blood pressure (81.68±9.54 vs 74.28±7.61 mmHg, P<0.001). In contrast, platelet count (Plt, 137.21±46.21 ×10
vs 147.94±50.66 ×10
/L, P<0.001) and oxygen saturation [(93.97±3.29)% vs (95.84±2.27)%, P<0.001] increased. No significant differences were found in white blood cell (WBC) count [5.35 (4.59, 6.44)×10
/L vs 5.43 (4.54, 6.53) ×10
/L, P=0.690], unsaturated iron-binding capacity (112.15±0.50 vs 111.96±0.25 μmol/L, P=0.074) and pulse rate (73.42±11.28 vs 73.19±7.18 beats/min, P=0.750). Furthermore, skin color of the face (conjunctiva, lips) and palms mitigated after therapeutic erythrocytapheresis, changing from purplish-red to red. The total incidence of adverse reactions during erythrocytapheresis was 13.98% (34/243), including citrate toxicity 12.75% (31/243), puncture site hematoma 0.82% (2/243) and blood volume imbalance 0.41% (1/243). Conclusion: Therapeutic erythrocytapheresis could rapidly decrease HCT, Hb, serum iron, transferrin and transferrin saturation levels in HAPC patients, with a low incidence of adverse reactions. Therefore, therapeutic erythrocytapheresis has broad clinical application prospects in Xizang Autonomous Region.
8.Effect of mechanism-based secondary preventive scheme on recurrence of intracranial arterial stenosis-related stroke cerebrovascular disease event and related factors analysis
Xirui LIU ; Xue WEI ; Linyan TONG ; Jinfang LI ; Dongmei WU ; Siyin GONG
Chongqing Medicine 2025;54(2):329-334
Objective To investigate the effect of secondary preventive scheme on recurrence rate of ce-rebrovascular event based on China ischemic stroke subclassification(CISS)of intracranial arterial stenosis is-chemic stroke(IS).Methods A total of 192 patients with intracranial arterial stenosis IS were prospectively included and the secondary preventive scheme was formulated according to whether or not based on the patho-genesis.Then the patients were divided into the personalized treatment group and conventional treatment group.The personalized group conducted the classification and was given different the secondary preventive schemes the artery-artery embolism group was given the active lipid-lowering scheme to make the low density lipoprotein(LDL)reaching the standard;the low hypoperfusion group was given the smooth pressure reduc-tion program;the carrier artery occlusion perforating artery group was given the routine secondary prevention program;the mixture mechanism group was given the corresponding schemes superposition according to dif-ferent mechanisms].The conventional treatment group was given the conventional secondary preventive scheme.The difference in the recurrence rate of cerebrovascular events on 90 d was compared between the two groups.Meanwhile the univariate and multivariate logistic regression were used to analyze the influencing fac-tors of recurrence of cerebrovascular events on 90 d in intracranial arterial stenosis IS.Results Among 192 study subjects,there were 90 cases in the personalized treatment group(20 cases of vector artery occlusion and perforator artery,44 cases of arterial-arterial embolization,6 cases of hypoperfusion and 20 cases of mixed mechanism).There were 102 cases in the conventional treatment group(16 cases of perforator artery occlu-sion of the vector artery,52 cases of arterial-arterial embolism,8 cases of hypoperfusion and 26 cases of mixed mechanism).The occurrence rate of cerebrovascular events on 90 d in the personalized treatment group was significantly decreased compared to the conventional treatment group(7.8%vs.17.6%,χ2=4.112,P=0.043).The Logistic regression analysis revealed that the active lipid-lowering scheme for LDL reaching the standard was the independent protective factor of the cerebrovascular event recurrence on 90 d(OR=0.128,95%CI:1.150-71.170).Conclusion The personalized secondary prevention scheme based on pathogenesis reduces the recurrence rate of cerebrovascular event in intracranial arterial stenosis IS,in which making the LDL reaching the standard by the active lipid-lowering scheme is the independent protective factor for cerebro-vascular event recurrence in intracranial arterial stenosis IS.
9.Study on the targets and mechanisms of 7-hydroxyethyl chrysin in prevention and treatment of high-altitude cerebral edema using proteomics technology.
Dongmei ZHANG ; Xiaolin LI ; Chenyu YANG ; Linlin JING ; Lei HE ; Huiping MA
Journal of Zhejiang University. Medical sciences 2025;54(4):549-558
OBJECTIVES:
To investigate the targets and mechanisms of 7-hydroxyethyl chrysin (7-HEC) in prevention and treatment of high-altitude cerebral edema (HACE) in rats.
METHODS:
Fifty-four male Wistar rats were randomly divided into normal control group, HACE model group, and 7-HEC-treated group (18 rats in each group). Except for the normal control group, rats in the two other groups were exposed to a hypobaric hypoxic chamber simulating a 7000 m altitude for 72 h to establish the HACE model. The 7-HEC-treated group was intraperitoneally injected with 7-HEC (150 mg·kg-¹·d-¹) for 3 consecutive days before modeling, while the model group received equivalent isotonic sodium chloride solution. Tandem Mass Tag (TMT) proteomics technology was used to detect differentially expressed proteins (DEPs) with screening criteria set at a fold change >1.2 and P<0.05. Western blotting was used to verify the expression levels of target proteins. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) network analysis were performed.
RESULTS:
Compared with the normal control group, 256 DEPs were identified in the HACE model group. Compared with the HACE model group, 87 DEPs were identified in the 7-HEC-treated group. Among them, 19 DEPs that were dysregulated in the HACE model group were restored after 7-HEC intervention, of which seven (HSPA4, Arhgap20, SERT, HACL1, CCDC43, POLR3A, and PCBD1) were confirmed by Western blotting. GO enrichment analysis of the DEPs between the HACE model and 7-HEC-treated groups revealed their involvement in 13 biological processes, five cellular components, and two molecular functions. KEGG pathway analysis indicated associations with the mRNA surveillance pathway, Th17 cell differentiation, serotonergic synapse, RNA polymerase, protein processing in the endoplasmic reticulum, peroxisome, neuroactive ligand-receptor interaction, folate biosynthesis. PPI network analysis demonstrated that HSPA4, POLR3A, and HACL1, which were validated by Western blotting, interacted with multiple signaling pathways and ranked among the top 20 hub proteins by degree value, suggesting their potential role as core regulatory factors. Arhgap20, SERT and PCBD1 also exhibited interactions with several proteins, suggesting their potential as key regulatory proteins, whereas no interactions for CCDC43 were identified.
CONCLUSIONS
This study applied TMT proteomics to identify seven potential therapeutic targets of 7-HEC for the prevention and treatment of HACE. These targets may be involved in the pathogenesis of HACE through multiple pathways, including maintaining cellular homeostasis, ameliorating oxidative stress, regulating energy metabolism, and reducing vascular permeability.
Animals
;
Male
;
Proteomics/methods*
;
Rats, Wistar
;
Flavonoids/therapeutic use*
;
Rats
;
Brain Edema/etiology*
;
Altitude Sickness/metabolism*
;
Protein Interaction Maps
10.Dihydromyricetin mitigates abdominal aortic aneurysm via transcriptional and post-transcriptional regulation of heme oxygenase-1 in vascular smooth muscle cells.
Weile YE ; Pinglian YANG ; Mei JIN ; Jiami ZOU ; Zhihua ZHENG ; Yuanyuan LI ; Dongmei ZHANG ; Wencai YE ; Zunnan HUANG ; Jiaojiao WANG ; Zhiping LIU
Acta Pharmaceutica Sinica B 2025;15(3):1514-1534
Abdominal aortic aneurysm (AAA) is a deadly condition of the aorta, carrying a significant risk of death upon rupture. Currently, there is a dearth of efficacious pharmaceutical interventions to impede the advancement of AAA and avert it from rupturing. Here, we investigated dihydromyricetin (DHM), one of the predominant bioactive flavonoids in Ampelopsis grossedentata (A. grossedentata), as a potential agent for inhibiting AAA. DHM effectively blocked the formation of AAA in angiotensin II-infused apolipoprotein E-deficient (ApoE-/-) mice. A combination of network pharmacology and whole transcriptome sequencing analysis revealed that DHM's anti-AAA action is linked to heme oxygenase (HO)-1 (Hmox-1 for the rodent gene) and hypoxia-inducible factor (HIF)-1α in vascular smooth muscle cells (VSMCs). Remarkably, DHM caused a robust rise (∼10-fold) of HO-1 protein expression in VSMCs, thereby suppressing VSMC inflammation and oxidative stress and preserving the VSMC contractile phenotype. Intriguingly, the therapeutic effect of DHM on AAA was largely abrogated by VSMC-specific Hmox1 knockdown in mice. Mechanistically, on one hand, DHM increased the transcription of Hmox-1 by triggering the nuclear translocation and activation of HIF-1α, but not nuclear factor erythroid 2-related factor 2 (NRF2). On the other hand, molecular docking, combined with cellular thermal shift assay (CETSA), isothermal titration calorimetry (ITC), drug affinity responsive target stability (DARTS), co-immunoprecipitation (Co-IP), and site mutant experiments revealed that DHM bonded to HO-1 at Lys243 and prevented its degradation, thereby resulting in considerable HO-1 buildup. In summary, our findings suggest that naturally derived DHM has the capacity to markedly enhance HO-1 expression in VSMCs, which may hold promise as a therapeutic strategy for AAA.

Result Analysis
Print
Save
E-mail