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.

Pandanus tectorius fruit, a natural product rich in tangeretin and ethyl caffeate, has been reported to have potential as anti-hypercholesterolemia agent via Scavenger Receptor Class B type 1 (SR-B1) pathway. However, due to its semi-polar properties, P. tectorius extract exhibits poor solubility when used as a medical remedy. The extract’s solubility can potentially be improved through a synthesis of nanoparticles of chitosan- P. tectorius fruit extract. This can also increase the extract’s SR-B1 gene expression activity. To date, no studies of nanoparticles of chitosan- P. tectorius fruit extract and its pathway via SR-B1 have been published anywhere. In this study, cytotoxicity properties against HepG2 were explored by MTT. Then luciferase assay was used to detect their effectiveness in increasing SR-B1 activity. An in vivo study using Sprague dawley was carried out to observe the extract nanoparticles’ effectiveness in reducing the cholesterol levels and the toxicity property in rat’s liver. As the results showed, the extract nanoparticles had no cytotoxic activity against HepG2 cells and exhibited higher SR-B1 gene expression activity than the non-nanoparticle form. As the in vivo study proved, nanoparticle treatment can reduce the levels of TC (197%), LDL (360%), and TG (109%), as well as increase the level of HDL cholesterol by 150%, in comparison to those for the untreated high-cholesterol diet group. From the toxicity study, it was found that there was non-toxicity in the liver. It can be concluded that nanoparticles of chitosan- P. tectorius fruit extract successfully increased P. tectorius fruit extract’s effectiveness in reducing hypercholesterolemia via SR-B1 pathway. Hence, it can be suggested that nanoparticles of chitosan- P. tectorius fruit extract is safe and suitable as an alternative treatment for controlling hypercholesterolemia via SR-B1 pathway.

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