Lotus Seedpod Extracts Reduced Lipid Accumulation and Lipotoxicity in Hepatocytes

Abstract

Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic disorders, including hepatic lipid accumulation and lipotoxicity. Plant-derived polyphenols have attracted considerable attention in the prevention of NAFLD. Lotus seedpod, rich in polyphenols, is a traditional Chinese herbal medicine. Previous studies have showed that lotus seedpod possess radioprotective, antioxidant, anti-cancer, and anti-inflammatory activities. In this study, the in vitro hepatoprotective effect of lotus seedpod extract (LSE) and its main component epigallocatechin (EGC) was examined. Firstly, oleic acid (OA), an unsaturated fatty acid, was used to induce the phenotype of NAFLD in human hepatocytes, HepG2 cells. LSE dose-dependently improved the OA-induced viability loss of HepG2 cells. Non-cytotoxic concentrations of LSE or EGC abolished intracellular lipid accumulation and oxidative stress in the OA-treated cells. In addition, LSE and EGC showed a minor effect on autophagy, and potential in reducing OA-induced occurrence of apoptosis confirmed by morphological and biochemical features, including an increase in the formation of apoptotic bodies, the exposure of phosphatidylserine, and activation of caspases. Molecular data showed the anti-apoptotic effect of LSE might be mediated via downregulation of the mitochondrial pathway. Our data imply that EGC-enriched LSE potentially could be developed as an anti-NAFLD agent.

Flavonoids Identification and Pancreatic Beta-Cell Protective Effect of Lotus Seedpod

“…Some phytochemicals and antioxidants could ameliorate oxidative stress-induced cytotoxicity and injury. Our recent studies reported that LSE could improve OA-increased oxidative stress and lipotoxicity in hepatocytes [20]. LSE could also inhibit LPS-mediated hepatic inflammation and ROS generation [21]; however, its effect on oxidative stress in beta-cells in response to H 2 O 2 is still unknown.…”

“…Many previous studies have indicated that a high concentration of H 2 O 2 (more than 100 μM) acts in many cell types, particularly in beta-cells with their high secretory and low antioxidant capacities [ 22 , 28 ], and can mainly lead to apoptosis by directly attacking cellular macromolecules, nucleic acid, and membranes. Previous investigations have shown that LSE is a potent antioxidant agent [ 20 , 21 ]. As shown in Figure 2 b,c, LSE had protective effects toward H 2 O 2 -induced cell viability loss and insulin resistance in RIN-m5F cells.…”

“…Therefore, H 2 O 2 at 200 μM for 24 h was selected as a further cellular oxidative injury model. The MTT assay was also performed to determine the effect of the test LSE (0–100 μg/mL) alone on RIN-m5F cell growth and to further evaluate the non-cytotoxic concentrations [ 20 ].…”

“…Western blot analysis was carried out in accordance with a previously reported procedure [20]. After treatments, the whole-cell lysate was mixed with RIPA buffer, including 0.1% sodium dodecyl sulfate (SDS), 0.5% deoxycholic acid, 1% NP-40, 50 mM Tris-base saline (TBS), and 150 mM NaCl (pH value 7.5), and extracted by utilizing sonication.…”

“…In the literature, LSOPC scavenged reactive carbonyls and reduced advanced glycation end-products (AGEs) formation [17] and alleviated the symptoms and progression of nonalcoholic fatty liver disease (NAFLD) in a high-fat diet (HFD)-induced obesity rat model [18], as well as enhanced glucose homeostasis in a DM model of streptozotocin (STZ)-injected mice [19]. Our recent studies have also reported the hepatoprotective activity of lotus seedpod aqueous extracts (LSE) against an unsaturated fatty acid oleic acid (OA) and endotoxin lipopolysaccharide (LPS)-induced liver injury [20,21]. However, there are limited reports on the detailed characterization of LSE.…”