[Research progress of puerarin antidepressant].

Puerarin, an isoflavonoid compound derived from TCM Puerariae Lobatae Radix, has garnered increasing attention for its potential in treating depression. By systematically reviewing relevant domestic and international research, this paper elaborated on the multi-target molecular mechanisms underlying the antidepressant effects of puerarin, including the regulation of the gut microbiota-gut-brain axis, inhibition of neuroinflammation, promotion of neurotrophy and neurogenesis, amelioration of oxidative stress and mitochondrial function, modulation of neurotransmitters and the hypothalamic-pituitary-adrenal(HPA) axis, and epigenetic modifications. The paper further highlighted its synergistically therapeutic potential in comorbidity models such as diabetes with depression and post-stroke depression, as well as its application in compound compatibility and the current status of clinical translation research. Despite breakthroughs in emerging fields like the regulation of neural circuit plasticity, intervention in neuronal apoptosis, and modulation of non-coding RNA networks, the clinical application of puerarin is primarily limited by its pharmacokinetic drawbacks, such as poor water solubility and low bioavailability, coupled with a lack of high-quality clinical evidence. This paper aims to provide a theoretical basis for developing puerarin into a novel antidepressant by deeply analyzing the complex network of its mechanisms and evaluating its prospects for clinical translation.