Ameliorative Effect of Vicenin-2 and Scolymoside on TGFBIp-Induced Septic Responses

Abstract

Transforming growth factor β-induced protein (TGFBIp) is an extracellular matrix protein whose expression in several cell types is greatly increased by TGF-β. TGFBIp is released by the human umbilical vein endothelial cells (HUVECs) and functions as a mediator of experimental sepsis. Cyclopia subternata is a medicinal plant commonly used in traditional medicine to relieve pain in biological processes. In this study, we investigated the antiseptic effects and underlying mechanisms of vicenin-2 and scolymoside, two active compounds in C. subternata against TGFBIp-mediated septic responses in HUVECs and mice. The anti-inflammatory activities of vicenin-2 or scolymoside were determined by measuring permeability, human neutrophils adhesion and migration, and activation of pro-inflammatory proteins in TGFBIp-activated HUVECs and mice. According to the results, vicenin-2 or scolymoside effectively inhibited lipopolysaccharide-induced release of TGFBIp and suppressed TGFBIp-mediated septic responses, such as hyperpermeability, adhesion and migration of leukocytes, and expression of cell adhesion molecules. In addition, vicenin-2 or scolymoside suppressed the production of tumor necrosis factor-α and interleukin 6 and activation of nuclear factor-κB and extracellular regulated kinases 1/2 by TGFBIp. Vicenin-2 or scolymoside reduced cecal ligation and puncture (CLP)-induced septic mortality and pulmonary injury. Collectively, these results indicate that vicenin-2 and scolymoside could be a potential therapeutic agent for treatment of various severe vascular inflammatory diseases via inhibition of the TGFBIp signaling pathway.

Structure Identification of ViceninII Extracted from Dendrobium officinale and the Reversal of TGF-β1-Induced Epithelial–Mesenchymal Transition in Lung Adenocarcinoma Cells through TGF-β/Smad and PI3K/Akt/mTOR Signaling Pathways

“…ViceninII exhibits significant anticancer activities that inhibit the growth of prostate cancer (PC-3, DU-145 and LNCaP cells) in-vitro and in-vivo [51,52] and induce apoptosis in hT-29 human colon cancer cells [53]. In addition, many critical literatures has been reported that ViceninII has shown anti-inflammatory effect through the inhibition of TGF-β-induced protein signaling pathway as well as induced apoptosis of lung cancer H23 cell via PI3K/Akt/mTOR signaling [54,55]. However, none of the previous investigations investigated the anti-metastasis effects and its molecular mechanism of ViceninII in lung adenocarcinoma A549 and H1299 cells.…”

The effects of flavonoids in experimental sepsis: A systematic review and meta‐analysis

“…As shown in Table 1, among the flavones tested, scolymoside (SCL) (26), vicenin‐2 (VCN) (29; Lee et al, 2015, 2020), and wogonin (WGN) (30) (Dai et al, 2021; Kwak et al, 2014) presented the most significant results of this class. These flavones increased both life expectancy and the survival rate of the animals with sepsis when compared with an untreated CLP group.…”

Antinociceptive Effect of Dendrobii caulis in Paclitaxel-Induced Neuropathic Pain in Mice

“…Rutin has attracted attention as a new antioxidant [77], and vicenin-2 has exhibited anticancer activity by inhibiting the growth of prostate cancer (DU-145, PC-3, and LNCaP cells) cells in vivo and in vitro [78,79] and by inducing apoptosis in HT-29 human colon cancer cells [80]. In addition, vicenin-2 has shown an anti-inflammatory effect by suppressing the protein signaling pathway triggered by TGFβ and inducing H23 cell death through PI3K/Akt/mTOR signaling [81,82]. Vicenin-2 is a major flavonoid component of D. caulis [78], and academic consensus suggests that flavonoids can cross the blood-brain barrier (BBB) and reach the central nervous system [83].…”