Hericium erinaceus Inhibits TNF‐α‐Induced Angiogenesis and ROS Generation through Suppression of MMP‐9/NF‐κB Signaling and Activation of Nrf2‐Mediated Antioxidant Genes in Human EA.hy926 Endothelial Cells

Abstract

Hericium erinaceus (HE) is an edible mushroom that has been shown to exhibit anticancer and anti-inflammatory activities. We investigated the antiangiogenic and antioxidant potentials of ethanol extracts of HE in human endothelial (EA.hy926) cells upon tumor necrosis factor-α- (TNF-α-) stimulation (10 ng/mL). The underlying molecular mechanisms behind the pharmacological efficacies were elucidated. We found that noncytotoxic concentrations of HE (50–200 μg/mL) significantly inhibited TNF-α-induced migration/invasion and capillary-like tube formation of endothelial cells. HE treatment suppressed TNF-α-induced activity and/or overexpression of matrix metalloproteinase-9 (MMP-9) and intercellular adhesion molecule-1 (ICAM-1). Furthermore, HE downregulated TNF-α-induced nuclear translocation and transcriptional activation of nuclear factor-κB (NF-κB) followed by suppression of I-κB (inhibitor-κB) degradation. Data from fluorescence microscopy illustrated that increased intracellular ROS production upon TNF-α-stimulation was remarkably inhibited by HE pretreatment in a dose-dependent manner. Notably, HE triggered antioxidant gene expressions of heme oxygenase-1 (HO-1), γ-glutamylcysteine synthetase (γ-GCLC), and glutathione levels, which may contribute to inhibition of ROS. Increased antioxidant status was associated with upregulated nuclear translocation and transcriptional activation of NF-E2 related factor-2 (Nrf2) in HE treated cells. Our findings conclude that antiangiogenic and anti-inflammatory activities of H. erinaceus may contribute to its anticancer property through modulation of MMP-9/NF-κB and Nrf2-antioxidant signaling pathways.

Protective Effects of Total Saponins of Aralia elata (Miq.) on Endothelial Cell Injury Induced by TNF-α via Modulation of the PI3K/Akt and NF-κB Signalling Pathways

“…However, surprisingly, we suggested in the current study that TAS administration for 2 h prior to TNF-α incubation dramatically prevented the HUVECs from TNF-α-triggered apoptosis by suppressing the overexpression of inflammatory factors, decreasing the viable apoptotic cell ratio, suppressing DNA fragmentation, and reducing caspase-3 activation. In addition, inflammatory cytokine-induced injury is a critical aetiology of TNF-α-induced endothelial damage [33]. Our results verified that TNF-α administration substantially increased the levels of inflammatory cytokines, such as interleukins, MCP-1, MMP-2, and MMP-9, that mainly contribute to the development of vessel dysfunction in atherosclerosis.…”

Allicin Decreases Lipopolysaccharide-Induced Oxidative Stress and Inflammation in Human Umbilical Vein Endothelial Cells through Suppression of Mitochondrial Dysfunction and Activation of Nrf2

“…HO-1 is an important inducible antioxidant enzyme in vascular tissue. Although recent studies have demonstrated that Nrf2 has a role in protecting against hyperoxic damage [18] and in angiogenesis [19, 20] in human endothelial cells, the underlying molecular mechanism by which allicin induces Nrf2 activation has not been fully elucidated.…”

Chondroprotective Effects of a Standardized Extract (KBH-JP-040) from Kalopanax pictus, Hericium erinaceus, and Astragalus membranaceus in Experimentally Induced In Vitro and In Vivo Osteoarthritis Models

“…Hence, arthritis treatment is targeted at the inflammatory components, leading to the alleviation of pain and swelling [ 24 ]. Several studies have demonstrated the anti-inflammatory properties of KP, HE, and AM [ 15 , 18 , 27 ] and/or their ingredients liriodendrin [ 16 , 28 ], betulin [ 29 , 30 ], and formononetrin [ 31 , 32 ]. Therefore, KBH-JP-040 from HE, KP, and AM was used in experimental rat chondrocytes and rabbit OA models in an effort to reduce inflammation, protect cartilage damage, relieve pain and improve joint pathology.…”

“…It is worth pointing out that the pharmacological functions of many compounds from KP, especially kalopanaxsaponin-A, have been shown to inhibit the overexpression of TNF-α and IL-1β and downregulation of COX-2 expression via modulating NF-κB/AP-1 [ 17 , 18 , 41 ]; and that HE treatment suppressed TNF-α-induced overexpression of MMP-9 and downregulated the nuclear translocation and transcriptional activation of NF-κB, followed by suppression of I-κB degradation [ 15 ]. Friedman [ 21 ] also reported that HE extracts reduce the expression of the matrix metalloproteinases MMP-2, MMP-9, COX-2, and 5-LOX in cells, which are all overexpressed in arthritic conditions.…”

“…Recent studies on the complementary treatment of OA have focused on traditional herbal medicines [ 2 , 3 , 12 ]. Kalopanax pictus (KP) [ 13 , 14 ], Hericium erinaceus (HE) [ 15 ], and Astragalus membranaceus (AM) [ 10 ] are widely used in Korean traditional medicine safely and reliably for the treatment of multiple diseases, including arthritis and inflammatory diseases. The major constituents of KP have been identified are liriodendrin, kalopanaxsaponin (A, B, C, D, E, F, G, H, I, J, and K), syringin, erythrakine etc.…”