Alpinetin Attenuates Persistent Inflammation, Immune Suppression, and Catabolism Syndrome in a Septic Mouse Model

Abstract

Patients who survive the acute phase of sepsis can progress to persistent inflammation, immunosuppression, and catabolism syndrome (PICS), which usually results in extended recovery periods and multiple complications. Alpinetin is a flavonoid isolated from Alpinia katsumadai Hayata that has been demonstrated to have anti-inflammatory, antibacterial, and antioxidant activities. The aim of this study was to investigate whether the administration of alpinetin could attenuate PICS in a septic mouse model. Mice were randomly divided into four groups: the (1) sham-operated group, (2) sham+alpinetin (1 mg/kg intravenously infused for once per day after sham operation), (3) cecal ligation and puncture (CLP), and (4) CLP+alpinetin (50 mg/kg intravenously infused for once per day after CLP). Eight days after sham operation or CLP surgery, mice were euthanized for subsequent examination. Alpinetin significantly improved the survival of septic mice. Also, it attenuated the CLP-induced persistent inflammation, immunosuppression, and catabolism syndrome. The level of plasma proinflammatory cytokines and apoptosis of T lymphocytes were obviously decreased by alpinetin as well. Moreover, oxidative stress in the organs was compelling lower in the alpinetin-treated CLP mice. In this clinically relevant model of sepsis, alpinetin ameliorates CLP-induced organ dysfunction and improves the likelihood of survival, possibly through suppressing the inflammatory response, oxidative stress, and apoptosis. These findings suggested that alpinetin could be a potential novel therapeutic approach to prevent sepsis-induced PICS.

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

“…These flavones increased both life expectancy and the survival rate of the animals with sepsis when compared with an untreated CLP group. Alpinetin (Alp) (1) (Liu et al, 2021), luteoloside (17) (Wang et al, 2021), and oroxylin A (ORO) (22) (Zhang et al, 2020) improved survival rates, but had no effects on life expectancy. In respect of baicalein (BCN) (4), of the three studies with this flavonoid, two improved only survival rate (Chen et al, 2022; Liu et al, 2015) and only one improved both survival rate and life expectancy (Kwak et al, 2014).…”

Inhibition of PFKFB Preserves Intestinal Barrier Function in Sepsis by Inhibiting NLRP3/GSDMD

“…Oxidative stress plays a critical role in regulating various biological processes, including cell death and immunity [43,44]. Oxidative stress has also been reported to be an essential initiator of pyroptosis and is closely related to septic organ failure [23,45,46].…”

Alpinetin: A Review of Its Pharmacology and Pharmacokinetics

“…Additionally, a novel feature of alpinetin was assessed by Liu et al in ameliorating CLP-induced persistent inflammation, immunosuppression, and catabolism syndrome (PICS). The results exhibited that administration of alpinetin (50 mg/kg intravenously infused for 8 days) remarkably enhanced the survival of septic mice and improved organ dysfunction via inhibiting the release of proinflammatory cytokines, decreasing apoptosis in T lymphocytes, attenuating lung injury, and repressing oxidative stress (Liu et al, 2021). Thereby, alpinetin may be a hopeful curative agentia to prevent PICS.…”