Synergistic radiation protective effect of purified Auricularia auricular-judae polysaccharide (AAP IV) with grape seed procyanidins.

The aim of this study was to investigate the synergistic antioxidant potential and protective effect of grape seed procyanidins (GSP) in combination with Auricularia auricular-judae polysaccharides (AAP IV) on radiation injury in splenocytes. Rat splenocyte irradiation resulted in significantly higher apoptosis rate, malondialdehyde (MDA) (p < 0.005), reactive oxygen species (ROS) (p < 0.01); cell viability, total superoxide dismutase (T-SOD) (p < 0.01), catalase (CAT) (p < 0.01), glutathione peroxidase (GSH-PX) (p < 0.05), activity and glutathione (GSH) (p < 0.01) levels were significantly reduced, compared with the control group. "GSP + AAP IV" treatment of rat splenocytes at doses of "GSP (0.3 µg/mL) + AAP IV (50 µg/mL)" displayed higher radioprotective and antioxidative effects than the administration of either GSP or AAP IV, as evident by lower levels of MDA (p < 0.001) concentration, as well as higher cell viability and T-SOD (p < 0.05), CAT (p < 0.005), GSH-PX (p < 0.01) and GSH content compared to the radiation group. In addition, in vivo studies have shown that "GSP + AAP IV" significantly ameliorated the decrease of spleen index (p < 0.005) and spleen GSH (p < 0.005) levels and significantly inhibited the increase of MDA (p < 0.005) levels of spleen with radiation-induced damage, compared with the non-treated group. The in vivo and in vitro results suggested that GSP and AAP IV have a synergistic protective effect against radiation-induced injury by improving the antioxidant and immunomodulation activities.

VSP-2 attenuates secretion of inflammatory cytokines induced by LPS in BV2 cells by mediating the PPARγ/NF-κB signaling pathway.

Neuroinflammation, characterized by microglial activation and the subsequent secretion of inflammatory cytokines, plays a pivotal role in neurodegenerative diseases and brain injuries, often leading to neuronal damage and death. Alleviating neuroinflammation has thus emerged as a promising strategy to protect neurons and ameliorate neurodegenerative disorders. While peroxisome proliferator-activated receptor gamma (PPARγ) agonists have demonstrated potential therapeutic actions on neuroinflammation, their prolonged use, such as with rosiglitazone, can lead to cardiac risks and lipid differentiation disorders. In this study, we investigated the effects of a newly synthesized PPARγ agonist, VSP-2, on secretion of inflammatory cytokines in BV2 cells. Treatment with VSP-2 significantly reduced the mRNA and protein levels of proinflammatory cytokines such as interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α). Furthermore, VSP-2 attenuated the phosphorylation of nuclear factor kappa B (NF-κB) (65 kD) and IκBα, as well as the nuclear translocation of NF-κB (65 kD). Additionally, the use of PPARγ small interfering RNA was able to attenuate the effects of VSP-2 on proinflammatory cytokines and the NF-κB pathway. In conclusion, our findings suggest that VSP-2 effectively suppressed the expressions of IL-1ß, IL-6, and TNF-α via the PPARγ/NF-κB signaling pathway. Given its potential therapeutic benefits, VSP-2 may emerge as a promising candidate for the treatment of neurodegenerative diseases or brain injuries associated with neuroinflammation.

In Vitro Bioassay-guided Isolation of Radioprotective Fractions from Extracts of Pinus koraiensis Bark.

OBJECTIVE: The aim of this study was to evaluate radioprotective effect of extracts of Pinus koraiensis bark and its fractions on rat splenocytes by using bioassay-guided isolation in order to obtain the best active fraction. MATERIALS AND METHODS: P. koraiensis bark was ground and extracted with water, 40% acetone, 95% ethanol. Bio-guided assay was selected as an evaluation method to further fractionate radioprotective component from P. koraiensis bark extract. Total phenolic and flavonoid contents in fractions were also measured. Rat splenocytes were prepared by using mechanical trituration method. DNA damage was assessed as comet parameters (tail DNA%, tail length, tail moment, olive tail moment). The levels of malondialdehyde (MDA), and activity of superoxide dismutase (SOD), catalase (CAT) in cultured rat splenocytes were also measured. RESULTS: The radioprotective effects decreased from rutin >95% ethanol extracts of Pinus koraiensis bark (95EEP) >40AEP > WEP. The stimulating effects decreased from rutin > n-butanol extract (NBE) > EAE. The results demonstrate that there exists toxic ingredients (PEE and dichloromethane extract), proliferative-promoting, radioprotective component (EAE and NBE) in 95EEP. fraction eluted from n-butanol fractions of 95EEP with 50% methanol solution (NBEPKB-50ME), a fraction of NBE result from bio-guided isolation, demonstrates good radioprotective efficacy on rat splenocytes. NBEPKB-50ME pretreated rat splenocytes demonstrated progressively reduced levels of MDA when compared with γ-ray exposed cells. Different dose of NBEPKB-50ME pretreatment with 8 Gy-irration showed an increase in enzymatic antioxidant. CONCLUSIONS: Proliferative-promoting efficacy, radioprotective effect of different solvents extracts of the bark of P. koraiensis were investigated in this work. NBEPKB-50ME was the best elution in NBE, especially in restoring SOD, CAT activities, content of GSH, decreasing DNA damage. SUMMARY: The radioprotective effects decreased from rutin > 95EEP > 40AEP > WEP. The extract of Petroleum ether, dichloromethane extract (DME) of 95% ethanol extract of P. koraiensis (PEE, DME) show toxic effect on rat splenocytes. The extract of Ethyl acetate, n-butanol extract of 95% ethanol extract of P. koraiensis (EAE, NBE) show proliferative-promoting, radioprotective effect on rat splenocytesSingle-cell gel electrophoresis was used to evaluate the spleen cell DNA damage parameters affected by gamma-radiation and addition of best component NBEPKB-50Me from extract of P. koraiensis barkNBEPKB-50ME pretreatment with 8 Gy-irradiation showed an increase in enzymatic antioxidant capacity. NBEPKB-50ME pretreated (80, 160, 320, 480 mg/ml) rat splenocytes demonstrated progressively reduced levels of MDA when compared with g-ray exposed cells. Abbreviations used: MDA: Malondialdehyde; SOD: Superoxide dismutase; CAT: Catalase; PEE: Petroleum ether Extract; DME: Dichloromethane extract; EAE: Ethyl acetate extract; NBE: n-butanol extract; WAP: Water extracts of Pinus koraiensis bark; 40AEP: 40% acetone extracts of Pinus koraiensis bark; 95EEP: 95% ethanol extracts of Pinus koraiensis bark; TPC: Total phenolic content; TFC: Total flavonoid content; NBEPKB-50ME: Fraction eluted from n-Butanol fractions of 95EEP with 50% methanol solution.

Target/signalling pathways of natural plant-derived radioprotective agents from treatment to potential candidates: A reverse thought on anti-tumour drugs.

Radiation damage can occur in nuclear power plant workers when physical protections fail, which results in nuclear leakage through the protective layers. Alternatively, workers may be unable to use physical protection in time (in the case of a sudden nuclear weapons attack). In addition, patients who receive local radiotherapy and are not allowed to adopt local physical protection may experience radiation damage. Thus, protection against chemical radiation has become indispensable. In view of the side effects caused by synthetic radioprotective agents (such as amisfostine), searching for radioprotective agents from plant sources is an alternative strategy. Radiation damage can cause multiple signalling pathway disturbances, leading to multiple organ injuries. Changes in these signalling pathways can lead to apoptosis, necrosis, and autophagy, as well as organ fibrosis, atrophy, and inflammation. Through literature searches, we determined that most targets for treating radiation injury are mechanistically opposite those of anti-tumour agents. This is likely attributable to the idea that anti-tumour agents promote cell necrosis or apoptosis, whereas the goal of anti-radiation agents is to promote cell survival or autophagy. This observation has important theoretical and practical significance when searching and developing new radioprotective agents derived from plant extracts. Further, it has important guiding value for meeting military needs and serving the public.

Effect and mechanism of Sorbus pohuashanensis (Hante) Hedl. flavonoids protect against arsenic trioxide-induced cardiotoxicity.

The cardiotoxicity of arsenic trioxide (ATO) limits its clinical application in cancer treatment. Evidences suggest that sorbus has antioxidant activity and its consumption has been linked with improved cardioprotection. In this study, we investigated the cardio-protective effect and mechanisms of Sorbus pohuashanensis (Hante) Hedl. flavonoids (SPF) against ATO in BALB/c mice and H9c2 cells. Eleven major flavonoids were confirmed by ultra-performance liquid chromatography electrospray ionization quadrupole time of flight mass spectrometry (UPLC-ESI-Q-TOF-MS). SPF recovered the ATO-induced disordered electrocardiogram (ECG) and abnormal cardiac structure in the heart of mice. At the same time, SPF significantly reduced levels of creatine kinase (CK), creatine kinase-MB (CK-MB) lactate dehydrogenase (LDH), and glutamic oxaloacetic transaminase (GOT) against ATO-induced injury and inhibited ATO-induced apoptosis both in vivo and in vitro. In addition, SPF regulated ATO-induced oxidative stress damage by increasing the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in vivo and in vitro, and reducing reactive oxygen species (ROS). Analysis of the oxidative stress pathways showed that SPF prevented the ATO-induced downregulation of phosphorylated protein kinase B (p-Akt) in vivo and in vitro. Pre-treatment of H9c2 cells with SPF inhibited attenuation of nuclear factor (Nrf2) and heme oxygenase (HO-1). Hence, SPF could be used as a preventive and therapeutic plant ingredient against ATO-induced cardiotoxicity.

Lead toxicity induces autophagy to protect against cell death through mTORC1 pathway in cardiofibroblasts.

Heavy metals, such as lead (Pb(2+)), are usually accumulated in human bodies and impair human's health. Lead is a metal with many recognized adverse health side effects and yet the molecular processes underlying lead toxicity are still poorly understood. In the present study, we proposed to investigate the effects of lead toxicity in cultured cardiofibroblasts. After lead treatment, cultured cardiofibroblasts showed severe endoplasmic reticulum (ER) stress. However, the lead-treated cardiofibroblasts were not dramatically apoptotic. Further, we found that these cells determined to undergo autophagy through inhibiting mammalian target of rapamycin complex 1 (mTORC1) pathway. Moreover, inhibition of autophagy by 3-methyladenine (3-MA) may dramatically enhance lead toxicity in cardiofibroblasts and cause cell death. Our data establish that lead toxicity induces cell stress in cardiofibroblasts and protective autophagy is activated by inhibition of mTORC1 pathway. These findings describe a mechanism by which lead toxicity may promote the autophagy of cardiofibroblasts cells, which protects cells from cell stress. Our findings provide evidence that autophagy may help cells to survive under ER stress conditions in cardiofibroblasts and may set up an effective therapeutic strategy for heavy metal toxicity.