RESUMO
Diosgenin extracted from fenugreek, yam and other foods exhibits a wide range of pharmacological activities, especially for the treatment of pain and other nervous system diseases. However, its role in oxaliplatin-induced peripheral neuropathy (OIPN) is unclear. To explore its detailed mechanism on the pain caused by chemotherapy, we carried out this experiment. In this study, the effects of diosgenin on injured PC12 cells and OIPN mice were examined. The results showed that diosgenin not only protected PC12 from injury, but also reduced the mechanical withdrawal threshold and cold hyperalgesia in OIPN mice. Diosgenin inhibited oxidative stress, the cell glial fibrillary acidic protein, and the pro-inflammatory cytokines such as tumor necrosis factor-α, toll-like receptor 4 and nuclear factor-κB in the brain. Furthermore, the fecal microbiota transplantation experiment indicated that diosgenin improved OIPN through regulation of the gut microbiota. All in all, diosgenin ameliorates peripheral neuropathy and is worthy of further study in the treatment of neuropathic pain.
Assuntos
Diosgenina , Microbioma Gastrointestinal , Neuralgia , Animais , Camundongos , Ratos , Diosgenina/farmacologia , Neuralgia/tratamento farmacológico , NF-kappa B/genética , NF-kappa B/metabolismo , Oxaliplatina , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismoRESUMO
Shunaoxin pills (SNX) have been used to treat cerebrovascular diseases in China since 2005. Hypertension is a major risk factor for cerebrovascular disease. This study aimed to explore the synergistic antihypertensive effect of SNX and nifedipine and whether SNX could alleviate nifedipine-induced renal lipotoxicity. During administration, systolic blood pressure was measured weekly. After 5 weeks administration, we examined pathological changes of kidney, renal function, the lipid metabolism index, and adipogenesis genes expression in the kidney tissues, and explored its underlying mechanism. Finally, network pharmacology was used for supplement and verification. As a result, SNX improved the antihypertensive effect of nifedipine and apparently improved nifedipine-induced renal pathological changes, dyslipidemia and the levels of adipogenesis gene expression in kidney tissues. SNX reduced the levels of interleukin-6 and interleukin-1ß in renal tissues, down-regulated the production of malondialdehyde, and increased superoxide dismutase activity and the protein expression of heme oxygenase-1 in kidney tissues. Network pharmacology also showed that SNX could improve nifedipine-induced renal lipotoxicity. The combination of SNX and nifedipine had certain benefits in the treatment of hypertension.