Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Heliyon. 2024 Aug 28;10(17):e37037. doi: 10.1016/j.heliyon.2024.e37037. 
eCollection 2024 Sep 15.

Getting insights into chemical composition and antiherpetic capability of jujube 
(Ziziphus jujuba mill.) drupes.

Chianese A(1), Mushtaq H(2), Nastri BM(1), Morone MV(1), Giugliano R(1), Khan 
H(2), Piccolella S(2), Zannella C(1), Pacifico S(2), Galdiero M(1), De Filippis 
A(1).

Author information:
(1)Department of Experimental Medicine, University of Campania "Luigi 
Vanvitelli", 80138, Naples, Italy.
(2)Department of Environmental, Biological and Pharmaceutical Sciences and 
Technologies, University of Campania "Luigi Vanvitelli", 81100, Caserta, Italy.

Food plant diversity in bioactive compounds makes them an exploitable resource 
in the search for effective natural products to prevent or treat viral 
infections. Therefore, in the framework aimed at studying the antiviral 
properties of extractive mixtures from fruits (and their waste) grown in the 
Campania Region (Italy), jujube drupes (Zizyphus jujuba Mill.) were our focus. 
The drupes were dissected into their peel, pulp and seed parts, each of which 
was extracted by ultrasound-assisted maceration and further fractionated, thus 
obtaining, beyond the sugar fraction, a polyphenolic fraction and a lipid 
fraction. UHPLC-HR MS/MS tools highlighted that the polyphenolic component of 
the seed was strongly dissimilar from that of the edible parts, being 
constituted by swertisin and its derivatives. Moreover, the peel mostly 
accounted for triglycosylated flavonols, whereas the pulp was rich in volatile 
aromatic glycosides. Among lipids, p-coumaroyl triterpenes mainly characterized 
the peel. All fractions were screened for their cytotoxicity, and non-toxic 
concentrations of each extract were tested against herpes simplex virus type 1 
(HSV-1) by plaque assays. Molecular tests and Western blot analyses were also 
carried out. The jujube mixtures, in detail the peel and pulp polyphenolic 
fractions, and peel lipophilic fraction (the latter enriched mainly in 
ursane-type triterpenes), showed a marked inhibitory activity against HSV-1 
acting in the early stages of viral infection and preventing attachment of the 
virus to the host cell. The acquired data suggest jujube active mixtures as 
promising candidates for the prevention and treatment of herpetic lesions.

© 2024 The Authors. Published by Elsevier Ltd.

DOI: 10.1016/j.heliyon.2024.e37037
PMCID: PMC11402244
PMID: 39281427

Conflict of interest statement: 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. Zhongguo Zhong Yao Za Zhi. 2024 May;49(9):2501-2511. doi: 
10.19540/j.cnki.cjcmm.20240310.201.

[Determination of nine components of fried Ziziphi Spinosae Semen extract in 
beagle dog plasma by UPLC-MS/MS and its application in pharmacokinetic 
research].

[Article in Chinese]

Xia KX(1), Yu X(1), Wu SY(1), Zhao LF(1), Wang YY(2), Kang C(1), Yuan Z(1), Li 
YF(1).

Author information:
(1)Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences 
Beijing 100700,China.
(2)Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences 
Beijing 100700,China School of Traditional Chinese Medicine,Shandong University 
of Traditional Chinese Medicine Ji'nan 250301,China.

This study established a convenient, rapid, and sensitive ultra-performance 
liquid chromatography tandem mass spectrometry(UPLC-MS/MS) method for 
simultaneous determination of magnoflorine,(R)-coclaurine, vicenin Ⅱ, 
isospinosin, spinosin, swertisin, N-nornuciferine, 6-feruloylspinosin, and 
jujuboside B in beagle dog plasma after oral administration of fried Ziziphi 
Spinosae Semen(FZSS) extract. The Waters HSS-T3 C_(18) column(2.1 mm×100 mm, 1.8 
μm) was used. The methanol-aqueous solution(containing 0.01% formic acid) was 
adopted as the mobile phase for gradient elution. The nine components and two 
internal standards were completely separated within 8 min. The mass spectrometry 
detection was performed in multiple reaction monitoring(MRM) mode by positive 
and negative ion switching of electrospray ionization. The analytical method was 
validated in terms of specificity, selectivity, linear range, accuracy, 
precision, recovery, matrix effect, and stability. It could meet the requirement 
of pharmacokinetic research after oral administration of FZSS extract to beagle 
dogs. The results showed that the time to reach the peak concentration(T_(max)) 
of magnoflorine,(R)-coclaurine, vicenin Ⅱ, isospinosin, spinosin, 
6-feruloylspinosin, and jujuboside B was 2.40-3.20 h, and the elimination 
halflife(t_(1/2)) was 2.08-6.79 h after a single-dose oral administration of 
FZSS to beagle dogs. The exposure of magnoflorine and spinosin was high, with a 
peak concentration(C_(max)) of 76.7 and 31.5 ng·mL~(-1) and an area under the 
curve(AUC_(0-∞)) of 581 and 315 ng·h·mL~(-1), respectively. The exposure of the 
remaining five compounds was lower, with a C_(max) of 0.81-13.0 ng·mL~(-1) and 
an AUC_(0-∞) of 6.00-106 ng·h·mL~(-1). This study provides a reference for the 
follow-up research of FZSS.

DOI: 10.19540/j.cnki.cjcmm.20240310.201
PMID: 38812154 [Indexed for MEDLINE]


3. J Ethnopharmacol. 2024 May 10;325:117824. doi: 10.1016/j.jep.2024.117824. Epub
 2024 Jan 24.

Cornus officinalis var. koreana Kitam extracts alleviate cadmium-induced renal 
fibrosis by targeting matrix metallopeptidase 9.

Wang Z(1), Yin G(1), Liao X(1), Zhou Z(1), Cao Y(1), Li X(1), Wu W(1), Zhang 
S(2), Lou Q Professor(3).

Author information:
(1)Joint National Laboratory for Antibody Drug Engineering, The First Affiliated 
Hospital of Henan University, Henan University, Kaifeng, 475004, PR China.
(2)The First Affiliated Hospital of Henan University, Kaifeng, 475004, PR China.
(3)Huaihe Hospital of Henan University, Joint National Laboratory for Antibody 
Drug Engineering, The First Affiliated Hospital of Henan University, Henan 
University, Kaifeng, 475000, PR China; Joint National Laboratory for Antibody 
Drug Engineering, The First Affiliated Hospital of Henan University, Henan 
University, Kaifeng, 475004, PR China. Electronic address: qiang_lou@126.com.

ETHNOPHARMACOLOGICAL RELEVANCE: Cornus officinalis var. koreana Kitam (Cornus 
officinalis) is a commonly used Chinese herbal medicine and has a good clinical 
efficacy in kidney and liver diseases. Recent years, a number of studies 
reported the significant effects of Cornus officinalis on renal fibrosis. 
However, it is still unclear about the underlying specific mechanism, the 
bioactive ingredients, and the target gene regulatory network.
AIM OF THE STUDY: We investigated the impact of Cornus officinalis extract on 
cadmium-induced renal fibrosis, screened the bioactive ingredients of Cornus 
officinalis using a pharmacological sub-network analysis, and explored the 
regulatory effects of Cornus officinalis extracts on target gene matrix 
metallopeptidase 9 (MMP9).
METHODS: Male C57BL/6N mice were treated with single or combinatorial agents 
such as saline, cadmium chloride, Cornus officinalis, Isoginkgetin and FSL-1. 
Isoginkgetin is a compound with anti-MMP9 activity. FSL-1 can induce MMP9 
expression. Masson staining and Western blot and immunohistochemistry analyses 
were used for assessing renal fibrosis. In addition, wound healing model was 
established using BUMPT (Boston university mouse proximal tubular) cells to 
investigate how Cornus officinalis affected cadmium-induced cell migration. The 
main Cornus officinalis bioactive compounds were identified by UHPLC-MS 
(Ultra-high-performance liquid chromatography - mass spectrometry). The MMP9 
target for Cornus officinalis active ingredients were confirmed through a 
pharmacological sub-network analysis.
RESULTS: Aqueous extracts of Cornus officinalis protected from renal dysfunction 
and kidney fibrosis induced by cadmium chloride in mice. In vitro experiments 
validated that Cornus officinalis extracts inhibited cell migration ability 
especially in cadmium chloride condition. The sub-network analysis and chemical 
components profiling technique revealed the active compounds of Cornus 
officinalis. Cellular thermal shift assay verified the binding abilities of 
three active components Daidzein, N-Acetyl-L-tyrosine or Swertisin with matrix 
metalloproteinase-9. Gelatin zymography assay revealed that the activity of MMP9 
was inhibited by the three active components. We further confirmed that MMP9 was 
involved in the process of Cornus officinalis extracts reducing renal fibrosis. 
Cornus officinalis attenuated the cadmium-induced renal fibrosis was correlated 
with decreased expression of MMP9, collagen I, α-SMA (alpha-smooth muscle actin) 
and vimentin.
CONCLUSIONS: This study demonstrated that Cornus officinalis extracts could 
alleviate the cadmium chloride-induced renal fibrosis by targeting MMP9, and 
might provide new insights into the mechanism of treating renal fibrosis by 
Cornus officinalis.

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

DOI: 10.1016/j.jep.2024.117824
PMID: 38278375 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of Competing Interest The authors 
declare that there are no conflicts of interest.


4. J Oleo Sci. 2023;72(8):787-797. doi: 10.5650/jos.ess23027.

Comparison of Flavonoid and Flavonoid Glycoside in the Inhibition of the Starch 
Hydrolyzing Enzymes and AGEs; A Virtual Approaches.

Sadeghi M(1), Miroliaei M(1), Rahimmalek M(2)(3), Taslimi P(4), Szumny A(2), 
Sadeghian N(4).

Author information:
(1)Faculty of Biological Science and Technology, Department of Cell and 
Molecular Biology & Microbiology, University of Isfahan.
(2)Department of Food Chemistry and Biocatalysis, Wrocław University of 
Environmental and Life Sciences.
(3)Department of Horticulture, College of Agriculture, Isfahan University of 
Technology.
(4)Department of Biotechnology, Faculty of Science, Bartin University.

Inhibition of α-amylase, α-glucosidase, and advanced glycation end products 
(AGEs) is considered a prospective method for the prevention of type II 
diabetes. As two flavonoids obtained from fruits, swertisin (SW) and apigenin 
(AP) have similar structures and display various pharmacological properties. To 
examine the effects of flavonoid structure on inhibition of AGEs adducts and 
carbohydrate hydrolyzing enzymes activity, molecular docking and molecular 
dynamic simulations (MDs) were used. The molecular docking method was performed 
by the Autodock program, and the ligand that showed the most negative binding 
energy was selected for further investigation. SW showed the potential ability 
to inhibit the AGEs formation and carbohydrate hydrolyzing enzymes activity. The 
stability of the receptor/SW complex was evaluated by MDs. Based on the findings 
of the present study, it was found that SW has the potential to reduce glycation 
and delay the activity of α-amylase and α-glucosidase enzymes.

DOI: 10.5650/jos.ess23027
PMID: 37532567 [Indexed for MEDLINE]


5. ACS Omega. 2023 Jul 17;8(29):26444-26457. doi: 10.1021/acsomega.3c03100. 
eCollection 2023 Jul 25.

Taming Food-Drug Interaction Risk: Potential Inhibitory Effects of Citrus Juices 
on Cytochrome Liver Enzymes Can Safeguard the Liver from Overdose 
Paracetamol-Induced Hepatotoxicity.

Shalaby AS(1), Eid HH(1), El-Shiekh RA(1), Mohamed OG(1)(2), Tripathi A(2)(3), 
Al-Karmalawy AA(4), Sleem AA(5), Morsy FA(6), Ibrahim KM(1), Tadros SH(1), 
Youssef FS(7).

Author information:
(1)Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Cairo 11562, 
Egypt.
(2)Natural Products Discovery Core, Life Sciences Institute, University of 
Michigan, Ann Arbor, Michigan 48109, United States.
(3)Department of Medicinal Chemistry, College of Pharmacy, University of 
Michigan, Ann Arbor, Michigan 48109, United States.
(4)Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ahram Canadian 
University, 6th of October City, Giza 12566, Egypt.
(5)Pharmacology Department, National Research Centre, Dokki, Cairo 12622, Egypt.
(6)Pathology Department, National Research Centre, Dokki, Cairo 12622, Egypt.
(7)Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, 
Abbasia, Cairo 11566, Egypt.

Paracetamol overdose is the leading cause of drug-induced hepatotoxicity 
worldwide. Because of N-acetyl cysteine's limited therapeutic efficacy and 
safety, searching for alternative therapeutic substitutes is necessary. This 
study investigated four citrus juices: Citrus sinensis L. Osbeck var. Pineapple 
(pineapple sweet orange), Citrus reticulata Blanco × Citrus sinensis L. Osbeck 
(Murcott mandarin), Citrus paradisi Macfadyen var. Ruby Red (red grapefruit), 
and Fortunella margarita Swingle (oval kumquat) to improve the herbal therapy 
against paracetamol-induced liver toxicity. UHPLC-QTOF-MS/MS profiling of the 
investigated samples resulted in the identification of about 40 metabolites 
belonging to different phytochemical classes. Phenolic compounds were the most 
abundant, with the total content ranked from 609.18 to 1093.26 μg gallic acid 
equivalent (GAE)/mL juice. The multivariate data analysis revealed that 
phloretin 3',5'-di-C-glucoside, narirutin, naringin, hesperidin, 
2-O-rhamnosyl-swertisin, fortunellin (acacetin-7-O-neohesperidoside), 
sinensetin, nobiletin, and tangeretin represented the crucial discriminatory 
metabolites that segregated the analyzed samples. Nevertheless, the antioxidant 
activity of the samples was 1135.91-2913.92 μM Trolox eq/mL juice, 
718.95-3749.47 μM Trolox eq/mL juice, and 2304.74-4390.32 μM Trolox eq/mL juice, 
as revealed from 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid, 
ferric-reducing antioxidant power, and oxygen radical absorbance capacity, 
respectively. The in vivo paracetamol-induced hepatotoxicity model in rats was 
established and assessed by measuring the levels of hepatic enzymes and 
antioxidant biomarkers. Interestingly, the concomitant administration of citrus 
juices with a toxic dose of paracetamol effectively recovered the liver injury, 
as confirmed by normal sections of hepatocytes. This action could be due to the 
interactions between the major identified metabolites (hesperidin, hesperetin, 
phloretin 3',5'-di-C-glucoside, fortunellin, poncirin, nobiletin, 
apigenin-6,8-digalactoside, 6',7'-dihydroxybergamottin, naringenin, and 
naringin) and cytochrome P450 isoforms (CYP3A4, CYP2E1, and CYP1A2), as revealed 
from the molecular docking study. The most promising compounds in the three 
docking processes were hesperidin, fortunellin, poncirin, and naringin. Finally, 
a desirable food-drug interaction was achieved in our research to overcome 
paracetamol overdose-induced hepatotoxicity.

© 2023 The Authors. Published by American Chemical Society.

DOI: 10.1021/acsomega.3c03100
PMCID: PMC10373174
PMID: 37521669

Conflict of interest statement: The authors declare no competing financial 
interest.