Bisdemethoxycurcumin Protects Small Intestine from Lipopolysaccharide‐Induced Mitochondrial Dysfunction via Activating Mitochondrial Antioxidant Systems and Mitochondrial Biogenesis in Broiler Chickens

Abstract

Bisdemethoxycurcumin is one of the three curcuminoids of turmeric and exhibits good antioxidant activity in animal models. This study is aimed at investigating the effect of bisdemethoxycurcumin on small intestinal mitochondrial dysfunction in lipopolysaccharide- (LPS-) treated broilers, especially on the mitochondrial thioredoxin 2 system and mitochondrial biogenesis. A total of 320 broiler chickens were randomly assigned into four experimental diets using a 2 × 2 factorial arrangement with diet (0 and 150 mg/kg bisdemethoxycurcumin supplementation) and stress (saline or LPS challenge) for 20 days. Broilers received a dose of LPS (1 mg/kg body weight) or sterile saline intraperitoneally on days 16, 18, and 20 of the trial. Bisdemethoxycurcumin mitigated the mitochondrial dysfunction of jejunum and ileum induced by LPS, as evident by the reduced reactive oxygen species levels and the increased mitochondrial membrane potential. Bisdemethoxycurcumin partially reversed the decrease in the mitochondrial DNA copy number and the depletion of ATP levels. Bisdemethoxycurcumin activated the mitochondrial antioxidant response, including the prevention of lipid peroxidation, enhancement of manganese superoxide dismutase activity, and the upregulation of the mitochondrial glutaredoxin 5 and thioredoxin 2 system. The enhanced mitochondrial respiratory complex activities in jejunum and ileum were also attributed to bisdemethoxycurcumin treatment. In addition, bisdemethoxycurcumin induced mitochondrial biogenesis via transcriptional regulation of proliferator-activated receptor-gamma coactivator-1alpha pathway. In conclusion, our results demonstrated the potential of bisdemethoxycurcumin to attenuate small intestinal mitochondrial dysfunction, which might be mediated via activating the mitochondrial antioxidant system and mitochondrial biogenesis in LPS-treated broilers.

Escherichia coli O88 induces intestinal damage and inflammatory response through the oxidative phosphorylation and ribosome pathway in Pekin ducks

“…Our results showed that oxidative phosphorylation complexes downregulated the genes and reduced the mitochondrial oxidative phosphorylation activity in jejunum tissue, resulting in impaired mitochondrial function by E. coli infection. This was similar to the report that showed that the activities of jejunal mitochondrial respiratory complexes and the level of ATP were reduced after intestinal damage ( Zhang et al., 2021 ). The mechanism was also demonstrated at the cellular level: LPS-activated macrophages are characterized by high glycolysis and low oxidative phosphorylation ( Vats et al., 2006 ; Rodríguez-Prados et al., 2010 ), and as a key component of macrophage polarization, these changes contribute to a kind of tissue self-repair in inflammation ( Ip et al., 2017 ; Carrasco-Pozo et al., 2020 ).…”

Identification of Molecular Targets and Underlying Mechanisms of Xiaoji Recipe against Pancreatic Cancer Based on Network Pharmacology

“…Bisdemethoxycurcumin, luteolin, quercetin, flavone, and beta-ecdysone were the top five active ingredients ranked by degree according to the component-target-disease network, which were potentially the main active ingredients in the treatment of pancreatic cancer. Bisdemethoxycurcumin is reported with antifibrosis, antiapoptosis, antioxidant, and anti-inflammatory characteristic in various diseases [44][45][46]. Bisdemethoxycurcumin is also reported with antitumor effects in hepatocellular carcinoma, breast cancer, and non-small-cell lung cancer [47][48][49].…”

Bisdemethoxycurcumin Attenuated Renal Injury via Activation of Keap1/Nrf2 Pathway in High-Fat Diet-Fed Mice

“…Nevertheless, due to its instability and low water solubility, curcumin presents a low oral bioavailability, resulting in limited therapeutic applications [28]. Besides curcumin, demethoxycurcumin and BDMC have also exhibited excellent beneficial pharmacological actions, including anti-oxidant, anti-inflammatory, neuroprotective, antihypertensive, and more [29][30][31]. Compared with curcumin and demethoxycurcumin, BDMC is more stable in physiology, indicating that BDMC may have more therapeutic applications [32,33].…”