Ginsenosides Rg5 and Rh3 protect scopolamine-induced memory deficits in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Panax ginseng (family Araliaceae) is traditionally used as a remedy for cancer, inflammation, stress and aging. AIM OF STUDY: To explore whether ginsenosides Rg5 and Rh3, the main constituents of heat-processed ginseng (the root of Panax ginseng), could protect memory deficit. MATERIALS AND METHODS: We isolated ginsenosides Rh3 and Rg5 from heated-processed ginseng treated with and without human feces, respectively. Then we investigated their protective effects on memory impairment using the passive avoidance, Y-maze and Morris water maze tasks in mice. Memory deficit was induced in mice by the intraperitoneal injection of scopolamine. RESULTS: Ginsenosides Rg5 or Rh3 increased the latency time reduced by scopolamine in passive avoidance test. Treatment with ginsenoside Rg5 or Rh3 significantly reversed the lowered spontaneous alteration induced by scopolamine in Y-maze task. Ginsenoisde Rg5 or Rh3 (10 mg/kg) significantly shortened the escape latencies prolonged by treatment with scopolamine on the last day of training trial sessions in Morris water maze task. Furthermore, ginsenosides Rg5 and Rh3 inhibited acetylcholinesterase activity in a dose-dependent manner, with IC50 values of 18.4 and 10.2 µM, respectively. The inhibitory potency of ginsenoside Rh3 is comparable with that of donepezil (IC50=9.9 µM). These ginsenosides also reversed hippocampal brain-derived neurotrophic factor (BDNF) expression and cAMP response element-binding protein (CREB) phosphorylation reduced by scopolamine. Of them, ginsenoside Rh3 more potently protected memory deficit. CONCLUSIONS: Ginsenoside Rg5 and its metabolite ginsenoside Rh3 may protect memory deficit by inhibiting AChE activity and increasing BDNF expression and CREB activation.

Anti-inflammatory mechanism of compound K in activated microglia and its neuroprotective effect on experimental stroke in mice.

Microglial activation plays a pivotal role in the pathogenesis of various neurologic disorders, such as cerebral ischemia, Alzheimer's disease, and Parkinson's disease. Thus, controlling microglial activation is a promising therapeutic strategy for such brain diseases. In the present study, we found that a ginseng saponin metabolite, compound K [20-O-D-glucopyranosyl-20(S)-protopanaxadiol], inhibited the expressions of inducible nitric-oxide synthase, proinflammatory cytokines, monocyte chemotactic protein-1, matrix metalloproteinase-3, and matrix metalloproteinase-9 in lipopolysaccharide (LPS)-stimulated BV2 microglial cells and primary cultured microglia. Subsequent mechanistic studies revealed that compound K suppressed microglial activation via inhibiting reactive oxygen species, mitogen-activated protein kinases, and nuclear factor-κB/activator protein-1 activities with enhancement of heme oxygenase-1/antioxidant response element signaling. To address the anti-inflammatory effects of compound K in vivo, we used two brain disease models of mice: sepsis (systemic inflammation) and cerebral ischemia. Compound K reduced the number of Iba1-positive activated microglia and inhibited the expressions of tumor necrosis factor-α and interleukin-1ß in the LPS-induced sepsis brain. Furthermore, compound K reduced the infarct volume of ischemic brain induced by middle cerebral artery occlusion and suppressed microglial activation in the ischemic cortex. The results collectively suggest that compound K is a promising agent for prevention and/or treatment of cerebral ischemia and other neuroinflammatory disorders.

Oleanane-type triterpenoids from Aceriphyllum rossii and their cytotoxic activity.

The hexane-soluble fraction of the roots of Aceriphyllum rossii was used to isolate seven new oleanane-type triterpenoids, aceriphyllic acids C-I (1-7), together with seven known triterpenoids. The structures of aceriphyllic acids C-I were determined as 3alpha-hydroxyolean-12-en-23,29-dioic acid (1), 3beta-hydroxyolean-12-en-23,29-dioic acid (2), 3beta,23-dihydroxyolean-12-en-29-oic acid (3), 3alpha-O-acetylolean-12-en-23,27-dioic acid (4), 3alpha-O-caffeoylolean-12-en-27-oic acid (5), 3alpha-O-acetylolean-12-en-23,29-dioic acid (6), and 3alpha-hydroxyolean-12-en-23-al-27-oic acid (7) by spectroscopic analyses. In the evaluation of the in vitro cytotoxicity of these compounds against the MCF-7 and LLC cancer cell lines, compounds 10 and 13 exhibited cytotoxic activity against the LLC cancer cell line with IC(50) values of 7.63 and 6.56 microM, respectively.