Tongqiao Huoxue Decoction modulates glycolysis and activates the BDNF-TrkB pathway by lactate to protect PC12 cells from OGD-induced injury.

Cerebral infarction (CI) is characterised by a high incidence, significant disability, and increased mortality. Tongqiao Huoxue Decoction (TQHXD), a classical formula, is designed to promote blood circulation and eliminate stasis. We investigated the effects of TQHXD on PC12 cells subjected to oxygen-glucose deprivation (OGD). The results demonstrated that during the early phase of OGD, TQHXD enhanced anaerobic glycolytic flux and increased ATP production, thereby compensating for energy deficits. Concurrently, lactate acts as a signalling molecule that binds to hydroxycarboxylic acid receptor 1 (HCAR1) and activates brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB), which protect PC12 cells from OGD-induced damage and reduce neuronal apoptosis. In the late phase of OGD, TQHXD facilitated the utilisation of lactate as an energy substrate in PC12 cells, generating ATP via lactate dehydrogenase B (LDHB), maintaining cellular energy homeostasis, protecting neurones, and reducing apoptosis. TQHXD modulates glycolysis and lactate metabolism, offering a potential therapeutic strategy for cerebral infarction and a possible sequential intervention approach for targeted therapy.