The Anti-Inflammatory Effects of Flavanol-Rich Lychee Fruit Extract in Rat Hepatocytes

Abstract

Flavanol (flavan-3-ol)-rich lychee fruit extract (FRLFE) is a mixture of oligomerized polyphenols primarily derived from lychee fruit and is rich in flavanol monomers, dimers, and trimers. Supplementation with this functional food has been shown to suppress inflammation and tissue damage caused by high-intensity exercise training. However, it is unclear whether FRLFE has in vitro anti-inflammatory effects, such as suppressing the production of the proinflammatory cytokine tumor necrosis factor α (TNF-α) and the proinflammatory mediator nitric oxide (NO), which is synthesized by inducible nitric oxide synthase (iNOS). Here, we analyzed the effects of FRLFE and its constituents on the expression of inflammatory genes in interleukin 1β (IL-1β)-treated rat hepatocytes. FRLFE decreased the mRNA and protein expression of the iNOS gene, leading to the suppression of IL-1β-induced NO production. FRLFE also decreased the levels of the iNOS antisense transcript, which stabilizes iNOS mRNA. By contrast, unprocessed lychee fruit extract, which is rich in flavanol polymers, and flavanol monomers had little effect on NO production. When a construct harboring the iNOS promoter fused to the firefly luciferase gene was used, FRLFE decreased the luciferase activity in the presence of IL-1β, suggesting that FRLFE suppresses the promoter activity of the iNOS gene at the transcriptional level. Electrophoretic mobility shift assays indicated that FRLFE reduced the nuclear transport of a key regulator, nuclear factor κB (NF-κB). Furthermore, FRLFE inhibited the phosphorylation of NF-κB inhibitor α (IκB-α). FRLFE also reduced the mRNA levels of NF-κB target genes encoding cytokines and chemokines, such as TNF-α. Therefore, FRLFE inhibited NF-κB activation and nuclear translocation to suppress the expression of these inflammatory genes. Our results suggest that flavanols may be responsible for the anti-inflammatory and hepatoprotective effects of FRLFE and may be used to treat inflammatory diseases.

Combination of citrus polymethoxyflavones, green tea polyphenols, and Lychee extracts suppresses obesity and hepatic steatosis in high‐fat diet induced obese mice

“…Previous studies indicate that lychee fruit extract contains oligomerized flavanols . Various in vitro and in vivo studies also demonstrated numerous biological activities of lychee fruit extract with oligomerized flavanols, including antioxidant, anticancer, antiviral , anti‐inflammatory , and improving insulin resistance . Dietary lychee fruit extract with oligomerized flavanols reduced adipose mass, adipocyte size, and adipokines secretion as well as hepatic steatosis in high fat diet‐fed mice through modulating multiple molecules such as PPARγ, mammalian target of rapamycin (mTOR)/SREBP‐1 and AMPK signaling .…”

Oligonol, a lychee fruit-derived low-molecular form of polyphenol mixture, suppresses inflammatory cytokine production from human monocytes

“…Such oligomerization can result in delivering increased levels of oligomeric proanthocyanidins likely by enhancing bioavailability compared to unoligomerized fruit and plant products [6]. Both in vivo and in vitro studies support the immune regulatory and anti-oxidative effects of Oligonol [8–13]. Decreased blood levels of IL-6 were reported in healthy humans after 4 weeks of Oligonol administration [10].…”

Flavanol‐rich lychee fruit extract alleviates diet‐induced insulin resistance via suppressing mTOR/SREBP‐1 mediated lipogenesis in liver and restoring insulin signaling in skeletal muscle

“…Both MCP‐1 and IL‐6 gene transcription are mediated by transcription factor, nuclear factor κB (NFκB) . Oligonol inhibited translocation of NFκB from cytosol to nucleus followed by reductions of target gene expression . Oligonol has been reported to inhibit NFκB activation under different pathological conditions including CCl4‐induced liver injury , diabetes‐induced liver and kidney damage , and dextran sulfate sodium‐induced colitis in vivo.…”

“…Oligonol (Amino Up Chemical Co., Sapporo, Japan) was derived from lychee fruit extract and green tea extract. Oligonol contained a polyphenol mixture of flavanols (≥80%) including 13–18% flavanol monomers (catechin, epicatechin, epicatechin gallate, and EGCG), 14–18% dimers (Procyanidin A1, A2, B1, and B2 and epicatechin‐EGCG), 2–6% trimers (Epicatechin‐procyanidin A2), and ≥ 45% other phenolic compounds (other trimers, tetramers, oligomers, and polymers) examined by HPLC . The acute and subchronic toxicity of oligonol has been evaluated by using rats .…”

“…Plant polyphenols such as epigallocatechin gallate (EGCG) and resveratrol have anti‐obesity properties to prevent obesity‐induced insulin resistance . Flavanol rich lychee extract, oligonol, consisting of catechins, procyanidins, and other phenolic compounds has been shown to reduce abdominal fat in health subjects, indicating that oligonol may ameliorate metabolic syndrome . Many recent studies further demonstrated that, similar to EGCG, oligonol inhibited adipogenesis via suppressing Akt/mTOR (mammalian target of rapamycin) and enhanced lipolysis via extracellular‐signal‐regulated kinases (ERK) activation in adipocytes .…”