Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Front Pharmacol. 2024 Sep 4;15:1465890. doi: 10.3389/fphar.2024.1465890. 
eCollection 2024.

A general prediction model for compound-protein interactions based on deep 
learning.

Ji W(1)(2), She S(1), Qiao C(1), Feng Q(1), Rui M(1), Xu X(1), Feng C(1).

Author information:
(1)School of Pharmacy, Jiangsu University, Zhenjiang, China.
(2)School of Medicine, Jiangsu University, Zhenjiang, China.

BACKGROUND: The identification of compound-protein interactions (CPIs) is 
crucial for drug discovery and understanding mechanisms of action. Accurate CPI 
prediction can elucidate drug-target-disease interactions, aiding in the 
discovery of candidate compounds and effective synergistic drugs, particularly 
from traditional Chinese medicine (TCM). Existing in silico methods face 
challenges in prediction accuracy and generalization due to compound and target 
diversity and the lack of largescale interaction datasets and negative datasets 
for model learning.
METHODS: To address these issues, we developed a computational model for CPI 
prediction by integrating the constructed large-scale bioactivity benchmark 
dataset with a deep learning (DL) algorithm. To verify the accuracy of our CPI 
model, we applied it to predict the targets of compounds in TCM. An herb pair of 
Astragalus membranaceus and Hedyotis diffusaas was used as a model, and the 
active compounds in this herb pair were collected from various public databases 
and the literature. The complete targets of these active compounds were 
predicted by the CPI model, resulting in an expanded target dataset. This 
dataset was next used for the prediction of synergistic antitumor compound 
combinations. The predicted multi-compound combinations were subsequently 
examined through in vitro cellular experiments.
RESULTS: Our CPI model demonstrated superior performance over other machine 
learning models, achieving an area under the Receiver Operating Characteristic 
curve (AUROC) of 0.98, an area under the precision-recall curve (AUPR) of 0.98, 
and an accuracy (ACC) of 93.31% on the test set. The model's generalization 
capability and applicability were further confirmed using external databases. 
Utilizing this model, we predicted the targets of compounds in the herb pair of 
Astragalus membranaceus and Hedyotis diffusaas, yielding an expanded target 
dataset. Then, we integrated this expanded target dataset to predict effective 
drug combinations using our drug synergy prediction model DeepMDS. Experimental 
assay on breast cancer cell line MDA-MB-231 proved the efficacy of the best 
predicted multi-compound combinations: Combination I (Epicatechin, Ursolic acid, 
Quercetin, Aesculetin and Astragaloside IV) exhibited a half-maximal inhibitory 
concentration (IC50) value of 19.41 μM, and a combination index (CI) value of 
0.682; and Combination II (Epicatechin, Ursolic acid, Quercetin, Vanillic acid 
and Astragaloside IV) displayed a IC50 value of 23.83 μM and a CI value of 
0.805. These results validated the ability of our model to make accurate 
predictions for novel CPI data outside the training dataset and evaluated the 
reliability of the predictions, showing good applicability potential in drug 
discovery and in the elucidation of the bioactive compounds in TCM.
CONCLUSION: Our CPI prediction model can serve as a useful tool for accurately 
identifying potential CPI for a wide range of proteins, and is expected to 
facilitate drug research, repurposing and support the understanding of TCM.

Copyright © 2024 Ji, She, Qiao, Feng, Rui, Xu and Feng.

DOI: 10.3389/fphar.2024.1465890
PMCID: PMC11408283
PMID: 39295942

Conflict of interest statement: The authors declare that the research was 
conducted in the absence of any commercial or financial relationships that could 
be construed as a potential conflict of interest. The author(s) declared that 
they were an editorial board member of Frontiers, at the time of submission. 
This had no impact on the peer review process and the final decision.


2. Plants (Basel). 2024 Sep 7;13(17):2513. doi: 10.3390/plants13172513.

Metabolomics Analysis of Phenolic Composition and Content in Five Pear Cultivars 
Leaves.

Jiao H(1), Guan Q(1), Dong R(1), Ran K(1), Wang H(1), Dong X(1), Wei S(1).

Author information:
(1)State Key Laboratory of Nutrient Use and Management, Shandong Institute of 
Pomology, Longtan Road No. 66, Taian 271000, China.

Phenolic compounds are the predominant chemical constituents in the secondary 
metabolites of plants and are commonly found in pears. In this study, we focused 
on the analysis of the phenolic composition and antioxidant activity of leaves 
from five pear cultivars (Cuiguan, Chaohong, Kuerle, Nanguoli, and Yali) and tea 
leaves (Fudingdabai as the control) using ultra-performance liquid 
chromatography coupled with electrospray ionization triple quadrupole mass 
spectrometry. The results indicated significant differences in the amount and 
composition of phenolic metabolites between tea and pear leaves, as well as 
among the five pear varieties. Only approximately one-third of the metabolites 
exhibited higher levels in pear leaves compared to that in tea leaves. The total 
phenol content in the Yali cultivar was higher than that in the other pear 
cultivars. Furthermore, specific phenolic metabolites with high expression were 
identified in the leaves of different groups. The levels of delphinidin 
3-glucoside, aesculin, prunin, cosmosiin, quercetin 3-galactoside, 
isorhamnetin-3-O-glucoside, nicotiflorin, narcissin, chlorogenic acid, and 
cryptochlorogenic acid were relatively high among the five pear cultivars. 
(-)-Gallocatechin gallate, 6-methylcoumarin, aesculetin, hesperidin, kaempferol, 
and caftaric acid were identified as specific metabolic substances unique to 
each type of pear leaf. Most of the differential metabolites showed positive 
correlations and were primarily enriched in the flavonoid biosynthesis, flavone 
and flavonol biosynthesis, and phenylpropanoid biosynthesis pathways. DPPH 
(1,1-Diphenyl-2-picrylhydrazyl radical) analysis indicated that the Yali 
cultivar exhibited the highest antioxidant activity compared to other varieties. 
This systematic analysis of the differences in phenolic metabolite composition 
and antioxidant activity between pear and tea leaves provides a theoretical 
foundation for the development and utilization of pear leaf resources.

DOI: 10.3390/plants13172513
PMCID: PMC11396794
PMID: 39273997

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


3. Fitoterapia. 2024 Mar;173:105825. doi: 10.1016/j.fitote.2024.105825. Epub 2024
 Jan 14.

Effect of the Pulsatilla decoction n-butanol extract on vulvovaginal candidiasis 
caused by Candida glabrata and on its virulence factors.

Zhang J(1), Jiang X(2), Shi G(2), Zhang H(2), Hu K(2), Wu D(2), Shao J(2), Liu 
T(3), Wang T(4), Wang C(5).

Author information:
(1)Department of Pathogenic Biology and Immunology, College of Integrated 
Chinese and Western Medicine (College of Life Science), Anhui University of 
Chinese Medicine, Hefei, China; Institute of Integrated Traditional Chinese and 
Western Medicine, Anhui University of Chinese Medicine, Hefei, China; College of 
Pharmacy, Anhui University of Chinese Medicine, Hefei, China.
(2)Department of Pathogenic Biology and Immunology, College of Integrated 
Chinese and Western Medicine (College of Life Science), Anhui University of 
Chinese Medicine, Hefei, China; Institute of Integrated Traditional Chinese and 
Western Medicine, Anhui University of Chinese Medicine, Hefei, China.
(3)Department of Pharmacy, The First Affiliated Hospital of Anhui Medical 
University, The Grade 3 Pharmaceutical Chemistry Laboratory of State 
Administration of Traditional Chinese Medicine, Hefei, China.
(4)Department of Pathogenic Biology and Immunology, College of Integrated 
Chinese and Western Medicine (College of Life Science), Anhui University of 
Chinese Medicine, Hefei, China; Institute of Integrated Traditional Chinese and 
Western Medicine, Anhui University of Chinese Medicine, Hefei, China; College of 
Pharmacy, Anhui University of Chinese Medicine, Hefei, China. Electronic 
address: wtm1818@163.com.
(5)Department of Pathogenic Biology and Immunology, College of Integrated 
Chinese and Western Medicine (College of Life Science), Anhui University of 
Chinese Medicine, Hefei, China; Institute of Integrated Traditional Chinese and 
Western Medicine, Anhui University of Chinese Medicine, Hefei, China. Electronic 
address: ahwcz63@sina.com.

Vulvovaginal candidiasis (VVC) caused by Candida glabrata (C. glabrata) is more 
persistent and resistant to treatment than when caused by Candida albicans (C. 
albicans) and has been on the rise in recent years. The n-butanol extract of 
Pulsatilla Decoction (BEPD) has been shown to be effective in treating VVC 
caused by C. glabrata, but the underlying mechanism of action remains unclear. 
In this study, the experimenter conducted in vitro and in vivo experiments to 
explore the effects of BEPD on the virulence factors of C. glabrata, as well as 
its efficacy, with a focus on possible immunological mechanism in VVC caused by 
C. glabrata. The contents of Anemoside B4, Epiberberine, Berberine, Aesculin, 
Aesculetin, Phellodendrine and Jatrorrhizine in BEPD, detected by 
high-performance liquid chromatography, were 31,736.64, 13,529.66, 105,143.72, 
19,406.20, 4952.67, 10,317.03, 2489.93 μg/g, respectively. In vitro experiments 
indicated that BEPD moderately inhibited the growth of C. glabrata, its 
adhesion, and biofilm formation, and affected the expression of efflux 
transporters in the biofilm state. In vivo experiments demonstrated that BEPD 
significantly reduced vaginal inflammatory manifestation and the release of 
proinflammatory cytokines and LDH in mice with VVC caused by C. glabrata. 
Moreover, it inhibited the Phosphorylation of EGFR, ERK, P38, P65, and C-Fos 
proteins. The results suggested that although BEPD moderately inhibits the 
growth and virulence factors of C. glabrata in vitro, it can significantly 
reduce vaginal inflammation by down-regulating the EGFR/MAPK signaling pathway 
in mice with VVC infected by C. glabrata.

Copyright © 2024. Published by Elsevier B.V.

DOI: 10.1016/j.fitote.2024.105825
PMID: 38219843 [Indexed for MEDLINE]

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


4. Se Pu. 2023 Aug;41(8):690-697. doi: 10.3724/SP.J.1123.2023.03018.

[Rapid determination of aesculin and aesculetin in Fraxini Cortex by high 
performance liquid chromatography-ultraviolet at equal absorption wavelength].

[Article in Chinese]

Qian ZM(1)(2), Wu MQ(2), Tan GY(2), Jin LL(2), Li N(3), Xie JY(1).

Author information:
(1)College of Medical Imaging Laboratory and Rehabilitation, Xiangnan 
University, Chenzhou 423000, China.
(2)Dongguan HEC Cordyceps R&D Co., Ltd., Dongguan 523850, China.
(3)College of Traditional Chinese Medicine, Yunnan University of Chinese 
Medicine, Kunming 650500, China.

Fraxini Cortex is a traditional Chinese herbal medicine that has been used for 
thousands of years to treat dampness-heat diarrhea, dysentery, red or white 
vaginal discharge, painful swelling or redness of the eyes, and nebula. It 
contains various chemical components, including coumarins, iridoids, phenolic 
acids, and flavonoids. Coumarins are important active ingredients in Fraxini 
Cortex and have antibacterial, anti-inflammatory, antioxidant, antitumor, and 
antiviral activities. Aesculin and aesculetin are two major coumarin components 
of Fraxini Cortex that are widely used in its quality evaluation. Previous HPLC 
methods for determination of aesculin and aesculetin present several 
limitations, such as long analysis times and high solvent and reference compound 
consumption. In this study, a rapid, eco-friendly and cost saving HPLC method 
for the determination of aesculin and aesculetin in Fraxini Cortex was 
established by using the core-shell column and equal absorption wavelength 
(EAW). Different factors influencing the extraction process, such as the 
extraction solvent, temperature, and time, were assessed to obtain the optimal 
extraction conditions. The results showed that Fraxini Cortex samples could be 
well extracted by ultrasonic extraction for 5 min with a 25% ethanol aqueous 
solution. A core-shell column was used, and different mobile phases and flow 
rates were investigated to obtain the best rapid-HPLC separation conditions. The 
optimized HPLC conditions were as follows: a Poroshell 120 EC-C18 column (50 
mm×4.6 mm, 2.7 μm), acetonitrile-0.1% formic acid aqueous solution (6∶94, v/v) 
as the eluent, a flow rate of 1.5 mL/min, and a column temperature of 25 ℃. The 
EAW of aesculin and aesculetin was a key factor in their determination using a 
single reference compound. EAW selection was performed in two steps. First, the 
UV spectra of two equimolar concentrations of the reference compounds (aesculin 
and aesculetin) were compared to determine the EAW of the two analytes. The EAW 
results were then verified by the HPLC analysis of the reference compound 
solutions. The final EAW of aesculin and aesculetin was 341 nm. The 
determination of aesculin and aesculetin using only one reference compound (i. 
e., aesculin) was achieved by HPLC-UV at this EAW. The newly developed HPLC 
method revealed a good linear relationship between the two target analytes 
(r=1.0000). The limits of detection (LODs) and limits of quantification (LOQs) 
were 1.5 μmol/L and 3.0 μmol/L, respectively, and the average recoveries of 
aesculin and aesculetin were 99.0% and 97.5%. The stabilities of the sample 
solutions were examined, and the two analytes demonstrated good stability for 24 
h. The contents of the target analytes in 10 batches of Fraxini Cortex were 
determined using the proposed EAW method and the classic external standard 
method (ESM), and comparable concentrations were obtained. The contents of 
aesculin and aesculetin in the 10 batches of Fraxini Cortex were 0.26%-2.80% and 
0.11%-1.47%, respectively. A t-test was conducted to compare the results of the 
proposed EAW technique with those obtained via the method reported in the 
Chinese Pharmacopoeia, and no significant difference between the two assay 
methods was noted (P>0.05). Comparison of the newly established EAW method with 
those reported in the literature revealed that our method required only 10 min 
to complete and used as little as 0.5 mL of the solvent and only one standard. 
Therefore, the developed EAW method is a rapid, simple, eco-friendly, and 
cost-effective analytical method that is suitable for the determination of 
aesculin and aesculetin in Fraxini Cortex and its related products. The proposed 
technique is an improved method for determining aesculin and aesculetin and 
contributes to the enhancement of the quality evaluation of Fraxini Cortex.

研究建立了一种快速、环保和节约对照品的秦皮化学成分含量测定方法。秦皮样品采用25%(v/v)乙醇水溶液超声提取5 min。样品提取溶液采用Poroshell 
120 EC-C18色谱柱(50 mm×4.6 mm, 2.7 μm)进行分析,0.1%甲酸水溶液-乙腈(94∶6, v/v)等度洗脱,流速1.5 
mL/min。采用紫外分光光度仪对等浓度的秦皮甲素和秦皮乙素进行紫外光谱扫描,初步筛选得到2个对照品的等吸收波长,并用高效液相色谱仪对筛选得到的等吸收波长进行确证,从而获得2个对照品的等吸收检测波长341 
nm。新建立的高效液相色谱紫外等吸收波长法的方法验证结果显示,秦皮甲素和秦皮乙素在各自的浓度范围内具有良好的线性关系(r=1.0000),检出限和定量限分别为1.5 
μmol/L和3.0 
μmol/L,平均加标回收率分别为99.0%(RSD=1.4%)和97.5%(RSD=0.9%)。通过比较高效液相色谱紫外等吸收波长法和传统高效液相色谱外标法对10批秦皮样品中秦皮甲素和秦皮乙素的含量测定结果,显示两种方法测定结果一致。此外还采用t检验对该方法与《中国药典》2020版方法的含量测定结果进行比较,对比结果表明两种测定方法无显著性差异(P>0.05)。该方法耗时10 
min,有害溶剂消耗0.5 
mL,只使用1个对照品,具有快速、简便、环保和对照品消耗少的特点,适用于秦皮中秦皮甲素和秦皮乙素的含量测定,为秦皮质量评价的技术提升提供了依据。

DOI: 10.3724/SP.J.1123.2023.03018
PMCID: PMC10398825
PMID: 37534556 [Indexed for MEDLINE]


5. Adv Appl Bioinform Chem. 2023 Apr 26;16:37-47. doi: 10.2147/AABC.S403175. 
eCollection 2023.

In silico Study of Antiviral Activity of Polyphenol Compounds from Ocimum 
basilicum by Molecular Docking, ADMET, and Drug-Likeness Analysis.

Kurnia D(1), Putri SA(1), Tumilaar SG(1), Zainuddin A(1), Dharsono HDA(2), Amin 
MF(3).

Author information:
(1)Department of Chemistry, Faculty of Mathematics and Natural Sciences, 
Universitas Padjadjaran, Sumedang, West Java, Indonesia.
(2)Department of Conservative Dentistry, Faculty of Dentistry, Universitas 
Padjadjaran, Sumedang, West Java, Indonesia.
(3)Dental Conservation, Faculty of Dentistry, Trisakti University, Jakarta, 
Indonesia.

AIM: The SARS-CoV-2 virus is a disease that has mild to severe effects on 
patients, which can even lead to death. One of the enzymes that act as DNA 
replication is the main protease, which becomes the main target in the 
inhibition of the SARS-CoV-2 virus. In finding effective drugs against this 
virus, Ocimum basilicum is a potential herbal plant because it has been tested 
to have high phytochemical content and bioactivity. Apigenin-7-glucuronide, 
dihydrokaempferol-3-glucoside, and aesculetin are polyphenolic compounds found 
in Ocimum basilicum.
PURPOSE: The purpose of this study was to analyze the mechanism of inhibition of 
the three polyphenolic compounds in Ocimum basilicum against the main protease 
and to predict pharmacokinetic activity and the drug-likeness of a compound 
using the Lipinski Rule of Five.
PATIENTS AND METHODS: The method used is to predict the molecular docking 
inhibition mechanism using Autodock 4.0 tools and use pkcsm and protox online 
web server to analyze ADMET and Drug-likeness.
RESULTS: The binding affinity for apigenin-7-glucuronide was -8.77 Kcal/mol, 
dihydrokaempferol-3-glucoside was -8.96 Kcal/mol, and aesculetin was -5.79 
Kcal/mol. Then, the inhibition constant values were 375.81 nM, 270.09 nM, and 
57.11 µM, respectively. Apigenin-7-glucuronide and dihydrokaempferol-3-glucoside 
bind to the main protease enzymes on the active sites of CYS145 and HIS41, while 
aesculetin only binds to the active sites of CYS145. On ADMET analysis, these 
three compounds met the predicted pharmacokinetic parameters, although there are 
some specific parameters that must be considered especially for aesculetin 
compounds. Meanwhile, on drug-likeness analysis, apigenin-7-glucuronide and 
dihydrokaempferol-3-glucoside compounds have one violation and aesculetin have 
no violation.
CONCLUSION: Based on the data obtained, Apigenin-7-glucuronide and 
dihydrokaempferol-3-glucoside are compounds that have more potential to have an 
antiviral effect on the main protease enzyme than aesculetin. Based on 
pharmacokinetic parameters and drug-likeness, three compounds can be used as 
lead compounds for further research.

© 2023 Kurnia et al.

DOI: 10.2147/AABC.S403175
PMCID: PMC10149097
PMID: 37131997

Conflict of interest statement: The authors declare no conflicts of interest, 
financial or otherwise.