Parkinson's disease (PD) is the second most common neurodegenerative disease amongst the middle‑aged and elderly populations. Several studies have confirmed that the microbiota‑gut‑brain axis (MGBA) serves a key role in the pathogenesis of PD. Changes to the gastrointestinal microbiome (GM) cause misfolding and abnormal aggregation of α‑synuclein (α‑syn) in the intestine. Abnormal α‑syn is not eliminated via physiological mechanisms and is transported into the central nervous system (CNS) via the vagus nerve. The abnormal levels of α‑syn aggregate in the substantia nigra pars compacta, not only leading to the formation of eosinophilic Lewis Bodies in the cytoplasm and mitochondrial dysfunction in dopaminergic (DA) neurons, but also leading to the stimulation of an inflammatory response in the microglia. These pathological changes result in an increase in oxidative stress (OS), which triggers nerve cell apoptosis, a characteristic of PD. This increase in OS further oxidizes and intensifies abnormal aggregation of α‑syn, eventually forming a positive feedback loop. The present review discusses the abnormal accumulation of α‑syn in the intestine caused by the GM changes and the increased levels of α‑syn transport to the CNS via the MGBA, resulting in the loss of DA neurons and an increase in the inflammatory response of microglial cells in the brain of patients with PD. In addition, relevant clinical therapeutic strategies for improving the GM and reducing α‑syn accumulation to relieve the symptoms and progression of PD are described.

Cigarette smoking-related lung injury is one of the most common and fatal etiologies of many respiratory diseases, for which no effective interventions are available. Astragaloside Ⅳ (ASⅣ) is an active component extracted from Astragalus membranaceus. It is prescribed as a treatment for upper respiratory tract infections. Here, we report the potential anti-inflammatory effects and mechanisms of ASⅣ on cigarette smoking extract- (CSE)-exposed RAW264.7 cells. Murine macrophages were exposed to CSE, followed by administration of ASⅣ at 25-100 μg/mL for 24 h. ASⅣ significantly rescued CSE-induced cell death by inhibition of release pro-inflammatory cytokines. We measured autophagy as an intracellular scavenger by analyzing autophagic flux using tandem mRFP-GFP-LC3 fluorescence microscopy. Following administration with ASⅣ in CSE-exposed RAW264.7 cells, there was a notable increase in autophagosomes and a range of autophagic vacuoles were generated, as seen with transmission electron microscopy. Loss of autophagy following transfection siRNA aggravated inflammatory injury and release of inflammatory cytokines. Mechanistically, ASⅣ-triggered autophagy is mediated by the TLR4/NF-κB signaling pathway to reduce inflammation. Taken together, our findings suggest that ASⅣ acts stimulates autophagy, and that ASⅣ induces autophagy by inhibiting the TLR4/NF-κB signaling pathway, contributing to alleviation of inflammation.

Recently, the use of traditional Chinese medicine (TCM) has become more generally accepted, including by the Food and Drug Administration. To expand the use of TCM worldwide, it is important to study the molecular mechanisms by which TCM and its active ingredients produce effects. Gastrodin is an active ingredient from Gastrodia elata Blume. It is reported that gastrodin has neuroprotective function in Parkinson’s disease. But its mechanisms of neuroprotection remain not clear in PD. Here, we build two C. elegans PD model using 6-OHDA and transgenic animal to observe the changes of PD worms treated with or without gastrodin to confirm the function of gastrodin, then utilize mutant worms to investigate DAF-2/DAF-16 signaling pathway, and finally verify the mechanism of gastrodin in PD. Gastrodin attenuates the accumulation of α-synuclein and the injury of dopaminergic neurons, improves chemotaxis behavior in Parkinson’s disease models, then recovers chemotaxis behavior by insulin-like pathway. DAF-2/DAF-16 is required for neuroprotective effect of dopamine neuron in PD. Our study demonstrated that gastrodin rescued dopaminergic neurons and reduced accumulation of α-synuclein protein, and the activity of gastrodin against Parkinson’s disease depended on the insulin-like DAF-2/DAF-16 signaling pathway. Our findings revealed that this insulin-like pathway mediates neuroprotection of gastrodin in a Parkinson’s disease model.

Atherosclsis is a critical actuator causing cardiac-cerebral vascular disease with a complicated pathogeneon, refered to the disorders of intestinal flora and persistent inflammation. Gastrodin (4-(hydroxymethyl) phenyl-β-D- Glucopyranoside) is the most abundant glucoside extracted from the Gastrodiaelata, which is a traditional Chinese herbal medicine for cardiac-cerebral vascular disease, yet its mechanisms remain little known. In the present study, the gastrodia extract and gastrodin attenuate the lipid deposition and foam cells on the inner membrane of the inner membrane of the thoracic aorta in the early atherosclerosis mice. Blood lipid detection tips that TC and LDL-C were reduced in peripheral blood after treatment with the gastrodia extract and gastrodin. Furthermore, unordered gut microbes are remodeled in terms of bacterial diversity and abundance at family and genus level. Also, the intestinal mucosa damage and permeability were reversed, accompaniedwith the reducing of inflammatory cytokines. Our findings revealed that the functions of gastrodia extract and gastrodin in cardiac-cerebral vascular disease involved to rescued gut microbes and anti-inflammation may be the mechanismof remission lipid accumulation.

Pulmonary fibrosis (PF) is a crippling disease characterized by progressive dyspnea and associated with a high mortality rate, but its origin is unknown and there is no effective treatment. Yifei Sanjie formula (YFSJF) is a Chinese medicine that is widely used for treatment of respiratory systems disease. However, the molecular basis for the function of YFSJF has not been determined. Here we investigate the contribution of YFSJF in BLM-induced PF mice. Administration with YFSJF significantly alleviated the degree of BLM-induced collagen I and III deposition and the inflammatory injuring in the lungs and suppressed hydroxyproline release in PF animals. The active components of YFSJF are comprised with flavonoid, amino acids, saponins, oligosaccharide, organic acid, vitamin, esters, purine nucleosides. Additionally, there was a significant increase in autophagosomes, after treatment with YFSJF in PF animals. Interestingly, autophagy dysfunction by the blocker chloroquine (CQ) resulted in collagen deposition and inducing the expression of fibrosis-related genes. In addition, YFSJF-induced autophagy is mediated by the PI3K-AKT-mTOR pathway, and knockdown of PI3K by siRNA up-regulated the expression of autophagy-related genes and down-regulated the expression of collagen in human lung fibroblasts (HLF). Our findings provide a detailed understanding that YFSJF-antifibrotic effects are mainly mediated by triggering autophagy, and suppressing phosphorylation of the PI3K-AKT-mTOR pathway is required for YFSJF-curative effect.

Pseudomonas aeruginosa can establish life-long chronic infection in patients with cystic fibrosis by generating genetic loss-of-function mutations, which enhance fitness of the bacterium in the airways. However, the precise role of the pathoadaptive mutations in persistence in chronic airways infection remains largely unknown. Here we demonstrate that pyocyanin, a well-described P. aeruginosa virulence factor that plays an important role in the initial infection, promotes autophagy in bronchial epithelial cells. Disruption of phzM, which is required for pyocyanin biosynthesis, leads to a significant reduction in autophagy in Beas-2B cells and lung tissues. Pyocyanin-induced autophagy is mediated by the EIF2AK4/GCN2-EIF2S1/eIF2α-ATF4 pathway. Interestingly, rats infected with the phzMΔ mutant strain have high mortality rate and numbers of colony-forming units, compared to those infected with wild-type (WT) P. aeruginosa PA14 strain, during chronic P. aeruginosa infection. In addition, the phzMΔ mutant strain induces more extensive alveolar wall thickening than the WT strain in the pulmonary airways of rats. As autophagy plays an essential role in suppressing bacterial burden, our findings provide a detailed understanding of why reduction of pyocyanin production in P. aeruginosa in chronic airways infections has been associated with better host adaptation and worse outcomes in cystic fibrosis.