Neuroinflammation is a major cause of central nervous system (CNS) damage and can result in long-term disability and mortality. Therefore, the development of effective anti-neuroinflammatory agents for neuroprotection is vital. To our surprise, the naturally occurring molecule alantolactone (Ala) was reported to significantly inhibit tumor growth and metastasis as a result of its excellent anti-inflammatory effects. Thus, we proposed that it could also act as an anti-neuroinflammatory agent. Thus, in this study, a coculture system of BV2 cells and PC12 cells were used as an in vitro neuroinflammatory model to investigate the anti-neuroinflammatory mechanism of Ala. The results indicated that Ala downregulated the expression of proinflammatory factors by suppressing the nuclear factor kappa light-chain enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Further evaluation using a middle cerebral artery occlusion and reperfusion (MCAO/R) rat model supported the conclusion that Ala could (1) alleviate cerebral ischemia-reperfusion injury; (2) reduce neurological deficits, cerebral infarct volume, and brain edema; and (3) attenuate the apoptosis and necrosis of neurons. In sum, Ala demonstrates anti-neuroinflammatory properties that contribute to the amelioration of CNS damage, and it could be a promising candidate for future applications in CNS injury treatment.

Oxidative stress and inflammation are important mechanisms of cerebral ischemia reperfusion (IR) injury. Luteolin (Lu), one of the major active components in the classical Tibetan prescription, which has been used in the treatment of cardiovascular diseases since 700 BC, has potential for IR injury therapy. Its hydrophobicity has impeded its further applications. In this study, we first prepared Lu micelles (M-Lu) by self-assembling with an amphiphilic copolymer via the thin film hydration method to improve the dispersion of Lu in water. The obtained M-Lu was about 30 nm, with a narrow particle size distribution, and a 5% (w/w) of Lu. The bioavailability of the micelles was further evaluated in vitro and in vivo. Compared to free Lu, M-Lu had a better penetration efficiency, which enhanced its therapeutic effect in IR injury restoration. M-Lu further strengthened the protection of nerve cells through the nuclear factor-κ-gene binding κ (NF-κB) and mitogen-activated protein kinases (MAPK) pathways and inhibited the apoptosis of cells by adjusting the expression of B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) in the case of oxidative stress damage. M-Lu induced stem cells to differentiate into neuron-like cells to promote the repair and regeneration of neurons. The results of in vivo pharmacodynamics of Lu on occlusion of the middle cerebral artery model further demonstrated that M-Lu better inhibited inflammation and the oxidative stress response by the down-regulation of the inflammatory cytokine, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, and the up-regulation of the activity of anti-oxidant kinase, such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-px), which further ameliorated the degree of IR injury. The M-Lu could be a new strategy for IR injury therapy.

Cerebral ischemia/reperfusion (I/R) injury causes a larger population of disable patients and deaths annually. Three Tibetan prescriptions have been applied in alleviating the I/R injury for a 1,000 years. Interestingly, ellagic acid (EA) is one of the commonly dominated phytochemicals in these 3 prescriptions. Therefore, it is noteworthy to evaluate the association between the pharmacodynamics effects of EA and I/R injury alleviation. In this study, we reveal that the EA can effectively reduce the infarction area, and prevent the neuron from apoptosis and damage in permanent middle cerebral artery occlusion rat model. The results of the histopathological study indicate that alleviation of brain damage is positively correlated with the EA dose. Further by biochemical analysis, it indicates that the EA can alleviate the brain damage by the anti-inflammatory and anti-oxidative response mediated by EA. The upregulation of zonula occludens-1 and down-regulation of Aquaporin 4 and matrix metalloprotein 9 (MMP-9) in injured brain tissues after being treated with EA suggested that the reconstruction of brain-blood-barrier (BBB), which can further prevent the brain from further injury by the other xenobiotics. In addition, EA will not activate the coagulation factors XII to induce coagulation formation during the treatment process. Therefore, EA is a promising candidate oral drug for I/R injury therapy.

Rhizoma coptidis, the root ofCoptis chinensis Franch, has been used in China as a folk medicine in the treatment of diabetes for thousands of years. Berberine, one of the active ingredients ofRhizoma coptidis, has been reported to improve symptoms of diabetes and to treat experimental cardiac hypertrophy, respectively. The objective of this study was to evaluate the potential effect of berberine on cardiomyocyte hypertrophy in diabetes and its possible influence on peroxisome proliferator-activated receptor-α(PPARα)/nitric oxide (NO) signaling pathway. The cardiomyocyte hypertrophy induced by high glucose (25.5 mmol/L) and insulin (0.1 μmol/L) (HGI) was characterized in rat primary cardiomyocyte by measuring the cell surface area, protein content, and atrial natriuretic factor mRNA expression level. Protein and mRNA expression were measured by western blot and real-time RT-PCR, respectively. The enzymatic activity of NO synthase (NOS) was measured using a spectrophotometric assay, and NO concentration was measured using the Griess assay. HGI significantly induced cardiomyocyte hypertrophy and decreased the expression of PPARαand endothelial NOS at the mRNA and protein levels, which occurred in parallel with declining NOS activity and NO concentration. The effect of HGI was inhibited by berberine (0.1 to 100 μmol/L), fenofibrate (0.3 μmol/L), orL-arginine (100 μmol/L). MK886 (0.3 μmol/L), a selective PPARαantagonist, could abolish the effects of berberine and fenofibrate.NG-nitro-L-arginine-methyl ester (100 μmol/L), a NOS inhibitor, could block the effects ofL-arginine, but only partially blocked the effects of berberine. These results suggest that berberine can blunt HGI-induced cardiomyocyte hypertrophyin vitro, through the activation of the PPARα/NO signaling pathway.

Post-stroke depression (PSD) is a common complication of stroke that can damage patients’ brains. More and more studies have been conducted on PSD in recent years, but the exact mechanism is still not understood. Currently, animal models provide an alternative approach to better understand the pathophysiology of PSD and may also pave the way for the discovery of new treatments for depression. This study investigated the therapeutic effect and mechanism of aloe-emodin (AE) on PSD rats. Previous studies have shown that AE positively affects PSD in rats by improving depression, increasing their activities and curiosities, enhancing the number of neurons, and ameliorating damage to brain tissue. Meanwhile, AE could up-regulate the expression of brain-derived neurotrophic factor (BDNF) and neurotrophic 3 (NTF3), but it could also down-regulate the expression of aquaporins (AQP3, AQP4, and AQP5), glial fibrillary acidic protein (GFAP), and transient receptor potential vanilloid 4 (TRPV4), which is helpful in maintaining homeostasis and alleviating encephaledema. AE may be a prospective solution in the future for the treatment of PSD patients.