Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. J Pharm Biomed Anal. 2025 Jan 1;252:116472. doi: 10.1016/j.jpba.2024.116472. 
Epub 2024 Sep 11.

Integrated serum pharmacochemistry, network pharmacology and experimental 
verification to explore the mechanism of Aconiti Lateralis Radix Praeparata in 
treatment of lung cancer.

Zhang W(1), Cai S(2), Luan W(2), Ding M(3), Di L(4).

Author information:
(1)School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 
210023, China; Jiangsu Engineering Research Center for Efficient Delivery System 
of Traditional Chinese Medicine, Nanjing 210023, China. Electronic address: 
wenzhang@njucm.edu.cn.
(2)School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 
210023, China; Jiangsu Engineering Research Center for Efficient Delivery System 
of Traditional Chinese Medicine, Nanjing 210023, China.
(3)School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 
210023, China; Jiangsu Engineering Research Center for Efficient Delivery System 
of Traditional Chinese Medicine, Nanjing 210023, China; Department of Pharmacy, 
Kunshan Hospital of Chinese Medicine, Suzhou China.
(4)School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 
210023, China; Jiangsu Engineering Research Center for Efficient Delivery System 
of Traditional Chinese Medicine, Nanjing 210023, China. Electronic address: 
diliuqing@njucm.edu.cn.

Aconiti Lateralis Radix Praeparata (Fuzi) is a traditional Chinese medicine 
(TCM) widely used in treating cancer. Our formerly investigations confirmed the 
anti-lung cancer efficacy of Fuzi, but systematic analysis of the ingredients of 
Fuzi absorbed into serum and the corresponding molecular mechanism in treating 
lung cancer remained unknown. In this work, UPLC-Q-TOF-MS was applied to detect 
the ingredients of Fuzi in rat serum. Next, the possible targets and key 
pathways of the components absorbed into serum of Fuzi were predicted by network 
pharmacology. Then, the binding activity of components and potential targets 
were performed by molecular docking. Afterwards, the proliferation, 
mitochondrial membrane potential (MMP), apoptosis and reactive oxygen species 
(ROS) of lung cancer cells after treatment with Fuzi-containing serum were 
determined by MTT assay, JC-1 fluorescent probe, Annexin V-FITC/PI double 
staining and DCFH-DA respectively. Finally, the predicted target was further 
validated with qRT-PCR. In total, identification of 20 components of Fuzi 
derived from rat serum were achieved. The prediction of network pharmacology 
indicated that these compounds might exert their therapeutic effects by 
modulating mTOR. The findings from molecular docking proved that fuziline, 
songorine, napelline and hypaconitine exhibited binding potential with the mTOR. 
Cancer cell experiments revealed that the Fuzi-containing serum inhibited cell 
proliferation, induced apoptosis, reduced MMP and increased ROS. Additionally, 
Fuzi-containing serum significantly reduced the mRNA expression of mTOR. This 
study revealed that fuziline, songorine, napelline and hypaconitine were the 
main ingredients of Fuzi absorbed into serum. Furthermore, Fuzi-containing serum 
demonstrated inhibitory effects on the proliferation of lung cancer cells and 
induced the apoptosis. Combined with the results of network pharmacology, 
molecular docking and biological verification, Fuzi-containing serum might exert 
its anti-lung cancer effect by inhibiting mTOR. This study would provide a 
deeper understanding of Fuzi in treating lung cancer and offer a scientific 
reference for its clinical utilization.

Copyright © 2024 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.jpba.2024.116472
PMID: 39278160 [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. Chem Biodivers. 2024 Aug;21(8):e202400977. doi: 10.1002/cbdv.202400977. Epub 
2024 Jul 16.

Two Novel Diterpenoid Alkaloids from Aconitum Pendulum.

Shen T(1), He SJ(1), Yang HY(1), Li GL(1), Xu JL(1), He YL(1).

Author information:
(1)Research Institute, School of Chemistry and Chemical Engineering, Lanzhou 
Jiaotong University, Lanzhou, 730070, Gansu, P. R. China.

Two previously uncharacterized compounds, an aconitine-type C19-diterpenoid 
alkaloid (1) and a napelline-type diterpenoid alkaloid C20-diterpenoid alkaloid 
(2), as well as ten known compounds (3-12), were isolated from Aconitum 
pendulum. Their structures were elucidated based on spectroscopic data, 
including 1D and 2D NMR, IR, HR-ESI-MS, and single-crystal X-ray diffraction 
analysis. The anti-insecticidal activities of these compounds were evaluated by 
contact toxicity tests against two-spotted spider mites, and compounds 1, 2, and 
9 showed moderate contact toxicity, with LC50 values of 0.86±0.09, 0.95±0.23, 
and 0.89±0.19 mg/mL, respectively. This study highlights the potential use of 
diterpenoid alkaloids as natural plant-derived pesticides for the management of 
plant pests.

© 2024 Wiley-VHCA AG, Zurich, Switzerland.

DOI: 10.1002/cbdv.202400977
PMID: 38837616 [Indexed for MEDLINE]


3. Int Immunopharmacol. 2022 Dec;113(Pt A):109307. doi: 
10.1016/j.intimp.2022.109307. Epub 2022 Oct 15.

12-Epi-Napelline regulated TGF-β/BMP signaling pathway mediated by BMSCs 
paracrine acceleration against osteoarthritis.

Peng J(1), Mao Z(1), Liu Y(1), Tian Y(1), Leng Q(1), Gu J(2), Tan R(3).

Author information:
(1)College of Life Science and Engineering, Southwest Jiaotong University, 
Chengdu 610031, China.
(2)Pharmacy College, Southwest Minzu University, Chengdu 610041, China.
(3)College of Life Science and Engineering, Southwest Jiaotong University, 
Chengdu 610031, China. Electronic address: tanrui@swjtu.edu.cn.

BACKGROUND: This study is to investigate the role of 12-Epi-Napelline, a new 
alkaloid isolated from aconitum, in promoting the paracrine of Bone Mesenchymal 
Stem Cells (BMSCs) and the synergistic therapeutic effects on osteoarthritis.
METHOD: We tested the cytotoxicity and optimization of 12-Epi-Napelline, and 
then simulated the osteoarthritis model in vitro damaging the chondrocytes by 
lipopolysaccharide (LPS) and RT-qPCR, Western blot and Immunofluorescence were 
used to detect the inflammatory factor IL-1β, COX-2, TNF-α, MMP-13 and anabolic 
cytokines of Col-2, BMP-2, TGF-β1 and Sox9 expression in chondrocytes after 
12-Epi-Napelline treatment. Under the treatment of different time, Col-2, BMP-2, 
TGF-β1 and Sox9 expression in BMSCs were detected by RT-qPCR, Western blot, and 
Immunofluorescence. By establishing an osteoarthritis model in vivo, the 
anti-osteoarthritis effect of 12-Epi-Napelline or BMSCs was evaluated.
RESULTS: The results showed the expressions of IL-1β, COX-2, TNF-α, and MMP-13 
were down-regulated in chondrocytes after 12-Epi-Napelline treatment, while the 
expression of Col-2, BMP-2, TGF-β1 and Sox9 were increased to normal 
chondrocytes. These increased expression also occurred in BMSCs. BMSCs had the 
trend of transforming into chondrocytes by regulating TGF-β signaling pathway 
under the treatment of 12-Epi-Napelline.
CONCLUSION: This study could confirm that 12-Epi-Napelline is not only effective 
in the treatment of osteoarthritis, but also can induce BMSCs to secrete growth 
factors that promote chondrocyte repair to help repair the damage caused by 
osteoarthritis.

Copyright © 2022 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.intimp.2022.109307
PMID: 36252476 [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.


4. Zhongguo Zhong Yao Za Zhi. 2022 Sep;47(17):4715-4722. doi: 
10.19540/j.cnki.cjcmm.20220207.704.

[Therapeutic effects of alkaloids in Tibetan medicine Bangna (Aconiti Penduli et 
Aconiti Flavi Radix) on osteoarthritis rats and mechanisms].

[Article in Chinese]

Wang Q(1), Peng J(1), Liu Y(1), Tian Y(1), Li J(1), Ren YY(1), Gu J(2), Tan 
R(1).

Author information:
(1)School of Life Science and Engineering, Southwest Jiaotong University Chengdu 
610031,China.
(2)College of Pharmacy, Southwest Minzu University Chengdu 610041,China.

This study aims to investigate the therapeutic effects of alkaloids in Tibetan 
medicine Bangna(Aconiti Penduli et Aconiti Flavi Radix) on osteoarthritis(OA) 
rats in vitro and in vivo and the underlying mechanisms. Chondrocytes were 
isolated from 2-3 week-old male SD rats and lipopolysaccharide(LPS) was used to 
induce OA in chondrocytes in vitro. Methyl thiazolyl tetrazolium(MTT) assay was 
used to investigate the toxicity of seven alkaloids(12-epi-napelline, songorine, 
benzoylaconine, aconitine, 3-acetylaconitine, mesaconitine, and 
benzoylmesaconine) to chondrocytes. Chondrocytes were classified into the 
control group, model group(induced by LPS 5 μg·mL~(-1) for 12 h), and 
administration groups(induced by LPS 5 μg·mL~(-1) for 12 h and incubated for 24 
h). The protein expression of inflammatory factors cyclooxygenase-2(COX-2), 
inducible nitric oxide synthetase(iNOS), tumor necrosis factor-α(TNF-α), and 
interleukin-1β(IL-1β) in each group were detected by Western blot, and the 
protein expression of matrix metalloprotease-13(MMP-13), aggrecan, collagen Ⅱ, 
fibroblast growth factor 2(FGF2) by immunofluorescence staining. For the in vivo 
experiment, sodium iodoacetate was used to induce OA in rats, and the expression 
of MMP-13, TNF-α, and FGF2 in cartilage tissues of rats in each group was 
detected by immunohistochemistry. The results showed that the viability of 
chondrocytes could reach more than 90% under the treatment of the seven 
alkaloids in a certain dose range. Aconitine, 12-epi-napelline, songorine, 
3-acetylaconitine, and mesaconitine could decrease the protein expression of 
inflammatory factors COX-2, iNOS, TNF-α and IL-1β compared with the model group. 
Moreover, 12-epi-napelline, aconitine, and mesaconitine could down-regulate the 
expression of MMP-13 and up-regulate the expression of aggrecan and collagen Ⅱ. 
In addition, compared with the model group and other Bangna alkaloids, 
12-epi-napelline significantly up-regulated the expression of FGF2. Therefore, 
12-epi-napelline was selected for the animal experiment in vivo. 
Immunohistochemistry results showed that 12-epi-napelline could significantly 
reduce the expression of MMP-13 and TNF-α in cartilage tissues, and up-regulate 
the expression of FGF2 compared with the model group. In conclusion, among the 
seven Bangna alkaloids, 12-epi-napelline can promote the repair of OA in rats by 
down-regulating the expression of MMP-13 and TNF-α and up-regulating the 
expression of FGF2.

DOI: 10.19540/j.cnki.cjcmm.20220207.704
PMID: 36164879 [Indexed for MEDLINE]


5. J Am Chem Soc. 2022 Aug 24;144(33):15355-15362. doi: 10.1021/jacs.2c06738.
Epub  2022 Aug 10.

Divergent Total Syntheses of Napelline-Type C20-Diterpenoid Alkaloids: 
(-)-Napelline, (+)-Dehydronapelline, (-)-Songorine, (-)-Songoramine, 
(-)-Acoapetaldine D, and (-)-Liangshanone.

Jin S(1), Zhao X(1), Ma D(1).

Author information:
(1)State Key Laboratory of Bioorganic & Natural Products Chemistry, Center for 
Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, 
University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 
Lingling Lu, Shanghai 200032, China.

The napelline-type alkaloids possess an azabicyclo[3.2.1]octane moiety and an 
ent-kaurane-type tetracyclic skeleton (6/6/6/5) along with varied oxidation 
patterns embedded in the compact hexacyclic framework. Herein, we disclose a 
divergent entry to napelline-type alkaloids that hinges on convergent assembly 
of the ent-kaurane core using a diastereoselective intermolecular Cu-mediated 
conjugate addition and subsequent intramolecular Michael addition reaction as 
well as rapid construction of the azabicyclo[3.2.1]octane motif via an 
intramolecular Mannich cyclization. The power of this strategy has been 
demonstrated through efficient asymmetric total syntheses of eight 
napelline-type alkaloids, including (-)-napelline, (-)-12-epi-napelline, 
(+)-dehydronapelline, (+)-12-epi-dehydronapelline, (-)-songorine, 
(-)-songoramine, (-)-acoapetaldine D, and (-)-liangshanone.

DOI: 10.1021/jacs.2c06738
PMID: 35948501 [Indexed for MEDLINE]