Protective effects of asiatic acid in a spontaneous type 2 diabetic mouse model

Abstract

Asiatic acid (AA) has been demonstrated to exhibit anti-diabetic activity. However, the mechanisms and underlying signaling pathways remain to be elucidated. The present study was performed to confirm the protective effect of AA and demonstrate its ability to regulate the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase-3β (GSK-3β) signaling pathway in db/db mice. Db/db mice fed on a high-fat diet were used to model diabetes mellitus. Modeled mice were divided randomly into the model control, pioglitazone hydrochloride tablet (PH) and AA groups. Age-matched C57 BL/6J mice served as normal controls. Lipid and glucose levels, and glycogen synthesis rates were assessed following treatment. Pathological changes were detected using hematoxylin and eosin staining. Expression of the PI3K/AKT/GSK-3β signaling pathway at the mRNA level was measured using quantitative polymerase chain reaction analysis. The model control group revealed typical characteristics of obesity and diabetes, including high glucose and lipid levels, and decreased glycogen synthesis. Four weeks of treatment with AA or PH ameliorated these abnormalities. AA and PH treatments mitigated the upregulation of PI3K, AKT, insulin receptor, and insulin receptor substrate-1 mRNA expression in modeled mice. Furthermore, AA and PH treatments decreased GSK-3β and glucose-6-phosphatase mRNA expression compared with the normal control group. The results of the present study confirmed that AA possesses anti-diabetic activity in db/db mice. The PI3K/AKT/GSK-3β signaling pathway may mediate this protective effect.

Pharmacological Properties, Molecular Mechanisms, and Pharmaceutical Development of Asiatic Acid: A Pentacyclic Triterpenoid of Therapeutic Promise

“…Mechanistically, it promoted cell survival machinery by promoting activation of Akt kinase and Bcl-xL in the pancreatic islets. The antidiabetic activity of AA was shown mediating PI3K/AKT/GSK-3β signaling mechanism in high-fat diet fed db/db mice (Sun et al, 2017 ). AA attenuated rise in expression of PI3K, AKT, insulin receptors, and insulin receptor substrate-1 and downregulated GSK-3β and glucose-6-phosphatase.…”

Asiatic acid protests against myocardial ischemia/reperfusion injury via modulation of glycometabolism in rat cardiomyocyte

“… 25 Asiatic acid is another pentacyclic triterpene showing hypoglycemic activity in different diabetic animal models. 10 , 26 , 27 We have observed that asiatic acid effectively prevents cardiomyocyte apoptosis after oxygen-glucose deprivation/ reperfusion injury. 11 Taken together, we hypothesized that asiatic acid may protect against ischemia/reperfusion injury by modulation of glycometabolism in cardiomyocyte.…”

<i>Centella asiatica</i> (L.) extract attenuates inflammation and improve insulin sensitivity in a coculture of lipopolysaccharide (LPS)-induced 3T3-L1 adipocytes and RAW 264.7 macrophages

“…However, asiatic acid, as an active compound in C. asiatica, has anti-inflammatory activity by downregulating the pro-inflammatory cytokines IL-6, IL-1β, and TNF-α in human corneal epithelial cells and the liver tissue of diabetic-induced mice (12,13). In addition, asiatic acid exerts anti-hyperglycemia effect in high fat diet (HFD)-induced diabetes mice through the PI3K/Akt/GSKβ signaling pathway (21). Another previous study showed that asiatic acid at a dose of 20 mg/kg body decreased blood-glucose level in diabeticinduced rat using streptozotocin (STZ) followed by improved glucose uptake into skeletal muscle tissues via the IRS-1/PI3K-Akt signaling pathway (22).…”