Isorhamnetin Has Potential for the Treatment of Escherichia coli-Induced Sepsis

Abstract

Isorhamnetin is a flavonoid that is abundant in the fruit of Hippophae rhamnoides L. It is widely studied for its ability to modulate inflammatory responses. In this study, we evaluated the potential of isorhamnetin to prevent gram-negative sepsis. We investigated its efficacy using an Escherichia coli-induced sepsis model. Our study reveals that isorhamnetin treatment significantly enhances survival and reduces proinflammatory cytokine levels in the serum and lung tissue of E. coli-infected mice. Further, isorhamnetin treatment also significantly reduces the levels of aspartate aminotransferase, alanine amino transferase and blood urea nitrogen, suggesting that it can improve liver and kidney function in infected mice. Docking studies reveal that isorhamnetin binds deep in the hydrophobic binding pocket of MD-2 via extensive hydrophobic interactions and hydrogen bonding with Tyr102, preventing TLR4/MD-2 dimerization. Notably, binding and secreted alkaline phosphatase reporter gene assays show that isorhamnetin can interact directly with the TLR4/MD-2 complex, thus inhibiting the TLR4 cascade, which eventually causes systemic inflammation, resulting in death due to cytokine storms. We therefore presume that isorhamnetin could be a suitable therapeutic candidate to treat bacterial sepsis.

Isorhamnetin Ameliorates Aspergillus fumigatus Keratitis by Reducing Fungal Load, Inhibiting Pattern-Recognition Receptors and Inflammatory Cytokines

“…7 Yang et al 49 proved that isorhamnetin treatment not only can significantly reduce the level of inflammatory cytokines in bronchoalveolar lavage fluid of mice, but also can protect mice from LPS-induced acute lung injury through inhibiting the activation of cyclooxygenase-2. Moreover, a recent study 50 revealed that isorhamnetin directly interacts with TLR4/MD-2 complex to prevent TLR4-mediated inflammatory cascade, which is consistent with the study by Kim et al 21 that isorhamnetin suppressed LPS induced inflammation in mouse microglia by inactivating NF-κB and blocking TLR4 pathway, reducing the expression of inflammatory factors such as TNF-α and IL-1β. In this study, we detected the expression of PRRs including TLR-2, TLR-4 and Dectin-1, and downstream inflammatory factors TNF-α and IL-1β in vitro and in vivo.…”

Antibacterial activity of Piper betle ethanolic extract against ESBL producing Escherichia coli in sepsis induced BALB/c mice

“…This result is not significantly different compared to treatment group. As our knowledge, there was no other study describing the effect of Piper betle extract towards sepsis induced mice, however Chauhan et al, 2019, describe significant improvement of sepsis induced mice in isorhamnetin treated group [28].…”

“…Another study revealed that all treated group mice survived during observation period [28], however the survival rate of treated group mice was longer only 6 hours compared to positive control group. Several factors such as bioavailability, metabolism, and excretion may affect the effect of the extract administered orally.…”

The bioactive components as well as the nutritional and health effects of sea buckthorn

“…Isorhamnetin, a avonoid abundant in the fruit of SB, showed a variety of anti-inammatory activities. [46][47][48][49] Besides ursolic acid and oleanolic acid, 45 two well-known anti-oxidant and anti-inammatory agents widely applied in cosmetics, casuarinin was also showed potent anti-inammatory property. 50 The detailed parameters of experiments including experimental models, dosage and possible mechanisms were listed in ESI Tab.…”