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.

Objective:To explore the medication law and academic thought of Professor Hu Guohua in treating diminished ovarian reserve (DOR) based on data mining.Methods:Collecting the medical records of DOR patients treated by Prof. Hu from January 1, 2021 to March 31, 2022. The TCM symptoms, tongue and pulse conditions, as well as the frequency, taste, meridian tropism and efficacy categories of TCM were analyzed by using the Traditional Chinese Medicine Inheritance Computing Platform V3.0 software. Commonly used drug combination analysis, high-frequency drug network relationship analysis, association rule analysis based on Apriori algorithm, cluster analysis based on K-means clustering algorithm, and core prescriptions were summarized.Results:A total of 85 DOR patients were included, involving 76 TCM symptoms, 15 tongue images, 11 pulse images. A total of 415 prescriptions were included, involving 164 kinds of Chinese materia medica. High-frequency drugs included Ligustri Lucidi Fructus, Angelicae Sinensis Radix, Astragali Radix, Cuscutae Semen, Herba Leonuri and Rhizoma Atractylodis Macrocephalae. The medicines were mostly warm, mild and cold in property, and the tastes were mostly sweet, bitter and pungent, mainly belonging to the liver, spleen and kidney meridians. 42 high-frequency drug combinations and 6 core prescriptions were obtained.Conclusions:Professor Hu treats DOR with the principle of tonifying the kidney and spleen to regulate body constitution, conditioning Chong Vessel and Conception Vessel to regulate the menstruation, soothing the liver and tranquillizing the heart to regulate the spirit. Professor Hu selects the medicines which are simplified and condensed, and is good at using drugs. The prescriptions are persistent and flexible, concerning the balance.