Galgravin

Molecules. 2015 Jul 15;20(7):12757-68.

Neolignans from Nectandra megapotamica (Lauraceae) Display in vitro Cytotoxic Activity and Induce Apoptosis in Leukemia Cells.[Pubmed: 26184150 ]

Nectandra megapotamica (Spreng.) Mez. (Lauraceae) is a well-known Brazilian medicinal plant that has been used in folk medicine to treat several diseases. In continuation of our ongoing efforts to discover new bioactive natural products from the Brazilian flora, this study describes the identification of cytotoxic compounds from the MeOH extract of N. megapotamica (Lauraceae) leaves using bioactivity-guided fractionation.
METHODS AND RESULTS:
This approach resulted in the isolation and characterization of eight tetrahydrofuran neolignans: calopeptin (1), machilin-G (2), machilin-I (3), aristolignin (4), nectandrin A (5), veraguensin (6), ganschisandrin (7), and Galgravin (8). Different assays were conducted to evaluate their cytotoxic activities and to determine the possible mechanism(s) related to the activity displayed against human leukemia cells. The most active compounds 4, 5 and 8 gave IC50 values of 14.2 ± 0.7, 16.9 ± 0.8 and 16.5 ± 0.8 μg/mL, respectively, against human leukemia (HL-60) tumor cells. Moreover, these compounds induced specific apoptotic hallmarks, such as plasma membrane bleb formation, nuclear DNA condensation, specific chromatin fragmentation, phosphatidyl-serine exposure on the external leaflet of the plasma membrane, cleavage of PARP as well as mitochondrial damage, which as a whole could be related to the intrinsic apoptotic pathway.

J Pharm Pharmacol. 2004 Sep;56(9):1179-84.

Evaluation of analgesic and anti-inflammatory activities of Nectandra megapotamica (Lauraceae) in mice and rats.[Pubmed: 15324487 ]

METHODS AND RESULTS:
The bioactivity-guided phytochemical investigation of the crude hydralcoholic extract of Nectandra megapotamica was carried out using the abdominal constriction test in mice, which led to the isolation of three active compounds: alpha-asarone (1), Galgravin (2) and veraguensin (3). The crude extract (EBCA, 300 mg kg(-1)) and isolated compounds 1,2, and 3, at different doses, were evaluated using the acetic acid-induced abdominal constriction test in mice, carrageenan-induced paw oedema in rats, and hot plate tests in rats. The EBCA showed a significant effect in the abdominal constriction and hot plate tests, but did not show activity in the rat paw oedema assay.
CONCLUSIONS:
All isolated compounds displayed activity in the abdominal constriction test, but only compound 1 was active in the hot plate test. Compounds 2 and 3 displayed activity in the anti-inflammatory assay. It was suggested that the analgesic effects obtained for EBCA could be due mainly to the presence of its major compound, alpha-asarone (1).

Cytotechnology. 2012 May;64(3):315-22.

Effects of veraguensin and galgravin on osteoclast differentiation and function.[Pubmed: 22526488]

The dried flower buds of Magnolia sp. are widely used as herbal medicines because of their anti-inflammatory, anti-malarial and anti-platelet activities.
METHODS AND RESULTS:
Here, we found that veraguensin and Galgravin, lignan compounds derived from Magnolia sp., dose-dependently inhibited osteoclast formation in co-cultures of bone marrow cells and osteoblastic cells. These compounds also inhibited receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast differentiation in RAW264.7 cells and bone marrow macrophages. In the RANKL-induced signaling pathway, veraguensin and Galgravin reduced p38 phosphorylation and suppressed the expression of c-Fos, a key transcription factor for osteoclastogenesis. Veraguensin and Galgravin also inhibited osteoclastic pit formation, which was accompanied by decreased mature osteoclast viability.
CONCLUSIONS:
In conclusion, these results indicate that veraguensin and Galgravin can inhibit bone resorption and may offer novel compounds for the development of drugs to treat bone-destructive diseases such as osteoporosis.

Biol Pharm Bull. 2005 Feb;28(2):289-93.

Neuroprotective effects of 2,5-diaryl-3,4-dimethyltetrahydrofuran neolignans.[Pubmed: 15684486]

We previously reported the neurotrophic effects of talaumidin (1) from Aristolochia arcuata MASTERS.
METHODS AND RESULTS:
In the present study, we compared the neurotrophic and neuroprotective effects of six other 2,5-diaryl-3,4-dimethyltetrahydrofuran neolignans isolated from the same plant, veraguensin (2), Galgravin (3), aristolignin (4), nectandrin A (5), isonectandrin B (6), and nectandrin B (7), with compound 1 in primary cultured rat neurons.
CONCLUSIONS:
Compounds 3-7 promoted neuronal survival and neurite outgrowth, among which compounds 6 and 7 showed neurotrophic activity comparable with that of 1. Furthermore, compounds 1-7 protected hippocampal neurons against amyloid beta peptide (Abeta25-35)-induced cytotoxicity, while compounds 1 and 4-7 protected against neuronal death from 1-methyl-4-phenylpyridinium ion (MPP+)-induced toxicity in cultured rat hippocampal neurons.

Zhongguo Zhong Yao Za Zhi. 1993 May;18(5):292-4, 318.

Anti-platelet activating factor constituents, 2,5-diaryltetrahydrofuran type lignans, from Piper futokadsura Sied. et Zucc.[Pubmed: 8216803]

METHODS AND RESULTS:
Besides the known components kadsurenone, futoquinol and futoxide, three anti-platelet activating factor principles have been found from the stem part of Piper futokadsura (Piperaceae), the Chinese drug haifengteng.
CONCLUSIONS:
They were separated and identified as Galgravin, galbelgin and veraguensin on the basis of HPLC and spectral analysis. The natural existence of these three anti-PAF constituents in haifengteng is reported for the first time.