Berberine Alleviates Acute Lung Injury in Septic Mice by Modulating Treg/Th17 Homeostasis and Downregulating NF-κB Signaling

Abstract

Purpose A common complication of sepsis is acute lung injury (ALI), which is associated with an acute onset, rapid disease changes, and high mortality. Regulatory T (Treg) and T helper 17 (Th17) cells comprise CD4 + T cell subsets, which strongly influence inflammation during ALI. In this study, we investigated the effect of berberine (BBR), an antioxidant, anti-inflammatory, and immunomodulatory drug, on the inflammatory response and immune state in mice with sepsis. Methods A mouse model of cecal ligation and puncture (CLP) was established. The mice were intragastrically administered 50 mg/kg BBR. We used histological techniques to evaluate inflammatory tissue injury and flow cytometry for analyzing Treg/Th17 levels. We also assessed NF-κB signaling pathways by Western blotting assays and immunofluorescence staining. Enzyme-linked immunosorbent assay (ELISA) was performed to measure the content of cytokines. Results Treatment with BBR considerably mitigated lung injury while improving survival, post-cecal ligation, and puncture (CLP). Treatment with BBR ameliorated pulmonary edema and hypoxemia in septic mice and inhibited the NF-κB signaling pathway. BBR also increased Treg cells and decreased Th17 proportions in the spleen and lung tissue of CLP-treated mice. Blocking Treg cells weakened the protective effect of BBR on sepsis-associated lung injury. Conclusion Overall, these results suggested that BBR is a potential therapeutic agent for sepsis.

Therapeutic potential of Coptis chinensis for arthritis with underlying mechanisms

“…Studies have shown that berberine can effectively treat RA, OA and GA, mainly by reducing the level of inflammatory factors, regulating intestinal flora, promoting uric acid excretion, and improving the inflammatory response damage of joints and their surrounding tissues ( Fan et al, 2021 ; Xu and Li, 2021 ). At the molecular level, CC can improve arthritis by regulating Wnt1/β-catenin, PI3K/AKT/mTOR and NF-κB signaling pathways, inhibiting the expression of pro-inflammatory factors such as interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), etc ( Zhao et al, 2014 ; Zhou et al, 2019 ; Shen et al, 2020 ; Chen et al, 2023 ). Berberine, palmatine, coptisine and other components are the main components of CC in the treatment of arthritis.…”

Pharmacokinetics, Tissue Distribution and Excretion of Demethyleneberberine, a Metabolite of Berberine, in Rats and Mice

“…Importantly, berberine has demonstrated promising potential effects in various areas, such as anti-cancer [20][21][22], anti-diabetic [23][24][25], anti-rheumatoid [26], anti-obesity [27,28] and probone regeneration [29,30]. It also exhibits certain protective effects on the liver [31,32], lung function [33,34] and nerves [35,36]. However, studies have found that despite berberine's significant therapeutic potential, its plasma bioavailability is extremely low, ranging from around 0.37% to 0.68% [37,38].…”