Respons Bifasik dan Modulasi Indeks Aterogenik Ekstrak Etanol Moringa oleifera pada Model Zebrafish Diet-Induced Obesity: Sebuah Evaluasi Farmakologis
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Latar Belakang: Dislipidemia terkait obesitas merupakan faktor risiko utama kardiovaskular. Moringa oleifera kaya akan fitosterol dan flavonoid yang berpotensi sebagai agen hipolipidemik. Namun, profil farmakodinamik dan respons bergantung-dosis (dose-dependent) pada model in vivo masih belum sepenuhnya dipahami, terutama terkait fenomena hormesis pada ekstrak kasar. Tujuan: Mengevaluasi efek modulasi profil lipid dan indeks aterogenik ekstrak etanol daun M. oleifera pada zebrafish model Diet-Induced Obesity (DIO). Metode: Zebrafish betina wild-type diinduksi obesitas melalui protokol overfeeding Artemia nauplii (model DIO) dan dialokasikan ke dalam lima kelompok (n=9-10 per kelompok pada analisis akhir): kontrol non-DIO, kontrol DIO, DIO + ekstrak 0,56 ppm, DIO + ekstrak 1,12 ppm, dan DIO + ekstrak 2,24 ppm. Setelah 40 hari, jaringan adiposa viseral diekstraksi untuk analisis kolorimetrik lipid. Indeks aterogenik (AI) dihitung sebagai proksi risiko kardiovaskular berbasis rasio lipoprotein. Hasil: Induksi DIO secara signifikan meningkatkan kolesterol total dan indeks aterogenik. Menariknya, ekstrak M. oleifera menunjukkan respons bifasik. Dosis 0,56 ppm secara signifikan merestorasi profil lipid dan menurunkan rasio LDL/HDL (AI) mendekati kelompok non-DIO (p<0,05), meskipun variabilitas antar-individu yang cukup besar pada dosis ini perlu diinterpretasi secara hati-hati. Sebaliknya, dosis 1,12 ppm gagal memperbaiki profil lipid dan justru memperburuk rasio aterogenik, yang secara tentatif mengindikasikan adanya batas terapeutik (therapeutic window) dan kemungkinan pergeseran ke arah pro-oksidan/stres metabolik pada dosis lebih tinggi. Pada dosis tertinggi (2,24 ppm), kolesterol total dan AI menunjukkan pemulihan parsial dibandingkan dosis 1,12 ppm; temuan sekunder ini kurang konsisten dibandingkan respons pada dosis 0,56 ppm dan memerlukan penelitian lebih lanjut sebelum diinterpretasikan secara mekanistik. Kesimpulan: Ekstrak etanol M. oleifera menunjukkan efek hipolipidemik yang paling konsisten pada dosis terendah yang diuji (0,56 ppm) melalui modulasi indeks aterogenik. Temuan ini menyoroti pentingnya standardisasi dosis serta karakterisasi toksikologis dan fitokimia lebih lanjut pada pengembangan fitofarmaka untuk menghindari efek paradoksikal
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