Effects Of Sesquiterpenes Research Articles

Molecular Descriptors and QSAR Models for Sedative Activity of Sesquiterpenes Administered to Mice via Inhalation.

Essential oils are often utilized for therapeutic purposes and are composed of complex structural molecules, including sesquiterpenes, with high molecular weight and potential for stereochemistry. A detailed study on the properties of selected sesquiterpenes was conducted as part of a broader investigation on the effects of sesquiterpenes on the central nervous system. A set of 18 sesquiterpenes, rigorously selected from an original list of 114, was divided into 2 groups i.e., the training and test sets, with each containing 9 compounds. The training set was evaluated for the sedative activity in mice through inhalation, and all compounds were sedatives at any dose in the range of 4 × 10-4-4 × 10-2 mg/cage, except for curzerene. Molecular determinants of the sedative activities of sesquiterpenes were evaluated using quantitative structure-activity relationship (QSAR) and structure-activity relationship (SAR) analyses. An additional test set of six compounds obtained from the literature was utilized for validating the QSAR model. The parental carbonyl cation and an oxygen-containing groups are possible determinants of sedative activity. The QSAR study using multiple regression models could reasonably predict the sedative activity of sesquiterpenes with statistical parameters such as the correlation coefficient r2 = 0.82 > 0.6 and q2 LOO = 0.71 > 0.5 obtained using the leave-one-out cross-validation technique. Molar refractivity and the number of hydrogen bond acceptors were statistically important in predicting the activities. The present study could help predict the sedative activity of additional sesquiterpenes, thus accelerating the process of drug development.

The Complexity of Sesquiterpene Chemistry Dictates Its Pleiotropic Biologic Effects on Inflammation

Sesquiterpenes (SQs) are volatile compounds made by plants, insects, and marine organisms. SQ have a large range of biological properties and are potent inhibitors and modulators of inflammation, targeting specific components of the nuclear factor-kappaB (NF-κB) signaling pathway and nitric oxide (NO) generation. Because SQs can be isolated from over 1600 genera and 2500 species grown worldwide, they are an attractive source of phytochemical therapeutics. The chemical structure and biosynthesis of SQs is complex, and the SQ scaffold represents extraordinary structural variety consisting of both acyclic and cyclic (mono, bi, tri, and tetracyclic) compounds. These structures can be decorated with a diverse range of functional groups and substituents, generating many stereospecific configurations. In this review, the effect of SQs on inflammation will be discussed in the context of their complex chemistry. Because inflammation is a multifactorial process, we focus on specific aspects of inflammation: the inhibition of NF-kB signaling, disruption of NO production and modulation of dendritic cells, mast cells, and monocytes. Although the molecular targets of SQs are varied, we discuss how these pathways may mediate the effects of SQs on inflammation.

The Hepatotoxicity of Alantolactone and Germacrone: Their Influence on Cholesterol and Lipid Metabolism in Differentiated HepaRG Cells.

The sesquiterpenes alantolactone (ATL) and germacrone (GER) are potential anticancer agents of natural origin. Their toxicity and biological activity have been evaluated using the differentiated HepaRG (dHepaRG) cells, a hepatocyte-like model. The half-maximal inhibitory concentrations of cell viability after 24-h treatment of dHepaRG cells are approximately 60 µM for ATL and 250 µM for GER. However, both sesquiterpenes induce reactive oxygen species (ROS) formation in non-toxic concentrations and significantly dysregulate the mRNA expression of several functional markers of mature hepatocytes. They similarly decrease the protein level of signal transducer and activator of transcription 3 (STAT3), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and their transcription target, intercellular adhesion molecule 1 (ICAM-1). Based on the results of a BATMAN-TCM analysis, the effects of sesquiterpenes on cholesterol and lipid metabolism were studied. Sesquiterpene-mediated dysregulation of both cholesterol and lipid metabolism was observed, during which these compounds influenced the protein expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and sterol regulatory element-binding protein 2 (SREBP-2), as well as the mRNA expression of HMGCR, CYP19A1, PLIN2, FASN, SCD, ACACB, and GPAM genes. In conclusion, the two sesquiterpenes caused ROS induction at non-toxic concentrations and alterations in cholesterol and lipid metabolism at slightly toxic and toxic concentrations, suggesting a risk of liver damage if administered to humans.

Inhibitory effects of sesquiterpenes from Saussurea lappa on the overproduction of nitric oxide and TNF-α release in LPS-activated macrophages

Nitric oxide (NO), derived from l-arginine, is produced by two types (constitutive and inducible) of nitric oxide synthase (NOS: cNOS and iNOS). The NO produced in large amounts by the iNOS is known to be responsible for inflammation, the vasodilation, and hypotension observed in septic shock and cancer metastasis. The inhibitors of the overproduction of NO, thus, may be useful candidates for the treatment of inflammatory diseases. We have found that the petroleum ether extract of Saussurea lappa Decne, which is a wild species wildly distributed in India, can strongly inhibit the overproduction of NO in mouse macrophage RAW 264.7 cells. Through bioassay-guided fractionation, 13 sesquiterpenes were isolated from the active petroleum ether extract. Furthermore, another five sesquiterpenes were synthesized by chemical methods. In the present study, their effects on LPS-induced NO production and TNF-α release are reported. Compounds 1, 3, 9, 17, and 18 showed significant inhibitory activities on the production of NO and release of TNF-α with IC50 values lower than 1 μmol/l. SAR studies suggest that the exocyclic double bond (Δ11(13)) is necessary for the inhibitory activities of sesquiterpenes on the NO production.

Effects of sesquiterpenes and amino acid–sesquiterpene conjugates from the roots of Saussurea lappa on inducible nitric oxide synthase and heat shock protein in lipopolysaccharide-activated macrophages

The methanolic extract of the roots of Saussurea lappa C larke, a Chinese medicinal herb Saussureae Radix, was found to inhibit nitric oxide (NO) production in lipopolysaccharide (LPS)-activated mouse peritoneal macrophages. Among the constituents from the methanolic extract, two sesquiterpene lactones (costunolide and dehydrocostus lactone) and two amino acid-sesquiterpene conjugates (saussureamines A and B) potently inhibited LPS-induced NO production (IC 50=1.2–2.8 μM). Saussureamines A and B in addition to costunolide and dehydrocostus lactone did not inhibit iNOS enzyme activity, but they inhibited both induction of inducible NO synthase and activation of nuclear factor-κB in accordance with induction of heat shock protein 72.

ChemInform Abstract: Effects of Sesquiterpenes and Triterpenes from the Rhizome of Alisma orientale on Nitric Oxide Production in Lipopolysaccharide‐Activated Macrophages: Absolute Stereostructures of Alismaketones‐B 23‐Acetate and ‐C 23‐Acetate.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Effects of sesquiterpenes and triterpenes from the rhizome of Alisma orientale on nitric oxide production in lipopolysaccharide-activated macrophages: Absolute stereostructures of alismaketones-B 23-acetate and -C 23-acetate

The methanolic extract from a Chinese herbal medicine, the rhizome of Alisma orientale, was found to exhibit inhibitory activity of nitric oxide (NO) production in lipopolysaccharide (LPS)-activated macrophages. Novel triterpenes, alismaketones-B 23-acetate and -C 23-acetate, were isolated from the active extract together with eight sesquiterpenes and eighteen protostane-type triterpenes. The absolute stereostructures of new triterpenes were characterized on the basis of chemical and physicochemical evidence, which included the chemical correlations with known triterpenes. The guaiane-type sesquiterpenes (alismol, orientalols A and C) and protostane- and seco-protostane-types triterpenes (alisols C monoacetate, E-23-acetate, F, H, I, L-23-acetate, and M-23-acetate, alismaketones-B 23-acetate and -C 23-acetate, alismalactone 23-acetate, and 3-methylalismalactone 23-acetate) inhibited LPS-induced NO production (IC 50 = 8.4–68 μM). Other triterpenes (alisols A, A monoacetate, B, B monoacetate, E, G, K-23-acetate, and N-23-acetate and 11-deoxyalisol B) also showed the potent inhibitory activity, but they showed cytotoxic effects more than 30 μM (MTT assay). In addition, alismol and alisol F were found to suppress iNOS induction.

Effects of sesquiterpenes from laurel (Laurus nobilis) on NO production in activated macrophages

Effects of sesquiterpenes from laurel (Laurus nobilis) on NO production in activated macrophages