Sirtuin 1 (Sirt1) is an essential modulator of cellular metabolism and has pleiotropic effects. It was recently reported that Sirt1 overexpression in kidney tubule ameliorates cisplatin-induced acute kidney injury (AKI). However, whether pharmacological activation of Sirt1 also has a beneficial effect against the disease remains unclear. In this study, we aimed to evaluate whether SRT1720, a potent and specific activator of Sirt1, could ameliorate cisplatin-induced AKI. We found that SRT1720 treatment ameliorated cisplatin-induced acute renal failure and histopathological alterations. Increased levels of tubular injury markers in kidneys were significantly attenuated by SRT1720. SRT1720 treatment also suppressed caspase-3 activation and apoptotic cell death. Increased expression of 4-hydroxynonenal, elevated malondialdehyde level, and decreased ratio of reduced glutathione/oxidized glutathione after cisplatin injection were significantly reversed by SRT1720. In addition, SRT1720 treatment decreased renal expression of pro-inflammatory cytokines and prevented macrophage infiltration into damaged kidneys. We also showed that the therapeutic effects of SRT1720 were associated with reduced acetylation of p53 and nuclear factor kappa-B p65 and preservation of peroxisome function, as evidenced by recovered expression of markers for number and function of peroxisome. These results suggest that Sirt1 activation by SRT1720 would be a useful therapeutic option for cisplatin-induced AKI.

These results suggest that apamin has therapeutic effect on AD through improvement of inflammatory condition.

Bee venom is a natural toxin produced by honeybees and plays an important role in defending bee colonies. Bee venom has several kinds of peptides, including melittin, apamin, adolapamine, and mast cell degranulation peptides. Apamin accounts for about 2%-3% dry weight of bee venom and is a peptide neurotoxin that contains 18 amino acid residues that are tightly crosslinked by two disulfide bonds. It is well known for its pharmacological functions, which irreversibly block Ca2+-activated K+ (SK) channels. Apamin regulates gene expression in various signal transduction pathways involved in cell development. The aim of this study was to review the current understanding of apamin in the treatment of apoptosis, fibrosis, and central nervous system diseases, which are the pathological processes of various diseases. Apamin's potential therapeutic and pharmacological applications are also discussed.

Liver fibrosis is characterized by changes in tissue architecture and extracellular matrix composition. Liver fibrosis affects not only hepatocytes but also the non-parenchymal cells such as hepatic stellate cells (HSCs), which are essential for maintaining an intact liver structure and function. Transforming growth factor β1 (TGF-β1) is a multifunctional cytokine that induces liver fibrosis through activation of Smad signaling pathways. To improve a new therapeutic approach, synthetic TGF-β1/Smad oligodeoxynucleotide (ODN) was used to suppress both TGF-β1 expression and Smad transcription factor using a combination of antisense ODN and decoy ODN. The aims of this study are to investigate the anti-fibrotic effects of TGF-β1/Smad ODN on simultaneous suppressions of both Smad transcription factor and TGF-β1 mRNA expression in the hepatic fibrosis model in vitro and in vivo. Synthetic TGF-β1/Smad ODN effectively inhibits Smad binding activity and TGF-β1 expression. TGF-β1/Smad ODN attenuated the epithelial mesenchymal transition (EMT) and activation of HSCs in TGF-β1-induced AML12 and HSC-T6 cells. TGF-β1/Smad ODN prevented the fibrogenesis and deposition of collagen in CCl4-treated mouse model. Synthetic TGF-β1/Smad ODN demonstrates anti-fibrotic effects that are mediated by the suppression of fibrogenic protein and inflammatory cytokines. Therefore, synthetic TGF-β1/Smad ODN has substantial therapeutic feasibility for the treatment of liver fibrotic diseases.

Kidney fibrosis is a common process of various kidney diseases leading to end-stage renal failure irrespective of etiology. Myofibroblasts are crucial mediators in kidney fibrosis through production of extracellular matrix (ECM), but their origin has not been clearly identified. Many study proposed that epithelial and endothelial cells become myofibroblasts by epithelial dedifferentiation and endothelial-mesenchymal transition (EndoMT). TGF-β1/Smad signaling plays a crucial role in partly epithelial-mensencymal transition (EMT) and EndoMT. Thus, we designed the TGF-β1/ Smad oligodeoxynucleotide (ODN), a synthetic short DNA containing complementary sequence for Smad transcription factor and TGF-β1 mRNA. Therefore, this study investigated the anti-fibrotic effect of synthetic TGF-β1/Smad ODN on UUO-induced kidney fibrosis in vivo model and TGF-β1-induced in vitro model.To examine the effect of TGF-β1/Smad ODN, we performed various experiments to evaluate kidney fibrosis. The results showed that UUO induced inflammation, ECM accumulation, epithelial dedifferentiation and EndoMT processes, and tubular atrophy. However, synthetic TGF-β1/Smad ODN significantly suppressed UUOinduced fibrosis. Furthermore, synthetic ODN attenuated TGF-β1-induced epithelial dedifferentiation and EndoMT program via blocking TGF-β1/Smad signaling. In conclusion, this study demonstrated that administration of synthetic TGF-β1/Smad ODN attenuates kidney fibrosis, epithelial dedifferentiation, and EndoMT processes.The findings propose the possibility of synthetic ODN as a new effective therapeutic tool for kidney fibrosis. K E Y W O R D SEndoMT, epithelial dedifferentiation, kidney fibrosis, TGF-β1/Smad oligodeoxynucleotide, UUO 334 | GWON et al. | MATERIALS AND METHODS | Synthesis of oligodeoxynucleotidesTarget site of TGF-β1 was selected using S-Fold program. Synthetic ODNs were synthesized on Macrogen (Seoul, Korea). TGF-β1/Smad ODN and scrambled (Scr) ODN 340 | GWON et al. F I G U R E 3 TGF-β1/Smad ODN attenuated kidney fibrosis and ECM accumulation in UUO-injured mice. A, Pathological stain withhematoxylin and eosin (H&E) and B, Masson's trichrome performed using kidney sections. Trichrome stain showed that TGF-β1/Smad ODN attenuated interstitial fibrosis. C, The quantitative analysis of blue-stained collagen in trichrome staining (n = 3). D, Collagen Ⅰ was detected by RT-PCR. This result demonstrated the effect of synthetic ODN on ECM accumulation. The graphs summarize the analysis of the Collagen Ⅰ mRNA expressions (n = 4). E, Immunohistochemistry stain showed that the expression of fibronectin was inhibited by TGF-β1/Smad ODN administration in UUO-injured mice. F, The quantitative graph of fibronectin expression. G, Representative Western blot data revealed that TGF-β1/Smad ODN diminished expression of fibronectin. β-actin was used to confirm equal volume protein sample loading (n = 3). Scale bar = 50 μm; +: treated; −: un-treated; *P < .05 compared to the normal control group; †P < .05 compared to the UUO group