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. Comput Biol Med. 2024 Sep;180:108969. doi: 10.1016/j.compbiomed.2024.108969. Epub 2024 Jul 31. Dissecting molecular mechanisms underlying the inhibition of β-glucuronidase by alkaloids from Hibiscus trionum: Integrating in vitro and in silico perspectives. Kamel EM(1), Alkhayl FFA(2), Alqhtani HA(3), Bin-Jumah M(3), Rudayni HA(4), Lamsabhi AM(5). Author information: (1)Chemistry Department, Faculty of Science, Beni-Suef University, Beni-Suef, 62514, Egypt. Electronic address: emad.abdelhameed@science.bsu.edu.eg. (2)Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, 51452, Buraydah, Saudi Arabia. (3)Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, P.O. BOX 84428, Riyadh, 11671, Saudi Arabia. (4)Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University, Riyadh, 11623, Saudi Arabia. (5)Departamento de Química, Módulo 13, Universidad Autónoma de Madrid, Campus de Excelencia UAM-CSIC Cantoblanco, 28049, Madrid, Spain; Institute for Advanced Research in Chemical Sciences (IAdChem), Universidad Autónoma de Madrid, 28049, Madrid, Spain. β-Glucuronidase, a crucial enzyme in drug metabolism and detoxification, represents a promising target for therapeutic intervention due to its potential to modulate drug pharmacokinetics and enhance therapeutic efficacy. Herein, we assessed the inhibitory potential of phytochemicals from Hibiscus trionum against β-glucuronidase. Grossamide and grossamide K emerged as the most potent β-glucuronidase inhibitors with IC50 values of 0.73 ± 0.03 and 1.24 ± 0.03 μM, respectively. The investigated alkaloids effectively inhibited β-glucuronidase-catalyzed PNPG hydrolysis through a noncompetitive inhibition mode, whereas steppogenin displayed a mixed inhibition mechanism. Molecular docking analyses highlighted grossamide and grossamide K as inhibitors with the lowest binding free energy, all compounds successfully docked into the same main binding site occupied by the reference drug Epigallocatechin gallate (EGCG). We explored the interaction dynamics of isolated compounds with β-glucuronidase through a 200 ns molecular dynamics (MD) simulation. Analysis of various MD parameters revealed that grossamide and grossamide K maintained stable trajectories and demonstrated significant energy stabilization upon binding to β-glucuronidase. Additionally, these compounds exhibited the lowest average interaction energies with the target enzyme. The MM/PBSA calculations further supported these findings, showing the lowest binding free energies for grossamide and grossamide K. These computational results are consistent with experimental data, suggesting that grossamide and grossamide K could be potent inhibitors of β-glucuronidase. Copyright © 2024 Elsevier Ltd. All rights reserved. DOI: 10.1016/j.compbiomed.2024.108969 PMID: 39089106 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. 2. Int Immunopharmacol. 2022 Nov;112:109190. doi: 10.1016/j.intimp.2022.109190. Epub 2022 Sep 15. Grossamide attenuates inflammation by balancing macrophage polarization through metabolic reprogramming of macrophages in mice. Zhao W(1), Xu D(2), Hong W(1), Zhang L(1), Wu Q(1), Gao M(1), Wang J(3). Author information: (1)Center for Molecular Metabolism, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing, People's Republic of China. (2)Center for Molecular Metabolism, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing, People's Republic of China. Electronic address: ncuskxudi@163.com. (3)Center for Molecular Metabolism, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing, People's Republic of China. Electronic address: wang.junsong@gmail.com. Macrophages exhibited different phenotypes in response to environmental cues. To meet the needs of rapid response to stimuli, M1-activated macrophages preferred glycolysis to oxidative phosphorylation (OXPHOS) in mitochondria to quickly produce energy and obtain ample raw materials to support cell activation at the same time. Activated macrophages produced free radicals and cytokines to eradicate pathogens but also induced oxidative damage and enhanced inflammation. Grossamide (GSE), a lignanamide from Polygonum multiflorum Thunb., exhibited notable anti-inflammatory effects. In this study, the potential of GSE on macrophage polarization was explored. GSE significantly down-regulated the levels of M1 macrophage biomarkers (Cd32a, Cd80 and Cd86) while increased the levels of M2 indicators (Cd163, Mrc1 and Socs1), showing its potential to inhibit LPS-induced M1 polarization of macrophages. This ability has close a link to its effect on metabolic reprogramming of macrophage. GSE shunted nitric oxide (NO) production from arginine by up-regulation of arginase and down-regulation of inducible nitric oxide synthase, thus attenuated the inhibition of NO on OXPHOS. LPS created three breakpoints in the tricarboxylic acid cycle (TCA) cycle of macrophage as evidenced by down-regulated isocitrate dehydrogenase, accumulation of succinate and the inhibited SDH activity, significantly decreased level of oxoglutarate dehydrogenase expression and its substrate α-ketoglutarate. Thus GSE reduced oxidative stress and amended fragmented TCA cycle. As a result, GSE maintained redox (NAD+/NADH) and energy (ATP/ADP) state, reduced extracellular acidification rate and enhanced the oxygen consumption rate. In addition, GSE decreased the release of inflammatory cytokines by inhibiting the activation of the LPS/TLR4/NF-κB pathway. These findings highlighted the central role of immunometabolism of macrophages in its functional plasticity, which invited future study of mode of action of anti-inflammatory drugs from viewpoint of metabolic reprogramming. Copyright © 2022 Elsevier B.V. All rights reserved. DOI: 10.1016/j.intimp.2022.109190 PMID: 36116152 [Indexed for MEDLINE] Conflict of interest statement: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. 3. Nat Prod Res. 2023 Oct-Nov;37(19):3357-3362. doi: 10.1080/14786419.2022.2072841. Epub 2022 May 19. Characterization of alkaloid profile of Hyoscyamus reticulatus L. and Atropa belladonna subsp. caucasica (Kreyer) Avet by LC-MS and NMR. Valiyeva A(1)(2), Felegyi-Tóth CA(2), Várnai B(2), Garaev E(1), Béni S(2), Kursinszki L(2). Author information: (1)Department of General and Toxicological Chemistry, Azerbaijan Medical University, Baku, Azerbaijan. (2)Department of Pharmacognosy, Semmelweis University, Budapest, Hungary. The alkaloid profile of Hyoscyamus reticulatus L. and Atropa belladonna subsp. caucasica (Kreyer) Avet have not been characterized yet. UHPLC-PDA-Q-TOF-MS/MS and LC-DAD-QqQ-MS/MS methods were used herein to characterize the metabolite profiles of these plants. Flash chromatography in combination with preparative- and semi preparative HPLC were utilized for the isolation of the compounds of interest. The structure of the isolated compounds was proposed based on their MS/MS fragmentation and NMR characteristics. As a total of 19 tropane derivatives, two tyramine derivatives (N-cis- and N-trans- feruloyl tyramine), a lignanamide (grossamide), an alkylamide (pellitorine) were identified in the root and herb extracts of H. reticulatus. Moreover, rutin and caffeoylquinic acids were found in the leaves and fruits, while kaempferol-3-O-glucoside-7-O-rhamnoside and quercetin-3-O-glucoside-rhamnoside-rhamnoside were exclusively characteristic for the leaves of H. reticulatus. The root and herb extracts of A. caucasica contained 16 tropane alkaloid derivatives along with methyl tropate and two tyramine derivatives. DOI: 10.1080/14786419.2022.2072841 PMID: 35587174 4. Fitoterapia. 2020 Oct;146:104717. doi: 10.1016/j.fitote.2020.104717. Epub 2020 Aug 31. Anti-inflammatory steroidal sapogenins and a conjugated chalcone-stilbene from Dracaena usambarensis Engl. Nchiozem-Ngnitedem VA(1), Omosa LK(2), Bedane KG(3), Derese S(4), Brieger L(5), Strohmann C(5), Spiteller M(6). Author information: (1)Department of Chemistry, University of Nairobi, P. O. Box 30197-00100, Nairobi, Kenya; Institute of Environmental Research (INFU), Department of Chemistry and Chemical Biology, Environmental Chemistry and Analytical Chemistry, TU Dortmund, Otto-Hahn-Straße 6, 44221 Dortmund, Germany. (2)Department of Chemistry, University of Nairobi, P. O. Box 30197-00100, Nairobi, Kenya. Electronic address: lkerubo@uonbi.ac.ke. (3)Department of Chemistry, Addis Ababa University, P.O. Box 33658, Addis Ababa, Ethiopia. (4)Department of Chemistry, University of Nairobi, P. O. Box 30197-00100, Nairobi, Kenya. (5)Inorganic Chemistry, Department of Chemistry and Chemical Biology, TU Dortmund, Otto-Hahn-Straße 6, 44227 Dortmund, Germany. (6)Institute of Environmental Research (INFU), Department of Chemistry and Chemical Biology, Environmental Chemistry and Analytical Chemistry, TU Dortmund, Otto-Hahn-Straße 6, 44221 Dortmund, Germany. Four new steroidal sapogenins, dracaenogenins CF (1-4), a new conjugated chalcone-stilbene, 3''-methoxycochinchinenene H (5) together with eight known compounds namely, (25S)-spirosta-1,4-dien-3-one (6), trans-resveratrol (7), 4,4'-dihydroxy-3'-methoxychalcone (8), N-trans-coumaroyltyramine (9), N-trans-p-coumaroyloctopamine (10), N-trans-feruloyloctopamine (11), 7-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-N2,N3-bis(4-hydroxyphenethyl)-6-methoxy-1,2-dihydronaphthalene-2,3-dicarboxamide (12) and grossamide (13) were isolated from the stems of Dracaena usambarensis Engl. from Kenya. It is important to note that compounds 12 and 13 are being reported from this genus for the first time. Structural elucidation of the isolated compounds was done using spectroscopic (NMR, UV, IR, optical rotation) and spectrometric (HRESIMS) techniques. The absolute and relative configurations of the isolated compounds were determined by employing single crystal X-ray crystallography analysis, NOESY correlations and coupling constants. The anti-inflammatory potencies of the isolated compounds were evaluated by measuring the levels of four cytokines (IL-1β, IL-2, GM-CSF and TNF-α) in the supernatant media of human peripheral blood mononuclear cells (PBMCs) stimulated by lipopolysaccharide (LPS). At the tested concentration of 100 μM, the new conjugated chalcone-stilbene 5, the dihydrochalcone, 8 and the lignanamide, 13 were substantially more potent than the standard drug, ibuprofen, inhibiting the release of all the cytokines, IL-1β, IL-2, GM-CSF and TNF-α from 0.06-58.04% compared to LPS control. These compounds should therefore be considered for development into anti-inflammatory drug candidates. Compound 7 significantly decreased the release of GM-CSF (6.11% of LPS control) and TNF-α (18.35% of LPS control). The cytokine TNF-α was sensitive to all the tested compounds 1-13. Copyright © 2020 Elsevier B.V. All rights reserved. DOI: 10.1016/j.fitote.2020.104717 PMID: 32877711 [Indexed for MEDLINE] 5. Food Chem. 2020 Aug 1;320:126530. doi: 10.1016/j.foodchem.2020.126530. Epub 2020 Mar 5. Impact of enzymatic hydrolysis on the nutrients, phytochemicals and sensory properties of oil hemp seed cake (Cannabis sativa L. FINOLA variety). Pap N(1), Hamberg L(2), Pihlava JM(3), Hellström J(4), Mattila P(5), Eurola M(6), Pihlanto A(7). Author information: (1)Natural Resources Institute Finland, Production Systems, Myllytie 1, FIN-31600 Jokioinen, Finland. Electronic address: nora.pap@luke.fi. (2)Natural Resources Institute Finland, Bioeconomy and Environment, Latokartanonkaari 9, FIN-00790 Helsinki, Finland. Electronic address: leena.hamberg@luke.fi. (3)Natural Resources Institute Finland, Production Systems, Myllytie 1, FIN-31600 Jokioinen, Finland. Electronic address: juha-matti.pihlava@luke.fi. (4)Natural Resources Institute Finland, Production Systems, Myllytie 1, FIN-31600 Jokioinen, Finland. Electronic address: jarkko.hellstrom@luke.fi. (5)Natural Resources Institute Finland, Production Systems, Itäinen Pitkäkatu 4 A, FIN-20520 Turku, Finland. Electronic address: pirjo.mattila@luke.fi. (6)Natural Resources Institute Finland, Natural Resources, Tietotie 4, FIN-31600 Jokioinen, Finland. Electronic address: merja.eurola@luke.fi. (7)Natural Resources Institute Finland, Production Systems, Myllytie 1, FIN-31600 Jokioinen, Finland. Electronic address: anne.pihlanto@luke.fi. Enzymatic hydrolysis of the oil hemp seed (FINOLA variety) cake and defatted hemp seed cake by SC-CO2 was carried out using Flavorpro 750 MDP and Promod 439 L enzymes, and proximate composition, proanthocyanidins, phytic acid, lignanamides and cannabinoids were determined from the separated phases. CIELAB* color parameters were measured, while trained panelists evaluated taste, color, and smell in 1-9 Hedonic scale. Ten lignanamides, seven cannabisin-type and three grossamide-type, were found, from the cannabinoids, only cannabidiolic acid was detected. Protein, fat, ash, lignanamides and proanthocyanidins remained mostly in the sediments after the hydrolysis process in the Flavorpro treated samples, while dry matter, fat and ash was released mostly to liquids in Promod treated samples. The defatting process by SC-CO2 resulted in a higher lightness and the enzymatic processing did not have effect on the color attributes. Sediments from the enzymatic treatment were tastier, with better color and smell than liquids. Copyright © 2020 Elsevier Ltd. All rights reserved. DOI: 10.1016/j.foodchem.2020.126530 PMID: 32222655 [Indexed for MEDLINE] Conflict of interest statement: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.