Traditional Chinese medicine regulating the PI3K/Akt/mTOR signaling pathway to intervene in vascular aging

Traditional Chinese medicine (TCM) participates in the initiation and progression of vascular aging and related vascular degenerative disorders by modulating the PI3K/Akt/mTOR signaling pathway. Its effects involve multiple biological processes, including autophagy, apoptosis, angiogenesis, and metabolic homeostasis. This study employed a narrative review methodology. No systematic review protocol was registered, and no quantitative data synthesis or meta-analysis was performed. Relevant literature published between January 2015 and June 2026 was retrieved from the core databases CNKI, PubMed, and Web of Science using the following Chinese and English keywords: “PI3K/Akt/mTOR,” “traditional Chinese medicine,” “vascular senescence,” “vascular aging,” and “atherosclerosis.” Original experimental studies were subsequently screened. Data extraction primarily focused on experimental evidence concerning the effects of TCM formulations or isolated compounds on key phosphorylated components of the PI3K/Akt/mTOR signaling pathway.The inclusion criteria were as follows: (1) explicit reporting of the effects of a TCM formulation or isolated compound on key phosphorylated components of the PI3K/Akt/mTOR signaling pathway; (2) the presence of appropriate in vivo or in vitro controls; and (3) complete and traceable study data. The exclusion criteria were as follows: (1) duplicate publications; (2) studies with unclear mechanistic descriptions or insufficient evidence to determine the regulatory relationship with the PI3K/Akt/mTOR pathway; and (3) conference abstracts for which the full text was unavailable. Ultimately, 44 relevant experimental studies were included. These studies were analyzed with respect to autophagy, apoptosis, angiogenesis, and metabolic homeostasis to characterize the molecular features underlying the vascular protective effects of different TCM interventions targeting the PI3K/Akt/mTOR pathway.The available evidence indicates that PI3K/Akt/mTOR signaling exhibits marked context-dependent regulatory characteristics under distinct vascular pathological conditions. In the setting of metabolic stress or chronic inflammation, including hypertension, diabetes, and atherosclerosis, paeoniflorin, geniposide, cryptotanshinone, and related TCM formulations may improve endothelial function by suppressing aberrant pathway activation, restoring autophagic homeostasis, attenuating inflammatory responses, and inhibiting phenotypic switching of vascular smooth muscle cells. In contrast, under conditions of hypoperfusion or tissue injury, such as ischemic stroke and vascular dementia, interventions including ginkgolide K, astragaloside IV, ginsenoside Rd, Poyu Decoction, Danlong Xingnao Formula, and Buyang Huanwu Decoction may moderately enhance PI3K/Akt/mTOR-related signaling, thereby promoting VEGF-mediated angiogenesis, modulating autophagic flux, and ameliorating neurovascular unit injury. Several studies have also suggested that formulations such as Jinkui Shenqi Pill may influence vascular calcification by regulating calcium–phosphate metabolism through this pathway.Overall, TCM may exert vascular protective effects through the multi-component, multi-target, and context-dependent modulation of the PI3K/Akt/mTOR signaling pathway. However, the existing evidence is derived predominantly from models of atherosclerosis, ischemic brain injury, and other vascular diseases. Studies that directly employ natural aging or accelerated-aging models and systematically assess vascular senescence markers, such as p16^INK4a^, p21, and senescence-associated β-galactosidase (SA-β-gal), remain limited. Accordingly, current evidence more strongly supports the ability of TCM to improve vascular function and related pathological injury than its direct anti-vascular-aging effects, which require further validation. Future studies should integrate natural aging models, cellular senescence markers, multi-omics approaches, and validated vascular age assessment systems to define the direct molecular targets, temporal patterns of action, and regulatory thresholds through which TCM compounds and formulations modulate the PI3K/Akt/mTOR pathway under distinct pathological conditions.