Research Article Details
| Article ID: | A01339 |
| PMID: | 34783554 |
| Source: | J Agric Food Chem |
| Title: | Novel Sesquiterpene Glycoside from Loquat Leaf Alleviates Type 2 Diabetes Mellitus Combined with Nonalcoholic Fatty Liver Disease by Improving Insulin Resistance, Oxidative Stress, Inflammation, and Gut Microbiota Composition. |
| Abstract: | Nonalcoholic fatty liver disease (NAFLD) is strongly associated with type 2 diabetes mellitus (T2DM). Sesquiterpene glycosides from loquat leaf achieved beneficial effects on metabolic syndromes such as NAFLD and diabetes; however, their specific activity and underlying mechanism on T2DM-associated NAFLD have not yet been fully understood. In the present study, we found that sesquiterpene glycoside 3 (SG3), a novel sesquiterpene glycoside isolated from loquat leaf, was able to prevent insulin resistance (IR), oxidative stress, and inflammation. In db/db mice, SG3 administration (25 and 50 mg/kg/day) inhibited obesity, hyperglycemia, and the release of inflammatory cytokines. SG3 (5 and 10 μM) also significantly alleviated hepatic lipid accumulation, oxidative stress, and inflammatory response induced by high glucose combined with oleic acid in HepG2 cells. Western blotting analysis showed that these effects were related to repair the abnormal insulin signaling and inhibit the cytochrome P450 2E1 (CYP2E1) and NOD-like receptor family pyrin domain-containing 3 (NLRP3), both in vivo and in vitro. In addition, SG3 treatment could decrease the ratio of Firmicutes/Bacteroidetes and increase the relative abundance of Lachnospiraceae, Muribaculaceae, and Lactobacillaceae after a high-throughput pyrosequencing of 16S rRNA to observe the changes of related gut microbial composition in db/db mice. These findings proved that SG3 could protect against NAFLD in T2DM by improving IR, oxidative stress, inflammation through regulating insulin signaling and inhibiting CYP2E1/NLRP3 pathways, and remodeling the mouse gut microbiome. It is suggested that SG3 could be considered as a new functional additive for a healthy diet. |
| DOI: | 10.1021/acs.jafc.1c05596 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| S04 | Anti-oxidative stress | oxidative stress | α-tocopherol: antioxidant | Vitamin E | Details |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| S06 | Regulating intestinal flora | intestine gut microbiota; gut microbiota | farnesoid X receptor (FXR); fibroblast growth factor-19 (FGF19) | Probiotics; Prebiotics; Rifaximin; Yaq-001; Cilofexor; EDP-305; EYP001a; INT-767 | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |