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. Cells. 2024 Apr 30;13(9):772. doi: 10.3390/cells13090772. Globospiramine from Voacanga globosa Exerts Robust Cytotoxic and Antiproliferative Activities on Cancer Cells by Inducing Caspase-Dependent Apoptosis in A549 Cells and Inhibiting MAPK14 (p38α): In Vitro and Computational Investigations. Manzano JAH(1)(2)(3), Abellanosa EA(3), Aguilar JP(2), Brogi S(4), Yen CH(5), Macabeo APG(3)(6), Austriaco N(2)(7). Author information: (1)The Graduate School, University of Santo Tomas, España Blvd., Manila 1015, Philippines. (2)UST Laboratories for Vaccine Science, Molecular Biology and Biotechnology, Research Center for the Natural and Applied Sciences, University of Santo Tomas, España Blvd., Manila 1015, Philippines. (3)Laboratory for Organic Reactivity, Discovery, and Synthesis (LORDS), Research Center for the Natural and Applied Sciences, University of Santo Tomas, España Blvd., Manila 1015, Philippines. (4)Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy. (5)Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. (6)Department of Chemistry, College of Science, University of Santo Tomas, España Blvd., Manila 1015, Philippines. (7)Department of Biological Sciences, College of Science, University of Santo Tomas, España Blvd., Manila 1015, Philippines. Bisindole alkaloids are a source of inspiration for the design and discovery of new-generation anticancer agents. In this study, we investigated the cytotoxic and antiproliferative activities of three spirobisindole alkaloids from the traditional anticancer Philippine medicinal plant Voacanga globosa, along with their mechanisms of action. Thus, the alkaloids globospiramine (1), deoxyvobtusine (2), and vobtusine lactone (3) showed in vitro cytotoxicity and antiproliferative activities against the tested cell lines (L929, KB3.1, A431, MCF-7, A549, PC-3, and SKOV-3) using MTT and CellTiter-Blue assays. Globospiramine (1) was also screened against a panel of breast cancer cell lines using the sulforhodamine B (SRB) assay and showed moderate cytotoxicity. It also promoted the activation of apoptotic effector caspases 3 and 7 using Caspase-Glo 3/7 and CellEvent-3/7 apoptosis assays. Increased expressions of cleaved caspase 3 and PARP in A549 cells treated with 1 were also observed. Apoptotic activity was also confirmed when globospiramine (1) failed to promote the rapid loss of membrane integrity according to the HeLa cell membrane permeability assay. Network pharmacology analysis, molecular docking, and molecular dynamics simulations identified MAPK14 (p38α), a pharmacological target leading to cancer cell apoptosis, as a putative target. Low toxicity risks and favorable drug-likeness were also predicted for 1. Overall, our study demonstrated the anticancer potentials and apoptotic mechanisms of globospiramine (1), validating the traditional medicinal use of Voacanga globosa. DOI: 10.3390/cells13090772 PMCID: PMC11082999 PMID: 38727308 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflicts of interest. 2. Molecules. 2022 Feb 5;27(3):1078. doi: 10.3390/molecules27031078. Voacanga globosa Spirobisindole Alkaloids Exert Antiviral Activity in HIV Latently Infected Cell Lines by Targeting the NF-kB Cascade: In Vitro and In Silico Investigations. de Jesus MSM(1)(2), Macabeo APG(3), Ramos JDA(1)(2)(4), de Leon VNO(2)(3), Asamitsu K(5), Okamoto T(5). Author information: (1)The Graduate School, University of Santo Tomas, España Blvd., Manila 1015, Philippines. (2)Department of Biological Sciences, College of Science, University of Santo Tomas, España Blvd., Manila 1015, Philippines. (3)Laboratory for Organic Reactivity, Discovery and Synthesis (LORDS), Research Center for Natural and Applied Sciences, University of Santo Tomas, España Blvd., Manila 1015, Philippines. (4)Molecular Diagnostics and Therapeutics Laboratory, Research Center for Natural and Applied Sciences, University of Santo Tomas, España Blvd., Manila 1015, Philippines. (5)Department of Molecular and Cellular Biology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 4678601, Japan. Erratum in Molecules. 2024 Jan 29;29(3):626. doi: 10.3390/molecules29030626. Since the efficiency in the transcription of the HIV genome contributes to the success of viral replication and infectivity, we investigated the downregulating effects of the spirobisindole alkaloids globospiramine (1), deoxyvobtusine (2), and vobtusine lactone (3) from the endemic Philippine medicinal plant, Voacanga globosa, during HIV gene transcription. Alkaloids 1-3 were explored for their inhibitory activity on TNF-α-induced viral replication in two latently HIV-infected cell lines, OM10.1 and J-Lat. The induction of HIV replication from OM10.1 and J-Lat cells elicited by TNF-α was blocked by globospiramine (1) within noncytotoxic concentrations. Furthermore, globospiramine (1) was found to target the NF-ĸB activation cascade in a dose-dependent manner when the transcriptional step at which inhibitory activity is exerted was examined in TNF-α-induced 293 human cells using transient reporter (luciferase) gene expression systems (HIV LTR-luc, ĸB-luc, and mutant ĸB-luc). Interrogation through molecular docking against the NF-ĸB p50/p65 heterodimer and target sites of the subunits comprising the IKK complex revealed high binding affinities of globospiramine (1) against the S281 pocket of the p65 subunit (BE = -9.2 kcal/mol) and the IKKα activation loop (BE = -9.1 kcal/mol). These findings suggest globospiramine (1) as a molecular inspiration to discover new alkaloid-based anti-HIV derivatives. DOI: 10.3390/molecules27031078 PMCID: PMC8840767 PMID: 35164343 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of the data; in the writing of the manuscript, or in the decision to publish the results. 3. J Nat Med. 2021 Mar;75(2):408-414. doi: 10.1007/s11418-020-01475-w. Epub 2021 Jan 19. Bisindole alkaloids from Voacanga grandifolia leaves. Nugroho AE(1), Ono Y(1), Jin E(1), Hirasawa Y(1), Kaneda T(1), Rahman A(1), Kusumawati I(2), Tougan T(3), Horii T(4), Zaini NC(2), Morita H(5). Author information: (1)Faculty of Pharmaceutical Sciences, Hoshi University, Ebara 2-4-41 Shinagawa-ku, Tokyo, 142-8501, Japan. (2)Faculty of Pharmacy, Airlangga University, Jalan Dharmawangsa Dalam, Surabaya, 60286, Indonesia. (3)Research Center for Infectious Disease Control, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka, 565-0871, Japan. (4)Department of Molecular Protozoology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka, 565-0871, Japan. (5)Faculty of Pharmaceutical Sciences, Hoshi University, Ebara 2-4-41 Shinagawa-ku, Tokyo, 142-8501, Japan. moritah@hoshi.ac.jp. Two new bisindole alkaloids, 12'-O-demethyl-vobtusine-5-lactam and isovobtusine-N-oxide (1 and 2), were isolated from the leaves of Voacanga grandifolia, together with two known bisindole alkaloids. Their structures were elucidated on the basis of 1D and 2D NMR data. 1 and 2 showed potent antimalarial activity against Plasmodium falciparum 3D7 and very low cytotoxic activity against a human cell line, HepG2 cells. DOI: 10.1007/s11418-020-01475-w PMID: 33462757 [Indexed for MEDLINE] 4. Zhong Yao Cai. 2012 Feb;35(2):226-9. [Study on the alkaloids constituents from Voacanga africana]. [Article in Chinese] Mei L(1), Deng Y, Li F, Guo DL, Lu CY. Author information: (1)Pharmaceutical College, Chengdu University of Traditional Chinese Medicine, The Ministry of Education Key Laboratory of Standardization of Chinese Herbal Medicine, State Key Laboratory Breeding Base of Systematic research, Development and Utilization of Chinese Medicine Resources, Chengdu 611137, China. Meilinger2011@hotmail.com OBJECTIVE: To study the alkaloids of Voacanga africana. METHODS: The alkaloids were isolated by normal phase silica gel and Sephadex LH-20 column chromatography. Their structures were elucidated by analysis of spectroscopic data. RESULTS: Eight alkaloids were isolated and their structures were elucidated as voacangine(1), voacangine hydroxyindolenine(2), 19R-epi-voacristine(3), epi-ibogaine(4), vobasine(5), 19-epi-heyneanine(6), vobtusine(7) and voacamine(8). CONCLUSION: Compounds 2-4 and 6 are isolated from this plant for the first time. PMID: 22822667 [Indexed for MEDLINE] 5. Eur J Med Chem. 2011 Jul;46(7):3118-23. doi: 10.1016/j.ejmech.2011.04.025. Epub 2011 Apr 19. Mycobacterium tuberculosis and cholinesterase inhibitors from Voacanga globosa. Macabeo AP(1), Vidar WS, Chen X, Decker M, Heilmann J, Wan B, Franzblau SG, Galvez EV, Aguinaldo MA, Cordell GA. Author information: (1)Phytochemistry Laboratory, Research Center for the Natural Sciences, University of Santo Tomas, Espana St., 1015 Manila, Philippines. allan-patrick.macabeo@chemie.uni-regensburg.de Globospiramine (1), a new spirobisindole alkaloid possessing an Aspidosperma-Aspidosperma skeleton, together with deoxyvobtusine (2), deoxyvobtusine lactone (3), vobtusine lactone (4) and lupeol (5), were isolated and identified from Voacanga globosa through a bioassay-guided purification. The gross structure and absolute stereochemistry of 1 were established by circular dichroism spectroscopy, HR-MS and unambiguous NMR spectroscopic experiments. In addition, a new biogenetic pathway for the formation of the spiro-Aspidosperma-Aspidosperma skeleton is proposed. Alkaloid 1 showed potent antituberculosis activity against Mycobacterium tuberculosis H(37)Rv as evidenced in microplate Alamar blue assay (MIC = 4 μg/mL) and low-oxygen recovery assay (LORA (MIC = 5.2 μg/mL). The bisindole alkaloids also exhibited promising activity against acetylcholinesterase and, especially butyrylcholinesterase, with deoxyvobtusine (2) (IC(50) = 6.2 μM) as the most strongly inhibiting compound. This study extends the variety of alkaloid structural platforms which exhibit antimycobacterial and anticholinesterase activity. Copyright © 2011 Elsevier Masson SAS. All rights reserved. DOI: 10.1016/j.ejmech.2011.04.025 PMID: 21546135 [Indexed for MEDLINE]