Gastrodin Alleviates Vascular Dementia in a 2-VO-Vascular Dementia Rat Model by Altering Amyloid and Tau Levels.

Vascular dementia (VaD) is the second most common type of dementia and has become a major public health challenge as the global population ages. VaD is caused by cerebrovascular disease, and most patients with VaD have been reported to also have Alzheimer's pathologies, which is the formation of neurofibrillary tangles and amyloid plaques that are mainly composed of hyperphosphorylated Tau and amyloid ß (Aß) respectively. However, the mechanisms of VaD are not completely understood, and very few drugs are available to treat this condition. Gastrodin (Gas) is the main bioactive component of the traditional Chinese herbal plant named Tian Ma (Gastrodia elata), and it has been used to treat neurasthenia in the clinical practice of Chinese Medicine for many years. Here, we hypothesize that Gas alleviates VaD in a rat model of permanent bilateral common carotid artery occlusion (2-VO)-induced VaD. Based on the results of the Morris water maze test and attention set shift test, either 22.5 or 90 mg/kg/day Gas improved the executive dysfunction and memory impairment of 2-VO rats following an intragastric administration for 4 weeks. Both 22.5 and 90 mg/kg/day Gas reduced Aß1-40 and Aß1-42 plaques in plasma and hippocampus of 2-VO rats. Mechanistically, in 2-VO rats, treatment with Gas (90 mg/kg/day) suppressed Aß plaque deposition by decreasing the hippocampus levels of phosphorylated Tau. Thus, Gas ameliorated the cognitive deficits of 2-VO rats by inhibiting the abnormal phosphorylation of Aß and Tau.

Isoforskolin and forskolin attenuate lipopolysaccharide-induced inflammation through TLR4/MyD88/NF-κB cascades in human mononuclear leukocytes.

The principal active component of isoforskolin (ISOF) is from the plant Coleus forskohlii, native to China, which has attracted much attention for its biological effects. We hypothesize that ISOF and forskolin (FSK) pretreatment attenuates inflammation induced by lipopolysaccharide (LPS) related to toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor kappa B (NF-κB) signaling. Mononuclear leukocytes (MLs) from healthy donors' blood samples were separated by using density gradient centrifugation. Protein levels of TLR4, MyD88, and NF-κB were detected using western blot and inflammatory cytokines interleukin (IL) 1ß, IL-2, IL-6, IL-21, IL-23, tumor necrosis factor (TNF) α, and TNF-ß were tested by enzyme-linked immunosorbent assay and Quantibody array in MLs. Our results showed that LPS augmented the protein levels of TLR4, MyD88, and NF-κB in MLs and the production of IL-1ß, IL-2, IL-6, IL-21, IL-23, TNF-α, and TNF-ß in supernatants of MLs. Despite treatment with ISOF and FSK prior to LPS, the protein levels of TLR4, MyD88, NF-κB, IL-1ß, IL-2, IL-6, IL-21, IL-23, TNF-α, and TNF-ß in MLs were apparently decreased. roflumilast (RF) and dexamethasone (DM) had a similar effect on MLs with ISOF and FSK. Our results, for the first time, have shown that ISOF and FSK attenuate inflammation in MLs induced by LPS through down-regulating protein levels of IL-1ß and TNF-α, in which TLR4/MyD88/NF-κB signal pathway could be involved.

Exosome may be the next generation of promising cell-free vaccines.

Traditional vaccines have limits against some persistent infections and pathogens. The development of novel vaccine technologies is particularly critical for the future. Exosomes play an important role in physiological and pathological processes. Exosomes present many advantages, such as inherent capacity being biocompatible, non-toxic, which make them a more desirable candidate for vaccines. However, research on exosomes are in their infancy and the barriers of low yield, low purity, and weak targeting of exosomes limit their applications in vaccines. Accordingly, further exploration is necessary to improve these problems and subsequently facilitate the functional studies of exosomes. In this study, we reviewed the origin, classification, functions, modifications, separation and purification, and characterization methods of exosomes. Meanwhile, we focused on the role and mechanism of exosomes for cancer and COVID-19 vaccines.