Panax notoginseng saponins suppress lipopolysaccharide‐induced barrier disruption and monocyte adhesion on bEnd.3 cells via the opposite modulation of Nrf2 antioxidant and NF‐κB inflammatory pathways

Abstract

Dysfunction of the blood‐brain barrier (BBB) is a prerequisite for the pathogenesis of many cerebral diseases. Oxidative stress and inflammation are well‐known factors accounting for BBB injury. Panax notoginseng saponins (PNS), a clinical commonly used drug against cerebrovascular disease, possess efficient antioxidant and anti‐inflammatory activity. In the present study, the protective effects of PNS on lipopolysaccharide (LPS)‐insulted cerebral microvascular endothelial cells (bEnd.3) were assessed and the underlying mechanisms were investigated. The results showed that PNS mitigated the decrease of Trans‐Endothelial Electrical Resistance, increase of paracellular permeability, and loss of tight junction proteins in bEnd.3 BBB model. Meanwhile, PNS suppressed the THP‐1 monocytes adhesion on bEnd.3 monolayer. Moreover, PNS prevented the pro‐inflammatory cytokines secretion and reactive oxygen species generation in bEnd.3 cells stimulated with LPS. Mechanism investigations suggested that PNS promoted the Akt phosphorylation, activated Nrf2 antioxidant signaling, and inhibited the NF‐κB activation. All the effects of PNS could be abolished by PI3K inhibition at different levels. Taken together, these observations suggest that PNS may act as an extrinsic regulator that activates Nrf2 antioxidant defense system depending on PI3K/Akt and inhibits NF‐κB inflammatory signaling to attenuate LPS‐induced BBB disruption and monocytes adhesion on cerebral endothelial cells in vitro.

25‑OH‑PPD inhibits hypertrophy on diabetic cardiomyopathy via the PI3k/Akt/GSK‑3β signaling pathway

“…These findings suggested that 25-OH-PPD was beneficial for the treatment of DM by reversing the complications of DMCM. This finding was consistent with a previous study that used diabetic rats in the presence of PPD and characterized the levels of collagen accumulation and the induction of cardiac hypertrophy and remodeling (11). DMCM is a major complication of DM and can induce cardiac dysfunction (dysfunction of sugar and fat metabolism) in diabetic patients (20).…”

“…PNS is a widely used traditional Chinese medicine extracted from the Sanqi or Tianqi plants. This agent exhibits a wide range of pharmacological and biochemical effects and can be used to treat specific diseases, such as cardiovascular and inflammatory disease, bleeding or pain due to injury, as well as trauma (11). Several chemical compounds and active ingredients have been isolated from PNS, including saponins, flavonoids and cyclopeptides.…”

Pro-Resolving Effect of Ginsenosides as an Anti-Inflammatory Mechanism of Panax ginseng

“…Ginsenoside Re enhanced the activation of Nrf2 in Aβ-induced SH-SY5Y cells [76]. The activation of the Nrf2-HO-1 pathway for M2 macrophage polarization is also supported by the findings that a red ginseng-derived saponin fraction suppressed inflammatory responses via the Nrf2-HO-1 pathway in an adipocyte-macrophage co-culture system [42], and that saponins from Panax notoginseng acted as an extrinsic regulator that activates the Nrf2 antioxidant defense system and inhibits NF-κB inflammatory signaling to attenuate LPS-induced monocyte adhesion on cerebral endothelial cells [77].…”

LC/MS Analysis of Saponin Fraction from the Leaves of Elaeagnus rhamnoides (L.) A. Nelson and Its Biological Properties in Different In Vitro Models

“…This extract ameliorated doxorubicin-induced chronic heart failure by inhibiting oxidative stress in rat model. Hu et al [ 37 ] also observed antioxidantive potential of P. notogineng saponins.…”