Suppressive Effects of Ginsenoside Rh1 on HMGB1-Mediated Septic Responses

Abstract

High mobility group box 1 (HMGB1) is considered as a late mediator of sepsis and the inhibition of HMGB1-mediated severe inflammatory responses, and restoration of endothelial integrity have emerged as attractive therapeutic strategies for the management of sepsis. Ginsenoside Rh1, a protopanaxatriol type ginsenoside, is one of the major bioactive components of Korean red ginseng, which has been increasingly used for enhancing cognition and physical health worldwide. Ginsenoside Rh1 exhibits potent biological activities such as antistress, anti-oxidant, anti-inflammatory and immunomodulatory effects. We examined the effects of ginsenoside Rh1 on HMGB1-mediated septic responses and survival rate in a mouse model of sepsis. Ginsenoside-Rh1 was administered after the HMGB1 challenge. The antiseptic activity of ginsenoside Rh1 was determined by measuring the permeability, leukocyte adhesion and migration, activation of pro-inflammatory proteins in HMGB1-activated human umbilical vein endothelial cells (HUVECs) and mice, and the survival rate in a sepsis mouse model. Ginsenoside Rh1 significantly reduced HMGB1 release in lipopolysaccharide (LPS)-activated HUVECs. Furthermore, ginsenoside Rh1 suppressed the production of tumor necrosis factor (TNF)-[Formula: see text], interleukin (IL)-6, activation of nuclear factor (NF)-[Formula: see text]B and extracellular signal-regulated kinase (ERK) 1/2 by HMGB1. Ginsenoside Rh1 also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. In addition, treatment with ginsenoside Rh1 reduced the cecal ligation and puncture (CLP)-induced release of HMGB1, sepsis-related mortality and tissue injury in vivo. Our results indicated that ginsenoside Rh1 might be useful in the treatment of sepsis by targeting HMGB1.

Influence of Herbal Medicines on HMGB1 Release, SARS-CoV-2 Viral Attachment, Acute Respiratory Failure, and Sepsis. A Literature Review

“…Ginsenoside Rh1 also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. In addition, treatment with ginsenoside Rh1 reduced the CLP-induced release of HMGB1, sepsis-related mortality and tissue injury in vivo [103].…”

Chinese Herbal Medicine for the Treatment of Depression: Effects on the Neuroendocrine-Immune Network

“…For instance, ginsenosides Rg1, Rg3, Rh1, Rh3, Rb1, Rk1, and Rf from Panax ginseng C.A. Meyer have been demonstrated to exhibit dual actions against neuroinflammation and hyperactivation of the HPA axis [106,108,[206][207][208][209][210][211][212][213][214][215], while 3,6'-disinapoyl sucrose and the oligosaccharide esters-enriched fraction, YZ50, from Polygala tenuifolia Willd have been shown to possess bioactivity that de-hyperactivates the HPA axis [216][217][218]. Additionally, poricoic acid A, isolated from Poria cocos (Schw.)…”

Biapenem as a Novel Insight into Drug Repositioning against Particulate Matter-Induced Lung Injury

“…For spectrophotometric quantification of MLMVEC permeability in response to increasing concentrations of PIPM in vitro, the flux of Evans blue-bound albumin across functional cell monolayers was measured using a modified two-compartment chamber model, as previously described [46][47][48]. For in vivo assays, mice in the BIPM or DEX groups were injected intravenously after the intratracheal instillation of PM 2.5 (10 mg/kg mouse body weight in 50 µL of saline) as described above.…”

“…Six hours later, mice were euthanized by cervical dislocation and BALF was collected. In vivo permeability was measured using an ELISA plate reader as described previously [46][47][48].…”