Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Mol Neurobiol. 2024 Sep 27. doi: 10.1007/s12035-024-04520-x. Online ahead of 
print.

Allocryptopine Attenuates Inflammatory Responses in Microglial Cells Via 
TLR4-Dependent NF-κB and p38 MAPK Pathways.

Nigdelioglu Dolanbay S(1), Şirin S(2), Aslim B(1).

Author information:
(1)Faculty of Science, Department of Biology, Gazi University, 06500, 
Teknikokullar, Ankara, Turkey.
(2)Faculty of Science, Department of Biology, Gazi University, 06500, 
Teknikokullar, Ankara, Turkey. sdasirin@hotmail.com.

Studies in the existing literature propose that allocryptopine possesses both 
antioxidant and anti-inflammatory properties, showcasing its neuroprotective 
effects by potentially mitigating oxidative stress and inflammation. This study 
aims to investigate the antioxidant and anti-inflammatory effects of 
allocryptopine on various targets and potential mechanisms that have not been 
previously explored in the literature. Initially, we used MTT and LDH methods to 
evaluate the effects of allocryptopine on cell viability in BV-2 cells exposed 
to LPS-induced damage. Subsequently, we evaluated the impact of allocryptopine 
on pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), other inflammatory 
mediators (Cox-2 and iNOS), and p38 MAPK genes and proteins through qRT-PCR and 
Western blot analyses. Also, we evaluated the impact of allocryptopine on NF-κB 
proteins (TLR4, MyD88, IκBα, p-p50, and p-p65) through ELISA assay. Molecular 
docking analyses were performed to investigate the potential binding of 
allocryptopine to target proteins (TLR4, MyD88, IκBα, p50, p65, MKK3, MKK4, 
MKK6, p38, AP-1 (c-Jun and ATF2), IL-1β, IL-6, TNF-α, Cox-2, and iNOS) 
associated with the TLR4, NF-κB, and p38 MAPK pathways. Our results indicate 
that allocryptopine exerts a comprehensive influence on pro-inflammatory 
cytokines and other inflammatory mediators by inhibiting TLR4 signaling and 
modulating the NF-κB and p38 MAPK pathways. The outcomes of our study suggest 
that the antioxidant and anti-inflammatory efficacy of allocryptopine is 
intricately linked to the modulation of key molecular pathways associated with 
oxidative stress and inflammation. These findings highlight the potential of 
allocryptopine as a therapeutic agent for addressing neurodegenerative diseases 
by safeguarding neuronal health.

© 2024. The Author(s), under exclusive licence to Springer Science+Business 
Media, LLC, part of Springer Nature.

DOI: 10.1007/s12035-024-04520-x
PMID: 39331354


2. Pharmaceuticals (Basel). 2024 Aug 14;17(8):1065. doi: 10.3390/ph17081065.

Establishment of Dissolution Test Method for Multi-Components in Traditional 
Chinese Medicine Preparations Based on In Vitro-In Vivo Correlation.

Guo P(1), Wang Q(1), Xiang X(2), Zhang Y(3), Pan Y(1), Zuo Z(3), Wang J(1)(4).

Author information:
(1)Department of Pharmaceutics, School of Pharmacy, Fudan University & Key 
Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai 201203, 
China.
(2)Department of Clinical Pharmacy and Pharmacy Administration, School of 
Pharmacy, Fudan University, Shanghai 201203, China.
(3)School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, 
Shatin, New Territories, Hong Kong SAR, China.
(4)Institute of Integrated Chinese and Western Medicine, Fudan University, 
Shanghai 200040, China.

In this study, a multi-component integrated dissolution evaluation system of 
Yuanhu Zhitong tablets (YZTs) was established based on in vitro and in vivo 
correlation (IVIVC). The dissolution tests of five quality markers (Q-markers), 
including tetrahydropalmatine, α-allocryptopine, protopine, corydaline, and 
byakangelicin, in YZTs were conducted under different dissolution conditions, 
and pharmacokinetic studies were performed in beagle dogs to construct a 
correlation model using numerical deconvolution. The data of the five 
ingredients were integrated in vitro and in vivo according to the 
biopharmaceutical classification system (BCS) to establish an IVIVC integrating 
multiple Q-markers. The dissolution media with the best correlation of 
components were obtained and validated. The results showed that all five 
components were classified as BCS I compounds, and α-allocryptopine, 
byakangelicin, tetrahydropalmatine, and corydaline showed good correlation in 
the paddle method, 75 rpm, with dissolution media of artificial gastric fluid, 
acetate buffer, acetate buffer and 0.1 M HCl, respectively. Protopine showed 
good correlation in the paddle method, 100 rpm, with dissolution media of 0.1 M 
HCl. The integrated BCS I Q-markers showed the best correlation in the medium of 
acetate buffer. The multi-component integrated dissolution evaluation system 
established in this experiment accurately predicted the pharmacokinetic data of 
YZTs by verifying the media, which can be used for the quality control of YZTs. 
The present study provides an effective and promising strategy for the 
dissolution evaluation for traditional Chinese medicine preparations.

DOI: 10.3390/ph17081065
PMCID: PMC11359531
PMID: 39204171

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


3. Comput Biol Chem. 2024 Oct;112:108144. doi:
10.1016/j.compbiolchem.2024.108144.  Epub 2024 Jul 9.

Exploring allocryptopine as a neuroprotective agent against oxidative 
stress-induced neural apoptosis via Akt/GSK-3β/tau pathway modulation.

Aslim B(1), Nigdelioglu Dolanbay S(2), Baran SS(3).

Author information:
(1)Gazi University, Faculty of Science, Department of Biology, Ankara 
06500, Turkey.
(2)Gazi University, Faculty of Science, Department of Biology, Ankara 
06500, Turkey. Electronic address: serapdolanbay@gazi.edu.tr.
(3)Gazi University, Faculty of Science, Department of Biology, Ankara 
06500, Turkey; Gazi University, Graduate School of Natural and Applied Sciences, 
Department of Biology, Ankara 06500, Turkey.

Alzheimer's disease (AD) is characterized by neuronal loss due to 
hyperphosphorylated proteins induced by oxidative stress. AD remains a 
formidable challenge in the medical field, as current treatments focusing on 
single biomarkers have yielded limited success. Hence, there's a burgeoning 
interest in investigating novel compounds that can target mechanisms, offering 
alternative therapeutic approaches. The aim of this study is to investigate the 
effects of allocryptopine, an isoquinoline alkaloid, on mechanisms related to AD 
in order to develop alternative treatment strategies. In this study, the in 
vitro AD cell model was obtained by inducing nerve growth factor 
(NGF)-differentiated PC12 (dPC12) cells to oxidative stress with H2O2, and also 
the effect mechanism of different allocryptopine concentrations on the in vitro 
AD cell model was studied. The treatments' antioxidative effects at the ROS 
level and their regulation of the cell cycle were assessed through flow 
cytometry, while their anti-apoptotic effects were evaluated using both flow 
cytometry and qRT-PCR. Additionally, the phosphorylation levels of Akt, GSK-3β, 
and tau proteins were analyzed via western blot, and the interactions between 
Akt, GSK-3β, CDK5 proteins, and allocryptopine were demonstrated through 
molecular docking. Our study's conclusive results revealed that allocryptopine 
effectively suppressed intracellular ROS levels, while simultaneously enhancing 
the Akt/GSK-3β signaling pathway by increasing p-Akt and p-GSK-3β proteins. This 
mechanism played a critical role in inhibiting neural cell apoptosis and 
preventing tau hyperphosphorylation. Moreover, allocryptopine demonstrated its 
ability to regulate the G1/S cell cycle progression, leading to cell cycle 
arrest in the G1 phase, and facilitating cellular repair mechanisms, potentially 
contributing to the suppression of neural apoptosis. The in silico results of 
allocryptopine were shown to docking with the cyclin-dependent kinase 5 (CDK 5) 
playing a role in tau phosphorylation Akt and GSK-3β from target proteins. 
Therefore, the in silico study results supported the in vitro results. The 
results showed that allocryptopine can protect dPC12 cells from oxidative 
stress-induced apoptosis and hyperphosphorylation of the tau protein by 
regulating the Akt/GSK-3β signaling pathway. Based on these findings, it can be 
suggested that allocryptopine, with its ability to target biomarkers and its 
significant effects on AD-associated mechanisms, holds promise as a potential 
candidate for drug development in the treatment of AD. Further research and 
clinical trials are recommended in the future.

Copyright © 2024 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.compbiolchem.2024.108144
PMID: 39004026 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of Competing Interest The authors 
declare the following financial interests/personal relationships which may be 
considered as potential competing interests: BELMA ASLIM reports financial 
support was provided by Scientific and Technological Research Council of Turkey. 
If there are other authors, they declare that they have no known competing 
financial interests or personal relationships that could have appeared to 
influence the work reported in this paper.


4. Int J Mol Sci. 2024 May 15;25(10):5398. doi: 10.3390/ijms25105398.

Protopine and Allocryptopine Interactions with Plasma Proteins.

Marciniak A(1), Kotynia A(1), Krzyżak E(1), Czyżnikowska Ż(1), Zielińska S(2), 
Kozłowska W(2), Białas M(3), Matkowski A(4), Jezierska-Domaradzka A(2).

Author information:
(1)Department of Basic Chemical Sciences, Wroclaw Medical University, Borowska 
211a, 50-556 Wrocław, Poland.
(2)Division of Pharmaceutical Biotechnology, Department of Pharmaceutical 
Biology and Biotechnology, Wroclaw Medical University, Borowska 211, 50-556 
Wrocław, Poland.
(3)Student Scientific Club, Division of Pharmaceutical Biotechnology, Department 
of Pharmaceutical Biology and Biotechnology, Wroclaw Medical University, 
Borowska 211, 50-556 Wrocław, Poland.
(4)Division of Pharmaceutical Biology and Botany, Department of Pharmaceutical 
Biology and Biotechnology, Wroclaw Medical University, Borowska 211a, 50-556 
Wrocław, Poland.

A comprehensive study of the interactions of human serum albumin (HSA) and 
α-1-acid glycoprotein (AAG) with two isoquinoline alkaloids, i.e., 
allocryptopine (ACP) and protopine (PP), was performed. The UV-Vis spectroscopy, 
molecular docking, competitive binding assays, and circular dichroism (CD) 
spectroscopy were used for the investigations. The results showed that ACP and 
PP form spontaneous and stable complexes with HSA and AAG, with ACP displaying a 
stronger affinity towards both proteins. Molecular docking studies revealed the 
preferential binding of ACP and PP to specific sites within HSA, with site 2 
(IIIA) being identified as the favored location for both alkaloids. This was 
supported by competitive binding assays using markers specific to HSA's drug 
binding sites. Similarly, for AAG, a decrease in fluorescence intensity upon 
addition of the alkaloids to AAG/quinaldine red (QR) complexes indicated the 
replacement of the marker by the alkaloids, with ACP showing a greater extent of 
replacement than PP. CD spectroscopy showed that the proteins' structures 
remained largely unchanged, suggesting that the formation of complexes did not 
significantly perturb the overall spatial configuration of these macromolecules. 
These findings are crucial for advancing the knowledge on the natural 
product-protein interactions and the future design of isoquinoline 
alkaloid-based therapeutics.

DOI: 10.3390/ijms25105398
PMCID: PMC11121924
PMID: 38791436 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare no conflicts of interest.


5. EFSA J. 2024 May 21;22(5):e8793. doi: 10.2903/j.efsa.2024.8793. eCollection
2024  May.

Safety and efficacy of a feed additive consisting of Macleaya cordata (Willd.) 
R. Br. extract and leaves (Sangrovit® Extra) for suckling and weaned piglets and 
other growing Suidae (Phytobiotics Futterzusatzstoffe GmbH).

EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP); 
Bampidis V, Azimonti G, Bastos ML, Christensen H, Durjava M, Dusemund B, Kouba 
M, López-Alonso M, López Puente S, Marcon F, Mayo B, Pechová A, Petkova M, Ramos 
F, Villa RE, Woutersen R, Brantom P, Chesson A, Dierick N, Martelli G, Schlatter 
J, Westendorf J, Casanova JO, Plaza DP, Manini P.

Following a request from the European Commission, EFSA was asked to deliver a 
scientific opinion on the safety and efficacy of Macleaya cordata (Willd.) R. 
Br. extract and leaves (Sangrovit® Extra) as a zootechnical feed additive for 
suckling and weaned piglets and other growing Suidae. The additive is 
standardised to contain a concentration of the sum of the four alkaloids 
sanguinarine, chelerythrine, protopine and allocryptopine of 1.25%, with 0.5% 
sanguinarine. Owing to the presence of the DNA intercalators sanguinarine and 
chelerythrine, a concern for genotoxicity was identified. The EFSA Panel on 
Additives and Products or Substances used in Animal Feed (FEEDAP) had no safety 
concerns for the target species when the additive is used at the recommended 
level of 0.750 mg sanguinarine/kg complete feed for suckling and weaned piglets 
and other growing Suidae. Since in all consumer categories the exposure to 
sanguinarine and chelerythrine via the use of Sangrovit® Extra exceeds the 
threshold of toxicological concern of 0.0025 μg/kg bw per day for DNA reactive 
mutagens and/or carcinogens, the FEEDAP Panel could not conclude on the safety 
for the consumers. The additive was shown to be irritant to the eyes but not 
irritant to skin or a skin sensitiser. The FEEDAP Panel could not exclude the 
potential of the additive to be a respiratory sensitiser. When handling the 
additive, exposure of unprotected users to sanguinarine and chelerythrine may 
occur. Therefore, to reduce the risk, the exposure of users should be reduced. 
The use of Sangrovit® Extra as a feed additive under the proposed conditions of 
use was considered safe for the environment. The additive Sangrovit® Extra had 
the potential to be efficacious in improving performance of weaned piglets at 
0.600 mg sanguinarine/kg complete feed. This conclusion was extended to suckling 
piglets and extrapolated to other growing Suidae.

© 2024 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH 
on behalf of European Food Safety Authority.

DOI: 10.2903/j.efsa.2024.8793
PMCID: PMC11106680
PMID: 38774115

Conflict of interest statement: If you wish to access the declaration of 
interests of any expert contributing to an EFSA scientific assessment, please 
contact interestmanagement@efsa.europa.eu.