Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. J Burn Care Res. 2024 Nov 4:irae162. doi: 10.1093/jbcr/irae162. Online ahead
of  print.

Metabolomic analysis of HUVEC after Thermal denaturation UHPLC-MS/MS-based 
metabolomics.

Wu F(1), Yan Z(1), Ran Y(1), Wang M(1), Yang S(1), Huang M(1), Zhou S(1), Zhang 
P(1), Liang P(1), Jiang B(2).

Author information:
(1)Department of Burns and Plastic Surgery, Xiangya Hospital, Central South 
University, Changsha, Hunan, 410008, P. R. China.
(2)Department of Pathophysiology, Xiangya School of Medicine, Central South 
University, Changsha, Hunan, 410008, P. R. China.

Preserving denatured dermis has been shown to promote wound healing and improve 
skin appearance and function. Angiogenesis is crucial for the healing of burn 
wounds. However, the metabolic mechanisms underlying angiogenesis during burn 
recovery remain unclear. In this study, ultra-high performance liquid 
chromatography-mass spectrometry analysis revealed six distinct metabolites in a 
heat-denatured cell model. A bioinformatics approach was used to predict the 
differentially expressed metabolites, and four metabolic pathways closely 
related to trauma repair were identified. These pathways might play a 
significant role in the regression of thermally injured endothelial cells. We 
also found that increasing D-mannose level promoted the angiogenic activity of 
human umbilical vein endothelial cells in the heat-denatured cell model, 
enhancing cell proliferation, migration, and tube formation. In summary, these 
findings revealed changes in metabolites and metabolic pathways in thermally 
injured endothelial cells, and demonstrated that D-mannose could promote 
angiogenesis during the recovery of thermally injured endothelial cells.

© The Author(s) 2024. Published by Oxford University Press on behalf of the 
American Burn Association. All rights reserved. For commercial re-use, please 
contact reprints@oup.com for reprints and translation rights for reprints. All 
other permissions can be obtained through our RightsLink service via the 
Permissions link on the article page on our site—for further information please 
contact journals.permissions@oup.com.

DOI: 10.1093/jbcr/irae162
PMID: 39495584


2. Brain Behav Immun. 2024 Nov 1:S0889-1591(24)00672-X. doi: 
10.1016/j.bbi.2024.10.031. Online ahead of print.

An initial investigation of transcutaneous delivery of plasmid DNA encoding 
interleukin-10 for the treatment of psoriatic skin conditions.

Rafael Correia Rocha I(1), Finch MR(1), Ball JB(1), Harland ME(1), Clements 
M(1), Green-Fulgham S(1), Song G(2), Liu Y(2), Banov D(2), Watkins LR(3).

Author information:
(1)Department of Psychology and Neuroscience, Center for Neuroscience, 
University of Colorado at Boulder, Boulder, CO, USA.
(2)Research & Development, PCCA, Houston, TX, USA.
(3)Department of Psychology and Neuroscience, Center for Neuroscience, 
University of Colorado at Boulder, Boulder, CO, USA. Electronic address: 
linda.watkins@colorado.edu.

Psoriasis is a chronic immune-mediated skin disorder characterized by intense 
local inflammation, epidermal hyperplasia, and leukocyte infiltration. Current 
treatment approaches for psoriasis aim to alleviate symptoms and prevent disease 
progression, including systemically administered drugs with whole body side 
effects. Despite some advances in psoriasis treatment, success has been quite 
limited. To begin to address this challenge, we undertook an initial 
investigation of whether transcutaneous delivery of an endogenous 
anti-inflammatory cytokine could provide an effective, local treatment of 
psoriatic-like skin conditions. To do this, we utilized a previously documented 
rodent model of psoriasis, induced via a single topical application of Imiquimod 
(IMQ) to the shaved back of rats. The therapeutic approach used for this initial 
investigation was delivery of plasmid DNA encoding rat interleukin-10 
(pDNA-rIL10), a non-viral gene therapy approach previously shown to be effective 
in suppressing neuroinflammatory disorders after localized delivery either 
intracerebrally or intrathecally. Translation of this CNS therapeutic for use in 
psoriatic-like skin disorders required reformulation to enable transcutaneous 
delivery. Toward that end, pDNA-rIL10 was topically applied in Lipoderm HMW, a 
base explicitly designed to deliver higher molecular weight compounds into skin. 
Here we show that a single topical application of pDNA-rIL10 in Lipoderm HMW was 
effective in decreasing mRNA levels of pro-inflammatory cytokines as well as 
reducing the recruitment of T-cells to IMQ-treated skin. Furthermore, this 
transcutaneous IL-10 gene therapy decreased signs of skin inflammation, 
reflected by reduced erythema. Moreover, the results provide an initial 
indication that IL10 may stimulate hair regrowth in psoriatic-like skin.

Copyright © 2024 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.bbi.2024.10.031
PMID: 39489354

Conflict of interest statement: Declaration of competing interest The authors 
declare the following financial interests/personal relationships which may be 
considered as potential competing interests: [Linda Watkins is a scientific 
co-founder of Xalud Therapeutics and Vetana Animal Health that are pursuing the 
use of this pDNA IL-10 gene therapy approach in clinical trials of 
osteoarthritis and like indications. Daniel Banov is an inventor of Lipoderm HMW 
and he, Guiyun Song, and Yi Liu are employees of PCCA.].


3. BMC Oral Health. 2024 Nov 1;24(1):1336. doi: 10.1186/s12903-024-05080-1.

D-mannose alleviates chronic periodontitis in rats by regulating the functions 
of neutrophils.

Li X(1)(2), Chen X(1)(2), Zhu Q(1)(2), Zhang P(1)(2), Nan S(1)(2), Lv L(3), Qi 
S(4)(5).

Author information:
(1)Department of Prothodontics, Shanghai Stomatological Hospital & School of 
Stomatology, Fudan University, Shanghai, China.
(2)Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, 
Fudan University, Shanghai, China.
(3)Ministry of Education Key Laboratory of Metabolism and Molecular Medicine, 
Department of Biochemistry and Molecular Biology, School of Basic Medical 
Sciences, Fudan University, Shanghai, China. lvlei@fudan.edu.cn.
(4)Department of Prothodontics, Shanghai Stomatological Hospital & School of 
Stomatology, Fudan University, Shanghai, China. qishengcai@fudan.edu.cn.
(5)Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, 
Fudan University, Shanghai, China. qishengcai@fudan.edu.cn.

BACKGROUND: Periodontitis is a chronic inflammatory disease characterized by the 
destruction of the components of the periodontium. It significantly impacts oral 
health and has been linked to systemic conditions like cardiovascular disease 
and diabetes. The critical role of neutrophils in the occurrence and development 
of chronic periodontitis has been paid increasing attention. The study aimed to 
explore the protective effects of D-mannose on chronic periodontitis and 
determine whether its underlying mechanisms is related to neutrophils.
METHODS: To explore the protective effects of D-mannose on chronic 
periodontitis, the eight-week-old Sprague Dawley rat model of lipopolysaccharide 
(LPS)-induced periodontitis was established, followed by D-mannose treatment by 
oral gavage. To evaluate the protective effects of D-mannose against periodontal 
bone loss, methylene blue staining, hematoxylin and eosin (H&E) staining, and 
micro-CT scanning were utilized. Then, immunofluorescence (IF), Western Blot, 
and RT-PCR were applied to assess the expression levels of pro-inflammatory 
cytokines (IL-1β, IL-6, and IL-17), anti-inflammatory cytokine (IL-10), tumor 
necrosis factor-alpha (TNF-α), granulocyte colony-stimulating factor (G-CSF), 
granulocyte-macrophage colony-stimulating factor (GM-CSF), ten-eleven 
translocation 2 (TET2), and key glycolytic enzymes (HK1, HK2, PFKFB3), and to 
examine D-mannose's impact on the recruitment and activation of neutrophils in 
the gingiva. Additionally, neutrophils isolated from the peripheral blood of 
healthy rats were treated with LPS and D-mannose, and changes in the expression 
levels of myeloperoxidase (MPO), IL-1β, IL-6, IL-17, IL-10, and TET2 were 
observed via IF.
RESULTS: In vivo, D-mannose inhibited LPS-induced alveolar bone resorption in 
rats. After D-mannose treatment, the expression levels of IL-17 (p<0.01) and 
TET2 (p<0.01) were suppressed by IF, and the expression levels of IL-1β 
(p<0.05), IL-17 (p<0.05) and TET2 (p<0.01) were downregulated by WB. The results 
of qPCR showed that D-mannose reduced the expression levels of IL-1β (p<0.05), 
IL-6 (p<0.01), IL-17 (p<0.01), TNF-α (p<0.01), G-CSF (p<0.01), GM-CSF (p<0.01), 
TET2 (p<0.01), HK1 (p<0.01), HK2 (p<0.01), and PFKFB3 (p<0.01). D-mannose also 
inhibited the recruitment and activation of neutrophils in LPS-treated rat 
gingival tissues. In vitro, the results of IF showed that D-mannose inhibited 
the activation of neutrophils stimulated by LPS, downregulated the expression of 
IL-1β (p < 0.05), IL-6, IL-17 (p < 0.01), and TET2 (p < 0.01), and upregulated 
the expression of IL-10 (p < 0.01).
CONCLUSIONS: D-mannose can alleviate chronic periodontitis in rats by regulating 
the functions of neutrophils, potentially associated with the expression of TET2 
and glycolysis, providing new insights into the potential application of 
D-mannose to chronic periodontitis.

© 2024. The Author(s).

DOI: 10.1186/s12903-024-05080-1
PMCID: PMC11529006
PMID: 39487474 [Indexed for MEDLINE]

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


4. ChemMedChem. 2024 Oct 30:e202400575. doi: 10.1002/cmdc.202400575. Online ahead
 of print.

Exploring C2 and N6 Substituent Effects on Truncated 4'-Thioadenosine 
Derivatives as Dual A2A and A3 Adenosine Receptor Ligands.

Naik SD(1), Kim M(2), Choi J(3), Kim G(2), Kim SW(2), Aswar VR(2), Tripathi 
SK(2), Gaikwad V(2), Yu J(4), Jeong LS(5).

Author information:
(1)Government College of Arts Science and Commerce Khandola, Department of 
Chemistry, INDIA.
(2)Seoul National University, College of Pharmacy, KOREA, REPUBLIC OF.
(3)Ewha Womans University, College of Pharmacy, KOREA, REPUBLIC OF.
(4)Ewha Womans University, College of Pharmacy, 52, Ewhayeodae-gil, 
Seodaemun-gu, 03760, Seoul, KOREA, REPUBLIC OF.
(5)Seoul National University, College of Pharmacy, -, 08826, Seoul, KOREA, 
REPUBLIC OF.

Based on high binding affinity of truncated 2-hexynyl-4'-thioadenosine (3a) at 
both A2A adenosine receptor (AR) and A3 AR, we explored structure-activity 
relationship (SAR) of the C2-substitution by altering chain length of the 
2-hexynyl moiety, thereby evaluating the hydrophobic pocket size. A series of 
truncated N6-substituted 4'-thioadenosine derivatives with C2-alkynyl 
substitution were successfully synthesized from D-mannose, using a 
palladium-catalyzed Sonogashira coupling reaction as the key step, whose 
structures were confirmed by the X-ray crystal structure of 4h. As the size of 
the alkynyl group at the C2-position increased, the binding affinity improved; 
however, when the substituted group was larger than hexynyl, the binding 
affinity decreased. The introduction of a bulky hydrophobic group such as 
3-halobenzyl group at the free N6-amino group decreased the binding affinity at 
hA2AAR. These results confirm our previous findings that a free amino group at 
N6-position and longer hydrophobic chain at C2-position are essential for hA2A 
AR binding affinity. The introduction of a bulky hydrophobic group at free 
N6-amino group maintained the binding affinity at hA3 AR. The binding mode of 
truncated 2-substituted-4'-thioadenosine derivatives to hA2A and hA3 AR were 
predicted by a molecular docking study.

© 2024 Wiley‐VCH GmbH.

DOI: 10.1002/cmdc.202400575
PMID: 39477794


5. Genes (Basel). 2024 Sep 26;15(10):1253. doi: 10.3390/genes15101253.

Cloning and Expression of Pigeon-Derived Escherichia coli Type 1 Pilus Clusters 
and Analysis of Amino Acid Sequence Characteristics of Functional Proteins.

Chen J(1), Dai W(1), Wang H(2), Lei W(1), Fang G(1), Dai D(1).

Author information:
(1)School of Animal Science and Food Engineering, Jinling Institute of 
Technology, Nanjing 210046, China.
(2)College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.

BACKGROUND: Type 1 pili, as an important virulence factor of E. coli, has 
certain homology between APEC and UPEC, but the homology degree is not clear 
enough.
OBJECTIVES: This study aims to compare the homology between them.
METHODS: The recombinant bacteria were constructed by homologous recombination. 
The pili were observed by TEM, and the hemagglutination characteristics were 
determined by MHSA. The complete gene sequence was determined by sequencing, and 
the amino acid sequences of the functional proteins of type 1 pili of APEC and 
UPEC were compared.
RESULTS: TEM showed that they could express pili, which were slender, straight, 
and dense. Stable-pUC-fimBH has MHSA but stable-pUC-fimBG does not. The amino 
acid sequence similarity of FimB of NJ05 and UPEC was 98.8%, FimE was 99.4%, and 
the similarity between them was 51.5%. Compared with UPEC's type 1 pili FimC and 
FimD sequences, the similarity was 99.52% and 87.8%, respectively. The amino 
acid sequence of FimA of NJ05 was 89-96%, similar to UPEC, and the N-terminal 
and C-terminal amino acid sequences were exactly the same. The gene sequence and 
amino acid sequence similarity of FimH between them were both above 99%. The 
similarity of the pilus binding domain of FimH was 52.8%, but only 27.6% in the 
receptor binding domain. A few of the same amino acid residues were found in the 
corresponding regions of FimA, FimF, FimG, and FimH.
CONCLUSIONS: The type 1 pili of APEC and UPEC come from the same origin, which 
is helpful to further reveal the pathogenic mechanism of E. coli infection in 
the poultry respiratory tract.

DOI: 10.3390/genes15101253
PMCID: PMC11508147
PMID: 39457377 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare no conflicts of interest.