Amomum tsao-ko crevost et lemaire ameliorates depression-like behaviors and hippocampal inflammation by inhibiting microglia activation and HMGB1/TLR4/NF-κB pathway in diabetic mice with depression.

Diabetic depression may be closely related to hippocampal inflammation. We hypothesized that Amomum tsao-ko Crevost et Lemaire (A. tsao-ko) might ameliorate depression-like behavior and glucose intolerance by modulating hippocampal inflammation. UPLC-Q-Exactive-MS/MS was used to identified the constituents in the ethanol extract of A. tsao-ko (EEAT). Then a diabetic depression (DD) model was established and treated for 4 weeks. Depression-like behaviors were assessed using the open field test, sucrose preference test and tail suspension test. The neuronal injury was observed by hematoxylin-eosin staining and Nissl staining. Oral glucose tolerance test, fasting blood glucose, hemoglobin Alc, fasting insulin and homeostasis model assessment of insulin resistance were used to evaluate the effects of EEAT on glucose metabolism. Serum lipids, neurotransmitters, neuroendocrine and inflammation levels were detected by biochemical kits and enzyme-linked immunosorbent assay. Activation of microglia markers was detected by immunofluorescence. Western blotting was used to detect the effect of EEAT on the HMGB1/TLR4/NF-κB protein expression. 48 chemical components were identified from EEAT. Animal experiments showed that EEAT improved the levels of glucose and lipid metabolism, alleviated depression-like behaviors, decreased the level of neurotransmitters and increased the secretion of neuroendocrine-related hormones. The activation of microglia and immunofluorescence intensity of neurogenesis also improved. At the same time, the expression of HMGB1, TLR4 and NF-κB proteins in the inflammatory pathway was also inhibited. EEAT had effects on improving DD symptoms, which may be achieved by down-regulating the HMGB1/TLR4/NF-κB protein expression.