Safety Assessment of Bangle (Zingiber purpureum Rosc.) Rhizome Extract: Acute and Chronic Studies in Rats and Clinical Studies in Human.

Bangle (Zingiber purpureum Rosc.) rhizome extract (BRE) contains phenylbutenoid dimers (banglenes), which exert neurotrophic effects and possess the potential capability to regenerate hippocampal neurons in mice. The acute and chronic oral toxicities of BRE powder were evaluated in Sprague-Dawley rats. A dose of BRE powder was estimated to be higher than 2000 mg/kg containing BRE 534 mg/kg as minimum lethal dose in a single-dose oral toxicity study. The no-observed-adverse-effect-level for the BRE powder was 1000 mg/kg/day (BRE 267 mg/kg) in the 90 day oral toxicity study. Four week clinical studies of BRE tablets in humans suggested that the ingestion of BRE tablets within 850 mg/man/day (BRE 227 mg/man/day) was safe for at least 1 month and in a usual manner. The C max, t max, and AUC of cis- and trans-(E)-3-(3,4-dimethoxyphenyl)-4-[(E)-3,4-dimethoxystyryl]cyclohex-1-enes (c- and t-banglenes) were calculated after the ingestion of BRE tablets (BRE 227 mg) and were 17.73 and 22.61 ng/mL, 1.8 and 1.8 h, and 71.47 and 95.53 ng/mL/h, respectively.

Bangle (Zingiber purpureum) Improves Spatial Learning, Reduces Deficits in Memory, and Promotes Neurogenesis in the Dentate Gyrus of Senescence-Accelerated Mouse P8.

Bangle (Zingiber purpureum) is a tropical ginger that is used as a spice in Southeast Asia. Phenylbutenoid dimers isolated from Bangle have exhibited neurotrophic effects in primary cultured rat cortical neurons and PC12 cells. Furthermore, chronic treatment with phenylbutenoid dimers enhances hippocampal neurogenesis in olfactory bulbectomized mice. In this study, we investigated the effects of Bangle extract on behavior and hippocampal neurogenesis in vivo. SAMP8 mice, which are an established model for accelerated aging, with age-related learning and memory impairments, were given a Bangle-containing diet for 1 month, and subsequent behavioral tests and immunohistochemistry for Ki67, a proliferating cell marker, were performed. We found that the Bangle-containing diet improved spatial learning and memory deficits in the Morris water maze and significantly increased the numbers of Ki67-positive cells in the dentate gyrus of the SAMP8 mice. In addition, the Bangle extract exhibited a neurotrophin-like activity as indicated by the induction of neurite sprouting in PC12 cells. Our results suggest that Bangle is beneficial for the prevention of age-related progression of cognitive impairment.

Novel neurotrophic phenylbutenoids from Indonesian ginger Bangle, Zingiber purpureum.

Two new curcuminoids 1 and 2, and a new phenylbutenoid dimer 3, were isolated from Bangle (Zingiber purpureum). Their structures were determined on the basis of comprehensive spectroscopic data and their biogenetic pathway. Compounds 1 and 2 are the first example of curcumin coupled with phenylbutenoid. Compounds 1 and 2 promoted neurite outgrowth of NGF-mediated PC12 cells at concentrations ranging from 1 to 10 µM. In addition, compound 1 was found to accelerate the prevention of Aß42 aggregation.

Evaluation of constituents of Piper retrofractum fruits on neurotrophic activity.

Three new compounds, 1-3, together with 22 known compounds, were isolated from the fruits of Piper retrofractum. The structures of the new compounds were elucidated on the basis of spectroscopic data analysis and comparison with literature values. Compound 1 was found to enhance the neurite outgrowth of NGF-mediated PC12 cells at concentrations ranging from 0.1 to 10 µM.

Resveratrol derivative-rich melinjo (Gnetum gnemon L.) seed extract suppresses multiple angiogenesis-related endothelial cell functions and tumor angiogenesis.

Angiogenesis is a promising target for cancer prevention and treatment. This study aimed to determine the antiangiogenic effects of melinjo (Gnetum gnemon L.) seed extract and its resveratrol derivative components, such as gnetin C (GC), gnetin L (GL), gnemonoside A (GMA), gnemonoside C (GMC), and gnemonoside D (GMD). An ethanol extract of melinjo seeds (EEMS) and the two gnetins markedly inhibited the proliferation and tube formation of human umbilical vein endothelial cells (HUVEC) stimulated with vascular endothelial growth factor and basic fibroblast growth factor. The inhibitory effects of GC and GL were much stronger than those of resveratrol. GMC and GMD inhibited only proliferation, whereas GMA had almost no effect on the two endothelial cell functions. The EEMS and GC also reduced the cell viability of tube-forming HUVEC, with accompanying ERK1/2 inactivation, and suppressed the migration of HUVEC. Furthermore, dietary intake of EEMS significantly inhibited tumor angiogenesis in a mouse dorsal air sac assay. In conclusion, we found that the EEMS and its resveratrol derivatives, particularly GC, suppress multiple angiogenesis-related endothelial cell functions and/or tumor angiogenesis, indicating that the melinjo seeds and the natural resveratrol derivatives may be useful for cancer prevention and treatment.

Stilbenoids isolated from the seeds of Melinjo (Gnetum gnemon L.) and their biological activity.

A 50% EtOH extract of the dried endosperms of melinjo (Gnetum gnemon L.) was purified by a combination of column chromatography, including highly porous polymer, octadecylated silica (ODS), hydroxypropylated dextran (LH-20), and silica gel, resulting in the isolation of a new stilbenoid 1, named gnetin L, along with five previously identified stilbenoids 2-6 (gnetin C, gnemonosides A, C, and D, and resveratrol). All of these stilbenoids showed 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity similar to that of ascorbic acid and dl-alpha-tocopherol. With the exception of gnemonoside A (3), these stilbenoids showed moderate antimicrobial activity. Inhibition of lipase from porcine pancreas was recognized in four stilbenoids excluding gnemonoside A (3) and resveratrol (6). Gnetin C (2), gnemonoside C (4), and gnemonoside D (5) inhibited the hydrolysis of starch by alpha-amylase from porcine pancreas. An EtOH extract containing these stilbenoids also showed DPPH radical scavenging effect, lipase and alpha-amylase inhibition activity, and antimicrobial activity against food microorganisms and enterobacteria. The present study indicates that melinjo and extracts containing these constituents are useful as health supplements.