Ursane-type Triterpene Glycosides from Rubus cochinchinensis Exhibited Insulin-Mimetic Activities in Differentiated 3T3-L1 Adipocytes

Diabetes mellitus is characterized by hyperglycemic due to impaired insulin secretion or resistance. In our search for anti-diabetic agents, we found that a 70% EtOH extract of Rubus cochinchinensis(Tratt) enhances glucose uptake in 3T3-L1 adipocytes. R. cochinchinensis is predominantly found in East Asia, particularly in Vietnam, Laos, Cambodia, and southern in China. Despite its widespread distribution, there have been few studies on its bioactivity or chemical constituents. In this study, activity-guided fractionation of 70% EtOH extract from the leaves of R. cochinchinensis resulted in the isolation of one new ursane-type glycoside, 3-O-β-acetyl-28-O-β-D-glucopyranosyl-rotundioic acid (1), along with four known compounds (2–5). The structures of these compounds were elucidated using 1D and 2D NMR and HRESIMS data. Notably, compound 4 significantly increased the uptake level of 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose (2-NBDG) in differentiated 3T3-L1 adipocytes. This study suggests the potential of R. cochinchinensis as a promising medicinal plant for treating diabetes via glucose uptake.

Biflorin Ameliorates Memory Impairments Induced by Cholinergic Blockade in Mice

To examine the effect of biflorin, a component of Syzygium aromaticum, on memory deficit, we introduced a scopolamine-induced cognitive deficit mouse model. A single administration of biflorin increased latency time in the passive avoidance task, ameliorated alternation behavior in the Y-maze, and increased exploration time in the Morris water maze task, indicating the improvement of cognitive behaviors against cholinergic dysfunction. The biflorin-induced reverse of latency in the scopolamine-treated group was attenuated by MK-801, an NMDA receptor antagonist. Biflorin also enhanced cognitive function in a naïve mouse model. To understand the mechanism of biflorin for memory amelioration, we performed Western blot. Biflorin increased the activation of protein kinase C-ζ and its downstream signaling molecules in the hippocampus. These results suggest that biflorin ameliorates drug-induced memory impairment by modulation of protein kinase C-ζ signaling in mice, implying that biflorin could function as a possible therapeutic agent for the treatment of cognitive problems.

Identification of Neuroactive Constituents of the Ethyl Acetate Fraction from Cyperi Rhizoma Using Bioactivity-Guided Fractionation

Cyperi Rhizoma (CR), the rhizome of Cyperus rotundus L., exhibits neuroprotective effects in in vitro and in vivo models of neuronal diseases. Nevertheless, no study has aimed at finding the neuroactive constituent(s) of CR. In this study, we identified active compounds in a CR extract (CRE) using bioactivity-guided fractionation. We first compared the anti-oxidative and neuroprotective activities of four fractions and the CRE total extract. Only the ethyl acetate (EA) fraction revealed strong activity, and further isolation from the bioactive EA fraction yielded nine constituents: scirpusin A (1), scirpusin B (2), luteolin (3), 6′-acetyl-3,6-diferuloylsucrose (4), 4′,6′ diacetyl-3,6-diferuloylsucrose (5), p-coumaric acid (6), ferulic acid (7), pinellic acid (8), and fulgidic acid (9). The activities of constituents 1-9 were assessed in terms of anti-oxidative, neuroprotective, anti-inflammatory, and anti-amyloid-β activities. Constituents 1, 2, and 3 exhibited strong activities; constituents 1 and 2 were characterized for the first time in this study. These results provide evidence for the value of CRE as a source of multi-functional neuroprotectants, and constituents 1 and 2 may represent new candidates for further development in therapeutic use against neurodegenerative diseases.