Sains Malaysiana 55(6)(2026): 1021-1032

http://doi.org/10.17576/jsm-2026-5506-07

 

α-Mangostin Suppresses TNF-α-Induced Biomarkers of Endothelial Dysfunction 

(α-Mangostin Menyekat Penanda Bio Disfungsi Endotel Teraruh TNF-α)

 

LUQMAN JAYA¹, MIERRAH-NATASHA MUHAMMAD NASIR², SITI-MARLIANA JASNI¹, NOR HISAM ZAMAKSHSHARI² & ERNA-ZULAIKHA DAYANG^1,*

 

¹Faculty of Medicine and Health Sciences, Universiti Malaysia Sarawak, 94300 Kota Samarahan, Sarawak, Malaysia

²Faculty of Resources Science and Technology, Universiti Malaysia Sarawak, 94300 Kota Samarahan, Sarawak, Malaysia

 

Diserahkan: 26 September 2025/Diterima: 3 Jun 2026

 

Abstract

Sepsis is a condition of dysregulated response to infection. Endothelial dysfunction is a key event in the onset and progression of sepsis, marked by a heightened pro-inflammatory response. Tumour necrosis factor-alpha (TNF-α), a major cytokine elevated in sepsis, induces the expression of adhesion molecules and cytokines which leads to the leukocyte recruitment. With limited treatment options to counteract sepsis-induced inflammation, natural compounds offer promising alternatives. α-Mangostin, a xanthone from Garcinia mangostana, exhibits anti-inflammatory properties, but its effects on TNF-α-activated endothelial cells remain underexplored. Herein, this study aimed to investigate the potential of α-Mangostin in modulating the inflammatory response of TNF-α-stimulated endothelial cells. Firstly, the structure of isolated α-Mangostin was confirmed via NMR and FTIR and the optimal non-toxic concentration of α-Mangostin in endothelial cells was pre-determined. Subsequently, a range of concentrations of α-Mangostin between 0.1-10 µM was added into TNF-α- stimulated human umbilical vein endothelial cells (HUVECs). After 4 h of exposure to TNF-α, cell lysates and medium supernatants were collected, and the effect of α-Mangostin in attenuating adhesion molecules (E-selectin, VCAM-1, and ICAM-1) and pro-inflammatory cytokine (IL-6) expression was measured using Western blot and ELISA, respectively. Additionally, the effect of the therapeutic concentration of α-Mangostin relative to an NF-κB inhibitor, BAY-11-7082, at a similar concentration, was compared. Cell viability assay, CCK-8, showed the IC₅₀ of HUVEC against α-Mangostin to be 10.69 µM. α-Mangostin downregulated E-selectin, VCAM-1, and ICAM-1, with 1 µM and 10 µM showing comparable efficacy. Additionally, α-Mangostin significantly reduced IL-6 secretion from TNF-α-induced endothelial cells from 0.1 µM to 10 µM. Suppression of anti-inflammatory molecules was higher than the positive control, BAY-11-7082, suggesting possible inhibitory action beyond NF-κB activation. These findings highlight the potential of α-Mangostin as a therapeutic candidate to counteract sepsis-related endothelial dysfunction.

Keywords: α-Mangostin; endothelial; Garcinia mangostana; inflammation; sepsis

 

Abstrak

Sepsis ialah satu keadaaan tindak balas yang tidak terkawal dalam badan akibat jangkitan. Kegagalan fungsi pada sel endotelial merupakan kunci utama dalam perkembangan sepsis dan ia sering diikuti dengan tindak balas pro-radang yang tidak terkawal. Ketika sepsis berlaku, peningkatan sitokin utama seperti faktor nekrosis tumor (TNF-α) merangsang pembentukan molekul lekatan yang mendorong penarikan leukosit ke arah sel endotelial. Namun, rawatan sepsis sedia ada adalah terhad dan keadaan ini mendorong kepada penerokaan sebatian semula jadi sebagai rawatan alternatif. α-Mangostin ialah xanthone yang boleh dijumpai daripada Garcinia mangostana. Kajian sebelum ini telah menilai α-Mangostin sebagai sebatian yang mempunyai ciri anti-radang. Namun, potensi α-Mangostin terhadap endotelial yang telah diaktifkan masih belum diterokai. Oleh itu, kajian ini meneroka potensi α-Mangostin terhadap sel endotelial vena umbilikal manusia (HUVECs) yang dirangsang dan diaktifkan oleh TNF-α. Dalam kajian ini, ekspresi molekul lekat dan sekresi sitokin pro-radang telah dikaji. Selain itu, perbandingan terapeutik α-Mangostin dan perencat NF-κB, BAY-11-7082 juga telah dinilai. Struktur α-Mangostin juga telah dipastikan melalui NMR dan FTIR. Seterusnya, kajian ini telah mengenal pasti kadar kepekatan optimum α-Mangostin yang tidak toksik terhadap HUVECs. Ekspresi molekul lekat telah dilakukan melalui pemblotan Western dan sekresi sitokin telah dinilai melalui ELISA. Melalui analisis sel keviabelan, kajian ini mendapati bahawa nilai IC₅₀ α-Mangostin adalah 10.69 μM. α-Mangostin telah mengurangkan ekspresi E-selektin, VCAM-1 dan ICAM-1. Di samping itu, sekresi IL-6 juga telah diturunkan secara signifikan dengan kepekatan 1 μM dan 10 μM menunjukkan kesepadanan. Kajian ini turut menunjukkan bahawa molekul lekat telah diturunkan oleh α-Mangostin lebih banyak berbanding BAY-11-7082, sekali gus membawa kepada kemungkinan α-Mangostin boleh merencat keradangan melangkaui NF-κB seperti melalui p38 dan MAPK. Penemuan terkumpul ini membuktikan bahawa α-Mangostin merupakan sebatian yang mempunyai potensi terapeutik terhadap sepsis yang berpunca daripada kegagalan fungsi endotelial.

Kata kunci: α-Mangostin; Garcinia mangostana; keradangan; sel endotelial; sepsis

 

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*Pengarang untuk surat-menyurat; email: ahdezulaikha@unimas.my