Inhibitory effects of tangeretin and trans-ethyl caffeate on the HMG-CoA reductase activity: Potential agents for reducing cholesterol levels

Inten Pangestika; Efriyana Oksal; Tengku Sifzizul Tengku Muhammad; Hermansyah Amir; Desy Fitrya Syamsumir; Mohd Effendy Abdul Wahid; Yosie Andriani

doi:10.1016/j.sjbs.2020.06.010

Inhibitory effects of tangeretin and trans-ethyl caffeate on the HMG-CoA reductase activity: Potential agents for reducing cholesterol levels

Saudi J Biol Sci. 2020 Aug;27(8):1947-1960. doi: 10.1016/j.sjbs.2020.06.010. Epub 2020 Jun 17.

Authors

Inten Pangestika¹, Efriyana Oksal¹, Tengku Sifzizul Tengku Muhammad^{1

2}, Hermansyah Amir³, Desy Fitrya Syamsumir¹, Mohd Effendy Abdul Wahid⁴, Yosie Andriani¹

Affiliations

¹ Institute of Marine Biotechnology, Universiti Malaysia Terengganu, Mengabang Telipot, 21030 Kuala Nerus, Terengganu, Malaysia.
² Research Management Center, Universiti Malaysia Terengganu, Mengabang Telipot, 21030 Kuala Nerus, Terengganu, Malaysia.
³ Educational Chemistry Program, Faculty of Teacher Training and Education, Bengkulu University, Bengkulu 38371, Indonesia.
⁴ School of Fisheries and Aquaculture Sciences, Universiti Malaysia Terengganu, Mengabang Telipot, 21030 Kuala Nerus, Terengganu, Malaysia.

Abstract

One of the pathways to reduce cholesterol production in the liver is through the inhibition of HMG-Coa reductase (HMGCR) by current drugs, statins. However, these have side effects if consumed in prolonged periods. Tangeretin and trans-ethyl caffeate as alternative drugs in reducing hypercholesterolemia and preventing atherosclerosis have never been reported. Their effects on inhibiting HMGCR activity were investigated through enzymatic method (in vitro and in vivo). The toxicity property was analyzed on the Serum Glutamate Oxalate Transaminase (SGOT)/Serum Glutamate Piruvate Transaminase (SGPT) levels and rat liver histology. The results showed that both compounds inhibited HMGCR activity significantly compare to the control simvastatin (p < 0.05). Tangeretin which showed very good activity in inhibiting HMGCR (83.8 of % inhibition, equal to simvastatin) was selected and used for anti-hypercholesterolemia in vivo assessment. Furthermore, tangeretin was shown to effectively reduced Total Cholesterol (TC) and Low Density Lipoprotein (LDL), and increased High Density Lipoprotein (HDL) levels significantly compared to the simvastatin group (p < 0.05). Tangeretin group was also proven to inhibit HMGCR rat liver activity significantly compare to the control simvastatin (p < 0.05). The toxicity study on the SGOT/SGPT levels and liver histology revealed that there were no side effects after administration by tangeretin. Results found that both tangeretin and trans-ethyl caffeate are potent candidates as anti-hypercholesterolemia agent in vitro. In addition, tangeretin was also shown to be safe and suitable as an alternative treatment for controlling hypercholesterolemia in vivo as well as have potency for preventing atherosclerosis.

Keywords: HMG-CoA reductase; Hypercholesterolemia; Tangeretin; Trans-ethyl caffeate.