Efek Ekstrak Kumis Kucing, Lengkuas, Kencur, dan Kelor terhadap Inhibisi Lipase Pankreas in Vitro dan Profil Metabolit Tikus Obesitas

Abstract

Obesitas disebut sebagai pandemi global dan biasanya diobati dengan orlistat, karena dapat menghambat penyerapan lemak dengan menginhibisi enzim lipase pankreas. Namun, jika dikonsumsi jangka panjang dapat menyebabkan efek serius, seperti gagal hati dan ginjal. Kumis kucing, lengkuas, kencur, dan kelor merupakan tanaman obat tradisional yang banyak digunakan di Indonesia untuk berbagai penyakit, dan terbukti sebagai antiobesitas berdasarkan meta-analisis. Namun, efektivitas masing-masing tanaman masih dapat ditingkatkan dengan cara formulasi seperti pada pengobatan tradisional asal Cina. Dengan demikian, penelitian ini bertujuan membandingkan efektivitas ekstrak tunggal dan beragam kombinasi dari kumis kucing, lengkuas, kencur, dan kelor sebagai inhibitor lipase pankreas secara in vitro dan mengevaluasi efek antiobesitas formula terbaik secara in vivo menggunakan tikus yang diinduksi pakan tinggi lemak. Penelitian dimulai dengan masing-masing sampel disonikasi dan dirancang menjadi 17 formula. Inhibisi lipase diukur secara kolorimetri. Lengkuas dan kelor, sebagai formula terbaik diberikan pada tikus SD jantan (n=25), yang dibagi menjadi kelompok normal (sehat), HFD (HFD 49 hari), orlistat (HFD 28 hari, lalu orlistat 21 hari), moringa (HFD dan ekstrak kelor 49 hari), dan galangal (HDF dan ekstrak lengkuas 49 hari). Darah dipreparasi dan diuji kadar profil lipid, uji aktivitas enzim alanin aminotransferase (ALT), aspartat aminotransferase (AST), superoksidase dismutase (SOD), dan glutation peroksidase (GSH-Px). Hati dan ginjal dilakukan histopatologi dengan pewarnaan hematoksilin-eosin. Seluruh data yang diperoleh dianalisis menggunakan one-way analysis of variance menggunakan R Studio. Inhibisi lipase tertinggi diamati pada ekstrak tunggal lengkuas dan kelor sebesar 94,38% dan 84,12%, yang mengindikasikan adanya efek aditif. Bobot badan tikus setelah pemberian ekstrak kelor meningkat 11,50%, sementara ekstrak lengkuas justru sebaliknya. Kelompok moringa juga menunjukkan peningkatan intake pakan hingga 27,68%, sedangkan penurunan intake galangal mencapai 21,94%. Nilai BMI tikus yang diberi ekstrak kelor juga menurun secara signifikan. Kadar profil lipid setelah perlakuan juga tergolong normal, bahkan ekstrak kelor menurunkan TC hingga 1,20%. Hal ini diduga karena kelor memiliki aktivitas inhibisi lipase pankreas yang lebih tinggi sehingga menghambat penyerapan lemak dan pada akhirnya bobot menurun, meskipun intake pakan meningkat. Aktivitas enzim ALT dan AST kelompok moringa dan galangal tergolong normal dan tidak berbeda signifikan terhadap orlistat. Pemberian kedua ekstrak juga meningkatkan aktivitas enzim SOD dan GSH-Px. Hasil histopatologi menunjukkan adanya perlemakan hati setelah pemberian ekstrak lengkuas, di mana tidak berbeda signifikan dari pemberian HFD. Sementara ekstrak kelor terbukti menurunkan perlemakan di hati. Meskipun demikian, kedua ekstrak tidak menyebabkan kerusakan ginjal yang signifikan.

Obesity is recognized as a global pandemic and is commonly managed by orlistat, which inhibits fat absorption by targeting pancreatic lipase enzymes. Prolonged administration of orlistat may result in severe adverse effects, including hepatic and renal failure. Orthosiphon aristatus, Alpinia galangal, Kaemferia galangal, and Moringa oleifera are traditional medicinal plants extensively utilized in Indonesia for various health disease and have demonstrated anti-obesity properties in meta-analyses. The therapeutic efficacy of these plants may be further enhanced through formulation strategies similar to those used in traditional Chinese medicine. This study aimed to compare the effectiveness of single extracts and various combinations of the four herbals as pancreatic lipase inhibitors in vitro, and to evaluate the anti-obesity effects of the most effective formulation in vivo using a high-fat diet-induced mouse model. Each sample was sonicated and formulated into 17 variants. Lipase inhibition was measured using a colorimetric assay. The two most effective formulations, galangal and moringa, were administered to male Sprague-Dawley rats (n=25), which were assigned to five groups: normal (healthy rats), HFD (HFD for 49 days), orlistat (HFD for 28 days, then followed by orlistat for 21 days), moringa (HFD with moringa extract for 49 days), and galangal (HFD with galangal extract for 49 days). Blood samples were collected for lipid profile analysis. Activities of ALT, AST, SOD, and GSH-Px were measured. Liver and kidney tissues were examined by histopathology with haematoxylin-eosin staining. Data were analyzed using oneway ANOVA in R Studio. The highest lipase inhibition was observed in single extracts of galangal and moringa at 94.38% and 84.12%, indicating an additive effect. The body weight of rats increased by 11.50% after administration of moringa extract, while galangal extract had the opposite effect. The moringa group also showed an increase in feed intake of up to 27.68%, while galangal intake decreased by 21.94%. The BMI values of rats administered moringa extract also reduced significantly. Lipid profile levels were also in normal range, with moringa extract reducing TC by 1.20%. It indicates that moringa's higher pancreatic lipase inhibitory activity, which inhibits fat absorption and ultimately leads to weight loss, despite increased feed intake. ALT and AST activities in the moringa and galangal groups remained within the normal range and were comparable to those observed with orlistat. Both moringa and galangal extracts increased SOD and GSH-Px activities. Histopathological analysis indicated that galangal extract induced fatty liver, mirroring the effects of HFD administration, whereas moringa extract reduced the incidence of fatty liver. Neither extract induced significant kidney damage.