Puerarin: A Multi-Faceted Neuroprotective Compound for Treating Neurodegenerative Diseases

General Description

Puerarin is an isoflavone with high bioactivity. It is a key active substance extracted from the traditional Chinese medicine Kudzu root (Gegen in Chinese), the dried root of Pueraria montana var. Lobata (Willd.) Maesen & S. M. Almeida ex Sanjappa & Predeep. Experimental and clinical studies have reported that puerarin has been widely used in the treatment of cardiovascular disease, diabetes mellitus and its complications, cancer, osteoporosis, nonalcoholic fatty liver and endometriosis. In recent years, puerarin has attracted much attention because of its excellent neuroprotective effect in AD, PD, and other central nervous system diseases.¹

Figure 1. Puerarin

Puerarin and PI3k/Akt signal pathway

By now, the potential mechanisms and direct targets for the diverse therapeutic effects of puerarin remain unclear. Many studies have pointed out that the activation of the PI3K/Akt signal pathway may be a key pathway for puerarin to protect the survival of various cells. Embryonic stem cells are the best platform for the research and screening of new drugs. Yin et al. found that puerarin could down-regulate the transcription level of RE1 silencing transcription factor (rest), a key factor for maintaining the self-renewal of embryonic stem cells, and up-regulate miR-21, a downstream target of rest, by activating PI3K/Akt pathway, thereby inhibiting the self-renewal of murine embryonic stem cells and turning them into endoderm and ectoderm differentiation. Endothelial-mesenchymal transition (EndMT) is closely related to cardiac fibrosis. Puerarin can inhibit EndMT and improve cardiac fibrosis. It was shown that puerarin alleviates HO-stimulated EndMT in human coronary artery endothelial cells (HCAECs) by inhibiting ROS and activating PI3K/Akt pathway. Chen et al. conducted a study using two animal models of pulmonary arterial hypertension (PAH), a rat model of monocrotaline (MCT)-induced PAH and a mouse model of hypoxia-induced hypoxic pulmonary hypertension (HPH). They confirmed that puerarin can effectively improve the structural and functional abnormalities of the pulmonary artery and right ventricle, and restore the PI3K/Akt pathway downregulated by MCT and hypoxia.¹

Puerarin improves neurological diseases¹

Nerve cell injury

PC12 cells are a differentiated cell line of rat adrenal medullary pheochromocytoma with general characteristics of neuroendocrine cells. It was found that puerarin significantly promoted Akt (Ser473) phosphorylation and inhibited TNF-α-induced apoptosis. Application of PI3K inhibitor LY294002 attenuated the effect of puerarin, indicating that puerarin inhibited TNF-α-induced apoptosis in PC12 cells by activating the PI3K/Akt pathway. The results showed that puerarin was able to dose-dependently inhibit H2O2-induced PC12 cells from apoptosis under oxidative stress by increasing the production of p-Akt and apoptotic factor p-BAD (Bcl-2/Bcl-XL-antagonist). These protective effects were reversed by the highly specific PI3K inhibitor wortmannin, suggesting that puerarin may exert antioxidant and anti-apoptotic effects by activating the PI3K/Akt pathway.

Alzheimer's disease

Alzheimer's disease(AD) is a neurodegenerative disease characterized by progressive memory and cognitive impairment, and behavioral and motor disorders. The main pathological features are plaques of β-amyloid (Aβ) and neurofibrillary tangles composed of hyperphosphorylated tau. As well as extensive synaptic and neuronal loss, oxidative stress and neuroinflammation, for which there is no effective treatment. More and more studies have confirmed that puerarin can effectively improve AD cognitive dysfunction through multiple mechanisms. Puerarin reduces Aβ deposition, decreases protein levels of hyperphosphorylated tau and its phosphorylation levels, alleviates neuroinflammation, and prevents neuronal loss. Puerarin can improve synaptic plasticity impairment in AD by regulating the p38 MAPK-CREB signal pathway.

References:

You may like