Integrated Anti-Hyperlipidemic Bioactivity of Whole Citrus grandis [L.] Osbeck Fruits− Multi-Ation Mechanism Evidenced By the Animal– And Cell-Models
Changes in human life style have increased the incidence of obesity which has become a risk factor to human health. In Taiwan, the annual production of Citrus grandis [L.] reaches 75,000 tons, while the amount of waste fruits could reach 5%. We propose that abundant phytochemicls present in the wastes can be beneficial to attenuate obesity with hyperlipidemia. Animal Wistar rat model showed that pomelo flesh, peels, carpel (the segmental membrane), as well as the essential oil attenuated obese as well as hyperlipidemia, and AMPK-SREBP-PPARS pathway was involved. To further verify the mechanism, the HepG2 cell model was used to test some representative pomelo phytonutrients including limonene(Ln), γ-terpinene( γT), p-synephrine(SP), β-sitosterol(βS), and hesperidin(Hn). Data interestingly revealed it to be a multiple mechanism of anti-lipogenic bioactiviety via downregulating the enzymes involved in both the cholesterol and triacylglyceride de novo biosynthesis (in dorder of decreasing bioactivity): aetyl CoA carboxylase (Hn, SP, βS, Ln = γT); fatty acid synthase (Ln, γT, SP, βS, Hn); HMG-CoA synthase (Ln, Hn, SP, βS, γT); and HMG-CoA reductase (Hn, Ln, βS, γT, SP); and via upregulation of cholesterol-7α-monooxygenase (CYP7A1) (Hn, βS). In addition, all pomelo fruit parts enhanced the fecal crude lipid and sterol excretion capability. Thus, fruits of C. grandis can serve as a rather promising as well as an integrative antihyperlipidemic agent.