Lignan-rich extract from Cinnamomum camphora leaf attenuates metabolic syndrome by modulating glycolipid metabolism and gut microbiota in T2DM mice

Background: Type 2 diabetes mellitus (T2DM) is a serious metabolic syndrome with high mortality and disability rates globally, which usually caused by unhealthy dietary patterns. Cinnamomum camphora leaf is a traditional Chinese medicinal herb used for attenuating hyperglycemia and digestive disorder, and high level of lignans has been found in C. camphora leaf. Purpose: This study aimed to examine the chemical composition of lignans extracted from C. camphora leaf (LCCL), and illustrate its therapeutic effect and mechanism on T2DM and its concomitant glycolipid metabolic disorder. Methods: The components of LCCL were separated and purified by silica gel and macroporous adsorption resin, and were distinguished through LC/MS and NMR. The antioxidant activity of LCCL was determined by free radical scavenging assay in vitro; the hypoglycemic and hypolipidemic abilities were evaluated by alpha-glucosidase, alpha-amylase and pancreatic lipase inhibition trials, respectively. T2DM model mice were established by high-sugar and high-fat (HSHF) feed together with streptozotocin (STZ) infection, and then grouped to assess the effect of LCCL treatment. Hematoxylin-eosin (H&E), Periodic Acid-Schiff (PAS) and oil red O staining were employed to analyze the histopathology. qRT-PCR assay, 16S rRNA analysis, and western blot were conducted to illuminate the anti-diabetic mechanism of LCCL. Results: 6 sesamin lignans were identifed from LCCL. The in vitro assays showed strong inhibitive abilities of LCCL with low IC50 on DPPH (33.68 +/- 0.54 mu g/ml),O-2(-) (39.25 +/- 0.61 mu g/ml), OH center dot (45.72 +/- 0.72 mu g/ml), alpha-glucosidase (0.82 +/- 0.14 mg/ml), alpha-amylase (0.86 +/- 0.11 mg/ml) and pancreatic lipase (0.91 +/- 0.12 mg/ml). LCCL treatment (100, 200 and 400 g kg(-1mg kg-1)) gradually decreased the fasting blood glucose (FBG) and fasting insulin (FINS), improved the glucose and insulin tolerance, down-regulated the homeostasis model assessment insulin resistance (HOMA-IR) indexes, alleviated the hepatic inflammatory response and oxidative stress, promoted the glycogen storage and depleted the fat accumulation in the liver. Besides, LCCL administration alleviated the glycolipid metabolism disorder in T2DM mice with a gut microbiota dependent manner, that significantly increased biodiversity, altered the composition of gut microbiota and increased the proportion of Lactobacillus. Conclusion: The lignan-rich extract of C. camphor leaf (LCCL), containing at least 6 lignans compounds, displayed promising antioxidant, hypoglycemic and hypolipidemic activities. The treatment of LCCL alleviated the glycolipid metabolism disorder in T2DM mice with a gut microbiota dependent manner. These finding suggested that LCCL should be further investigated to develop its complementary therapeutic effect on T2DM.