Background Hederagenin is a naturally occurring pentacyclic triterpenoid found in several medicinal plants traditionally used for treating renal and metabolic disorders. Its ability to mitigate renal senescence in diabetic kidney disease (DKD) and the associated epigenetic mechanisms have not yet been fully elucidated. Methods db/db mice were used in vivo to model DKD-associated renal senescence, while palmitic acid-treated human renal proximal tubular epithelial cells (HK-2 cells) were used in vitro as a senescence model. Renal injury, senescence, DNA damage, and Klotho expression were evaluated using histological, biochemical, and molecular analyses. GEO datasets derived from human DKD samples and corresponding controls were analyzed to assess Klotho expression. Integrated target-binding and methylation analyses were performed to examine the interaction between hederagenin and DNA methyltransferase 1 (DNMT1), as well as the effects of hederagenin on Klotho promoter methylation and DNMT1 occupancy. Results Hederagenin reduced renal senescence, fibrosis, and DNA damage in vivo and in vitro, while restoring Klotho expression, which was decreased in patient datasets and experimental models. Mechanistically, hederagenin directly bound DNMT1, diminished DNMT1 recruitment to the Klotho promoter, and attenuated aberrant promoter hypermethylation, thereby reactivating Klotho. Conclusion Hederagenin mitigates renal senescence in DKD through a DNMT1–Klotho DNA methylation axis, supporting its ethnopharmacological potential for DKD management.
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Open Access
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Open Access
Original Article
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To study the relationship between qi stagnation constitution and suboptimal health status (SHS) or lifestyle.
From 2012 to 2013, we conducted a cross-sectional survey of 24159 Chinese individuals aged 12–80 years. The qi stagnation constitution was assessed using the Constitution in Chinese Medicine Questionnaire. Health status was evaluated through medical records and the Subhealth Measurement Scale V1.0 (SHMS V1.0). Health-promoting lifestyles were measured using the Health-Promoting Lifestyle Profile Ⅱ (HPLP-Ⅱ).
Of the 24159 participants, 16.1% and 15.2% were classified as “always” and “sometimes” having the qi stagnation constitution, respectively. Those classified as “rarely” having the qi stagnation constitution scored higher on both the HPLP-Ⅱ and SHMS V1.0. The participants classified as “always” having the qi stagnation constitution showed a significant association with SHS or disease compared to other imbalanced constitutions. Those in the “always” category were approximately 21 times more likely to be classified as having SHS (odds ratio [OR]: 21.17, 95% confidence interval [CI]: 15.74–28.45), whereas those in the “sometimes” category were approximately six times more likely (OR: 5.89, 95% CI: 5.04–6.90). Accordingly, the qi stagnation constitution score was significantly associated with the diagnosis of SHS, with an area under the curve of 0.77 (P < .001). A score of 18.75 yielded the highest Youden Index (0.407), with a sensitivity of 60.5% and a specificity of 80.3%. Significant associations were observed between health-promoting lifestyles and qi stagnation constitution severity in an ordinal regression analysis (P < .001). Protective factors included stress management (OR: 1.59), self-actualization (OR: 1.57), and exercise (OR: 1.36). In contrast, poorer interpersonal relationships (OR: 0.79), greater health responsibilities (OR: 0.86), and poorer nutrition (OR: 0.91) were associated with increased severity.
Modulating the qi stagnation constitution through lifestyle interventions may help prevent the progression of SHS to disease, which aligns with core preventive principles in traditional Chinese medicine.
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