Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. J Asian Nat Prod Res. 2022 Apr;24(4):388-396. doi: 
10.1080/10286020.2021.1935895. Epub 2021 Jun 16.

Trifluoromethylation of dihydrocoptisines and the effect on structural stability 
and XBP1-activating activity.

Li X(1), Zhang HJ(1), Li ZH(1), Wu LQ(1), Deng AJ(1), Qin HL(1).

Author information:
(1)State Key Laboratory of Bioactive Substance and Function of Natural 
Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and 
Peking Union Medical College, Beijing 100050, China.

In order to obtain new dihydrocoptisine-type compounds with stable structure and 
activating XBP1 transcriptional activity, (±)-8-trifluoromethyldihydrocoptisine 
derivatives as target compounds were synthesized from quaternary ammonium 
chlorides of coptisine alkaloids as starting materials by a one-step reaction. 
The structures of the synthesized compounds were confirmed by 1H-, 13C-, and 
19F-NMR as well as HRESIMS methods. These compounds showed more significant 
structural stability and activating XBP1 transcription activity in vitro than 
dihydrocoptisine as positive control. No obvious cytotoxicity on normal cell 
in vitro was observed with (±)-8-trifluoromethyldihydrocoptisines. 
Trifluoromethylation can be used as one of the fluorine modification strategies 
for dihydrocoptisines to guide follow-up studies on structural modification of 
coptisine-type alkaloids and on anti-Ulcerative colitis drugs with coptisines.

DOI: 10.1080/10286020.2021.1935895
PMID: 34132154 [Indexed for MEDLINE]


2. Phytochemistry. 2018 Aug;152:204-212. doi: 10.1016/j.phytochem.2018.05.007.
Epub  2018 May 21.

Impact of drought and salt stress on the biosynthesis of alkaloids in 
Chelidonium majus L.

Yahyazadeh M(1), Meinen R(2), Hänsch R(2), Abouzeid S(3), Selmar D(4).

Author information:
(1)Institute for Plant Biology, TU Braunschweig, Mendelssohnstr. 4, 38106 
Braunschweig, Germany; Department of Horticultural Sciences, Faculty of 
Agricultural Sciences, University of Guilan, 41635-1314 Rasht, Iran.
(2)Institute for Plant Biology, TU Braunschweig, Humboldtstr. 1, 38106 
Braunschweig, Germany.
(3)Institute for Plant Biology, TU Braunschweig, Mendelssohnstr. 4, 38106 
Braunschweig, Germany.
(4)Institute for Plant Biology, TU Braunschweig, Mendelssohnstr. 4, 38106 
Braunschweig, Germany. Electronic address: d.selmar@tu-bs.de.

When plants are exposed to various stress situations, their alkaloid 
concentration frequently is enhanced. This well-known phenomenon is presumably 
due to a passively enhanced rate of biosynthesis, caused by greatly elevated 
concentrations of NADPH in stressed plants. Here, we used Chelidonium majus L. 
plants, which accumulate high concentrations of dihydrocoptisine in their 
leaves, to study the impact of drought and salt stress on the biosynthesis and 
accumulation of alkaloids. In comparison to well-watered controls, in the 
transcriptome of the gene encoding the key enzyme in alkaloid biosynthesis, 
stylopine synthase, is enhanced in stressed C. majus plants. If we presuppose 
that increased transcript levels correlate with increased enzymatic activity of 
the gene products, these data indicate, for the first time, that stress-related 
increases in alkaloid concentration might not only be caused by the well-known 
stress-related passive shift, but may also be due to an enhancement of enzymatic 
capacity.

Copyright © 2018 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.phytochem.2018.05.007
PMID: 29783187 [Indexed for MEDLINE]


3. Life Sci. 2018 Jan 15;193:47-56. doi: 10.1016/j.lfs.2017.12.004. Epub 2017 Dec
 6.

Protective effect of coptisine free base on indomethacin-induced gastric ulcers 
in rats: Characterization of potential molecular mechanisms.

Luo C(1), Chen H(2), Wang Y(1), Lin G(1), Li C(1), Tan L(1), Su Z(1), Lai X(1), 
Xie J(3), Zeng H(4).

Author information:
(1)Guangdong Provincial Key Laboratory of New Drug Development and Research of 
Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, 
Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China.
(2)The First Affiliated Hospital of Chinese Medicine, Guangzhou University of 
Chinese Medicine, Guangzhou, Guangdong 510405, PR China.
(3)Guangdong Provincial Key Laboratory of Clinical Research on Traditional 
Chinese Medicine Syndrome, The Second Affiliated Hospital, Guangzhou University 
of Chinese Medicine, Guangzhou 510120, PR China. Electronic address: 
xiejianhui123@aliyun.com.
(4)The First Affiliated Hospital of Chinese Medicine, Guangzhou University of 
Chinese Medicine, Guangzhou, Guangdong 510405, PR China. Electronic address: 
gancaozhf@126.com.

AIMS: The aim of this study was to comparatively investigate the potential 
gastroprotective effect and underlying mechanisms of coptisine free base (CFB, 
8-hydroxy-7, 8-dihydrocoptisine), berberine and lansoprazole against 
indomethacin-induced gastric ulcer in rats.
MATERIALS AND METHODS: CFB (10, 20 and 40mg/kg), berberine (20mg/kg) and 
lansoprazole (30mg/kg) were orally administrated to rats prior to indometacin 
ingestion, and gastric lesions were evaluated macroscopically and 
histologically, and further analyzed by ELISA, qRT-PCR and Western blot.
KEY FINDINGS: CFB exerted comparable or superior gastroprotective effect to 
berberine in protecting against indomethacin-induced gastric injury. CFB 
pretreatment significantly enhanced the levels of superoxide dismutase (SOD) and 
glutathione (GSH), and markedly decreased the malonaldehyde (MDA) content. CFB 
administration effectively suppressed the levels of myeloperoxidase (MPO), 
interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and angiotensin II (Ang 
II). Besides, CFB substantially up-regulated the mRNA expressions of 
cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), and promoted gastric 
mucosal prostaglandin E2 level (PGE2). Furthermore, CFB pretreatment remarkably 
increased the translocation of nuclear factor erythroid 2-related factor 2 
(Nrf2) from cytosol into the nucleus, and the expression of heme oxygenase-1 
(HO-1), while significantly decreased the expression of mitogen activated 
protein Kinase Kinase 6 (MKK6) and translocation of p38 mitogen-activated 
protein kinase (p38 MAPK).
SIGNIFICANCE: This was the first investigation reporting the anti-ulcer effect 
of protoberberine alkaloid free base on in vivo rodent model. The 
gastroprotective mechanism of CFB might involve favorable regulation of 
antioxidant and anti-inflammatory status mediated, at least partially, by the 
Nrf2 signaling pathway and p38 MAPK translocation.

Copyright © 2017 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.lfs.2017.12.004
PMID: 29223540 [Indexed for MEDLINE]


4. Front Pharmacol. 2017 Sep 5;8:619. doi: 10.3389/fphar.2017.00619. eCollection 
2017.

Colitis Is Effectively Ameliorated by (±)-8-Acetonyl-dihydrocoptisine via the 
XBP1-NF-κB Pathway.

Zhang H(1), Song G(2), Zhang Z(1), Song H(1), Tang X(1), Deng A(1), Wang W(1), 
Wu L(1), Qin H(1).

Author information:
(1)State Key Laboratory of Bioactive Substances and Functions of Natural 
Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and 
Peking Union Medical CollegeBeijing, China.
(2)Department of Pharmacology, Logistics University of PAPFTianjin, China.

Ulcerative colitis (UC) is a recurrent, chronic intestinal disease. Available 
treatments for UC are poor effective and/or cause severe adverse events. X-box 
binding protein 1 (XBP1) and nuclear factor-κB (NF-κB) have been reported to 
play important roles in UC. Specifically, deletion or downregulation of XBP1 
leads to spontaneous enteritis and results in imbalanced secretion of NF-κB and 
other proinflammatory cytokines. (±)-8-acetonyl-dihydrocoptisine, i.e., 
(±)-8-ADC, is a monomer semi-synthesized from coptisine. In vitro, (±)-8-ADC 
activated the transcriptional activity of XBP1, inhibited expression of NF-κB, 
and reduced production of proinflammatory cytokines, such as tumor necrosis 
factor alpha (TNF-α) and interleukin-1 beta (IL-1β), in 
lipopolysaccharide-stimulated IEC6 cells. Therefore, silencing XBP1 would reduce 
the inhibition effect of (±)-8-ADC on NF-κB expression and the cytokines 
secretion in vitro. In a dextran sulfate sodium-induced colitis mouse model, 
oral administration of (±)-8-ADC ameliorated weight loss and colon contracture, 
and decreased the average disease activity index score and pathological damage. 
Simultaneously, (±)-8-ADC also increased XBP1 expression, and decreased NF-κB 
expression and secretion of myeloperoxidase, TNF-α, IL-6 and IL-1β in the colon. 
Therefore, (±)-8-ADC may ameliorate UC via the XBP1-NF-κB pathway and should be 
considered as a therapeutic candidate for UC.

DOI: 10.3389/fphar.2017.00619
PMCID: PMC5591823
PMID: 28928666


5. Eur J Pharmacol. 2017 Sep 15;811:222-231. doi: 10.1016/j.ejphar.2017.06.027. 
Epub 2017 Jun 23.

Anti-inflammatory activity of coptisine free base in mice through inhibition of 
NF-κB and MAPK signaling pathways.

Chen HB(1), Luo CD(2), Liang JL(2), Zhang ZB(2), Lin GS(2), Wu JZ(1), Li CL(2), 
Tan LH(2), Yang XB(3), Su ZR(4), Xie JH(5), Zeng HF(6).

Author information:
(1)The First Affiliated Hospital of Chinese Medicine, Guangzhou University of 
Chinese Medicine, Guangzhou 510405, People's Republic of China.
(2)Guangdong Provincial Key Laboratory of New Drug Development and Research of 
Chinese Medicine, School of Chinese Materia Medica, Guangzhou University of 
Chinese Medicine, Guangzhou 510006, People's Republic of China.
(3)Guangdong Provincial Key Laboratory of Clinical Research on Traditional 
Chinese Medicine Syndrome, The Second Affiliated Hospital, Guangzhou University 
of Chinese Medicine, Guangzhou 510120, People's Republic of China.
(4)Guangdong Provincial Key Laboratory of New Drug Development and Research of 
Chinese Medicine, School of Chinese Materia Medica, Guangzhou University of 
Chinese Medicine, Guangzhou 510006, People's Republic of China; Dongguan 
Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of 
Chinese Medicine, Dongguan 523808, People's Republic of China.
(5)Guangdong Provincial Key Laboratory of Clinical Research on Traditional 
Chinese Medicine Syndrome, The Second Affiliated Hospital, Guangzhou University 
of Chinese Medicine, Guangzhou 510120, People's Republic of China. Electronic 
address: xiejianhui888@hotmail.com.
(6)The First Affiliated Hospital of Chinese Medicine, Guangzhou University of 
Chinese Medicine, Guangzhou 510405, People's Republic of China. Electronic 
address: gancaozhf@126.com.

Coptisine is one of the main constituents of Coptis chinensis which has been 
widely used for the remedy of inflammatory disorders. Although the biological 
activities of coptisine have been well known, the pharmacological properties of 
its free base have seldomly been elucidated thus far. The aim of this study was 
to investigate the potential anti-inflammatory properties of coptisine free base 
(CFB, 8-hydroxy-7,8-dihydrocoptisine) on three animal models, namely 
xylene-induced ear edema, acetic acid-induced vascular permeability and 
carrageenan-induced paw edema. The results exhibited that CFB exerted a 
dose-dependent suppression on ear edema induced by xylene, significantly 
mitigated the aggravation of vascular permeability caused by acetic acid and paw 
edema induced by carrageenan. Additionally, CFB significantly suppressed the 
productions of interleukin-1β (IL-1β), interleukin-6 (IL-6), prostaglandinE2 
(PGE2) and tumor necrosis factor (TNF-α) in the drug-treated groups as compared 
with the vehicle group after treatment with carrageenan. Signaling events of 
nuclear factor-κB (NF-κB) translocation, such as p-IKKα, p-IKKβ, p-IκBα and p65 
(nucleus) were significantly inactivated, while inhibitor of nuclear factor κBα 
(IκBα) and p65 (cytosolic) were markedly up-regulated by CFB. Furthermore, CFB 
also significantly suppressed the mitogen-activated protein kinase (MAPK) 
pathway by blocking the phosphorylation of p-p38 (phospho-p38 mitogen-activated 
protein kinases) and p-JNK (phospho-c-jun N-terminal kinase) but not p-ERK 
(phospho-extracellular signal-regulated kinase). Hence, CFB efficiently 
prevented inflammation, at least partially, via inhibition of NF-κB and MAPK 
pathways. These findings provided a pioneering pharmacological basis for the 
anti-inflammatory effect of CFB and suggested CFB might be a potential candidate 
for the therapy of inflammatory disorders.

Copyright © 2017 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.ejphar.2017.06.027
PMID: 28648405 [Indexed for MEDLINE]