Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. J Extracell Vesicles. 2023 Oct;12(10):e12363. doi: 10.1002/jev2.12363.

Inhibition of extracellular vesicle-derived miR-146a-5p decreases progression of 
melanoma brain metastasis via Notch pathway dysregulation in astrocytes.

Rigg E(1), Wang J(2)(1)(3), Xue Z(1)(3), Lunavat TR(1)(4), Liu G(1)(3), Hoang 
T(2), Parajuli H(2), Han M(2)(1)(3), Bjerkvig R(2), Nazarov PV(5), Nicot N(6), 
Kreis S(7), Margue C(7), Nomigni MT(7), Utikal J(8)(9)(10), Miletic H(2)(11), 
Sundstrøm T(12)(13), Ystaas LAR(2), Li X(1)(3), Thorsen F(2)(1)(12)(14).

Author information:
(1)Department of Biomedicine, University of Bergen, Bergen, Norway.
(2)Department of Neurosurgery, Qilu Hospital of Shandong University and 
Institute of Brain and Brain-Inspired Science, Cheeloo College of Medicine, 
Shandong University, Jinan, China.
(3)Shandong Key Laboratory of Brain Function Remodeling, Jinan, China.
(4)Department of Neurology, Molecular Neurogenetics Unit-West, Massachusetts 
General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
(5)Bioinformatics Platform and Multiomics Data Science Research Group, 
Department of Cancer Research, Luxembourg Institute of Health, Luxembourg.
(6)LuxGen Genome Center, Luxembourg Institute of Health, Laboratoire National de 
Santé, Dudelange, Luxembourg.
(7)Department of Life Sciences and Medicine, University of Luxembourg, 
Luxembourg.
(8)Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.
(9)Department of Dermatology, Venereology and Allergology, University Medical 
Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany.
(10)DKFZ Hector Cancer Institute at the University Medical Center Mannheim, 
Mannheim, Germany.
(11)Department of Pathology, Haukeland University Hospital, Bergen, Norway.
(12)Department of Neurosurgery, Haukeland University Hospital, Bergen, Norway.
(13)Department of Clinical Medicine, University of Bergen, Bergen, Norway.
(14)Molecular Imaging Center, Department of Biomedicine, University of Bergen, 
Bergen, Norway.

Melanoma has the highest propensity of all cancers to metastasize to the brain 
with a large percentage of late-stage patients developing metastases in the 
central nervous system (CNS). It is well known that metastasis establishment, 
cell survival, and progression are affected by tumour-host cell interactions 
where changes in the host cellular compartments likely play an important role. 
In this context, miRNAs transferred by tumour derived extracellular vesicles 
(EVs) have previously been shown to create a favourable tumour microenvironment. 
Here, we show that miR-146a-5p is highly expressed in human melanoma brain 
metastasis (MBM) EVs, both in MBM cell lines as well as in biopsies, thereby 
modulating the brain metastatic niche. Mechanistically, miR-146a-5p was 
transferred to astrocytes via EV delivery and inhibited NUMB in the Notch 
signalling pathway. This resulted in activation of tumour-promoting cytokines 
(IL-6, IL-8, MCP-1 and CXCL1). Brain metastases were significantly reduced 
following miR-146a-5p knockdown. Corroborating these findings, miR-146a-5p 
inhibition led to a reduction of IL-6, IL-8, MCP-1 and CXCL1 in astrocytes. 
Following molecular docking analysis, deserpidine was identified as a functional 
miR-146a-5p inhibitor, both in vitro and in vivo. Our results highlight the 
pro-metastatic function of miR-146a-5p in EVs and identifies deserpidine for 
targeted adjuvant treatment.

© 2023 The Authors. Journal of Extracellular Vesicles published by Wiley 
Periodicals LLC on behalf of International Society for Extracellular Vesicles.

DOI: 10.1002/jev2.12363
PMCID: PMC10533779
PMID: 37759347 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare that there are no conflicts 
of interest.


2. J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Oct 1;877(27):3221-5. doi:
 10.1016/j.jchromb.2009.06.005. Epub 2009 Jun 10.

Liquid chromatography/tandem mass spectrometry method for the quantification of 
deserpidine in human plasma: Application to a pharmacokinetic study.

Zhang H(1), Zhong D, Zhang Z, Dai X, Chen X.

Author information:
(1)Center for Drug Metabolism and Pharmacokinetics Research, Shanghai Institute 
of Materia Medica, Chinese Academy of Sciences, 646 Songtao Road, Shanghai 
201203, PR China.

A sensitive and rapid liquid chromatography/tandem mass spectrometric (LC/MS/MS) 
method was developed and validated for the determination of deserpidine in human 
plasma. The plasma samples were prepared using liquid-liquid extraction (LLE) 
with ethyl ether-dichloromethane (3:2, v/v). Chromatographic separation was 
accomplished on an Ultimate XB-C18 column. The mobile phase consisted of 
methanol-5mM ammonium acetate-formic acid (72:28:0.036, v/v/v). Detection of 
deserpidine and the internal standard tropisetron was achieved by tandem mass 
spectrometry with an electrospray ionization interface in positive ion mode. The 
lower limit of quantification was 4.0pg/ml. The linear range of the method was 
from 4.0 to 2000pg/ml. The intra- and inter-day precisions were lower than 14.7% 
in terms of relative standard deviation (RSD), and the accuracy was within 
+/-8.7% in terms of relative error (RE). This validated method was successfully 
applied for the evaluation of pharmacokinetics of deserpidine after a single 
oral administration dose of 0.25mg deserpidine to 22 healthy volunteers.

DOI: 10.1016/j.jchromb.2009.06.005
PMID: 19620026 [Indexed for MEDLINE]


3. J Nat Prod. 2005 Nov;68(11):1629-31. doi: 10.1021/np050179x.

Synthesis of deserpidine from reserpine.

Varchi G(1), Battaglia A, Samorì C, Baldelli E, Danieli B, Fontana G, Guerrini 
A, Bombardelli E.

Author information:
(1)Istituto CNR per la Sintesi Organica e Fotoreattività ISOF, Area della 
Ricerca di Bologna, Via P., Gobetti 101, 40129 Bologna, Italy. 
G.Varchi@isof.cnr.it

The Rauwolfia alkaloids reserpine (1) and deserpidine (2), two alkaloids from 
Rauwolfia species, have been widely used for their antihypertensive action. 
Deserpidine (2) is a compound with limited availability from natural sources, 
and its synthesis from 1 in six steps (41% overall yield) is reported here.

DOI: 10.1021/np050179x
PMID: 16309312 [Indexed for MEDLINE]


4. J Pharm Sci. 1979 Nov;68(11):1433-5. doi: 10.1002/jps.2600681126.

Antibody specificity studies for reserpine, its metabolites, and synthetic 
reserpine congeners: radioimmunoassay.

Loeffler LJ, Schran HF.

Progress in the development of radioimmunoassay techniques for reserpine and 
related compounds is reported. A conjugate of reserpine with human serum albumin 
was prepared, involving linkage at the indole nitrogen atom of reserpine. 
Injection of the purified conjugate into sheep elicited antibodies of high 
titer, which bound reserpine selectively. Tritiated reserpine was employed in 
the procedure, and dextran-coated charcoal was utilized to separate free and 
bound forms of the drug. Antibodies exhibited a selectivity for reserpine and 
did not cross-react significantly with major human metabolites. Cross-reactivity 
of antibodies with other reserpine derivatives (i.e., syrosingopine, 
deserpidine, and rescinnamine) also was investigated. A stable tritiated or 
radioiodinated reserpine derivative of high specific activity is being sought to 
improve assay sensitivity for use in bioequivalence and bioavailability studies. 
In the absence of any extraction or concentration procedures, at least a 10-fold 
increase in immunoassay sensitivity would be required to follow reserpine levels 
in humans given normal doses of the drug. The methods show promise also for the 
assay of reserpine derivatives such as deserpidine, which exhibits 
cross-reactivity to reserpine antibodies.

DOI: 10.1002/jps.2600681126
PMID: 574544 [Indexed for MEDLINE]


5. Am J Hosp Pharm. 1979 Jul;36(7):923-7.

Drug interaction exposures in an ambulatory Medicaid population.

Jinks MJ, Hansten PD, Hirschman JL.

The incidence of selected potential drug-drug interactions (DDIs) in a 
population of ambulatory patients was studied using data extracted from the 
automated records of Medicaid drug benefit programs. The system to extract DDI 
data was devised to assist peer review committees in drug use review. The system 
yields two types of reports: (1) individual patient profiles and (2) summary 
reports of all potential DDIs detected within the Medicaid population being 
reviewed. Potential drug interactions are classified as major, moderate or minor 
and by route of drug administration. Three months of drug claims from two 
Medicaid programs were reviewed for potential DDIs involving digitalis 
preparations, antihypertensive agents (rescinnamine, deserpidine, guanethidine, 
methyldopa, reserpine, Rauwolfia serpentina extracts) and coumarin 
anticoagulants. The overall incidence of potential DDI exposures for the three 
classes was 2.7%, based on drug profiles of 333,641 patients. DDI exposure 
monitoring can be a useful tool in acquiring further knowledge of DDIs occurring 
in ambulatory patients.

PMID: 382843 [Indexed for MEDLINE]