beta-Eudesmol

The rhizome of Atractylodes lancea (Thunb.) DC.

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

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

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. In the present study, we report the cytotoxic effect of beta-Eudesmol on the human leukemia HL60 cells and its molecular mechanisms. The cytotoxic effect of beta-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. These data suggest that beta-Eudesmol induces apoptosis in HL60 cells via the mitochondrial apoptotic pathway, which is controlled through JNK signaling.

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

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

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. 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. 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.

Chemotype diversity of Psidium guajava L.[Pubmed:29913321]

Phytochemistry. 2018 Sep;153:129-137.

The essential oil of Psidium guajava L. has been studied for pharmacological and industrial purposes, without considering the plant's genotype regarding the heterogeneity of its composition. The present study aimed to characterize the chemotype diversity of the essential oil extracted from the leaves of 22 genotypes of P. guajava grown in two different environments in the state of Espirito Santo, Brazil, and to identify the different chemical markers present in these plants. Essential oil from the leaves of the P. guajava genotypes was extracted by hydrodistillation, and its chemical composition was analyzed by gas chromatography-flame ionization detection (GC-FID) and gas chromatography-mass spectrometry (GC-MS). Thirty-three compounds were identified, comprising 87.5-99.0% of the total composition, with a prevalence of sesquiterpenes in all samples. The major compounds identified consisted of (E)-trans-Caryophyllene, alpha-Humulene, trans-Nerolidol, beta-Bisabolene, beta-Bisabolol, and Hinesol, the first of which was identified as a possible chemical marker for the species. Multivariate factor analysis of the chemical composition of P. guajava oil identified three chemotypes: Commercial - PAL, SEC, PS, PET, C7, C11, and C17MI, characterized by high levels of beta-Selinene, alpha-Selinene, Hinesol, and 14-hydroxy-epi-(E)-caryophyllene, with beta-Selinene and alpha-Selinene as the chemical markers; C10 and C13, exhibiting high levels of Elemol, trans-Nerolidol, trans-beta-Eudesmol, and (2Z, 6Z)-Farnesol, which were indicated as chemical markers, and Cortibel - C1, C2, C3, C4, C5, C6, C8, C9, C12, C14, C15, C16, C17LI, which retained high levels of alpha-Cedrene, cis-alpha-Bergamotene, alpha-Humulene, Humulene epoxide, epi-alpha-Cadinol, beta-Bisabolol, and alpha-Bisabolol, with beta-Bisabolol and alpha-Bisabolol as the chemical markers. The use of guava genotypes with different chemotypes, that are agronomically favorable to fruit production and essential oil exploitation adds value to the crop and renders it more sustainable. Given guava crops produce large amounts of leaf biomass, resulting from successive prunings, the extraction of their essential oil, which retains commercially valuable compounds, can be feasible.

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

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

Abnormal angiogenesis is implicated in various diseases including cancer and diabetic retinopathy. 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. 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.

beta-eudesmol, an oxygenized sesquiterpene, affects efferent adrenal sympathetic nerve activity via transient receptor potential ankyrin 1 in rats.[Pubmed:29966754]

Neurosci Lett. 2018 Sep 25;684:18-24.

The autonomic nervous system innervates various peripheral tissue functions. Various external stimuli affect autonomic nerve activity, however, there is little information about the involvement of sensory receptors in the responses. The TRPA1 is a calcium-permeable non-selective cation channel which plays a crucial role in the susceptibility to various stimuli. beta-Eudesmol, an oxygenated sesquiterpene found in hop essential oil and beer, activates the TRPA1. Intragastric administration of beta-Eudesmol decreased efferent adrenal sympathetic nerve activity (ASNA) in rats, whereas subcutaneous administration did not. ASNA suppression by beta-Eudesmol was not observed in TRPA1 knockout rats. The beta-Eudesmol derived ASNA suppression was partially, but significantly, eliminated by subdiaphragmatic vagotomy in rats, suggesting the afferent vagal nerve from the gastrointestinal tract to the brain is involved in the effect of beta-Eudesmol on ASNA. Our results indicate that beta-Eudesmol suppresses ASNA, partly through TRPA1 and the afferent vagus nerve. These findings introduce the physiological significance of the TRPA1 in the control of ASNA.

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

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

beta-Eudesmol, a sesquiterpenoid isolated from "So-jutsu" (Atractylodis lanceae rhizomas), is known to have various unique effects on the nervous system. 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-dion e (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. 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.

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

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

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. 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.

Effect of beta-Eudesmol on NQO1 suppression-enhanced sensitivity of cholangiocarcinoma cells to chemotherapeutic agents.[Pubmed:29914576]

BMC Pharmacol Toxicol. 2018 Jun 19;19(1):32.

BACKGROUND: Cholangiocarcinoma (CCA), an epithelial malignancy of the biliary tree, is one of the aggressive cancers with poor prognosis and unsatisfactory response to chemotherapy with acquired resistance. NAD(P)H-quinone oxidoreductase 1 (NQO1), an antioxidant/detoxifying enzyme, plays important roles in chemo-resistance and proliferation in several cancer cells. The study aimed to investigate the inhibitory effect of beta-Eudesmol on NQO1 enhanced chemotherapeutic effects of 5-fluorouracil (5-FU) and doxorubicin (DOX) in the high NQO1-expressing human CCA cell line, NQO1-KKU-100. In addition, the molecular events associated with the inhibition of the cell proliferation, cell migration, and induction of apoptosis were investigated. METHODS: Human CCA KKU-100 cells were exposed to beta-Eudesmol at various concentrations. NQO1 enzyme activity and protein expression were measured by enzymatic assay and Western blot analysis, respectively. Sulforhodamine B (SRB) assay and wound healing assay were performed to detect the inhibitory effect of beta-Eudesmol on cell proliferation, cell migration, and sensitivity to 5-FU and DOX. Apoptotic induction was detected by flow cytometry with annexin V/PI and DAPI nuclear staining. Caspase 3/7 activation was determined by fluorescence microscopy. The mechanism of enhanced chemo-sensitivity was evaluated by Western blot analysis. RESULTS: beta-Eudesmol significantly suppressed NQO1 enzyme activity (both in KKU-100 cells and cell lysates) and protein expression in KKU-100 cells in a concentration-dependent manner. beta-Eudesmol exhibited potent cytotoxicity on KKU-100 cells with mean +/- SD IC50 values of 47.62 +/- 9.54 and 37.46 +/- 12.58 muM at 24 and 48 h, respectively. In addition, it also potentiated the cytotoxic activities and inhibitory activities of 5-FU and DOX on cell migration through induction of cell apoptosis and activation of caspase 3/7. Western blot analysis suggested that beta-Eudesmol enhanced chemosensitivity was associated with the suppression of NQO1 protein and activation of Bax/Bcl-2 protein expression ratio in CCA cells. CONCLUSIONS: beta-Eudesmol may serve as a potential anti-CCA candidate particularly when used in combination with conventional chemotherapeutics. The mechanisms involved may be mediated via NQO1 suppression-related apoptosis pathway.

Beta-Eudesmol is a natural oxygenated sesquiterpene, activates hTRPA1, with an EC50 of 32.5 μM. Beta-Eudesmol increases appetite through TRPA1.

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