Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Insect Biochem Mol Biol. 2024 Oct 23;175:104205. doi: 
10.1016/j.ibmb.2024.104205. Online ahead of print.

The fate of a Solanum steroidal alkaloid toxin in the cabbage looper 
(Trichoplusia ni).

Ziemke T(1), Wang P(1), Duplais C(2).

Author information:
(1)Department of Entomology, Cornell AgriTech, Cornell University, 14464, 
Geneva, NY, USA.
(2)Department of Entomology, Cornell AgriTech, Cornell University, 14464, 
Geneva, NY, USA. Electronic address: c.duplais@cornell.edu.

Plants produce complex chemical defenses against herbivores, resulting in the 
emergence of detoxification strategies in phytophagous insects. While enzymatic 
detoxification and target site mutagenesis are well-documented, the quantitative 
contribution of excretion remains less studied. We focus on the cabbage looper 
(Trichoplusia ni), a generalist herbivore, to elucidate the detoxification of a 
steroidal alkaloid, solanidine, produced in potato (Solanum tuberosum). Through 
larval feeding experiments and chemical analysis of metabolites using 
high-resolution mass spectrometry, we identify solanidine 3-O-β-glucopyranoside 
and solanidine 3-phosphate as major metabolization products of solanidine. 
Glycosylation and phosphorylation reactions have not previously been observed in 
cabbage looper. Modified solanidine derivatives exhibit reduced lipophilicity, 
preventing passive transport as predicted by physicochemical analyses, and only 
solanidine was detected in body tissue. In addition, the metabolism of 
solanidine in a T. ni mutant strain with midgut cadherin protein knocked out was 
also investigated to examine the potential role of the cadherin, an important 
receptor for Bt toxins, in steroidal alkaloid detoxification. T. ni 
cadherin-knockout strain showed lower solanidine conversion (33.9% ± 2.2) and 
uptake (27.41 ± 0.49 nmol/g) compared to the wild-type strain (51.3% ± 4.1, 
33.66 ± 2.48 nmol/g) but similar excretion kinetics. Although solanidine 
negatively impacted the feeding performance of both strains the 
cadherin-knockout does not affect the feeding performance. Our study expands the 
metabolization enzyme repertoire in cabbage loopers, emphasizing the complexity 
of detoxification mechanisms in generalist herbivores.

Copyright © 2024 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.ibmb.2024.104205
PMID: 39454684

Conflict of interest statement: Declaration of competing interest The authors 
declare that they have no conflict of interest.


2. Pharmaceuticals (Basel). 2024 Jul 15;17(7):948. doi: 10.3390/ph17070948.

Ethnomedicinal Usage, Phytochemistry and Pharmacological Potential of Solanum 
surattense Burm. f.

Hasan K(1), Sabiha S(1), Islam N(2), Pinto JF(1), Silva O(1).

Author information:
(1)Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, 
Universidade de Lisboa, 1649-003 Lisbon, Portugal.
(2)Department of Zoology, Faculty of Biological Sciences, University of 
Rajshahi, Rajshahi 6205, Bangladesh.

Solanum surattense Burm. f. is a significant member of the Solanaceae family, 
and the Solanum genus is renowned for its traditional medicinal uses and 
bioactive potential. This systematic review adheres to PRISMA methodology, 
analyzing scientific publications between 1753 and 2023 from B-on, Google 
Scholar, PubMed, Science Direct, and Web of Science, aiming to provide 
comprehensive and updated information on the distribution, ethnomedicinal uses, 
chemical constituents, and pharmacological activities of S. surattense, 
highlighting its potential as a source of herbal drugs. Ethnomedicinally, this 
species is important to treat skin diseases, piles complications, and toothache. 
The fruit was found to be the most used part of this plant (25%), together with 
the whole plant (22%) used to treat different ailments, and its decoction was 
found to be the most preferable mode of herbal drug preparation. A total of 338 
metabolites of various chemical classes were isolated from S. surattense, 
including 137 (40.53%) terpenoids, 56 (16.56%) phenol derivatives, and 52 
(15.38%) lipids. Mixtures of different parts of this plant in water-ethanol have 
shown in vitro and/or in vivo antioxidant, anti-inflammatory, antimicrobial, 
anti-tumoral, hepatoprotective, and larvicidal activities. Among the 
metabolites, 51 were identified and biologically tested, presenting antioxidant, 
anti-inflammatory, and antitumoral as the most reported activities. Clinical 
trials in humans made with the whole plant extract showed its efficacy as an 
anti-asthmatic agent. Mostly steroidal alkaloids and triterpenoids, such as 
solamargine, solanidine, solasodine, solasonine, tomatidine, xanthosaponin A-B, 
dioscin, lupeol, and stigmasterol are biologically the most active metabolites 
with high potency that reflects the new and high potential of this species as a 
novel source of herbal medicines. More experimental studies and a deeper 
understanding of this plant must be conducted to ensure its use as a source of 
raw materials for pharmaceutical use.

DOI: 10.3390/ph17070948
PMCID: PMC11280019
PMID: 39065797

Conflict of interest statement: The authors confirm that the contents of this 
article have no conflicts of interest.


3. Clin Pharmacol Ther. 2024 Nov;116(5):1269-1277. doi: 10.1002/cpt.3380. Epub
2024  Jul 22.

Solanidine Metabolites as Diet-Derived Biomarkers of CYP2D6-Mediated Tamoxifen 
Metabolism in Breast Cancer Patients.

Medwid S(1), Schwarz UI(1)(2), Choi YH(3), Keller D(4), Ross C(1), Kim 
RB(1)(2)(4)(5).

Author information:
(1)Department of Medicine, Western University, London, Ontario, Canada.
(2)Department of Physiology and Pharmacology, Western University, London, 
Ontario, Canada.
(3)Department of Epidemiology and Biostatistics, Western University, London, 
Ontario, Canada.
(4)London Health Sciences Centre, London, Ontario, Canada.
(5)Lawson Health Research Institute, London, Ontario, Canada.

Tamoxifen is an important antiestrogen for the treatment of hormone 
receptor-positive breast cancer and undergoes bioactivation by CYP2D6 to its 
active metabolite endoxifen. Genetic variation in CYP2D6 has been linked to 
endoxifen levels during tamoxifen therapy. Recent studies have suggested 
solanidine, a glycoalkaloid phytochemical in potatoes, undergoes CYP2D6-mediated 
metabolism to 4-OH-solanidine (m/z 414) and 3,4-seco-solanidine-3,4-dioic acid 
(SSDA; m/z 444). Using a retrospective cohort of 1,032 breast cancer patients on 
tamoxifen therapy, we examined the association of solanidine metabolites with 
CYP2D6 activity and its correlation with tamoxifen metabolism. Solanidine, 
4-OH-solanidine, or SSDA was detected in 99.7% (N = 1,029) of plasma samples. 
Decreased solanidine metabolite ratios were found in CYP2D6 intermediate and 
poor metabolizers (P < 0.0001). Patients on CYP2D6 strong inhibitors had a 77.6% 
and 94.2% decrease in 4-OH-solandine/solanidine (P < 0.0001) and SSDA/solanidine 
(P < 0.0001), respectively. The ratio of endoxifen to tamoxifen was highly 
correlated with both 4-OH-solandine/solanidine (ρ = 0.3207, P < 0.0001) and 
SSDA/solanidine (ρ = 0.5022, P < 0.0001) ratios. Logistic regression modeling 
was used to determine that 4-OH-solanidine/solanidine and SSDA/solanidine ratios 
below 2.1 and 0.8, respectively, predicted endoxifen concentrations of <16 nM. 
In conclusion, solanidine, 4-OH-solanidine, and SSDA are diet-derived biomarkers 
of CYP2D6 activity. Moreover, in patients on tamoxifen therapy, 
4-OH-solanidine/solanidine and SSDA/solanidine predicted endoxifen levels 
including the inhibitory effects of concomitantly prescribed CYP2D6-interacting 
medications. Accordingly, 4-OH-solanidine/solanidine or SSDA/solanidine ratio 
has the potential to be particularly useful prior to initiation of tamoxifen or 
for determining the impact of CYP2D6 drug interactions, as well as prior to 
switching from an aromatase inhibitor to tamoxifen.

© 2024 The Author(s). Clinical Pharmacology & Therapeutics published by Wiley 
Periodicals LLC on behalf of American Society for Clinical Pharmacology and 
Therapeutics.

DOI: 10.1002/cpt.3380
PMID: 39039708 [Indexed for MEDLINE]


4. J Biotechnol. 2024 Aug 10;391:81-91. doi: 10.1016/j.jbiotec.2024.05.008. Epub 
2024 May 31.

Enhancement of production of glycoalkaloids by elicitors along with 
characterization of gene expression of pathways in Solanum xanthocarpum.

Singh B(1), Nathawat S(2), Saxena A(2), Khangarot K(3), Sharma RA(3).

Author information:
(1)AIB, Amity University Rajasthan, Jaipur 303002, India. Electronic address: 
bharatsingh217@gmail.com.
(2)AIB, Amity University Rajasthan, Jaipur 303002, India.
(3)Department of Botany, University of Rajasthan, Jaipur 302004, India.

Solanum xanthocarpum fruits are used in the treatment of cough, fever, and heart 
disorders. It possesses antipyretic, hypotensive, antiasthmatic, aphrodisiac and 
antianaphylactic properties. In the present study, 24 elicitors (both biotic and 
abiotic) were used to enhance the production of glycoalkaloids in cell cultures 
of S. xanthocarpum. Four concentrations of elicitors were added into the MS 
culture medium. The maximum accumulation (5.56-fold higher than control) of 
demissidine was induced by sodium nitroprusside at 50 mM concentration whereas 
the highest growth of cell biomass (4.51-fold higher than control) stimulated by 
systemin at 30 mM concentration. A total of 17 genes of biosynthetic pathways of 
glycoalkaloids were characterized from the cells of S. xanthocarpum. The greater 
accumulation of demissidine was confirmed with the expression analysis of 11 key 
biosynthetic pathway enzymes e.g., acetoacetic-CoA thiolase, 3- hydroxy 3-methyl 
glutaryl synthase, β-hydroxy β-methylglutaryl CoA reductase, mevalonate kinase, 
farnesyl diphosphate synthase, squalene synthase, squalene epoxidase, 
squalene-2,3- epoxide cyclase, cycloartenol synthase, UDP-glucose: solanidine 
glucosyltransferase and UDP-rhamnose: solanidine rhamno-galactosyl transferase. 
The maximum expression levels of UDP-rhamnose: solanidine rhamno-galactosyl 
transferase gene was recorded in this study.

Copyright © 2024. Published by Elsevier B.V.

DOI: 10.1016/j.jbiotec.2024.05.008
PMID: 38825191 [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.


5. Mol Nutr Food Res. 2024 Mar;68(6):e2300639. doi: 10.1002/mnfr.202300639. Epub 
2024 Feb 22.

Structural Impact of Steroidal Glycoalkaloids: Barrier Integrity, Permeability, 
Metabolism, and Uptake in Intestinal Cells.

Keuter L(1), Wolbeck A(1), Kasimir M(1), Schürmann L(1), Behrens M(1), Humpf 
HU(1).

Author information:
(1)Institute of Food Chemistry, University of Münster, Corrensstr. 45, 48149, 
Münster, Germany.

SCOPE: Potato tubers represent an essential food component all over the world 
and an important supplier of carbohydrates, fiber, and valuable proteins. 
However, besides their health promoting effects, potatoes contain α-solanine and 
α-chaconine, which are toxic steroidal glycoalkaloids (SGAs). Other solanaceous 
plants like eggplants and tomatoes produce SGAs as well, different in their 
chemical structure. This study aims to investigate toxic effects (cholinesterase 
inhibition, membrane, and barrier disruption), permeability, metabolism, and 
structure-activity relationships of SGAs.
METHODS AND RESULTS: α-solanine, α-chaconine, α-solasonine, α-solamargine, 
α-tomatine, and their respective aglycones solanidine, solasodine, and 
tomatidine are analyzed using Ellman assay, cellular impedance spectroscopy, 
cell extraction, and Caco-2 intestinal model. Additionally, metabolism is 
analyzed by HPLC-MS techniques. The study observes dependencies of barrier 
disrupting potential and cellular uptake on the carbohydrate moiety of SGAs, 
while permeability and acetylcholinesterase (AChE) inhibition are dominated by 
the steroid backbone. SGAs show low permeabilities across Caco-2 monolayers in 
subtoxic concentrations. In contrast, their respective aglycones reveal higher 
permeabilities, but are extensively metabolized.
CONCLUSION: Besides structure-activity relationships, this study provides new 
information on the overall effects of steroidal alkaloids on intestinal cells 
and closes a gap of knowledge for the metabolic pathway from oral uptake to 
final excretion.

© 2024 The Authors. Molecular Nutrition & Food Research published by Wiley‐VCH 
GmbH.

DOI: 10.1002/mnfr.202300639
PMID: 38389193 [Indexed for MEDLINE]