Advances in pharmacological effects of tanshinone ⅡA on pain

Pain is one of the most serious problems plaguing human health today. Drug therapy is one of the main ways to treat pain in clinic. The analgesic drugs commonly used in clinical treatment of pain are often accompanied by many side effects, the analgesic effect is still not ideal. Salvia miltiorrhiza is a traditional medicinal material with the same origin as food and medicine. It has the functions of promoting blood circulation and removing blood stasis, relieving pain through menstrual circulation, and contains many effective ingredients such as tanshinone and salvianolic acid. Tanshinone is a kind of rosin diterpenoid compound, which mainly consists of o-quinone type and p-quinone type parent nucleus, and tanshinone Ⅱ A is the representative compound. The pharmacological mechanism of tanshinone Ⅱ A in labor pain mainly includes:(1) Regulate inflammatory factors.Inflammatory cytokines played an important role in the occurrence and progression of pain. It was found that the analgesic effect of tanshinone ⅡA was related to the antiinflammatory effect. Tanshinone Ⅱ A showed anti-injurious activity in various pain models, such as bone cancer pain and sciatic nerve ligation, and related studies found that tanshinone Ⅱ A could inhibit the expression of inflammatory factors TNF-α, IL-1β and IL-6 in the spinal cord of model rats. In the spinal nerve ligation model,tanshinone ⅡA also promoted the release of anti-inflammatory cytokine IL-10 in the spinal cord of rats.(2) Regulate signal pathways related to regulating spinal cord oxidation and apoptosis. Apoptosis and oxidation played an important role in the process of pain. When nerve injury was caused by stimulation, oxidative stress and apoptosis of nerve cells were involved in the mechanism of hyperalgesia. Tanshinone Ⅱ A sodium sulfonate could relieve pain by regulating apoptosis-related pathways. In neuralgia model, tanshinone ⅡA could reduce the apoptosis of spinal cord neurons by inhibiting oxidative stress response in rat spinal cord tissue. In addition,tanshinone ⅡA also decreased the expression of proapoptotic protein in spinal dorsal horn of CCI rats. They included caspase-3, Bcl-2, Bax protein, and enhancer binding protein homologous protein, Increased the expression of anti-apoptosis protein Bcl-2.(3) Inhibit the activation of spinal cord glial cells. Tanshinone Ⅱ A could exert its labor pain effect by inhibiting the activation of astrocytes, including inhibiting the expression of chemotherapy-induced neuralgia, inflammatory pain and inflammatory cytokines IL-6, IL-1β and TNF-α, and inhibiting the activation of inflammatory signaling pathways related to astrocyte activation. Such as NF-κB signaling pathway, c-Jun N-terminal kinase signaling pathway, etc. In addition, tanshinone Ⅱ A also inhibited the activation of microglia by inhibiting the expression of CX3CR1 receptor on the surface of microglia and inhibiting the phosphorylation of ERK, JNK and p38 signaling pathways.(4) Decrease the expression of glutamate receptors in spinal cord. NMDA is an ionic glutamate receptor in the central nervous system, and its subunit NR2B is closely related to pain. The overexpression of NR2B in spinal cord could lead to the decrease of pain threshold, which was an important mechanism of pain generation. The mechanical threshold and thermal threshold of CCI rats were increased by tanshinone ⅡA, and the expression of spinal dorsal horn 2B subunit was significantly decreased after tanshinone Ⅱ A treatment in CCI rats. Therefore, it was concluded that the analgesic effect of tanshinone ⅡA on CCI model may be related to the decreased expression of NR2B in spinal dorsal horn. In conclusion, tanshinone ⅡA can effectively play the role of labor pain, and has great potential for development in the field of medicine and health products.