Tesis

Efek amygdalin, 6-Shogaol, dan resveratrol terhadap penghambatan diferensiasi monosit menjadi makrofag subtipe M4: Studi in silico dan in vitro = Effects of amygdalin, 6-Shogaol, and resveratrol on differentiation inhibition of M4 macrophage derived monocyte: In silico and in vitro studies.

Penelitian ini membahas modulasi maturasi dan diferensiasi makrofag sebagai akibat aktivitas reseptor CXCL4 dan pengaruhnya terhadap ketidakstabilan plak aterosklerosis. Senyawa herbal seperti 6-shogaol, amygdalin, dan resveratrol menarik perhatian karena potensinya dalam sistem imun. Dalam penelitian ini, dilakukan dua metode. Pertama, in silico docking digunakan untuk mengeksplorasi potensi penemuan obat baru yang menargetkan modulasi makrofag akibat induksi kemokin CXCL4. Hasil analisis in silico menunjukkan afinitas pengikatan tertinggi amygdalin terhadap reseptor CXCL4 dibandingkan 6-shogaol atau resveratrol. Kedua, studi in vitro dilakukan menggunakan PBMC dari 11 subjek sehat yang dikultur dengan M-CSF, CXCL4, atau amygdalin (10ng/mL atau 20ng/mL) dengan pemeriksaan CD36 melalui teknik flowcytometri. Meskipun secara statistik tidak bermakna, terdapat kecendrungan peningkatan ekspresi CD36 pada kelompok yang diberikan 20ng/mL amygdalin, menunjukkan dampak pada fagositosis sel. Pemeriksaan ELISA menunjukkan kecendrungan peningkatan produksi TNF-α yang berkaitan dengan kemampuan fagositosis sel, sementara ekspresi MMP7 cenderung menurun, terkait dengan kemampuan adhesi molekul yang lebih rendah. Kesimpulannya, pemberian amygdalin berpotensi mencegah perkembangan makrofag M4 yang berperan dalam ketidakstabilan plak aterosklerosis. Namun, hasil ini memerlukan validasi lebih lanjut dengan jumlah sampel yang lebih besar dan variasi konsentrasi amygdalin. Meskipun demikian, penelitian ini memberikan wawasan penting tentang potensi obat baru untuk mengatasi masalah aterosklerosis melalui modulasi makrofag dan implikasi penting molekul TNF-α serta MMP7 yang perlu dieksplorasi lebih lanjut.
Kata Kunci : Makrofag M4, CXCL4/PF4, CXCR3, CCR1


This research discusses the modulation of macrophage maturation and differentiation as a result of CXCL4 receptor activity and its influence on atherosclerotic plaque instability. Herbal compounds such as 6-shogaol, amygdalin, and resveratrol have drawn attention due to their potential in the immune system. The study employed two methods. Firstly, in silico docking was used to explore the potential discovery of new drugs targeting macrophage modulation induced by CXCL4 chemokine. In silico analysis revealed that amygdalin had the highest binding affinity to the CXCL4 receptor compared to 6- shogaol or resveratrol. Secondly, in vitro studies were conducted using PBMCs from 11 healthy subjects, cultured with M-CSF, CXCL4, or amygdalin (at 10ng/mL or 20ng/mL) with CD36 examination using flow cytometry. Although not statistically significant, there was a tendency for increased CD36 expression in the group treated with 20ng/mL amygdalin, indicating an impact on cell phagocytosis. ELISA examination showed a trend of increased TNF-α production associated with enhanced cell phagocytosis, while MMP7 expression tended to decrease, indicating lower molecular adhesion capability. In conclusion, amygdalin administration has the potential to prevent the development of M4 macrophages, which play a role in atherosclerotic plaque instability. However, these findings require further validation with larger sample sizes and variations in amygdalin concentrations. Nonetheless, this research provides crucial insights into the potential of novel drugs to address atherosclerosis through macrophage modulation and the important implications of TNF-α and MMP7 molecules that need further exploration.
Keywords: M4 macrophage, CXCL4/PF4, CXCR3, CCR1