Worldwide, there are plants known as psychoactive plants that naturally contain psychedelic active components. They have a high concentration of neuroprotective substances that can interact with the nervous system to produce psychedelic effects. Despite these plants' hazardous potential, recreational use of them is on the rise because of their psychoactive properties. Early neuroscience studies relied heavily on psychoactive plants and plant natural products (NPs), and both recreational and hazardous NPs have contributed significantly to the understanding of almost all neurotransmitter systems. Worldwide, there are many plants that contain psychoactive properties, and people have been using them for ages. Psychoactive plant compounds may significantly alter how people perceive the world.
1. ACS Catal. 2024 Jul 9;14(14):11034-11043. doi: 10.1021/acscatal.4c02032. eCollection 2024 Jul 19. Simulation-Guided Engineering Enables a Functional Switch in Selinadiene Synthase toward Hydroxylation. Srivastava PL(1), Johns ST(2), Voice A(2), Morley K(2), Escorcia AM(2), Miller DJ(1), Allemann RK(1), van der Kamp MW(2). Author information: (1)School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff CF10 3AT, U.K. (2)School of Biochemistry, University of Bristol, University Walk, Bristol BS8 1TD, U.K. Engineering sesquiterpene synthases to form predefined alternative products is a major challenge due to their diversity in cyclization mechanisms and our limited understanding of how amino acid changes affect the steering of these mechanisms. Here, we use a combination of atomistic simulation and site-directed mutagenesis to engineer a selina-4(15),7(11)-diene synthase (SdS) such that its final reactive carbocation is quenched by trapped active site water, resulting in the formation of a complex hydroxylated sesquiterpene (selin-7(11)-en-4-ol). Initially, the SdS G305E variant produced 20% selin-7(11)-en-4-ol. As suggested by modeling of the enzyme-carbocation complex, selin-7(11)-en-4-ol production could be further improved by varying the pH, resulting in selin-7(11)-en-4-ol becoming the major product (48%) at pH 6.0. We incorporated the SdS G305E variant along with genes from the mevalonate pathway into bacterial BL21(DE3) cells and demonstrated the production of selin-7(11)-en-4-ol at a scale of 10 mg/L in batch fermentation. These results highlight opportunities for the simulation-guided engineering of terpene synthases to produce predefined complex hydroxylated sesquiterpenes. © 2024 The Authors. Published by American Chemical Society. DOI: 10.1021/acscatal.4c02032 PMCID: PMC11264211 PMID: 39050902 Conflict of interest statement: The authors declare no competing financial interest. 2. Plants (Basel). 2022 Dec 6;11(23):3399. doi: 10.3390/plants11233399. Neutrophil Immunomodulatory Activity of Nerolidol, a Major Component of Essential Oils from Populus balsamifera Buds and Propolis. Schepetkin IA(1), Özek G(2), Özek T(2), Kirpotina LN(1), Kokorina PI(3), Khlebnikov AI(3), Quinn MT(1). Author information: (1)Department of Microbiology and Cell Biology, Montana State University, Bozeman, MT 59717, USA. (2)Department of Pharmacognosy, Faculty of Pharmacy, Anadolu University, Eskisehir 26470, Turkey. (3)Kizhner Research Center, Tomsk Polytechnic University, Tomsk 634050, Russia. Propolis is a resinous mixture of substances collected and processed from various botanical sources by honeybees. Black poplar (Populus balsamifera L.) buds are one of the primary sources of propolis. Despite their reported therapeutic properties, little is known about the innate immunomodulatory activity of essential oils from P. balsamifera and propolis. In the present studies, essential oils were isolated from the buds of P. balsamifera and propolis collected in Montana. The main components of the essential oil from P. balsamifera were E-nerolidol (64.0%), 1,8-cineole (10.8%), benzyl benzoate (3.7%), α-terpinyl acetate (2.7%), α-pinene (1.8%), o-methyl anisol (1.8%), salicylaldehyde (1.8%), and benzyl salicylate (1.6%). Likewise, the essential oil from propolis was enriched with E-nerolidol (14.4%), cabreuva oxide-VI (7.9%), α-bisabolol (7.1%), benzyl benzoate (6.1%), β-eudesmol (3.6%), T-cadinol (3.1%), 2-methyl-3-buten-2-ol (3.1%), α-eudesmol (3.0%), fokienol (2.2%), nerolidol oxide derivative (1.9%), decanal (1.8%), 3-butenyl benzene (1.5%), 1,4-dihydronaphthalene (1.5%), selina-4,11-diene (1.5%), α-cadinol (1.5%), linalool (1.4%), γ-cadinene (1.4%), 2-phenylethyl-2-methyl butyrate (1.4%), 2-methyl-2-butenol (1.3%), octanal (1.1%), benzylacetone (1.1%), and eremoligenol (1.1%). A comparison between P. balsamifera and propolis essential oils demonstrated that 22 compounds were found in both essential oil samples. Both were enriched in E-nerolidol and its derivatives, including cabreuva oxide VI and nerolidol oxides. P. balsamifera and propolis essential oils and pure nerolidol activated Ca2+ influx in human neutrophils. Since these treatments activated neutrophils, the essential oil samples were also evaluated for their ability to down-regulate the neutrophil responses to subsequent agonist activation. Indeed, treatment with P. balsamifera and propolis essential oils inhibited subsequent activation of these cells by the N-formyl peptide receptor 1 (FPR1) agonist fMLF and the FPR2 agonist WKYMVM. Likewise, nerolidol inhibited human neutrophil activation induced by fMLF (IC50 = 4.0 μM) and WKYMVM (IC50 = 3.7 μM). Pretreatment with the essential oils and nerolidol also inhibited human neutrophil chemotaxis induced by fMLF, again suggesting that these treatments down-regulated human neutrophil responses to inflammatory chemoattractants. Finally, reverse pharmacophore mapping predicted several potential kinase targets for nerolidol. Thus, our studies have identified nerolidol as a potential anti-inflammatory modulator of human neutrophils. DOI: 10.3390/plants11233399 PMCID: PMC9739404 PMID: 36501438 Conflict of interest statement: The authors declare no conflict of interest. 3. Molecules. 2022 Jun 10;27(12):3759. doi: 10.3390/molecules27123759. Neuropeltis acuminata (P. Beauv.): Investigation of the Chemical Variability and In Vitro Anti-inflammatory Activity of the Leaf Essential Oil from the Ivorian Species. Kambiré DA(1)(2), Kablan ACL(1), Yapi TA(3), Vincenti S(2), Maury J(2), Baldovini N(4), Tomi P(2), Paoli M(2), Boti JB(3), Tomi F(2). Author information: (1)UPR de Chimie Organique, Département de Mathématiques, Physique et Chimie, UFR des Sciences Biologiques, Université Péléforo Gon Coulibaly, Korhogo BP 1328, Côte d'Ivoire. (2)Laboratoire Sciences Pour l'Environnement, Université de Corse-CNRS, UMR 6134 SPE, Route des Sanguinaires, 20000 Ajaccio, France. (3)Laboratoire de Constitution et Réaction de la Matière, UFR-SSMT, Université Félix Houphouët-Boigny, Abidjan BP V34, Côte d'Ivoire. (4)Institut de Chimie de Nice, CNRS UMR 7272, Université Côte d'Azur, Parc Valrose, CEDEX 2, 06108 Nice, France. The variability of chemical composition of the leaf essential oil (EO) from Neuropeltis acuminata, a climbing liana growing wild in Ivory Coast, was investigated for the first time. The in vitro anti-inflammatory activity was also evaluated. Thirty oil samples were isolated from leaves collected in three forests of the country and analyzed using a combination of Column Chromatography (CC), Gas Chromatography with Retention Indices (GC(FID)), Gas Chromatography-Mass Spectrometry (GC-MS), and 13Carbon-Nuclear Magnetic Resonance (13C-NMR). Fractionation by CC led to the first-time isolation from natural source of δ-cadinen-11-ol, whose structural elucidation by one dimension (1D) and 2D-NMR spectroscopy is reported here. Finally, 103 constituents accounting for 95.7 to 99.6% of the samples' compositions were identified. As significant variations of the major constituents were observed, the 30 oil compositions were submitted to hierarchical cluster and principal components analyses. Five distinct groups were evidenced: Group I, dominated by (E)-β-caryophyllene, kessane, and δ-cadinene, while the main constituents of Group II were germacrene B, ledol, α-humulene, (E)-γ-bisabolen-12-ol, and γ-elemene. Group III exhibited guaiol, germacrene D, atractylone, (E)-γ-bisabolen-12-ol, δ-cadinene and bulnesol as main compounds. Group IV was dominated by (E)-nerolidol, guaiol, selina-4(15),7(11)-diene and bulnesol, whereas (E)-β-caryophyllene, α-humulene and α-muurolene were the prevalent compounds of Group V. As the harvest took place in the same dry season in the three forests, the observed chemical variability could be related to harvest sites, which includes climatic and pedologic factors, although genetic factors could not be excluded. The leaf oil sample S24 behaved as a high inhibitor of LipOXygenase (LOX) activity (half maximum Inhibitory Concentration, IC50: 0.059 ± 0.001 mg mL-1), suggesting an anti-inflammatory potential. DOI: 10.3390/molecules27123759 PMCID: PMC9230793 PMID: 35744884 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflict of interest. 4. J Agric Food Chem. 2022 Aug 31;70(34):10417-10428. doi: 10.1021/acs.jafc.1c06912. Epub 2022 Apr 18. Terpenes and Cannabinoids Yields and Profile from Direct-Seeded and Transplanted CBD-Cannabis sativa. Zheljazkov VD(1), Noller JS(1)(2), Maggi F(3), Dale R(4). Author information: (1)Department of Crop and Soil Science, Oregon State University, 3050 Southwest Campus Way, Corvallis, Oregon 97331, United States. (2)Global Hemp Innovation Center, Oregon State University, 170 Southwest Waldo Place, Corvallis, Oregon 97331, United States. (3)Chemistry Interdisciplinary Project (ChIP), School of Pharmacy, University of Camerino, 62032 Camerino, Italy. (4)Dale Farms, Culver, Oregon 97734, United States. Following recent legalization, the production of hemp (Cannabis sativa L.) for high-value plant compounds became a major crop in many countries across the world. In this study, we profiled popular plant compounds being extracted for emerging markets, terpenes and cannabinoids, developed in two different planting systems of a single, high-cannabidiol (CBD), low-Δ9-tetrahydrocannabinol (Δ9-THC), dioecious hemp cultivar 'Culver' in central Oregon, U.S.A. One system is the current conventional system of an open, all-female, clonal transplant (OFCT) production system. This is compared to a dioecious, densely seeded (DDS) production system. Overall, the essential oil (EO, chiefly terpenes) and cannabinoid profiles of plants harvested from the two systems were comparable. In comparison to the DDS plots, the EO obtained from colas of the OFCT plots had higher concentrations of α-pinene, myrcene, limonene, β-bisabolene, γ-cadinene, caryophyllene oxide, guaiol, 10-epi-γ-eudesmol, β-eudesmol, bulnesol, epi-α-bisabolol, α-humulene, and CBD, although lower concentrations of 1,8-cineole, (E)-caryophyllene, γ-elemene, α-selinene, selina-4(15),7(11)-diene, selina-3,7(11)-diene, and germacrene B. Of the various plant parts (female leaves and chaff, male flowers) tested in the DDS plots, the highest EO yield was obtained from the chaff. The main EO constituents of female leaves were (E)-caryophyllene (14-21%), caryophyllene oxide (13-16%), α-humulene (5-6%), humulene epoxide II (3.5-3.8%), epi-α-bisabolol (2.7-5.5%), CBD, and α-eudesmol (1.1-2.6%). The principal EO constituents of female chaff from the DDS system were (E)-caryophyllene (∼21%), α-humulene (6.6%), β-selinene (4.5%), α-selinene (3.6%), selina-3,7(11)-diene (9.8%), selina-4(15),7(11)-diene (6.3%), caryophyllene oxide (5.2%), and cannabichromene (3.1%). The major EO constituents of the male flowers were CBD (19.3%), caryophyllene oxide (11%), α-humulene (4.1%), epi-α-bisabolol (3.9%), selina-3,7(11)-diene (3.4%), and β-selinene (3.4%). Cannabinoids were not detected in the EO distilled for 30 min, but they were present in the EO from 240 min of distillation. The EO content of female leaves and male flowers was relatively low, whereas the EO content of the female chaff from the DDS system was significantly greater. Breaking with conventional knowledge, the EO of male flowers may accumulate up to 19% CBD. Distillation of plants from both production systems converted CBD-A to CBD, CBDV-A to CBDV, CBG-A to CBG, and THC-A to THC as a result of the thermal decarboxylation of acidic cannabinoids but otherwise did not affect the total cannabinoid content. Most of the cannabinoids remained in the distilled biomass after the extraction of terpenes (EO). Therefore, the distilled, terpene-free biomass represents a high-value product that could be further extracted for cannabinoids or used as a component in various products. DOI: 10.1021/acs.jafc.1c06912 PMID: 35436102 [Indexed for MEDLINE] 5. Plants (Basel). 2021 Mar 5;10(3):488. doi: 10.3390/plants10030488. Antimicrobial Activities of Sesquiterpene-Rich Essential Oils of Two Medicinal Plants, Lannea egregia and Emilia sonchifolia, from Nigeria. Ogundajo AL(1), Ewekeye T(2), Sharaibi OJ(2), Owolabi MS(1), Dosoky NS(3), Setzer WN(3)(4). Author information: (1)Department of Chemistry, Natural Products Research Unit, Faculty of Science, Lagos State University, Badagry- Expressway, P.M.B. 0001 LASU Post Office, Ojo, Lagos 100268, Nigeria. (2)Department of Botany, Faculty of Science, Lagos State University, Badagry- Expressway, P.M.B. 0001 LASU Post Office, Ojo, Lagos 100268, Nigeria. (3)Aromatic Plant Research Center, 230 N 1200 E, Suite 100, Lehi, UT 84043, USA. (4)Department of Chemistry, University of Alabama in Huntsville, Huntsville, AL 35803, USA. Lannea egregia (Anacardiaceae) and Emilia sonchifolia (Asteraceae) are plants used in traditional medicine in southwestern Nigeria. The essential oils from the leaves of L. egregia and E. sonchifolia were obtained by hydrodistillation and analyzed by gas chromatography-mass spectrometry. Both essential oils were dominated by sesquiterpenoids. The major components in L. egregia leaf essential oil were α-panasinsen (34.90%), (E)-caryophyllene (12.25%), α-copaene (11.39%), and selina-4,11-diene (9.29%), while E. sonchifolia essential oil was rich in γ-himachalene (25.16%), (E)-caryophyllene (15.72%), and γ-gurjunene (8.58%). The essential oils were screened for antimicrobial activity against a panel of bacteria and fungi and displayed minimum inhibitory concentrations ranging from 156 μg/mL to 625 μg/mL. Based on these results, either L. egregia or E. sonchifolia essential oil may be recommended for exploration as complementary antibacterial or antifungal agents. DOI: 10.3390/plants10030488 PMCID: PMC8000775 PMID: 33807551 Conflict of interest statement: The authors declare no conflict of interest.