Berberine protects renal tubular cells against hypoxia/reoxygenation injury via the Sirt1/p53 pathway

Abstract

Berberine (BBR) has been demonstrated to protect against renal ischemia/reperfusion injury; however, the underlying molecular mechanism is largely unknown. In the present study, we examined the role of silent information regulator 1 (Sirt1)/p53 in the protective effect of BBR on hypoxia/reoxygenation (H/R)-mediated mitochondrial dysfunction in rat renal tubular epithelial cells (NRK-52E cells). NRK-52E cells were preconditioned with small interfering RNA targeting Sirt1 (Sirt1-siRNA) and BBR before subjected to H/R. Cell damage was assessed by CCK8 assay and detection of oxidative parameters. The apoptotic rate was determined by flow cytometry and Hoechst 33258 staining. The expression of apoptotic markers, Sirt1, p53 and the translocation of p53 were examined by Western blotting assay. Nuclear p53 deacetylation by Sirt1 was detected using immunoprecipitation. Compared with the H/R group, BBR pretreatment increased cell viability and inhibited mitochondrial oxidative stress and apoptosis. Protein expression of Sirt1 was also enhanced along with a reduction of p53. Furthermore, both nuclear translocation of p53 and its acetylation were inhibited in NRK-52E cells pretreated with BBR. However, the knockdown of Sirt1 counteracted the renoprotection of BBR. BBR preconditioning protects rat renal tubular epithelial cells against H/R-induced mitochondrial dysfunction via regulating the Sirt1/p53 pathway.

Synthesis and In Vitro Photocytotoxicity of 9-/13-Lipophilic Substituted Berberine Derivatives as Potential Anticancer Agents

“…As shown in Figure 6A, while the nuclei of the cells were round in shape homogenously in the control without the testing compound, those treated with berberine (1), compound 5e, 6e, or 7e showed typical morphological features of apoptosis such as cell blebbing and nuclear shrinkage. Figure 6B shows that HepG2 cells treated with 0.5 µM of compound 7e stained with Hoechst 33,258 in dark or light, and examined under fluorescence microscopy for topical morphological changes, such as chromatin condensation and DNA fragmentation [34]. Evidently, the proliferation of the cancer cells was inhibited by the testing compounds in vitro.…”

“…The apoptotic cells change in morphology, such as chromatin condensation, nuclear shrinking, and DNA fragmentation. It can be characterized through Hoechst 33,258 stained cell nucleus [34] under a fluorescent microscope. Thus, to further study the role of apoptosis played in the superior cytotoxicity of compounds 5e, 6e, and 7e, we incubated HepG2 cells in 0.5 µM of berberine (1), or its three derivatives separately.…”

Berberine chloride ameliorated PI3K/Akt‐p/SIRT‐1/PTEN signaling pathway in insulin resistance syndrome induced in rats

“…In recent years with regard to the side effects of artificial medicines, increasing attention has been paid by researchers to herbal medicines. Our in vivo study revealed that treatment with BER‐chloride has negative influence on insulin resistance through activating two proteins involved in several physiological processes, SIRT‐1 and AMPK (Lin et al, ). Those two proteins able to activate each other, AMPK activate SIRT‐1 by elevation the concentration of nicotinamide phosphoribosyltransferase and SIRT‐1 stimulates AMPK through deacetylation of serine‐threonine kinase LKB1 (Hardie, ; Sun et al, ).…”

Berberine chloride ameliorated PI3K/Akt-p/SIRT-1/PTEN signaling pathway in insulin resistance syndrome-induced rats

“…Our in vivo study revealed that treatment with BER-chloride has negative effect on insulin resistance by activating two proteins involved in several physiological processes, SIRT-1 and AMPK [49]. Those two proteins able to activate each other, AMPK activates SIRT-1 by elevation the level of nicotinamide phosphoribosyltransferase and SIRT-1 stimulates AMPK through deacetylation of serine-thereonine kinase LKB1 [50, 51].…”