PMID- 38047238
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231205
IS  - 1658-3612 (Electronic)
IS  - 1658-3612 (Linking)
VI  - 19
IP  - 1
DP  - 2024 Feb
TI  - The immunomodulatory activity of Orthosiphon aristatus against atopic dermatitis: 
      Evidence-based on network pharmacology and molecular simulations.
PG  - 164-174
LID - 10.1016/j.jtumed.2023.10.005 [doi]
AB  - OBJECTIVES: To explore the potential activity of Orthosiphon aristatus (OA) 
      against atopic dermatitis (AD). METHODS: Phytocompounds from OA were identified 
      through chromatography analysis, then continued to target identification and 
      functional annotation to explore the potential target of OA. Then, network 
      pharmacology from annotated proteins determined protein targets for OA 
      phytocompounds. Protein with highest rank according to the betweenness and 
      closeness algorithm then continued to molecular docking and validated through 
      molecular dynamics analysis. RESULTS: Chromatography data analysis revealed 
      thirty-six compounds, predominantly classified as carboxylic acid, fatty acyls, 
      and polyphenols. Upon identifying these compounds, network biology-based target 
      identification revealed their potential bioactivity in modulating inflammation in 
      AD. Tumour Necrosis Factor-alpha (TNF-alpha) and Prostaglandin G/H synthase 2 (PTGS2) 
      emerged as the most probable targets based on hub centrality in the 
      protein-protein interaction network. Later, molecular docking analyses 
      highlighted sixteen compounds with good inhibitory activity against these two 
      proteins. Notably, molecular dynamics simulation revealed that three compounds 
      out of the previous sixteen potential compounds were more likely to act as the 
      TNF-alpha and PTGS2 inhibitor as well as their native inhibitor. Those compounds are 
      (1R,9R)-5-Cyclohexyl-11- (propylsulfonyl)-7,11- diazatricyclo[7.3.1.02,7]trideca- 
      2,4-dien-6-one, also known as ZINC8297940, as the best TNF-alpha inhibitor along with 
      dl-Leucineamide and Benazol P as the potential inhibitor of PTGS2. CONCLUSIONS: 
      These findings suggest that OA may exert therapeutic effects against AD by 
      controlling inflammation through TNF-alpha and PTGS2 signalling pathways.
CI  - (c) 2023 The Authors.
FAU - Pandaleke, Thigita A
AU  - Pandaleke TA
AD  - Doctoral Program of Medical Science, Universitas Brawijaya, Malang, East Java, 
      Indonesia.
AD  - Department of Dermatology and Venereology, Faculty of Medicine, Sam Ratulangi 
      University, RD Kandou Hospital, Jl. Raya Tanawangko No.56, Manado 95163, North 
      Sulawesi, Indonesia.
FAU - Handono, Kusworini
AU  - Handono K
AD  - Department of Clinical Pathology, Faculty of Medicine, Universitas Brawijaya - 
      Saiful Anwar Hospital, Malang, East Java, Indonesia.
FAU - Widasmara, Dhelya
AU  - Widasmara D
AD  - Department of Dermatology and Venereology, Faculty of Medicine, Universitas 
      Brawijaya - Saiful Anwar Hospital, Malang, East Java, Indonesia.
FAU - Susianti, Hani
AU  - Susianti H
AD  - Department of Clinical Pathology, Faculty of Medicine, Universitas Brawijaya - 
      Saiful Anwar Hospital, Malang, East Java, Indonesia.
LA  - eng
PT  - Journal Article
DEP - 20231104
PL  - Saudi Arabia
TA  - J Taibah Univ Med Sci
JT  - Journal of Taibah University Medical Sciences
JID - 101621911
PMC - PMC10692725
OTO - NOTNLM
OT  - Atopic dermatitis
OT  - Benazol P
OT  - PTGS2 inhibitor
OT  - TNF-alpha inhibitor
OT  - ZINC8297940
OT  - dl-Leucineamide
EDAT- 2023/12/04 06:42
MHDA- 2023/12/04 06:43
PMCR- 2023/11/04
CRDT- 2023/12/04 05:21
PHST- 2023/05/15 00:00 [received]
PHST- 2023/08/11 00:00 [revised]
PHST- 2023/10/26 00:00 [accepted]
PHST- 2023/12/04 06:43 [medline]
PHST- 2023/12/04 06:42 [pubmed]
PHST- 2023/12/04 05:21 [entrez]
PHST- 2023/11/04 00:00 [pmc-release]
AID - S1658-3612(23)00154-3 [pii]
AID - 10.1016/j.jtumed.2023.10.005 [doi]
PST - epublish
SO  - J Taibah Univ Med Sci. 2023 Nov 4;19(1):164-174. doi: 
      10.1016/j.jtumed.2023.10.005. eCollection 2024 Feb.