Mercuric chloride induced brain toxicity in mice: The protective effects of puerarin-loaded PLGA nanoparticles.

Mercury is a toxic, environmentally heavy metal that can cause severe damage to all organs, including the nervous system. The functions of puerarin include antioxidant, anti-inflammatory, nerve cell repair, regulation of autophagy, and so forth. But because of the limited oral absorption of puerarin, it affects the protective effect on brain tissue. The nano-encapsulation of Pue can improve its limitation. Therefore, this study investigated the protective effect of Pue drug-loaded PLGA nanoparticles (Pue-PLGA-nps) on brain injury induced by mercuric chloride (HgCl2 ) in mice. The mice were divided into normal saline (NS) group, HgCl2 (4 mg/kg) group, Pue-PLGA-nps (50 mg/kg) group, HgCl2 + Pue (4 mg/kg + 30 mg/kg) group, and HgCl2 + Pue-PLGA-nps (4 mg/kg + 50 mg/kg) group. After 28 days of treatment, the mice were observed for behavioral changes, antioxidant capacity, autophagy and inflammatory response, and mercury levels in the brain, blood, and urine were measured. The results showed that HgCl2 toxicity caused learning and memory dysfunction in mice, increased mercury content in brain and blood, and increased serum levels of interleukin (IL-6), IL-1ß, and tumor necrosis factor-α in the mice. HgCl2 exposure decreased the activity of T-AOC, superoxide dismutase, and glutathione peroxidase, and increased the expression of malondialdehyde in the brain of mice. Moreover, the expression levels of TRIM32, toll-like receptor 4 (TLR4), and LC3 proteins were upregulated. Both Pue and Pue-PLGA-nps interventions mitigated the changes caused by HgCl2 exposure, and Pue-PLGA-nps further enhanced this effect. Our results suggest that Pue-PLGA-nps can ameliorate HgCl2 -induced brain injury and reduce Hg accumulation, which is associated with inhibition of oxidative stress, inflammatory response, and TLR4/TRIM32/LC3 signaling pathway.

Quercetin Alleviates Kidney Damage Caused by Mercury Chloride：The protective effects of quercetin on autophagy and inflammation were studied based on TRIM32/TLR4/LC3 pathway.

OBJECTIVE: Mercury is one of the heavy metal pollutants causing serious harm to human health. Quercetin was observed to repair kidney damage through the TLR4/TRIM32 pathway, and the detoxification effect of quercetin on heavy metal poisoning was observed. METHODS: For the study, the researchers divided 40 male mice from the KM strain into five groups: control, HgCl2, QU30, HgCl2+QU15, and HgCl2+QU30. The biological effects of those mice in each group were detected by the biochemical experiment, histopathology experiment and protein expression experiment respectively. RESULTS: HgCl2 had effects in increasing the level of malondialdehyde (MDA) and decreasing the activity of antioxidant enzymes (P<0.05). HgCl2 induced inflammation by increasing tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and Toll Like Receptor 4 (TLR-4) (P< 0.05). The expression of creatinine (CRE) and urea nitrogen (BUN) showed that HgCl2 promoted kidney injury. HgCl2 altered renal tissue integrity and TRIM32 expression which resulted in the increased autophagy associated protein levels of LC3. In contrast, quercetin reduced oxidative stress, autophagy, inflammation and histopathological changes (P< 0.05). CONCLUSION: Quercetin has the renal protection effects of anti-inflammation, anti-oxidation and anti-autophagy.

Changes in the content of Puerarin-PLGA nanoparticles in mice under the influence of alcohol and analysis of their antialcoholism.

To observe the metabolic changes and antialcoholic effect of Puerarin-PLGA nanoparticles (PUE-NP) in mice. PUE-NP was prepared and characterized by particle size distribution and morphology. The mouse models with acute alcoholism were established to observe their behavioral changes after alcohol poisoning. The expressions of biologically active enzymes such as CRE, BUN, AST, ALT in serum and SOD and TLR4 in liver of mice in each group were detected, and the pathological changes in liver and kidney tissues were observed by HE staining. The PUE-NP metabolism in mice was determined by in vitro release assay and HPLC. PUE-NP nanoparticles had good morphology and structure, and the mouse models with alcohol poisoning were established successfully. Compared with alcohol group, puerarin and PUE-NP increased the disappearance latency time of righting reflex, and the recovery time of righting reflex was significantly shortened. Water maze results showed that Puerarin and PUE-NP had inhibitory effect on impaired memory. HPLC results showed that PUE-NP reached its peak in mice after 1 h, and the content percentage was twice that of puerarin preparation alone, and the distribution time of puerarin concentration in vivo was prolonged, indicating that PLGA nanoparticles had a loading and slow-release effect on puerarin and increased the bioavailability of puerarin in mice. In addition, compared with the alcohol group, Puerarin and PUE-NP improved serum ALT, AST, CRE, and BUN levels in mice, enhanced SOD activity in liver, and inhibited TLR4 expression. The effect was better in the PUE-NP group than in the Puerarin group. PUE-NP delayed the release and metabolism of Puerarin and had better effect in the treatment of the alcoholic liver and kidney injury.

Co-Targeting Nucleus Accumbens Associate 1 and NF-κB Signaling Synergistically Inhibits Melanoma Growth.

Nucleus-accumbens-associated protein-1 (NAC1) is a cancer-related transcriptional factor encoded by the NACC1 gene, which is amplified and overexpressed in various human cancers and has been appreciated as one of the top potential cancer driver genes. NAC1 has therefore been explored as a potential therapeutic target for managing malignant tumors. Here, we show that NAC1 is a negative regulator of NF-κB signaling, and NAC1 depletion enhances the level of the nuclear NF-κB in human melanoma. Furthermore, the inhibition of NF-κB signaling significantly potentiates the antineoplastic activity of the NAC1 inhibition in both the cultured melanoma cells and xenograft tumors. This study identifies a novel NAC1-NF-κB signaling axis in melanoma, offering a promising new therapeutic option to treat melanoma.