Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. J Integr Plant Biol. 2024 Oct 25. doi: 10.1111/jipb.13782. Online ahead of 
print.

Haplotype-resolved genome of a heterozygous wild peach reveals the 
PdaWRKY4-PdaCYP716A1 module mediates resistance to aphids by regulating betulin 
biosynthesis.

Wang JX(1)(2)(3)(4), Li Y(1)(2)(5), Wang XW(1)(2)(5), Cao K(1)(5), Chen 
CW(1)(5), Wu JL(1)(5), Fang WC(1), Zhu GR(1)(2), Chen XJ(1), Guo DD(1), Wang 
J(1), Zhao YL(1), Fan JQ(1), Liu SN(1), Li WQ(1), Bie HL(1), Xu Q(3), Wang 
LR(1)(2)(5).

Author information:
(1)Zhengzhou Fruit Research Institute, National Key Laboratory for Germplasm 
Innovation & Utilization of Horticultural Crops, Chinese Academy of Agricultural 
Sciences, Zhengzhou, 451100, China.
(2)Western Research Institute, Chinese Academy of Agricultural Sciences, 
Changji, 831100, China.
(3)College of Horticulture & Forestry Sciences, Huazhong Agricultural 
University, Wuhan, 430070, China.
(4)Key Laboratory of Agricultural Biosafety and Green Production of Upper 
Yangtze River (Ministry of Education), College of Horticulture and Landscape 
Architecture, Southwest University, Beibei, 400715, Chongqing, China.
(5)National Horticulture Germplasm Resources Center of China (NPGRC), Zhengzhou 
Fruit Research Institute, Chinese Academy of Agricultural Sciences, Zhengzhou, 
451100, China.

Wild species of domesticated crops provide valuable genetic resources for 
resistance breeding. Prunus davidiana, a wild relative of peach with high 
heterozygosity and diverse stress tolerance, exhibits high resistance against 
aphids. However, the highly heterozygous genome of P. davidiana makes 
determining the underlying factors influencing resistance traits challenging. 
Here, we present the 501.7 Mb haplotype-resolved genome assembly of P. 
davidiana. Genomic comparisons of the two haplotypes revealed 18,152 structural 
variations, 2,699 Pda_hap1-specific and 2,702 Pda_hap2-specific genes, and 1,118 
allele-specific expressed genes. Genome composition indicated 4.1% of the P. 
davidiana genome was non-peach origin, out of which 94.5% was derived from 
almond. Based on the haplotype genome, the aphid resistance quantitative trait 
locus (QTL) was mapped at the end of Pda03. From the aphid resistance QTL, 
PdaWRKY4 was identified as the major dominant gene, with a 9-bp deletion in its 
promoter of the resistant phenotype. Specifically, PdaWRKY4 regulates aphid 
resistance by promoting PdaCYP716A1-mediated anti-aphid metabolite betulin 
biosynthesis. Moreover, we employed a genome design to develop a breeding 
workflow for rapidly and precisely producing aphid-resistant peaches. In 
conclusion, this study identifies a novel aphid resistance gene and provides 
insights into genome design for the development of resistant fruit cultivars.

© 2024 Institute of Botany, Chinese Academy of Sciences.

DOI: 10.1111/jipb.13782
PMID: 39451079


2. Esophagus. 2024 Oct 16. doi: 10.1007/s10388-024-01091-7. Online ahead of
print.

Betulin gel alleviates esophageal stricture following endoscopic submucosal 
dissection: an animal study.

Ma D(#)(1), Yang F(#)(1)(2), Yu Q(#)(1), Zhou X(#)(3), Li Z(1), Wang Y(#)(4), 
Chen J(#)(5).

Author information:
(1)Department of Gastroenterology, Changhai Hospital, Naval Medical University, 
NO. 168, Changhai Road, Shanghai, 200433, China.
(2)Department of Gastroenterology, People's Hospital of Leshan, Leshan, Sichuan, 
China.
(3)Department of Spleen and Stomach Diseases, The Affiliated Traditional Chinese 
Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, China.
(4)Department of Gastroenterology, Changhai Hospital, Naval Medical University, 
NO. 168, Changhai Road, Shanghai, 200433, China. wyf170606@163.com.
(5)Department of Gastroenterology, Changhai Hospital, Naval Medical University, 
NO. 168, Changhai Road, Shanghai, 200433, China. cjlj702@163.com.
(#)Contributed equally

BACKGROUND: Esophageal stenosis is a troublesome complication after 
circumferential ESD. This study examined the efficacy of betulin gel in 
preventing esophageal stenosis after ESD in a porcine model.
METHODS: Twelve pigs were randomized to betulin group and control group evenly. 
At the distal esophagus, circumferential ESD was performed in all animals. In 
the betulin group, betulin gel was applied at days 1, 3, and 7. Endoscopy 
examination was performed at day 3, 1 week, 2 weeks, and 4 weeks post-ESD. Then 
pigs were killed for macroscopic and histologic esophageal evaluation.
RESULTS: The rate of esophageal stricture was lower in the betulin group 
(53.3 ± 12.5% vs 88.3% ± 2.9, p = 0.02). Betulin-treated pigs had lower 
dysphagia score (2.0 ± 0 vs 3.3 ± 0.5, p < 0.001), less weight loss 
(11.78% ± 2.16 vs 15.85% ± 3.63, p = 0.04), and better passability of the open 
and closed biopsies forceps (83.33% vs. 0%, p = 0.015, and 100% vs. 0%, 
p = 0.002) 4 weeks post-ESD. Histologically, better re-epithelization 
(63.2 ± 10.7 mm vs 22.8 ± 10.1 mm, p < 0.001), slighter submucosal fibrosis 
(0.95 ± 0.17 mm vs 2.32 ± 0.48 mm, p = 0.002), lower muscularis propria damage 
score (1 vs 3, p < 0.001), and less inflammatory cells (307 vs 675 per 
high-power field, p = 0.002) were noted in the betulin group. The expression 
levels of TGF-β1, collagen i, collagen III, and α-SMA were significantly lower 
in the betulin group compared to the control group (p < 0.05).
CONCLUSIONS: Betulin gel shows promise in reducing fibrosis, enhancing repair, 
and preventing esophageal stricture after ESD, suggesting a potential new 
strategy for prevention.

© 2024. The Author(s) under exclusive licence to The Japan Esophageal Society.

DOI: 10.1007/s10388-024-01091-7
PMID: 39407007


3. Mol Med Rep. 2024 Dec;30(6):232. doi: 10.3892/mmr.2024.13356. Epub 2024 Oct
11.

Exploring the protective effect and molecular mechanism of betulin in 
Alzheimer's disease based on network pharmacology, molecular docking and 
experimental validation.

Wang N(#)(1), Cui J(#)(2), Sun Z(1), Chen F(3), He X(1).

Author information:
(1)Laboratory of Brain and Cognitive Science, School of Basic Medical Sciences, 
Dali University, Dali, Yunnan 671003, P.R. China.
(2)Yunnan Institute of Materia Medica, Yunnan Province Company Key Laboratory 
for TCM and Ethnic Drug of New Drug Creation, Kunming, Yunnan 650111, P.R. 
China.
(3)Department of Psychiatry, The Affiliated Mental Health Center of Jiangnan 
University, Wuxi, Jiangsu 214151, P.R. China.
(#)Contributed equally

Alzheimer's disease (AD) is a neurodegenerative disorder that impairs learning 
and memory, with high rates of mortality. Birch bark has been traditionally used 
in the treatment of various skin ailments. Betulin (BT) is a key compound of 
birch bark that exhibits diverse pharmacological benefits and therapeutic 
potential in AD. However, the therapeutic effects and molecular mechanisms of BT 
in AD remain unclear. The present study aimed to predict the potential 
therapeutic targets of BT in the treatment of AD, and to determine the specific 
underlying molecular mechanisms through network pharmacology analysis and 
experimental validation. PharmMapper was used to predict the target genes of BT, 
and four disease databases were searched to screen for AD targets. The 
intersection targets were identified using the jveen website. Drug‑disease 
target protein‑protein interaction networks and hub genes were obtained and 
visualized using the Search Tool for the Retrieval of Interacting Genes/Proteins 
database and Cytoscape. The Database for Annotation, Visualization and 
Integrated Discovery was used for Gene Ontology (GO) and Kyoto Encyclopedia of 
Genes and Genomes (KEGG) enrichment analyses, and AutoDock was used for 
molecular docking analysis of BT and hub genes. Subsequently, the 
network‑predicted mechanisms of BT in AD were verified in vitro. A total of 495 
BT and 1,386 AD targets were identified, and 120 were identified as potential 
targets of BT in the treatment of AD. The results of the molecular docking 
analysis revealed a strong binding affinity between BT and the hub genes. In 
addition, enrichment analyses of GO and KEGG pathways indicated that the 
neuroprotective effects of BT mainly involved the 'PI3K‑Akt signaling pathway'. 
The results of in vitro experiments demonstrated that pretreatment with BT for 2 
h may ameliorate formaldehyde (FA)‑induced cytotoxicity and morphological 
changes in HT22 cells, and decrease FA‑induced Tau hyperphosphorylation and 
reactive oxygen species levels. Furthermore, the PI3K/AKT signaling pathway was 
activated and the expression levels of downstream proteins, namely GSK3β, Bcl‑2 
and Bax, were modified following pre‑treatment with BT. Overall, the results of 
network pharmacology and in vitro analyses revealed that BT may reduce 
FA‑induced AD‑like pathology by modulating the PI3K/AKT signaling pathway, 
highlighting it as a potential multi‑target drug for the treatment of AD.

DOI: 10.3892/mmr.2024.13356
PMCID: PMC11529172
PMID: 39392030 [Indexed for MEDLINE]

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


4. Curr Drug Deliv. 2024 Oct 2. doi: 10.2174/0115672018329544240922151617. Online
 ahead of print.

Betulin-NLC-hydrogel for the Treatment of Psoriasis-like Skin Inflammation: 
Optimization, Characterisation, and In vitro and In vivo Evaluation.

Prakash D(1), Chaudhary A(1), Chaudhary A(2).

Author information:
(1)School of Pharmacy, Abhilashi University, Mandi, Himachal Pradesh, India.
(2)School of Pharmacy, Chitkara University, Baddi, Himachal Pradesh.

PURPOSE: Psoriasis is a chronic inflammatory skin disorder that poses 
significant challenges regarding effective and targeted drug delivery. Bioactive 
substances like betulin have shown tremendous utility in treating these 
conditions; however, they pose limited utility owing to their physicochemical 
characteristics. Here, we aimed to develop a novel topical dosage form for 
treating psoriasis, utilising betulin-loaded solid lipid nanoparticles (NLCs) 
incorporated into a hydrogel matrix.
METHODS: The optimization of the formulation was meticulously conducted using a 
design of experiments methodology, and its diverse physicochemical attributes 
were thoroughly examined. Evaluating betulin's in vitro release pattern from the 
NLC-hydrogel demonstrated consistent and regulated drug release properties. 
Additionally, the formulation demonstrated improved skin penetration abilities 
as determined by in vitro skin permeation experiments employing Franz diffusion 
cells- furthermore, the therapeutic effectiveness of the betulin-NLC-hydrogel 
was assessed by an in vivo experiment carried out using an imiquimod-induced 
psoriasis-like skin inflammation model in BALB/c female mice.
RESULTS: The NLCs exhibited a pH of 5.67±0.86, particle size of 148.16±12.66 nm, 
and zeta potential of -22.84±2.37 mV, ensuring stability and suitability for 
topical use. The gel, with a pH of 6.05±0.43 and viscosity of 17550±120 cPs, 
showed enhanced skin hydration and lipid restoration. Drug release studies 
indicated a slower release from NLCs and gel, improving skin retention. 
Stability tests revealed that the formulations were stable at room temperature 
but not at elevated temperatures. The in vitro safety profile of the formulation 
revealed no significant adverse effects on HaCaT cell lines. The NLC gel 
demonstrated significant anti-psoriatic activity, reducing inflammation and 
cytokine levels.
CONCLUSION: The betulin-NLC-hydrogel formulation exhibited promising 
characteristics for the topical treatment of psoriasis, showcasing optimised 
drug delivery, sustained release, and notable therapeutic efficacy. The findings 
from this study provide a foundation for the potential clinical translation of 
this innovative topical dosage form for improved psoriasis management.

Copyright© Bentham Science Publishers; For any queries, please email at 
epub@benthamscience.net.

DOI: 10.2174/0115672018329544240922151617
PMID: 39360545


5. Bull Exp Biol Med. 2024 Sep;177(5):621-625. doi: 10.1007/s10517-024-06236-3. 
Epub 2024 Sep 30.

In Vitro Hemocompatibility of Arabinogalactan, Betulin, and Betulin Derivatives.

Drozd NN(1), Kuznetsova SA(2), Skurydina ES(2), Vasilieva NY(2)(3), Levdansky 
VA(2).

Author information:
(1)National Medical Research Center of Hematology, Ministry of Health of the 
Russian Federation, Moscow, Russia. nndrozd@mail.ru.
(2)Institute of Chemistry and Chemical Technology of the Siberian Branch of the 
Russian Academy of Sciences, Federal Research Center Krasnoyarsk Science Center 
of the Siberian Branch of the Russian Academy of Sciences, Krasnoyarsk, Russia.
(3)Siberian Federal University, Krasnoyarsk, Russia.

The hemocompatibility of arabinogalactan, betulin and its derivatives was 
evaluated in vitro and samples suitable for creation of nanostructures or 
materials in contact with blood were selected. The prospects of arabinogalactan 
as a component of the construct (nanostructure) for drug delivery are due to the 
fact that it did not affect blood/plasma coagulation (at concentrations of 
0.0033-3.333 mg/ml and 0.00465-4.65 mg/ml, respectively), platelet aggregation 
(0.00182-0.182 mg/ml), and demonstrated the degree of erythrocyte hemolysis less 
than 3%. Sodium salt of betulin monosulfate, diarginine salt of betulin 
disulfate (up to 0.465 mg/ml), and especially betulin and allobetulin formate 
with procoagulant properties (degree of hemolysis less than 2%) can be used to 
create a material, for example, sponge, gel, active against blood coagulation.

© 2024. Springer Science+Business Media, LLC, part of Springer Nature.

DOI: 10.1007/s10517-024-06236-3
PMID: 39347869 [Indexed for MEDLINE]