Mechanism of Action of Acalypha Indica L. Root Ethanol Extract in Obesity Animal Model: Focus on Lipid Profile, Anti-Proinflammatory Adipokine and Adhesion Molecular Through PPAR-α pathway
By: apt. Rani Wardani Hakim, S.Si., M.Biomed
Cases of obesity worldwide have now increased 3 times compared to 1975. In Indonesia, based on data from the Basic Health Research (Riskesdas) in 2018, adults with obesity increased by 21.8 percent compared to the 2013 Riskesdas data. fructose is directly related to the development of obesity and complications of the metabolic syndrome. The incidence and prevalence of obesity has increased along with the increase in fructose consumption in the last 40 years. A high-fructose diet is widely consumed by young adults and children at this time, especially in the form of high fructose corn syrup (HFCS), which is widely contained in beverages and packaged foods. Consumption of a high-fructose diet continuously is at risk of causing obesity and its complications. In obesity conditions, fat accumulation occurs, especially in the abdomen (visceral) so that fat cells undergo changes, one of which is the release of inflammatory mediators (inflammatory) that can cause complications of cardiovascular disease. One of the cardiovascular complications that often accompanies obesity is a disorder of fat metabolism (dyslipidemia), namely high values of total cholesterol, VLDL-cholesterol, LDL-cholesterol, triglycerides, and low values of HDL-cholesterol. Cardiovascular disease can pose a serious economic burden on a family and will increase the burden of health costs in communities around the world.
Currently, there are intensive efforts to develop new drug candidates derived from herbal plants. This is because conventional therapy to treat obesity and dyslipidemia causes many side effects, including gastrointestinal disorders. One of the herbs that are useful for treating cardiovascular complications is cat root or earrings which has the scientific name Acalypha indica Linn. (Ai). In India, Ai has been empirically proven to reduce the symptoms of diabetes, hyperlipidemia and complications of hypertension. Acalypha indica is also a plant that is easily available and grows wild in Indonesian nature. Previous research has shown that Ai leaf extract contains a lot of phenolic compounds, including the flavonoid group, which has antioxidant and anti-inflammatory effects which are the basis for overcoming obesity conditions related to metabolic syndrome. Polyphenol compounds work as antioxidants that counteract free radicals that are released in the inflammatory process in obesity conditions. There are studies that prove that consumption of a diet rich in polyphenolic compounds in obese conditions may not be able to lose weight, but can prevent complications of obesity. Research using Ai roots is still very limited, while recent studies have shown that Ai roots contain the highest phenolic compounds compared to leaves and stems.
This study aims to prove the mechanism of action of Ai root ethanol extract in obese animal models focusing on fat profiles, inflammatory mediators released by fat cells and adhesion molecules in the aorta via the PPAR-α pathway. Based on the results of previous studies, Ai has been shown to work through the PPAR-α pathway, which is the same mechanism of action as fibrates (gemfibrozil) triglyceride-lowering drugs. The Ai compounds responsible for the mechanism of action, namely nicotiflorin, geraniin and kaempferol will be analyzed based on the binding interaction between Ai and the target protein using molecular docking studies.
In this study, 24 male Sprague-Dawley rats were used which were given a high-fructose cholesterol (DTFK) diet for 16 weeks, as controls were rats given a normal diet. The DTFK feed given was in the form of 20-30 grams of standard feed per rat that had been mixed with 10% cholesterol obtained from quail egg yolks and 1.5 mL of 55% fructose solution which was fed to rats twice a day for 16 weeks (1.65 g of fructose). /day). The experimental animal groups were divided as follows: Normal diet group; DTFK; DTFK+Ai with 400mg/kgBB; and DTFK + gemfibrozil 31 mg/kgBW. Therapy was given in the morning for 8 weeks continuously with DTFK once a day in the afternoon orally using a probe. Parameters measured were initial and final body weight, Lee’s index (rat body mass index), serum lipid profile; inflammation marker compounds known as inflammatory adipokines, namely adiponectin, leptin, TNF-, and IL-6; adhesion molecules due to inflammation, namely VICAM-1, and ICAM-1, as well as PPAR-α levels. The percentage of fat cell size and the number of macrophages that appear on the histology is crown like structure (CLS). Seluruh data hasil penelitian dianalisis secara statisitik.
Berdasarkan hasil penelitian ini, Ai secara bermakna dapat mencegah kenaikan berat badan tikus yang diinduksi DTFK dengan mempertahankan nilai Indeks Lee <300 (mencegah obesitas). Ditemukan juga bahwa Ai menurunkan kadar kolesterol, trigliserida, dan meningkatkan HDL-kolesterol walaupun tidak berbeda bermakna secara statistik. Selain itu, Ai dapat menurunkan kadar adipokin proinflamasi TNF-α, IL-6 dan leptin; serta menurunkan persentase ukuran adiposit pada luas 1000-4000 /m2 secara bermakna. Pemberian Ai juga meningkatkan kadar adipokin antiinflamasi adiponektin, menurunkan CLS, meningkatkan PPAR-α di jaringan lemak viseral serta menurunkan ekspresi VCAM-1, ICAM-1 di jaringan aorta, meskipun tidak bermakna secara stastistik. Oleh karena itu dapat disimpulkan bahwa pemberian Ai memberikan efek protektif dengan menjaga indeks massa tubuh dan menurunkan kadar senyawa penanda proinflamasi yang dilepaskan jaringan lemak viseral yang menjadi kunci timbulnya berbagai komplikasi obesitas. Efek Ai ini sebagian dilakukan melalui pengaruhnya terhadap ekpresi PPAR-a di jaringan lemak viseral. Masih diperlukan penelitian lebih lanjut untuk membuktikan mekanisme kerja Ai terhadap obesitas dan komplikasinya.