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. Biol Pharm Bull. 2018;41(8):1219-1227. doi: 10.1248/bpb.b18-00037. O-Methylbulbocapnine and Dicentrine Suppress LPS-Induced Inflammatory Response by Blocking NF-κB and AP-1 Activation through Inhibiting MAPKs and Akt Signaling in RAW264.7 Macrophages. Yodkeeree S(1)(2), Ooppachai C(1)(2), Pompimon W(3), Limtrakul Dejkriengkraikul P(1)(2). Author information: (1)Department of Biochemistry, Faculty of Medicine, Chiang Mai University. (2)Center for Research and Development of Natural Products for Health, Chiang Mai University. (3)Laboratory of Natural Products, Department of Chemistry, Faculty of Science, Lampang Rajabhat University. The natural aporphine alkaloids including crebanine (CN), O-methylbulbocapnine (OMP), and dicentrine (DC), and protoberberine alkaloids, tetrahydropalmatine (THP) and N-methyl tetrahydropalmatine (NTHP), have been found in Stephania venosa. Previous reports demonstrated CN and THP exhibited anti-inflammatory properties. In this study, we investigated anti-inflammatory effect of CN analogs including OMP, DC, THP, and NTHP in RAW264.7 macrophages. The pre-treatment of macrophages with CN, OMP and DC suppressed lipopolysaccharide (LPS)-induced pro-inflammatory cytokines and mediators including interleukin-6 (IL-6), tumor necrosis factor alpha, prostaglandin E2 and nitric oxide, in which the rank-order of inhibitory potency was DC>CN≥OMP. Whereas, high dose THP (30-40 µg/mL) reduced LPS-induced IL-6 production in RAW264.7 cells but NTHP did not effect. Moreover, CN, OMP and DC inhibited the LPS-induced expression of inducible nitric oxide synthase and cyclooxygenase-2. OMP and DC inhibited LPS-induced nuclear factor kappa B (NF-κB) activation by suppressing the phosphorylation of NF-κB at Ser536, but not the nucleus translocation and inhibitor of kappaB (IκB)-α degradation. In addition, OMP and DC also reduced the phosphorylation and nucleus translocation of activator protein-1 (AP-1). Furthermore, OMP and DC suppressed the LPS-activated myeloid differentiation factor 88 (MyD88), Akt and mitogen-activated protein kinases (MAPKs) signaling pathway, which were the upstream signaling regulators of AP-1 and NF-κB. Collectively, OMP and DC have an anti-inflammatory effect on RAW264.7 macrophages by the suppression of pro-inflammatory cytokines and mediators. The inhibitory property of OMP and DC is mediated by blockage the activation of MyD88, MAPKs, Akt, NF-κB and AP-1 signaling molecules. DOI: 10.1248/bpb.b18-00037 PMID: 30068871 [Indexed for MEDLINE] 2. Chem Pharm Bull (Tokyo). 2018;66(2):162-169. doi: 10.1248/cpb.c17-00687. Alkaloids from Stephania venosa as Chemo-Sensitizers in SKOV3 Ovarian Cancer Cells via Akt/NF-κB Signaling. Mon MT(1)(2), Yodkeeree S(1)(3), Punfa W(1)(3), Pompimon W(4), Limtrakul P(1)(3). Author information: (1)Department of Biochemistry, Faculty of Medicine, Chiang Mai University. (2)Department of Biochemistry, University of Medicine-2. (3)Center for Research and Development of Natural Products for Health, Chiang Mai University. (4)Laboratory of Natural Products, Department of Chemistry, Faculty of Science, Lampang Rajabhat University. Crebanine (CN), tetrahydropalmatine (THP), O-methylbulbocapnine (OMBC) and N-methyl tetrahydropalmatine (NMTHP) are isoquinoline derived natural alkaloids isolated from tubers of Stephania venosa. We investigated chemo-sensitizing effects of these alkaloids in ovarian cancer cells and evaluated underlying molecular mechanisms involved in chemo-sensitivity. Detection of cell apoptosis was evaluated by using flow cytometry. Cell viability was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Chou-Talalay median effect principle was used to evaluate potential drug interactions. Protein analyses were performed on ovarian carcinoma cells using Western blotting upon treatment with anticancer drug and alkaloids. Aporphine alkaloids, such as CN and OMBC, enhanced cisplatin sensitivity in intrinsic cisplatin resistant SKOV3 cells, but not in cisplatin sensitive A2780 cells. Protoberberine alkaloids, such as THP and NMTHP, had no synergistic effect on cisplatin sensitivity in either cell line. Chemo-sensitizing effects of CN and OMBC in SKOV3 cells were mediated via activating apoptosis-induced cell death through caspase-3, -8 and cleaved poly ADP-ribose polymerase (PARP) and via inhibiting anti-apopotic and survival protein expression, such as Bcl-xL, Baculoviral IAP repeat-containing protein 3 (cIAP-2), survivin and interleukin (IL) -6. Cisplatin stimulated protein kinase B (Akt) and nuclear factor-kappaB (NF-κB) signaling pathways, but not mitogen-activated protein kinase (MAPK), activator protein 1 (AP-1) and signal transducer and activator of transcription 3 (STAT3) in SKOV3 cells. Akt/NF-κB signaling was blocked by CN and OMBC leading to increased sensitization to cisplatin. These findings demonstrate that CN and OMBC sensitizes SKOV3 cells to cisplatin via inhibition of Akt/NF-κB signaling and the down regulation of NF-κB mediated gene products. Our results suggest that alkaloids obtained from S. venosa could be used as chemo-sensitizers in ovarian cancer to sensitize and minimize the dose related toxicity of platinum-based chemotherapeutic drugs. DOI: 10.1248/cpb.c17-00687 PMID: 29386467 [Indexed for MEDLINE] 3. Phytother Res. 2017 Sep;31(9):1357-1368. doi: 10.1002/ptr.5861. Epub 2017 Jul 13. Stephanine from Stephania venosa (Blume) Spreng Showed Effective Antiplasmodial and Anticancer Activities, the Latter by Inducing Apoptosis through the Reverse of Mitotic Exit. Le PM(1), Srivastava V(2), Nguyen TT(3), Pradines B(4)(5)(6), Madamet M(4)(5)(6), Mosnier J(4)(5)(6), Trinh TT(3), Lee H(2). Author information: (1)Measurement Science and Standards, National Research Council Canada, 1200 Montreal Road, Ottawa, ON, K1A 0R6, Canada. (2)Health Science North Research Institute, 41 Ramsey Lake Road, Sudbury, ON, P3E 5J1, Canada. (3)Institute of Chemistry and Graduate University of Science and Technology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet Road, Hanoi, Vietnam. (4)Unité Parasitologie et Entomologie, Département des Maladies Infectieuses, Institut de Recherche Biomédicale des Armées, Marseille, France. (5)Aix Marseille Université, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, CNRS 7278, IRD 198, Inserm 1095, Institut hospitalo-universitaire (IHU) Méditerranée Infection, Marseille, France. (6)Centre National de Référence du Paludisme, Marseille, France. Extracts from the tubers of Stephania venosa (Blum) Spreng growing in Vietnam significantly inhibited cell proliferation against a number of cancer cells including HeLa, MDA-MB231 and MCF-7 cells. A bioassay-guided fractionation led to the isolation of four aporphine and one tetrahydroprotoberberine alkaloids: dehydrocrebanine 1, tetrahydropalmatine 2, stephanine 3, crebanine 4 and O-methylbulbocapnine 5. The characterization of these compounds was based on MS, NMR and published data. A study by structure-bioactivity relationship on these isolates showed that stephanine is the most active compound. Cell biological studies showed that stephanine induces the reverse of mitotic exit, eventually leading to cell death by apoptosis. This data suggests that stephanine has a unique mode of cell-killing activity against cancer cells, which is seldom observed with known synthetic compounds. In addition to its anticancer property, our data from an in vitro study showed that S. venosa also possesses effective antiplasmodial activity and stephanine was also the most interesting compound but is the most cytotoxic with the lowest selectivity index. Copyright © 2017 Her Majesty the Queen in Right of Canada Phytotherapy Research StartCopTextCopyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 Her Majesty the Queen in Right of Canada Phytotherapy Research Copyright © 2017 John Wiley & Sons, Ltd. DOI: 10.1002/ptr.5861 PMID: 28703314 [Indexed for MEDLINE] 4. Nat Prod Res. 2014;28(15):1159-64. doi: 10.1080/14786419.2014.921166. Epub 2014 Jun 4. A new alkaloid from the fruit of Nandina domestica Thunb. Peng CY(1), Liu JQ, Zhang R, Shu JC. Author information: (1)a Key Laboratory of Modern Preparation of Traditional Chinese Medicines, Ministry of Education, Jiangxi University of Traditional Chinese Medicine , Nanchang 330004 , P.R. China. A new steroidal alkaloid, (20S,22R,24R)-24-ethyl-3-oxocholest-4-en-22-amino, named as nandsterine (1), together with 10 known alkaloids, palmatine (2), O-methylbulbocapnine (3), nantenine (4), dehydronantenine (5), glaucine (6), didehydroglaucine (7), dehydrocorydaline (8), jatrorrhizine (9), magnoflorine (10) and berberine (11), was isolated from the fruit of Nandina domestica Thunb. Their structures were elucidated by using spectroscopic methods as well as by comparing with the published data. Compound 1 was a new class of steroidal alkaloid isolated from the family Berberidaceae, meanwhile compounds 2, 3, 6-8 and 10 were obtained from N. domestica for the first time. Compound 1 exhibited cytotoxicity against HL-60 cells (human leukaemia) with IC50 values of 52.1 μM. DOI: 10.1080/14786419.2014.921166 PMID: 24897106 [Indexed for MEDLINE] 5. Chem Pharm Bull (Tokyo). 2013;61(11):1156-65. doi: 10.1248/cpb.c13-00584. Epub 2013 Aug 28. Anti-invasion effect of crebanine and O-methylbulbocapnine from Stephania venosa via down-regulated matrix metalloproteinases and urokinase plasminogen activator. Yodkeeree S(1), Wongsirisin P, Pompimon W, Limtrakul P. Author information: (1)Department of Biochemistry, Faculty of Medicine, Chiang Mai University. The alkaloids isolated from Stephania venosa (S. venosa) have been shown to inhibit the proliferation and to induce the apoptosis of cancer cells. However, the anti-metastatic effect of the alkaloids on cancer cell invasion is unknown. In this study, we investigated the anti-invasive properties of four alkaloids from S. venosa, crebanine (CN), O-methylbulbocapnine (OMBC), tetrahydropalmatine (THP), and N-methyltetrahydropalmatine (NMTHP), in HT1080 human fibrosacroma cells. Treatment of the cells with 15 µg/mL of CN and OMBC reduced the chemo-invasion of HT1080 cells to 45 and 50%, respectively, whereas THP and NMTHP had a negative effect. On the other hand, CN and OMBC had no effect on cell migration. Matrix metalloproteinases (MMPs) and urokinase plasminogen activator (uPA) are the extracellular matrix (ECM) degradation enzymes that play an important role in cancer cell metastasis. Results from zymography and western blot analysis showed that CN and OMBC comparatively reduced MMP-2, MMP-9, MT1-MMP and uPA expression in a dose-dependent manner. However, CN and OMBC had no effect on the activity of collagenase, MMP-2 and MMP-9. We also found that CN and OMBC reduced the nuclear translocation and DNA binding activity of nuclear factor kappa B (NF-κB), which is the expressed mediator of ECM degradation enzymes. These findings demonstrated that CN and OMBC mediated HT1080 cell invasion by the reduction of MMP-2, MMP-9, uPA and MT1-MMP expression, possibly by targeting of NF-κB signaling pathway in the HT1080 cells. DOI: 10.1248/cpb.c13-00584 PMID: 23985774 [Indexed for MEDLINE]