Nerolidol, a Sesquiterpene Alcohol, Attenuates Acute Myocardial Infarction in Rats

Cardiovascular diseases have a high morbidity and mortality rate and their treatment is not effective in reducing the damage caused by tissue reperfusion during an acute myocardial infarction (MI). This study aimed to investigate whether nerolidol (NRD), a sesquiterpene alcohol, would attenuate the MI in isoproterenol-treated rat model. MI was induced by the administration of two doses of ISO (100 mg/kg, i.p.) in an interval of 24 h. The animals were divided into 4 groups: control (CTR) (vehicle – saline NaCl 0.9% + TWEEN 80 0.2%), ISO (ISO + vehicle), ISO + NRD (NRD 50 or 100 mg/kg). Electrocardiogram, contractile parameters, cardiac enzymes, infarction size and antioxidant parameters in the heart were measured. ISO group showed a significant rise in ST-segment, QTc and heart rate associated to a reduction of left ventricular developed pressure (LVDP), +dP/dt and –dP/dt. Increase in content of creatine kinase (CK), CK-MB, lactate dehydrogenase (LDH), TBARS and infarction size as well as fall in activities of superoxide dismutase (SOD) and catalase (CAT) were observed. NRD significantly prevented almost all the parameters of ISO-induced MI mentioned above. Our results suggests that nerolidol has a significant effect on the protection of heart through maintaining endogenous antioxidant enzyme activities.

Pavonia odorata- An Overview of Traditional, Phytochemical and Pharmacological Studies

Medicinal plants are of great use in sustaining human health. The plant Pavonia odorata commonly called as fragrant swamp mallow, sugandhabala belonging to family Malvaceae is used traditionally for the treatment of haemorrhage, inflammation, fever, urinary disorders etc in traditional and alternative systems of medicine. The plant was known to contain sesquiterpene alcohol panonenol. The review article describes various pharmacological studies conducted on the plant species. Apart from that, molecular docking studies performed, and studies carried out in Ayurveda and Siddha systems of medicine on this plant species are also discussed in the manuscript. The study indicates that the plant has undergone fewer phytochemical studies, needs to be explored further.

Compounds with Distinct Targets Present Diverse Antimicrobial and Antibiofilm Efficacy against Candida albicans and Streptococcus mutans, and Combinations of Compounds Potentiate Their Effect

Candida albicans and Streptococcus mutans interact synergistically in biofilms associated with a severe form of dental caries. Their synergism is driven by dietary sucrose. Thus, it is necessary to devise strategies to hinder the development of those biofilms and prevent cavities. Six compounds [tt-farnesol (sesquiterpene alcohol that decreases the bacterium acidogenicity and aciduricity and a quorum sensing fungal molecule), myricetin (flavonoid that interferes with S. mutans exopolysaccharides production), two 2’-hydroxychalcones and 4’-hydroxychalcone (intermediate metabolites for flavonoids), compound 1771 (inhibitor of lipoteichoic synthase in Gram-positive bacteria)] with targets in both fungus and bacterium and their products were investigated for their antimicrobial and antibiofilm activities against single-species cultures. The compounds and concentrations effective on single-species biofilms were tested alone and combined with or without fluoride to control initial and pre-formed dual-species biofilms. All the selected treatments eliminated both species on initial biofilms. In contrast, some combinations eliminated the bacterium and others the fungus in pre-formed biofilms. The combinations 4’-hydroxychalcone+tt-farnesol+myricetin, 4’-hydroxychalcone+tt-farnesol+fluoride, and all compounds together with fluoride were effective against both species in pre-formed biofilms. Therefore, combinations of compounds with distinct targets can prevent C. albicans and S. mutans dual-species biofilm build-up in vitro.

Sesquiterpene Alcohol Cedrol Chemosensitizes Human Cancer Cells and Suppresses Cell Proliferation by Destabilizing Plasma Membrane Lipid Rafts

Chemosensitization of cancer cells with small molecules may improve the therapeutic index of antitumoral agents by making tumor cells sensitive to the drug regimen and thus overcome the treatment resistance and side effects of single therapy. Cell membrane lipid rafts are known to transduce various signaling events in cell proliferation. Sensitizing cancer cells may cause modulation of membrane lipid rafts which may potentially be used in improving anticancer drug response. Cedrol, a natural sesquiterpene alcohol, was used to treat human leukemia K562 and colon cancer HT-29 cell lines, and effects were observed. Cedrol decreased the cell viability by inducing apoptosis in both cell lines by activation of pro-apoptosis protein BID and inhibition of anti-apoptosis proteins Bcl-XL, Bcl-2, and XIAP. Cedrol activated the caspase-9-dependent mitochondrial intrinsic pathway of apoptosis. Furthermore, cedrol inhibited the levels of pAKT, pERK, and pmTOR proteins as well as nuclear and cytoplasmic levels of the p65 subunit of NF-κB. Cedrol caused redistribution of cholesterol and sphingomyelin contents from membrane lipid raft, which was confirmed by a combined additive effect with methyl-β-cyclodextrin (lipid raft-disrupting agent). Lipid raft destabilization by cedrol led to the increased production of ceramides and inhibition of membrane-bound NADPH oxidase 2 enzyme activity. Cholesterol/sphingomyelin-redistributing abilities of cedrol appear as a novel mechanism of growth inhibition of cancer cells. Cedrol can be classified as a natural lipid raft-disrupting agent with possibilities to be used in general studies involving membrane lipid raft modifications.

Bioassay-guided isolation and identification of anti-obesity phytochemicals from fruits of Amomum tsao-ko

Amomum tsao-ko (Zingiberaceae), an important traditional medicinal herb, possesses many biological activities, including anti-inflammatory effects. Though the anti-obesity properties of the crude ethanol extract of A. tsao-ko fruits have been reported, the anti-adipogenic properties of its phytochemical constituents have not been reported. Therefore, in the present study, we isolated the active constituents of A. tsao-ko and investigated their anti-adipogenic effects. The bioassay-guided isolation of the phytochemicals from the ethanol extract of A. tsao-ko fruits identified four bioactive compounds, comprising one fatty acid (1), one sesquiterpene alcohol (2), and two phenolic compounds (3 and 4). Their structures were elucidated by a combination of 1D and/or 2D nuclear magnetic resonance and mass spectrometry. The anti-adipogenic activities of the four compounds evaluated by Oil Red O staining in 3T3-L1 cells revealed that the treatment with the isolated compounds 1 and 3 reduced the lipid accumulation in 3T3-L1 adipocytes more strongly than the compounds 2 and 4, in a dose-dependent manner.

(3S,6E)-nerolidol-mediated rendezvous of Cyclocephala paraguayensis beetles in bottle gourd flowers

Cyclocephalini beetles of the genus Cyclocephala (Coleoptera: Melolonthidae: Dynastinae) use flowers of some plants as food, shelter, and mating sites. However, little is known about floral scent chemistry involved in this interaction. Here we show that a sesquiterpene alcohol mediates attraction of Cyclocephala paraguayensis Arrow, on bottle gourd flowers, Lagenaria siceraria (Cucurbitaceae). Both males and females started to aggregate on the flowers at twilight; after that, mating began and remained for the entire night. GC-FID/EAD analysis of the L. siceraria floral scent collected in the field revealed that only the major constituent of the airborne volatiles elicited electroantennographic responses on male and female antennae of C. paraguayensis. This compound was identified as (3S,6E)-nerolidol, which was tested in two field trapping trials in Brazil. In the first bioassay, traps baited with nerolidol (mix of isomers) captured significantly more adult C. paraguayensis than control traps. In the second field trial, catches in traps baited with a mixture of isomers or enantiopure nerolidol were significantly higher than captures in control traps, but the treatments did not differ significantly. Analysis from the gut content of adult C. paraguayensis showed the presence of pollen, suggesting that they also use bottle gourd flowers for their nourishment. Taken together, these results suggest that (3S,6E)-nerolidol plays an essential role in the reproductive behavior of C. paraguayensis by eliciting aggregation, mating, and feeding.

(3S,6E)-Nerolidol-mediated rendezvous of Cyclocephalini beetles, Cyclocephala paraguayensis, in bottle gourd flowers

Cyclocephalini beetles of genus Cyclocephala (Coleoptera: Melolonthidae: Dynastinae) use flowers of some plants as food, shelter, and mating stands. However, little is known about floral scent chemistry involved in this interaction. Here we show that a sesquiterpene alcohol mediates attraction of Cyclocephala paraguayensis Arrow on bottle gourd flowers, Lagenaria siceraria (Curcubitaceae). Both males and females started to aggregate on flowers at twilight; after that, mating began and remained for the entire night. The major constituent of the airborne volatiles from L. siceraria was fully characterized as (3S,6E)-nerolidol, which elicited electroantennographic responses on male and female antennae. Field bioassays showed that traps baited with the natural stereoisomer or a mix of nerolidol isomers captured significantly more males and females of C. paraguayensis than control traps. Analysis from the gut content of these Cyclocephalini beetles showed the presence of pollen, suggesting that they also use bottle gourd flowers for their nourishment. Taken together, these results suggest that (3S,6E)-nerolidol plays an essential role in the reproductive behavior of C. paraguayensis by eliciting aggregation, mating, and feeding.

BID and the α-bisabolol-triggered cell death program: converging on mitochondria and lysosomes

Abstractα-Bisabolol (BSB) is a plant-derived sesquiterpene alcohol able to trigger regulated cell death in transformed cells, while deprived of the general toxicity in several mouse models. Here, we investigated the involvement of lysosomal and mitochondrial compartments in the cytotoxic effects of BSB, with a specific focus on the BH3-only activator protein BID. We found that BSB particularly accumulated in cancer cell lines, displaying a higher amount of lipid rafts as compared to normal blood cells. By means of western blotting and microscopy techniques, we documented rapid BSB-induced BID translocation to lysosomes and mitochondria, both of them becoming dysfunctional. Lysosomal membranes were permeabilized, thus blocking the cytoprotective autophagic flux and provoking cathepsin B leakage into the cytosol. Multiple flow cytometry-based experiments demonstrated the loss of mitochondrial membrane potential due to pore formation across the lipid bilayer. These parallel events converged on neoplastic cell death, an outcome significantly prevented by BID knockdown. Therefore, BSB promoted BID redistribution to the cell death executioner organelles, which in turn activated anti-autophagic and proapoptotic mechanisms. This is an example of how xenohormesis can be exploited to modulate basic cellular programs in cancer.