Protective Effect of n‐Butanol Extract from Viola yedoensis on Immunological Liver Injury

Abstract

Viola yedoensis Makino was used to treat inflammation, viral hepatitis, acute pyogenic infection, and ulcerative carbuncles. However, the protective effect on immunological liver injury (ILI) of V. yedoensis had been rarely reported. This study aimed to explore the protective effect of n‐butanol extract (BE) from V. yedoensis on ILI in vitro and in vivo. In vitro, the BE significantly inhibited the secretions of Hepatitis B surface antigen (HBsAg) and Hepatitis B e antigen (HBeAg) in the HepG2.2.15 cells and the replication of HBV DNA. The research data in vivo revealed that the BE reduced the levels of alanine transaminase (ALT), aspartate transaminase (AST), and methane dicarboxylic aldehyde (MDA) in liver tissues of the ConA‐induced mice, while increased the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH‐PX), and the effective contents of tumor necrosis factor‐α (TNF‐α), interferon‐γ (IFN‐γ) and the BE could ameliorate liver histological lesions. These results motivated a further investigation into the chemical constituents of BE. Four coumarins (esculetin, prionanthoside, cichoriin, and esculin) and one flavonoid (quercetin‐3‐O‐galactoside) were isolated from the BE by silica gel column chromatography and recrystallization, of which structures were eventually confirmed by 1H‐NMR, 13C‐NMR, and MS.

The pharmacological and pharmacokinetic properties of esculin: A comprehensive review

“…(Akter et al, 2020; Liu et al, 2015; Ma & Zhao, 2008). In addition, esculin has been detected in a variety of Asteraceae plants, such as Artemisia capillaris Thunb., Artemisia japonica Thunb., and Artemisia capillaris Thunb., and even fruits Prunus domestica L. and Prunus salicina L. (Chu et al, 2021; Jaiswal et al, 2013). However, the esculin contents of these plants are low.…”

“…Studies have shown that esculin can improve oxidative stress injury by enhancing the activities of SOD and GSH‐PX. Chu et al found that the extract of Viola yedoensis Makino (3–12 g/kg) rich in esculin increased the activities of SOD and GSH‐PX and inhibited the production of malondialdehyde in concanavalin A‐induced mice (Chu et al, 2021). Esculin (12.5–50 mg/kg) protected mice from ethanol‐induced gastric mucosal damage by increasing the level of SOD and decreasing both the myeloperoxidase activity and the malondialdehyde amount (Rios et al, 2010).…”

“…The extract of Platycladus Orientalis (L.) Franco (25–400 μg/mL) rich in esculin inhibited the expression of NO, IL‐6 (interleukin‐6), and TNF‐α (tumor necrosis factor‐α) in LPS‐induced RAW 264.7 macrophages (Ren, Zheng, Lin, Han, & Liao, 2017). The extract of Viola yedoensis Makino (3–12 g/kg) rich in esculin also inhibited the production of TNF‐α and interferon‐γ in concanavalin A‐induced mice (Chu et al, 2021). Esculin (10–40 mg/kg) improved tissue damage and paw swelling in adjuvant‐induced arthritis rats by inhibiting the expression of a variety of pro‐inflammatory factors such as IL‐1β, TNF‐α, and IL‐6 (Zheng et al, 2015).…”

“…The Nrf2 (nuclear factor-erythroid 2-related factor 2)-ARE (antioxidant response elements) signaling pathway is the primary defense mechanism for inhibiting oxidative stress (Satoh, McKercher, & Lipton, 2013). Nrf2-ARE signaling pathway exerts antioxidant effect by regulating the expression of a variety of antioxidant proteins A-induced mice (Chu et al, 2021). Esculin (12.5-50 mg/kg) protected mice from ethanol-induced gastric mucosal damage by increasing the level of SOD and decreasing both the myeloperoxidase activity and the malondialdehyde amount (Rios et al, 2010).…”

CX3CR1 deficiency exacerbates immune-mediated hepatitis by increasing NF-κB-mediated cytokine production in macrophage and T cell

“…Viral hepatitis and autoimmunity hepatitis (AHI) are the most common forms of immune-mediated hepatitis. 1 Chemokine-directed immune cell infiltration plays an essential role in the pathogenesis of immune-mediated hepatic injury. 2 The chemokine C-X3C motif ligand 1 (CX3CL1) and its sole receptor, C-X3C motif receptor 1 (CX3CR1), are involved in the recruitment of monocytes/macrophages and T cells and play critical roles in many diseases.…”