Synergistic protection of matrine and lycopene against lipopolysaccharide‑induced acute lung injury in mice

Abstract

Acute lung injury (ALI) is a major cause of morbidity and mortality globally, and is characterized by widespread inflammation in the lungs. Increased production of reactive oxygen species is hypothesized to be associated with ALI. Matrine and lycopene are active products present in traditional Chinese medicine. Matrine is an effective inhibitor of inflammation, whereas lycopene decreases lipid peroxidation. Therefore, it was hypothesized that combinatorial treatment with matrine and lycopene may provide synergistic protection against ALI. In the present study, mice were treated with dexamethasone (DEX; 5 mg/kg), matrine (25 mg/kg), lycopene (100 mg/kg), and matrine (25 mg/kg) + lycopene (100 mg/kg) for 7 days prior to injury induction using lipopolysaccharide (LPS; 5 mg/kg) for 6 h. Lung tissues were collected following the sacrifice of the mice and hematoxylin and eosin staining was used for histological analysis. Malondialdehyde (MDA), glutathione (GSH) and myeloperoxidas (MPO) levels were examined by respective kits. The expressions of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were evaluated by ELISA. The expressions of IκBα and NF-κB p65 were examined by reverse transcription-quantitative polymerase chain reaction, western blotting and immunohistochemistry. The results indicated that the combined treatment exhibited a similar effect to DEX, both of which attenuated lung structural injuries, downregulated the expressions of IL-6, TNF-α, MPO and MDA, and upregulated that of GSH. Furthermore, the combined treatment and DEX inhibited NF-κB p65 activation. The present study revealed that combined treatment with matrine and lycopene exhibited protective effects on an LPS-induced mouse model of ALI, suggesting that they may serve as a potential alternative to glucocorticoid therapy for ALI.

A Systematic Review of the Pharmacology, Toxicology and Pharmacokinetics of Matrine

“…In a non-tumorigenic human skin keratinocytes (HaCaT) model, MT combined with acitretin negatively regulates the phosphorylation of PI3K/Akt/mTOR signaling pathway, and plays a synergistic role in inducing autophagy and cell cycle G0/G1 phase arrest ( Jiang W. W. et al, 2019 ). Studies have shown that the combination of MT and lycopene possessed a synergistic protective effect on a LPS-induced acute lung injury (ALI) mouse model through the inhibition of the NF-κB pathway ( Li W.W. et al., 2019 ). Rong et al.…”

The Role of Lycopene in Chronic Lung Diseases

“…In a murine model (C57BL/6 mice) for emphysema, lycopene administration lessened the detrimental effects of chronic cigarette smoke exposure [42]. Lycopene treatment was found to ease LPS-induced acute lung injury (ALI) in murine animal models [46], BALB/c mice, and LPSinduced ALI in a rat model [47]. Lycopene extracted from tomatoes could reduce the burden of lung fibrosis's pathological effects in a rodent study [52].…”

“…One method of generating ALI in these animals was through the administration of lipopolysaccharide (LPS). One study investigated the synergistic protective efficacy of lycopene and matrine, an alkaloid found in kinds of Sophora plants, against LPS-induced ALI compared to the corticosteroid dexamethasone (DEX) in BALB/c mice [46]. Mice were intraperitoneally injected with DEX (5 mg/kg BW), matrine (25 mg/kg BW), lycopene (100 mg/kg BW), or a combination of the matrine + lycopene treatments for seven days before a final dosage of LPS (5 mg/kg BW).…”

Phytochemicals: Potential Therapeutic Interventions Against Coronavirus-Associated Lung Injury

“…Matrine (tetracycloquinolizindine) ( Li W. W. et al, 2019 ), antidesmone (tetrahydroquinoline) ( Lu et al, 2017 ), cepharanthine (bisbenzylisoquinoline) ( Huang et al, 2014 ), epigoitrin (pyrrolidine) ( Luo et al, 2019 ), isotetrandrine (bisbenzyltetrahydroisoquinoline) ( Liang et al, 2014 ), neferine (bisbenzylisoquinline) ( Zhao et al, 2010 ), and oxysophoridine (quinolizidine) ( Fu et al, 2015 ) are other alkaloids that have shown anti-lung injury effects evaluated by in vivo and in vitro experiments. Accordingly, they regulated the proinflammation mediators and oxidative markers ( Table 1 ).…”