Borneol protects against cerulein‐induced oxidative stress and inflammation in acute pancreatitis mice model

Abstract

Borneol is a commonly used flavouring substance in traditional Chinese medicine, which possesses several pharmacological activities including analgesic, antiinflammatory, and antioxidant properties. The aim of this study was to investigate the effects of borneol on cerulein‐induced acute pancreatitis (AP) model. Swiss albino mice were pretreated with borneol (100 and 300 mg/kg) daily for 7 days, before six consecutive injections of cerulein (50 μg/kg/hr, intraperitoneally). The protective effect of borneol was studied by biochemical, enzyme linked immunosorbent assay, histological, immunoblotting, and immunohistochemical analysis. Oral administration of borneol significantly attenuated pancreatic damage by reducing amylase, lipase levels and histological changes. Borneol attenuated cerulein‐induced oxidative‐nitrosative stress by decreasing malondialdehyde, nitrite levels, and elevating reduced glutathione levels. Pancreatic inflammation was ameliorated by inhibiting myeloperoxidase activity and pro‐inflammatory cytokine (Interleukins and TNF‐α) levels. Furthermore, borneol administration significantly increased nuclear factor E2‐related factor 2 (Nrf2), superoxide dismutase (SOD1) expression and reduced phospho‐NF‐κB p65 expression. Treatment with borneol significantly inhibited TNF‐α, IL‐1β, IL‐6, and inducible nitric oxide synthase expression in cerulein‐induced AP mouse model. Together, these results indicate that borneol which is currently used as US‐FDA approved food adjuvant has the potential to attenuate cerulein‐induced AP possibly by reducing the oxidative damage and pancreatic inflammation by modulating Nrf2/NF‐κB pathway.

N-Acetylcysteine Reduces the Pro-Oxidant and Inflammatory Responses during Pancreatitis and Pancreas Tumorigenesis

“…Interestingly, in total pancreas lysates, we found increased 4-HNE levels only in cerulein-treated Ela-Kras G12D , but not cerulein-treated WT mice (Figure 1A); this increase was also observed in the plasma of cerulein-treated Ela-Kras G12D mice compared to their untreated siblings (Figure S1A), indicating that pancreatitis induces both local and systemic oxidative damages, selectively in Ela-Kras G12D mice. It is well-known that pancreatitis induces redox unbalance in WT rodents [9][10][11]. The absence of a significant increase in 4-HNE in our cerulein-treated WT mouse model is not synonymous with the absence of redox alterations; it probably means that a longer period and/or higher doses of cerulein treatment are needed to induce significant oxidative damage level.…”

“…In both WT and Ela-Kras G12D groups, the total pancreas weight of NAC-treated mice was significantly reduced compared to that of cerulein-treated mice (Figures 4B and 5B). Circulating amylase levels, as well as AST and ALT rates, increase during pancreatitis due to pancreas and liver damage, respectively [9]. NAC treatment significantly reduced the circulating levels of amylase, AST and ALT only in cerulein-treated Ela-Kras G12D , but not in WT mice; for the latter, a protective tendency was observed for circulating amylase levels without reaching a statistical significance (Figures 4C and 5C).…”

“…Yet, the precise redox changes driven by pancreatitis during PDAC initiation are still not clearly elucidated. Indeed, multiple studies have characterized the redox alterations occurring during inflammation-induced metabolic dysfunction and pancreatitis in wild-type rodents [9][10][11][12][13][14][15][16]; however, there is a lack of information regarding the main redox changes taking place during the initiation of pancreas tumorigenesis (presence of Kras mutations). To fill this gap of knowledge in the field, we herein compared mice expressing Kras wild-type alleles (control mice) with those expressing acinar-specific mutated Kras G12D oncogenic allele.…”

Inhibition of discoidin domain receptors by imatinib prevented pancreatic fibrosis demonstrated in experimental chronic pancreatitis model

“…To analyze the pancreas protein expression, immunoblotting technique was used as described earlier 27 , 28 . Small portions of pancreatic tissues were homogenized in RIPA lysis buffer.…”

Potential therapeutic applications of phytoconstituents as immunomodulators: Pre‐clinical and clinical evidences

“…In addition, terpenoids have been evaluated in several animal models. For example, Sapana et al, have evaluated the antiinflammatory property of borneol in a model of cerulein developed acute pancreatitis (Bansod et al, 2020). In detail, the antiinflammatory activity of borneol was supported by the reduction in inflammatory and NF‐kB signalling pathways.…”