beta-Eudesmol

Eur J Pharmacol. 2005 Apr 11;512(2-3):105-15.

Antiangiogenic activity of beta-eudesmol in vitro and in vivo.[Pubmed: 15840394 ]

Abnormal angiogenesis is implicated in various diseases including cancer and diabetic retinopathy.
METHODS AND RESULTS:
In this study, we examined the effect of beta-Eudesmol, a sesquiterpenoid alcohol isolated from Atractylodes lancea rhizome, on angiogenesis in vitro and in vivo. Proliferation of porcine brain microvascular endothelial cells and human umbilical vein endothelial cells (HUVEC) was inhibited by beta-Eudesmol (50-100 microM). It also inhibited the HUVEC migration stimulated by basic fibroblast growth factor (bFGF) and the tube formation by HUVEC in Matrigel. beta-Eudesmol (100 microM) blocked the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 induced by bFGF or vascular endothelial growth factor. Furthermore, beta-Eudesmol significantly inhibited angiogenesis in subcutaneously implanted Matrigel plugs in mice and in adjuvant-induced granuloma in mice.
CONCLUSIONS:
These results indicate that beta-Eudesmol inhibits angiogenesis, at least in part, through the blockade of the ERK signaling pathway. We considered that beta-Eudesmol may aid the development of drugs to treat angiogenic diseases.

J Asian Nat Prod Res. 2008 Jan-Feb;10(1-2):159-67.

Beta-eudesmol suppresses tumour growth through inhibition of tumour neovascularisation and tumour cell proliferation.[Pubmed: 18253884]

In the present study, we investigated the potential anti-angiogenic mechanism and anti-tumour activity of beta-Eudesmol using in vitro and in vivo experimental models.
METHODS AND RESULTS:
Proliferation of human umbilical vein endothelial cells (HUVEC) stimulated with vascular endothelial growth factor (VEGF, 30 ng/ml) and basic fibroblast growth factor (bFGF, 30 ng/ml) was significantly inhibited by beta-Eudesmol (50-100 microM). beta-Eudesmol (100 microM) also blocked the phosphorylation of cAMP response element binding protein (CREB) induced by VEGF (30 ng/ml) in HUVEC. beta-Eudesmol (10-100 microM) inhibited proliferation of HeLa, SGC-7901, and BEL-7402 tumour cells in a time- and dose-dependent manner. Moreover, beta-Eudesmol treatment (2.5-5 mg/kg) significantly inhibited growth of H(22) and S(180) mouse tumour in vivo.
CONCLUSIONS:
These results indicated that beta-Eudesmol inhibited angiogenesis by suppressing CREB activation in growth factor signalling pathway. This is the first study to demonstrate that beta-Eudesmol is an inhibitor of tumour growth.

J Pharmacol Exp Ther. 2002 Jun;301(3):803-11.

Beta-eudesmol induces neurite outgrowth in rat pheochromocytoma cells accompanied by an activation of mitogen-activated protein kinase.[Pubmed: 12023507]

beta-Eudesmol, a sesquiterpenoid isolated from "So-jutsu" (Atractylodis lanceae rhizomas), is known to have various unique effects on the nervous system.
METHODS AND RESULTS:
We examined in detail the mechanism by which beta-Eudesmol modified neuronal function using rat pheochromocytoma cells (PC-12). beta-Eudesmol at concentrations of 100 and 150 microM significantly induced neurite extension in PC-12 cells, which was accompanied, at the highest concentration, by suppression of [(3)H]thymidine incorporation. beta-Eudesmol at concentrations of 100 and 150 microM also evoked a significant increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) in these cells, as determined by the fura 2 assay. Much of this increase remained even after the extracellular Ca(2+) was chelated by EGTA. The [Ca(2+)](i) increase induced by beta-Eudesmol was partially inhibited by the phosphoinositide-specific phospholipase C (PI-PLC) inhibitor 1-[6-[[17beta-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U-73122) (2 microM) under extracellular Ca(2+)-free conditions. Furthermore, beta-Eudesmol, in a concentration-dependent fashion, caused an accumulation of inositol phosphates. beta-Eudesmol (150 microM) promoted phosphorylation of both mitogen-activated protein kinase (MAPK) and cAMP-responsive element binding protein in a time-dependent manner. These phosphorylations were suppressed by the MAPK kinase inhibitor 2-(2'-amino-3'-methoxyphenol)-oxanaphthalen-4-one (PD98059) (50 microM), U-73122 (2 microM), the calmodulin inhibitor N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W7) (1-10 microM), and the protein kinase A inhibitor N-[2-(4-bromocinnamylamino)ethyl]-5-isoquinoline (H89) (1-10 microM). beta-Eudesmol-induced neurite extension was significantly inhibited by both U-73122 (2 microM) and PD98059 (30 microM), suggesting the involvement of PI-PLC and MAPK in neurite outgrowth.
CONCLUSIONS:
beta-Eudesmol, being a small molecule, may therefore be a promising lead compound for potentiating neuronal function. Furthermore, the drug may be useful in helping to clarify the mechanisms underlying neuronal differentiation.

Sci Rep . 2017 Nov 17;7(1):15785.

β-Eudesmol, an oxygenized sesquiterpene, stimulates appetite via TRPA1 and the autonomic nervous system[Pubmed: 29150643]

Abstract Transient receptor potential ankyrin 1 (TRPA1) is a calcium-permeable non-selective cation channel, which is activated by various noxious or irritant substances in nature. TRPA1 activators have been generally recognized as noxious, however, foods and beverages containing TRPA1 activators are preferably consumed; the reasons for this discrepancy are not well understood. We demonstrate that TRPA1 is involved in the stimulatory appetite control mechanism. β-Eudesmol is an oxygenated sesquiterpene contained in medicinal or edible plants which activates TRPA1. Oral administration of β-eudesmol brought significant increments in food intake in rats and elevated plasma ghrelin levels. Gastric vagal nerve activity (GVNA) has been reported to affect feeding behavior. In vivo electrophysiological measurement of GVNA revealed that oral-ingestion of β-eudesmol significantly increased GVNA. This GVNA elevation was eliminated by TRPA1 inhibitor (HC-030031) treatment prior to β-eudesmol administration. The physiological effects of β-eudesmol, for example, incremental increase in food intake, ghrelin elevation and activation of GVNA, were significantly reduced in TRPA1 knockout rats. Our results indicated that β-eudesmol stimulates an increase in appetite through TRPA1, and suggests why TRPA1 activator containing foods and beverages are preferably consumed.

Bull Entomol Res. 2008 Oct;98(5):467-73.

Interference of beta-eudesmol in nestmate recognition in Atta sexdens rubropilosa (Hymenoptera: Formicidae).[Pubmed: 18439338]

METHODS AND RESULTS:
Leaf-cutter ant species (Atta spp.) are key pests of cultivated crops in the Neotropics, and recent studies have demonstrated that workers of Atta spp., particularly of Atta sexdens rubropilosa, exhibit aggressive behavior among nestmates when in contact with the sesquiterpene beta-Eudesmol, found in leaves of Eucalyptus maculata. However, the underlying mechanism sparking this behavior pattern has yet to be investigated. This work aimed to elucidate the mechanism by which this substance elicits aggression in workers of A. sexdens rubropilosa.
CONCLUSIONS:
The results, thus obtained, showed that beta-Eudesmol is able to modify the chemical composition of the workers cuticle, impairing nestmate recognition, triggering alarm behavior and leading to nestmate aggression.

Phytother Res. 2013 Mar;27(3):338-43.

β-Eudesmol induces JNK-dependent apoptosis through the mitochondrial pathway in HL60 cells.[Pubmed: 22585533 ]

beta-Eudesmol, a natural sesquiterpenol present in a variety of Chinese herbs, is known to inhibit the proliferation of human tumor cells. However, the molecular mechanisms of the effect of beta-Eudesmol, on human tumor cells are unknown.
METHODS AND RESULTS:
In the present study, we report the cytotoxic effect of β-eudesmol on the human leukemia HL60 cells and its molecular mechanisms. The cytotoxic effect of β-eudesmol on HL60 cells was associated with apoptosis, which was characterized by the presence of DNA fragmentation. beta-Eudesmol-induced apoptosis was accompanied by cleavage of caspase-3, caspase-9, and poly (ADP-ribose) polymerase; downregulation of Bcl-2 expression; release of cytochrome c from mitochondria; and decrease in mitochondrial membrane potential (MMP). Activation of c-Jun N-terminal kinases (JNK) mitogen-activated protein kinases was observed in beta-Eudesmol-treated HL60 cells, and the inhibitor of JNK blocked the beta-Eudesmol-induced apoptosis, downregulation of Bcl-2, and the loss of MMP.
CONCLUSIONS:
These data suggest that beta-Eudesmol induces apoptosis in HL60 cells via the mitochondrial apoptotic pathway, which is controlled through JNK signaling.