The tumor suppressor protein p53 plays an important role in the development and progression of colon cancer, and the subcellular organelle localization directly affects its function. Wogonin (5,7-dihydroxy-8-methoxyflavone), a mono-flavonoid extracted from root of Scutellaria baicalensis Georgi, possesses acceptable toxicity and has been used in colorectal cancer (CRC) chemoprevention in pre-clinical trials by oncologist. However, the underlying anti-colon cancer mechanisms of wogonin are not yet fully understood. In the present study, the effect of wogonin on the initiation and development of colitis-associated cancer through p53 nuclear translocation was explored. AOM-DSS CRC animal model and human CRC HCT-116 cell model were used to evaluate the in vivo and in vitro anti-colon cancer action of wogonin. We observed that wogonin showed a dramaticlly preventive effect on colon cancer. Our results showed that wogonin caused apoptotic cell death in human CRC HCT-116 cell through increased endoplasmic reticulum (ER) stress. Meanwhile, excessive ER stress facilitated the cytoplasmic localization of p53 through increasing phosphor-p53 at S315 and S376 sites, induced caspase-dependent apoptosis and inhibited autophagy. Furthermore, we verified the chemoprevention effect and toxicity of wogonin in vivo by utilizing an AOM-DSS colon cancer animal model. We found that wogonin not only reduced tumor multiplicity, preserved colon length to normal (6.79 ± 0.34 to 7.41 ± 0.56, P < 0.05) but also didn’t induce side effects on various organs. In conclusion, these results explain the anti-tumor effect of wogonin in CRC and suggest wogonin as a potential therapeutic candidate for the therapeutic strategy in CRC treatment.

Aconitine (AC) is the primary bioactive and secondary metabolite alkaloidin of Aconitum species which is accounted for more than 60% of the total diester-diterpenoid alkaloids in Aconite. To evaluate the analgesic effects of AC, 4 different pain models including hot plate assay, acetic acid writhing assay, formalin and CFA induced pain models were adopted in this study. In hot plate experiment, AC treatment at concentration of 0.3 mg/kg and 0.9 mg/kg improved the pain thresholds of mice similar to the positive drug aspirin at the concentration of 200 mg/kg (17.12% and 20.27% VS 19.21%). In acetic acid writhing experiment, AC significantly reduced the number of mice writhing events caused by acetic acid, and the inhibition rates were 68% and 76%. These results demonstrated that AC treatment revealed significant analgesic effects in both acute thermal stimulus pain model and chemically-induced visceral pain model. The biphasic nociceptive responses induced by formalin were significantly inhibited after AC treatment for 1h or 2h. The inhibition rates were 33.23% and 20.25% of AC treatment for 1h at 0.3 mg/kg and 0.9 mg/kg in phase I. In phase II, the inhibition rates of AC and aspirin were 36.08%, 32.48% and 48.82% respectively, which means AC showed similar analgesic effect to non-steroidal anti-inflammatory compounds. In the chronic CFA-induced nociception model, AC treatment also improved mice pain threshold to 131.33% at 0.3 mg/kg, which was similar to aspirin group (152.03%). Above all, our results verified that AC had obviously analgesic effects in different mice pain models.

Cobaltite spinel oxides (CuCo2O4), which show electrocatalytic activity for oxygen evolution reaction (OER), are readily synthesized using a facile hydrothermal method, with a stationary ratio, uniform flower-like mesopores morphology, and high crystallinity. We have carried out first-principles calculations on the mechanism of the reaction pathway and the Gibbs free energy diagram of CuCo2O4 structures using density functional theory (DFT) and purely confirmed by experimental results. This catalyst performed an outstanding OER performance with an overpotential 230 mV at 10 mA∙cm− 2 in 1 M KOH, which was close to IrO2 with an overpotential 190 mV at 10 mA∙cm− 2. This work provides a facile method for electrocatalytic oxygen production with enhanced conductivity and enhanced OER by replacing cobalt with copper.

Cobaltite spinel oxides (CuCo 2 O 4 ), which show electrocatalytic activity for oxygen evolution reaction (OER), are readily synthesized using a facile hydrothermal method, with a stationary ratio, uniform owerlike mesopores morphology, and high crystallinity. We have carried out rst-principles calculations on the mechanism of the reaction pathway and the Gibbs free energy diagram of CuCo 2 O 4 structures using density functional theory (DFT) and purely con rmed by experimental results. This catalyst performed an outstanding OER performance with an overpotential 230 mV at 10 mA•cm − 2 in 1 M KOH, which was close to IrO 2 with an overpotential 190 mV at 10 mA•cm − 2 . This work provides a facile method for electrocatalytic oxygen production with enhanced conductivity and enhanced OER by replacing cobalt with copper.