ABSTRACT
Our previous studies have shown that puerarin, an active component of the traditional Chinese medicine-Pueraria Lobata, can improve glycometabolism in high-fat diet (HFD) mice with diabetes by activating the glucagon-like peptide-1 receptor (GLP-1R) pathway. This study intends to further evaluate the effect of puerarin on depressive symptoms in HFD mice. Long-term HFD induces type 2 diabetes and depressive-like symptoms in mice. Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of the Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Traditional Chinese Medicine (approval No. AEWC-025). The experiment was divided into: control group, model group, model/puerarin (150 mg·kg-1·day-1) group, and model/fluoxetine (15 mg·kg-1·day-1) group. The oral glucose tolerance test (OGTT) and behavioral experimental analysis were performed after 6 weeks of continuous administration. Afterwards, enzyme-linked immunosorbent assay (ELISA) was used to detect interleukin-1β (IL-1β), interleukin-6 (IL-6), 5-hydroxytryptamine (5-HT), and corticosterone (CORT) in serum of mice for each group. Western blot assays were used to detect the level of activation and expression of proteins related to neuroplasticity and depressive disorder in the hippocampus. Moreover, HT-22 cell line was used to investigate the protective effect of puerarin on cell morphology and survival. The results show that puerarin can effectively maintain the survival of HT22 in an environment with high glucose and corticosterone. Meantime, the glycemic regulation of diabetic mice was improved after treatment of puerarin, the depressive symptoms were alleviated, the 5-HT increased, and the corticosterone, IL-1β, and IL-6 decreased in the serum. The up-regulation of related proteins in GLP-1R/Wnt/mTOR (mammalian target of rapamycin) signaling in hippocampus suggests that its effect on ameliorating depression in diabetic mice may be related to the activation of GLP-1R/Wnt/mTOR signaling pathway. This study shows that puerarin can significantly ameliorate the depressive symptoms of HFD induced diabetic mice which might be achieved through activating the GLP-1R/Wnt/mTOR signaling pathway and improving hippocampal neuroplasticity.
ABSTRACT
To investigate the potential hypoglycemic effect of nanosuspensions of honokiol and explore the underlying mechanisms, a high fat diet (HFD) was studied in C57BL/6J mice divided into five groups: normal diet (ND), HFD, HFD/honokiol-sodium carboxymethyl cellulose (CMC-Na) (Hono-CMC, 100 mg·kg-1), HFD/honokiol- Nano (Hono-Nano, 80 mg·kg-1), HFD/metformin (HFD/Met, 200 mg·kg-1). Fasting blood glucose (FBG) and body weights (BW) of mice were measured every seven days. After 30-day treatment, an oral glucose tolerance test (OGTT) was performed, and blood and tissue samples were collected for analysis. All animal experiments were approved by the Research Animal Care Committee of Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine. The data showed Hono-Nano and metformin reduced FBG, BW, and markedly improved OGTT of mice compared to HFD group (P<0.05). Hono-CMC produced nonsignificant impact on FBG, BW of mice, while OGTT of mice was improved by Hono-CMC (P<0.05). Meanwhile, none of these treated groups showed significant effects on regulating serum insulin levels, but all of them exhibited decreased serum glucagon levels notably compared to the HFD group (P<0.05). Western blot analysis revealed that honokiol up-regulated levels of p-AMPK and p-FOXO1 in liver tissue of HFD mice (P<0.05), which resulted in activation of AMPK and inhibition of FOXO1. Moreover, the expression of PEPCK (a key enzyme of gluconeogenesis) was decreased by honokiol (P<0.05). Taken together, our findings demonstrate that nanosuspension of honokiol is more effective than CMC-Na-suspension of honokiol on blood glucose controlling in HFD mice. The hypoglycemic effects of honokiol might rely on suppressing hepatic gluconeogenesis via activating AMPK and inhibiting FOXO1.
ABSTRACT
The diabetes is mainly treated by the oral administration of western medicines at present. Despite their rapid curative effect, there have been still many reports for the western medicines about their clinical adverse reactions, failure of effective prevention and treatment of complications and drug resistance. Hence, they are not suitable for long-term administration. Traditional Chinese medicines have a long history in treating diabetes mellitus (DM) , which is commonly known as Xiaokezheng in the theory of traditional Chinese medicines. In recent years, many scholars have taken extracts from traditional Chinese medicines or separated active constituents as the study objects in the expectation of developing new-type drugs for treating and preventing diabetes. Therefore, a large number of study reports have been emerged in this field. Due to their significant glucose-reducing effect and specific effect in treating complications of diabetes, traditional Chinese medicine Gardeniae Fructus and its iridoid component geniposide shall be given full attention. This paper summarized the advance in studies on the curative effect and action mechanism of Gardeniae Fructus and geniposide in preventing and treating diabetes.