Aim: This study investigates the antipsoriasis activities of the Deprungsith formulation and its bioactive components, focusing on their potential inhibitory effects on human cytochrome P450 (CYP450) enzymes.
Background: The development of psoriasis is influenced by a
combination of genetic, immune, metabolic, environmental, and infectious
factors. The hallmark symptoms include red, scaly patches of skin that itch and
flake, typically appearing on the scalp, trunk, limbs, and genital area. While
psoriasis is rarely life-threatening, its chronic nature can severely impact a
patient's quality of life.
Experimental Procedure: HaCaT cells and peripheral blood
mononuclear cells (PBMCs) from healthy subjects (n=9) and psoriasis patients
(n=10) were exposed to Deprungsith formulation, EPMC, ligustilide, and
cyclosporin for 24 and 48 hours. The antiproliferative effects were assessed
using the MTT assay, while cell apoptosis and cell cycle arrest were analyzed
by flow cytometry. The mRNA expression of pro-inflammatory cytokines was
determined using RT-PCR. CYP450 inhibitory effects were evaluated using a
bioluminescent-based assay.
Results: Deprungsith formulation and its bioactive components
inhibited HaCaT cell and PBMC proliferation with weak to moderate potency. The
combination of EPMC and ligustilide exhibited additive effects. Most test
substances arrested cell transition at the sub-G1 and S phases, leading to
early and late apoptosis induction. Prolonged exposure (48 hours) reduced
necrosis in PBMCs. The mRNA expression of pro-inflammatory cytokines, including
IL-6, IL-12p19, IL-23, and TNF-α, was significantly downregulated. Deprungsith
formulation, EPMC, ligustilide, and ferulic acid inhibited the activities of
CYP1A2, CYP2C9, CYP2D6, and CYP3A4 with weak to moderate potency.
Conclusion: Deprungsith formulation and its bioactive components
induced cell apoptosis by inhibiting specific cell cycle phases, which was
correlated with the downregulation of pro-inflammatory cytokines IL-6,
IL-12p19, IL-23, and TNF-α. The risk of adverse drug reactions and toxicity due
to potential CYP450 interactions when Deprungsith formulation is considered
low. Additional in vivo validation and a more detailed exploration of the
clinical relevance would strengthen the findings and provide a clearer
therapeutic perspective.
Author
(s) Details
Kesara Na-Bangchang
Graduate Program in Bioclinical Sciences, Chulabhorn International College
of Medicine, Thammasat University (Rangsit Campus), Pathumthani 12120,
Thailand, Center of Excellence in Pharmacology and Molecular Biology of Malaria
and Cholangiocarcinoma, Thammasat University (Rangsit Campus), Pathumthani
12120, Thailand and Drug Discovery and Development Center, Office of Advanced
Science and Technology, Thammasat University (Rangsit Campus), Pathumthani
12120, Thailand.
Monthaka
Teerachaisakul
Department of Thai Traditional and Alternative Medicine, Ministry of Public
Health, Nonthaburi 11,000, Thailand.
Phunuch Muhamad
Drug Discovery and Development Center, Office of Advanced Science and
Technology, Thammasat University (Rangsit Campus), Pathumthani 12120, Thailand.
Yosita Kasemnitichok
Graduate Program in Bioclinical Sciences, Chulabhorn International College
of Medicine, Thammasat University (Rangsit Campus), Pathumthani 12120,
Thailand.
Nattida Sangnarong
Center of Excellence in Pharmacology and Molecular Biology of Malaria and
Cholangiocarcinoma, Thammasat University (Rangsit Campus), Pathumthani 12120,
Thailand.
Kanyarat Boonprasert
Graduate Program in Bioclinical Sciences, Chulabhorn
International College of Medicine, Thammasat University (Rangsit Campus),
Pathumthani 12120, Thailand and Center of Excellence in Pharmacology and
Molecular Biology of Malaria and Cholangiocarcinoma, Thammasat University
(Rangsit Campus),
Pathumthani 12120, Thailand.
Mayuri Tarasuk
Graduate Program in Bioclinical Sciences, Chulabhorn International College
of Medicine, Thammasat University (Rangsit Campus), Pathumthani 12120, Thailand
and Center of Excellence in Pharmacology and Molecular Biology of Malaria and
Cholangiocarcinoma, Thammasat University (Rangsit Campus), Pathumthani 12120,
Thailand.
Tullayakorn
Plengsuriyakarn
Graduate Program in Bioclinical Sciences, Chulabhorn International College
of Medicine, Thammasat University (Rangsit Campus), Pathumthani 12120, Thailand
and Center of Excellence in Pharmacology and Molecular Biology of Malaria and
Cholangiocarcinoma, Thammasat University (Rangsit Campus), Pathumthani 12120,
Thailand.
Please see the book here:- https://doi.org/10.9734/bpi/prrat/v10/3510
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