The Hypoglycemic and Synergistic Effect of Loganin, Morroniside, and Ursolic Acid Isolated from the Fruits ofCornus officinalis

Abstract

Hypoglycemic activity-guided separation of ethanol extracts from the fruits of Cornus officinalis Sieb. et Zucc (CO) led to the isolation of loganin, morroniside, and ursolic acid. The antidiabetic capacity of CO extracts and related compounds was further investigated in diabetes mellitus mice. The results suggested that both CO extracts and pure compounds could ameliorate diabetes-associated damages and complications. Oral administration of loganin and morroniside decreased fasting blood glucose levels in diabetes mellitus mice. Ursolic acid exhibited the highest reactive oxygen species scavenging activity and α-glucosidase inhibitory activity. Notably, we noticed an interesting synergistic effect between loganin and ursolic acid. Given these favorable hypoglycemic properties, C. officinalis, a food and medicinal plant in China, may be used as a valuable food supplement for the treatment of diabetes mellitus.

The novel protective effects of loganin against 1‐methyl‐4‐phenylpyridinium‐induced neurotoxicity: Enhancement of neurotrophic signaling, activation of IGF‐1R/GLP‐1R, and inhibition of RhoA/ROCK pathway

“…Growing evidence demonstrated that drugs targeting on activations of IGF‐1R or GLP‐1R pathways possess their therapeutic potential on neurodegenerative disease, including PD (Bassil et al, ; Kim et al, ). Loganin is a glucose‐lowering botanic compound (He et al, ), and we previously reported its neuroprotection‐mediated activation of IGF‐1R signaling in motor neurons (Tseng et al, ). Recently, the potential protection of loganin has been revealed in different experimental models of PD (Xu et al, ; Yao et al, ).…”

“…Loganin is a major iridoid glycoside that exhibits hypoglycemic activity of fruits of Cornus officinalis (He et al, ). Loganin has been proved to possess glucose‐lowering ability in diabetic mice (He et al, ) and is suggested as a valuable supplement for the treatment of diabetes mellitus and diabetes complications (He et al, ; Jiang, Zhang, Hou, & Zhu, ; Yamabe et al, ). Growing evidence from several cellular and animal models of neurodegenerative disorders demonstrates the potential neuroprotective effects of loganin in PD (Xu et al, ; Yao et al, ).…”

Cornus mas and Cornus Officinalis—Analogies and Differences of Two Medicinal Plants Traditionally Used

“…Among terpenoids only ursolic acid ( 112 ) has been reported in the fruits of cornelian cherry and Asiatic dogwood (Jayaprakasam et al, 2006; Wang H. et al, 2008; Jang et al, 2014; He et al, 2016). This compound was often reported as an active constituent found in ethanolic and methanolic extracts from fruits of C. officinalis (Gao et al, 2008).…”

“…This compound was often reported as an active constituent found in ethanolic and methanolic extracts from fruits of C. officinalis (Gao et al, 2008). In addition, other three triterpenoid acids ( 113–115 ), including oleanolic acid, have been identified in C. officinalis (Jayaprakasam et al, 2006; Wang H. et al, 2008; Jang et al, 2014; He et al, 2016). …”

“…Ursolic acid ( 112 ) also present in both species is capable to stimulate the glucose uptake through the phosphorylation of insulin receptor (Zhang et al, 2006). Specific antidiabetic effects were reported for 7- O -galloyl-D-seduheptulose ( 120 ) and iridoids [e.g., loganin ( 1 ), morroniside ( 8 )] present in C. officinalis (Yamabe et al, 2009; Park et al, 2010, 2013; He et al, 2016) as well as for cyanidin 3- O -galactoside ( 58 ) and cyanidin 3- O -glucoside ( 59 ) present in C. mas (Jayaprakasam et al, 2005). On the other hand, loganin ( 1 ) and ursolic acid ( 112 ) were not able to affect an expression of phosphoenolpyruvate carboxykinase (PEPCK) in rat hepatoma H4IIE cell line on the contrary methanolic extract of C. officinalis fruit (50 μg/ml) which exerted insulin mimetic effect in this manner, and one of its fraction enhanced insulin secretion by rat insulin-secreting BRIN-BD11 cells in response to high glucose concentration (16.7 mM; Chen et al, 2008).…”