Brucine alleviates neuropathic pain in mice via reducing the current of the sodium channel.

ETHNOPHARMACOLOGICAL RELEVANCE: Strychnos nux-vomica L. (Loganiaceae) is grown extensively in South Asian. The dried seed of this plant, nux vomica, has been clinically used in Chinese medicine for relieving rheumatic pain, reducing swelling and treating cancer. Brucine, the second abundant alkaloid constituent of nux vomica, shows excellent clinical therapeutic effect, especially in relieving pain, but mechanism of brucine in relieving pain is still unclear. AIM OF THE STUDY: Explore the analgesic effect of brucine, reveal the molecular mechanism of brucine analgesia. MATERIALS AND METHODS: Antinociceptive effects of brucine were assessed in acute and chronic pain mice model. Electrophysiological experiments were used to evaluate the effects of brucine on neuronal activity and sodium channel function. RESULTS: In acute pain models, brucine significantly inhibits response induced by nociceptive heat and mechanical stimulation. Furthermore, thermal hypersensitivity and mechanical allodynia were also alleviated by brucine treatment in a chronic constriction injury (CCI) mouse model. Sodium channel plays a crucial role in neuropathic pain. Electrophysiological results show that brucine inhibits the excitability of DRG neurons directly, the number of action potential (AP) was significantly reduced after brucine treatment, and this kind of inhibition is due to brucine inhibits both tetrodotoxin-sensitive (TTXs) and tetrodotoxin-resistant (TTXr) sodium channel. CONCLUSIONS: Taken together, brucine is a novel drug candidate in treating acute and chronic pain diseases, which might be attributed to inhibition the excitability of sodium channel directly.

Matrine inhibits itching by lowering the activity of calcium channel.

Sophorae Flavescentis Radix (SFR) is a medicinal herb with many functions that are involved in anti-inflammation, antinociception, and anticancer. SFR is also used to treat a variety of itching diseases. Matrine (MT) is one of the main constituents in SFR and also has the effect of relieving itching, but the antipruritic mechanism is still unclear. Here, we investigated the effect of MT on anti-pruritus. In acute and chronic itch models, MT significantly inhibited the scratching behavior not only in acute itching induced by histamine (His), chloroquine (CQ) and compound 48/80 with a dose-depended manner, but also in the chronic pruritus models of atopic dermatitis (AD) and acetone-ether-water (AEW) in mice. Furthermore, MT could be detected in the blood after intraperitoneal injection (i.p.) and subcutaneous injection (s.c.). Finally, electrophysiological and calcium imaging results showed that MT inhibited the excitatory synaptic transmission from dorsal root ganglion (DRG) to the dorsal horn of the spinal cord by suppressing the presynaptic N-type calcium channel. Taken together, we believe that MT is a novel drug candidate in treating pruritus diseases, especially for histamine-independent and chronic pruritus, which might be attributed to inhibition of the presynaptic N-type calcium channel.

Tetramethylpyrazine attenuates carbon tetrachloride-caused liver injury and fibrogenesis and reduces hepatic angiogenesis in rats.

Liver fibrosis represents a frequent event following chronic insult to trigger wound healing reactions with abnormalities of angiogenesis in the liver. Capillarization of liver sinusoidal endothelial cell (LSEC) is the pivotal event during liver angiogenesis. In the current study, we sought to investigate the effect of tetramethylpyrazine (TMP) on carbon tetrachloride (CCl4)-induced liver injury and fibrosis in rats, and to further examine the molecular mechanisms of TMP-induced anti-angiogenic effect. We found that TMP significantly ameliorated histopathological feature of liver fibrosis characterized by decreased collagen deposition, hepatocyte apoptosis, and expression of biochemical indicators, such as aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP). Moreover, TMP appeared to play an essential role in controlling pathological angiogenesis. In addition, TMP attenuated angiogenesis by downregulation of vascular endothelial growth factor-A (VEGF-A), vascular endothelial growth factor receptor 2 (VEGF-R2), platelet-derived growth factor-BB (PDGF-BB), and platelet-derived growth factor-ß receptor (PDGF-ßR), four important factors transmitting pro-angiogenic pathways. Besides, TMP inhibited LSEC capillarization in CCl4-induced liver fibrotic model with the morphological features of increasing sinusoidal fenestrae. Importantly, we found that disruption of angiogenesis is required for TMP to inhibit hepatocyte apoptosis in rats. Treatment with TMP significantly inhibited the expression of Bax, and up-regulated Bcl-2 expression. Interestingly, treatment with angiogenesis-inducer AngII dramatically eliminated the effect of TMP on Bax/Bcl-2 axis. Overall, these results provide novel perspectives to reveal the protective effect of TMP on liver, opening up the possibility of using TMP based anti-angiogenic drugs for the liver diseases.