Potensi Sediaan Aphrofit® Yang Mengandung Eurycoma longifolia Jack. Terhadap Kualitas Sperma Dan Ekspresi Gen ATM dan GPX4 Pada Tikus Model Disfungsi Seksual Serta Mekanisme Aksinya Secara In Silico

Elya Manik, Prof. Dr. Mustofa, M.Kes., Apt. ; drg. Fara Silvia Yuliani, M.Sc., Ph.D.

2025 | Tesis | S2 Ilmu Kedokteran Dasar dan Biomedis

Latar Belakang: Disfungsi seksual akibat penggunaan fluoxetine dapat menurunkan kualitas sperma melalui stres oksidatif dan gangguan jalur perbaikan DNA. Sediaan kapsul Aphrofit® yang mengandung Eurycoma longifolia Jack. berpotensi sebagai agen protektif karena kandungan senyawa bioaktifnya seperti eurycomanone dan eurycomalactone.
Tujuan: Mengkaji aktivitas Aphrofit® dalam memperbaiki kualitas sperma pada tikus jantan disfungsi seksual akibat fluoxetine melalui metabolomic profiling dan mekanisme aksi secara in silico serta pegaruhnya pada ekspresi ATM dan GPX4.

Metode: Penelitian menggunakan desain post-test only control group dan repeated measured dengan enam kelompok perlakuan (KNO: Kelompok Negatif Normal; KNF: Kelompok Negatif model fluoxetine; KPC: fluoxetine + Kelompok Positif CoQ10; P1 - P3: fluoxetine + Aphrofit® masing-masing 45, 90, 180mg/KgBB. Metabolomic Profiling ekstrak E. longifolia Jack. dilakukan menggunakan LC-HRMS untuk identifikasi senyawa aktif dilanjutkan dengan mengkaji pengaruh pemberian sediaan pada berat badan, berat testis, kualitas sperma (motilitas, viabilitas, konsentrasi, morfologi), serta ekspresi gen ATM dan GPX4 melalui qRT-PCR.

Hasil: Profiling untargeted LC-HRMS ditemukan178 senyawa dari 25 golongan kimia dalam Aphrofit®. Terdapat 13 senyawa menunjukkan efek positif terhadap kualitas sperma berdasarkan pencarian literatur. Targeted profiling menunjukkan bahwa eurycomanone dan eurycomalactone merupakan senyawa quassinoid dominan dengan intensitas area tinggi. Uji in silico menunjukkan afinitas ikatan kuat terhadap ATM dan GPX4. Secara in vivo, Aphrofit® meningkat signifikan pada motilitas, viabilitas, dan morfologi normal sperma (terutama pada kelompok P3, p<0 p=0,013.>

Kesimpulan: Aphrofit® terbukti efektif meningkatkan kualitas sperma dan menginduksi ekspresi gen ATM dan GPX4. Senyawa quassinoid utama dalam E. Longifolia Jack yang terdeteksi adalah eurycomanone dan eurycomalactone.

Background: Sexual dysfunction induced by fluoxetine has been shown to impair sperm quality through oxidative stress & disruptions in DNA repair pathways. Aphrofit® capsules, containing Eurycoma longifolia Jack., hold potential as a protective agent due to their bioactive constituents, notably eurycomanone & eurycomalactone.
Objective: Assess the activity of Aphrofit® in improving sperm quality in fluoxetine-induced sexual dysfunction male rats through metabolomic profiling and in silico mechanism of action and its effect on ATM and GPX4 expression.
Methods: The study used a post-test-only control group design with repeated measures involving six treatment groups. KNO (normal negative control), KNF (fluoxetine-Induced Negative Model, KPC (fluoxetine + CoQ10 positive control); P1-P3: fluoxetine + Aphrofit® at 45, 90, & 180 mg/kg BW, respectively. Metabolomic profiling of E. longifolia Jack extract was performed using LC-HRMS to identify active compounds. Evaluations included body weight, testicular weight, & sperm parameters (motility, viability, concentration, & morphology), as well as ATM & GPX4 gene expression, which was analyzed using qRT-PCR.
Results: Untargeted LC-HRMS profiling identified 178 compounds belonging to 25 chemical classes in Aphrofit®, with 13 compounds demonstrating literature-supported positive effects on sperm quality. Targeted profiling revealed eurycomanone & eurycomalactone as dominant quassinoids with high peak intensities. In silico analysis showed strong binding affinities to ATM & GPX4 proteins. In vivo assessments indicated significant improvements in sperm motility, viability, & normal morphology (particularly in P3 group, p < 0 xss=removed>Conclusion: Aphrofit® effectively enhances sperm quality & induces the expression of ATM & GPX4 genes. Eurycomanone & Eurycomalactone were identified as the major quassinoids responsible for these effects

Kata Kunci : Eurycoma longifolia Jack., ATM, GPX4, In silico, In vivo, qRT-PCR, sperma