The purpose of this study was to evaluate the hepatoprotective effect of maltol, a food-flavoring agent, on alcohol-induced acute oxidative damage in mice. Maltol used in this study was isolated from red ginseng (Panax ginseng C.A Meyer) and analyzed by high performance liquid chromatography (HPLC) and mass spectrometry. For hepatoprotective activity in vivo, pretreatment with maltol (12.5, 25 and 50 mg/kg; 15 days) drastically prevented the elevated activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and triglyceride (TG) in serum and the levels of malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) in liver tissue (p < 0.05). Meanwhile, the levels of hepatic antioxidant, such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) were elevated by maltol pretreatment, compared to the alcohol group (p < 0.05). Histopathological examination revealed that maltol pretreatment significantly inhibited alcohol-induced hepatocyte apoptosis and fatty degeneration. Interestingly, pretreatment of maltol effectively relieved alcohol-induced oxidative damage in a dose-dependent manner. Maltol appeared to possess promising anti-oxidative and anti-inflammatory capacities. It was suggested that the hepatoprotective effect exhibited by maltol on alcohol-induced liver oxidative injury may be due to its potent antioxidant properties.

Cisplatin, a potent anticancer drug, is usually causing nephrotoxicity; limiting its therapeutic application and efficiency. Maltol may be used to prevent such toxic effect. The aim of this study was to investigate the underlying protective mechanisms of maltol on nephrotoxicity by cisplatin using a cisplatin-treated mouse model and a cellular toxicity model of HEK293 cells. The blood urea nitrogen (BUN), creatinine (CRE) and neutrophil gelatinase-associated lipocalin (NGAL) levels in mice were increased by cisplatin but decreased to normal ranges by maltol pretreatment (50 and 100 mg/kg) for ten days. Besides, maltol pretreatment decreased oxidative stress, lipid peroxidation and apoptosis in cisplatin-treated mice. The inhibitory action of maltol on inflammatory responses was achieved by reducing the expressions in NF-κB, IL-1β, iNOS, and TNF-α in the mice in vivo. Additionally, maltol restored the reduction of PI3K/Akt and mTOR levels by cisplatin through increasing AMPK expression in cisplatin-treated HEK293 cells. Maltol also suppressed the expression of Bax and caspase 3 by inhibiting the p53 activity in HEK293 cells. Overall, maltol may serve as a valuable potential drug to prevent cisplatin-induced nephrotoxicity, and the underlying molecular mechanisms of maltol action may involve intracellular AMPK/PI3K/Akt and p53 signaling pathways.

The aim of this paper is to evaluate the protective effect of 5-hydroxymethyl-2-furfural (5-HMF) on acute alcohol-induced liver oxidative injury in mice. 5-HMF, a maillard reaction product, was isolated from the fruits of Schisandra chinensis for animal experiments. Experimental ICR mice were pretreated with different doses of 5-HMF (7.5, 15, and 30 mg/kg) for seven days by gavage feeding. Biochemical markers and enzymatic antioxidants from serum and liver tissue were examined. Our results showed that the activities of ALT (alanine aminotransferase), AST (aspartate transaminase), TC (total cholesterol), TG (triglyceride), L-DLC (low density lipoprotein) in serum and the levels of MDA (malondialdehyde) in liver tissue, decreased significantly (p < 0.05) in the 5-HMF-treated group compared with the alcohol group. On the contrary, enzymatic antioxidants CAT (catalase), GSH-Px (glutathione peroxidase), and GSH SOD (superoxide dismutase) were markedly elevated in liver tissue treated with 5-HMF (p < 0.05). Furthermore, the hepatic levels of pro-inflammatory response marker tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) were significantly suppressed (p < 0.05). Histopathological examination revealed that 5-HMF (30 mg/kg) pretreatment noticeably prevented alcohol-induced hepatocyte apoptosis and fatty degeneration. It is suggested that the hepatoprotective effects exhibited by 5-HMF on alcohol-induced liver oxidative injury may be due to its potent antioxidant properties.

Platycodin D (PD) is the main active saponin of Platycodon grandiflorum (PG) and is reported to exhibit multiple biological effects, including anti-tumor, anti-inflammation, and anti-obesity properties. Although recently there have been many research reports on the chemical constituents of the plant's roots, only few works have been reported on the aerial parts of PG. In the present study, we report the first isolation of PD from the aerial parts of PG and its protective effect against acute alcohol-induced liver oxidative injury and inflammatory response in mice. In brief, the protective effect was evaluated by tracking biochemical markers, enzymatic antioxidants and proinflammatory cytokines in serum and liver tissue. The results indicated that PD pretreatment significantly decreased the levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (L-DLC) in serum and malondialdehyde (MDA) in liver. PD was also found to increase the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in the liver (p < 0.05). In addition, PD markedly decreased the levels of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6, which was caused by alcohol exposure (p < 0.05). In contrast, histopathological examinations revealed that PD pretreatment noticeably prevented alcohol-induced hepatocyte apoptosis and steatosis. Collectively, the present study clearly suggests that the protective effect exhibited by PD on alcohol-induced liver oxidative injury may occur via the alleviation of oxidative stress and inflammatory response.

Maltol, a food-flavoring agent and Maillard reaction product formed during the processing of red ginseng (Panax ginseng, C.A. Meyer), has been confirmed to exert a hepatoprotective effect in alcohol-induced oxidative damage in mice. However, its beneficial effects on acetaminophen (APAP)-induced hepatotoxicity and the related molecular mechanisms remain unclear. The purpose of this article was to investigate the protective effect and elucidate the mechanisms of action of maltol on APAP-induced liver injury in vivo. Maltol was administered orally at 50 and 100 mg/kg daily for seven consecutive days, then a single intraperitoneal injection of APAP (250 mg/kg) was performed after the final maltol administration. Liver function, oxidative indices, inflammatory factors—including serum alanine and aspartate aminotransferases (ALT and AST), tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), liver glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), cytochrome P450 E1 (CYP2E1) and 4-hydroxynonenal (4-HNE) were measured. Results demonstrated that maltol possessed a protective effect on APAP-induced liver injury. Liver histological changes and Hoechst 33258 staining also provided strong evidence for the protective effect of maltol. Furthermore, a maltol supplement mitigated APAP-induced inflammatory responses by increasing phosphorylated nuclear factor-kappa B (NF-κB), inhibitor kappa B kinase α/β (IKKα/β), and NF-kappa-B inhibitor alpha (IκBα) in NF-κB signal pathways. Immunoblotting results showed that maltol pretreatment downregulated the protein expression levels of the B-cell-lymphoma-2 (Bcl-2) family and caspase and altered the phosphorylation of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) in a dose-dependent manner. In conclusion, our findings clearly demonstrate that maltol exerts a significant liver protection effect, which may partly be ascribed to its anti-inflammatory and anti-apoptotic action via regulation of the PI3K/Akt signaling pathway.

The purpose of this study was to investigate the anti-hepatoma activity of maltol, a Maillard reaction product, in H22 tumor-bearing mice.

Background The polyether antibiotic nigericin has been demonstrated recently to have anti-tumor activity in multiple cancers. But the biochemical basis for its anti-cancer effects has not been fully elucidated. The objective of this study was to investigate the potential mechanisms of nigericin in pancreatic cancer (PC) cells. Methods PC cells were exposed to increasing concentrations of nigericin at different time periods, and the corresponding IC50 values were calculated. Then the effects on the biological functions of PC cells were evaluated. Subsequent experiments including the high-throughput RNA sequencing, qRT-PCR, western blot, TOP/FOP-Flash reporter, Co-Immunoprecipitation and luciferase report assays were employed to reveal the potential mechanisms of nigericin. In addition, the inhibitory effects of nigericin on PC cells were also accessed in the subcutaneous tumor model. Results The data showed that nigericin was extremely sensitive to PC cells, and could influence the abilities of cell proliferation, colony formation, apoptosis, migration and invasion. The results in vitro implied that nigericin suppressed the Wnt/β-catenin signaling by up-regulating PRKCA and HBP1 mRNA expressions. Furthermore, the dual strands of pre-miR-374b were proved to down-regulate the PRKCA and HBP1 expressions coordinately, and over-expression of pre-miR-374b partly antagonized the suppressing effects of PC cells induced by nigericin. Meanwhile, the inhibitory effects of nigericin on PC cells were also confirmed in mice. Conclusion These findings demonstrated that suppressing the Wnt/β-catenin signaling pathway by targeting pre-miR-374b-PRKCA/HBP1 axis might represent a novel molecular mechanism of nigericin in PC. Nigericin remained a candidate for a potential pre-clinical application for PC.