Astaxanthin targets IL-6 and alleviates the LPS-induced adverse inflammatory response of macrophages.

Numerous natural compounds are recognized for their anti-inflammatory properties attributed to antioxidant effects and the modulation of key inflammatory factors. Among them, astaxanthin (AST), a potent carotenoid antioxidant, remains relatively underexplored regarding its anti-inflammatory mechanisms and specific molecular targets. In this study, human monocytic leukemia cell-derived macrophages (THP-1) were selected as experimental cells, and lipopolysaccharides (LPS) served as inflammatory stimuli. Upon LPS treatment, the oxidative stress was significantly increased, accompanied by remarkable cellular damage. Moreover, LPSs escalated the expression of inflammation-related molecules. Our results demonstrate that AST intervention could effectively alleviate LPS-induced oxidative stress, facilitate cellular repair, and significantly attenuate inflammation. Further exploration of the anti-inflammatory mechanism revealed AST could substantially inhibit NF-κB translocation and activation, and mitigate inflammatory factor production by hindering NF-κB through the antioxidant mechanism. We further confirmed that AST exhibited protective effects against cell damage and reduced the injury from inflammatory cytokines by activating p53 and inhibiting STAT3. In addition, utilizing network pharmacology and in silico calculations based on molecular docking, molecular dynamics simulation, we identified interleukin-6 (IL-6) as a prominent core target of AST anti-inflammation, which was further validated by the RNA interference experiment. This IL-6 binding capacity actually enabled AST to curb the positive feedback loop of inflammatory factors, averting the onset of possible inflammatory storms. Therefore, this study offers a new possibility for the application and development of astaxanthin as a popular dietary supplement of anti-inflammatory or immunomodulatory function.

Tea consumption and risk of bone health: an updated systematic review and meta-analysis.

INTRODUCTION: Current research evaluating the association between tea consumption and bone health still has inconsistent findings. MATERIALS AND METHODS: The electronic databases of Embase, PubMed, Scopus, and Web of Science were systematically searched from inception until December 2022 to identify eligible studies. The calculation of summary relative risks (RRs) and 95% confidence intervals (CIs) was carried out using random-effects models. I2 statistics and Forest plots were used to assess the heterogeneity of RR values across studies. RESULTS: The pooled relative risks for bone health-related outcomes of interest among tea drinkers, compared to non-drinkers, were 0.910 (95% confidence interval 0.845 to 0.980) for fractures, based on 20 studies, 0.332 (0.207-0.457) for BMD (13 studies), 0.800 (0.674-0.950) for osteoporosis (10 studies), and 1.006 (0.876-1.156) for osteopenia (5 studies). Subgroup analysis of locations showed that the pooled relative risks were 0.903 (0.844-0.966) for the hip, 0.735 (0.586-0.922) for the femur, 0.776 (0.610-0.988) for the lumbar, 0.980 (0.942-1.021) for the forearm and wrist, 0.804 (0.567-1.139) for the phalanges, and 0.612 (0.468-0.800) for Ward's triangle. One-stage dose-response analysis revealed that individuals who consumed less than 4.5 cups of tea per day had a lower risk of bone health-related outcomes than those who did not consume tea, with statistically significant results. CONCLUSION: There is an association between tea consumption and a reduced risk of fractures, osteoporosis, hip, femur, and lumbar, as well as increased BMD.

Ganoderic acid T improves the radiosensitivity of HeLa cells via converting apoptosis to necroptosis.

The use of natural substances derived from traditional Chinese medicine and natural plants as safe radiosensitizing adjuvants is a new trend for cancer radiotherapy. Ganoderma lucidum has been used as a traditional Chinese medicine with a history of more than 2000 years. Ganoderic acid T (GAT) is a typical triterpene of G. lucidum, which has strong cytotoxicity to cancer cells, but whether it has radiation sensitization effect has not been explored. In this work, we treated the HeLa cells with different concentrations of GAT before exposure to gamma-ray radiation and investigated its influence on the radiosensitivity. The cell viability, apoptosis rate, necoptosis rate, intracellular ATP level, cell cycle, the amount of H2AX and 53BP1, reactive oxygen species, and mitochondrial membrane potential were examined. Apoptotic, necroptotic, and autophagic biomarker proteins, including caspase 8, cytochrome c, caspase 3, RIPK, MLKL, P62, and LC3, were analyzed. As a result, we confirmed that with treatment of GAT, the gamma-ray radiation induced both apoptosis and necroptosis in HeLa cells, and with increase of GAT, the percentage ratio of necroptosis was increased. The involved pathways and mechanisms were also explored and discussed.

Ganoderic acid D induces synergistic autophagic cell death except for apoptosis in ESCC cells.

ETHNOPHAMACOLOGICAL RELEVANCE: Ganoderma lucidum has been used as a medicinal mushroom for more than 2000 years in China. Ganoderic acid D (GAD) as a representative active triterpenoid from Ganoderma lucidum is known to possess anticancer activity. However, the mechanism involved in its anticancer cell process is still largely elusive. AIM OF THE STUDY: Our study aimed to investigate the anticancer effects of GAD on the esophageal squamous cell carcinoma (ESCC) cells and the underlying mechanisms at the cell level. MATERIALS AND METHODS: EC9706 and Eca109 cells were treated with GAD (0, 10, 20, 40 µM) for 24 h. The cell viability, cell cycle, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), apoptosis rate, caspase-3 activity, autophagic flux, lysosomal function were examined. Cell cycle, apoptotic, autophagy and mTOR signal pathway related proteins such as P53, Cyclin B1, CytoC, PARP, Beclin-1, P62, LC3, PI3K, AKT and mTOR were analyzed by Western blot approach. RESULTS: GAD inhibited cell proliferation and induced both apoptosis and autophagic cell death. In particular, we found that in the early stage of the autophagic process, GAD could initiate and enhance the autophagy signal while in the late stage it on the contrary could block the autophagic flux by impairing the autophagosome-lysosome fusion and inhibited the lysosomal degradation. Besides the autophagic cell death, GAD also induced the apoptosis mediated by caspase-related process in parallel. The mechanism involved for the synergistic apoptotic and autophagic cell death was also explored. We found that GAD down-regulated the expression of PI3K, AKT and mTOR phosphorylated proteins in the mTOR signaling pathway which thus led to the synergistic effect on apoptosis and autophagic cell death in the ESCC cells. CONCLUSIONS: In summary, this study has documented that GAD may inhibit cell proliferation through the mTOR pathway in ESCC cells, and induce synergistic apoptosis and autophagic cell death by disrupting the autophagic flux. This work therefore also suggests that GAD may be used as an efficient anticancer adjuvant for ESCC cancer therapy.