Jie Liu

The protective effects of Hua-Feng-Dan recipes against chronic cerebral hypoperfusion-induced ischemia were examined; RNA-seq and 16 S-rRNA-seq were used to explore the molecular mechanisms. Male Sprague-Dawley rats underwent unilateral common carotid artery ligation surgery to establish chronic cerebral hypoperfusion (CCH) models. Then, the CCH rats were treated with various Hua-Feng-Dan recipes in diet for 20 days. Finally, behavioral tests were performed, followed by histopathology. Hippocampal RNA was isolated for RNA-seq and RT-qPCR analyses; Colon bacterial DNA was isolated for 16 S rRNA-seq and bioinformatics. The CCH rats exhibited cognition deficits evidenced by Behavioral tests. The neurons in the hippocampus CA1 area were damaged. Hua-Feng-Dan recipes as Reduced_H (0.5 g/kg), Original, and Nonferment improved behavioral deficits and morphological changes, while Reduced_L (0.25 g/kg) was ineffective. RNA-seq revealed distinct gene expression pattern among groups. Ingenuity pathway analysis of differentially expressed genes revealed Hua-Feng-Dan recipes ameliorated Canonical pathways involved in cytosolic Ca ²⁺ overload, disruption of IGF homeostasis and Neutrophil degranulation; attenuated CCH-activated Upstream regulators such as IL1B, IL6, TNF, IGF1, and glucose metabolism. CCH-decreased Firmicutes/Bacteroidetes ratio were recovered by Hua-Feng-Dan recipes. CCH-increased Prevotellaceae and decreased Lachnospiraceae were attenuated; CCH-increased ASV1 and decreased ASV39 were brought to normal after Hua-Feng-Dan treatments. Similar to the efficacy against CCH, Reduced_L was ineffective in transcriptome and gut microbiota analysis. Hua-Feng-Dan recipes (Reduced_H, Original, and Nonferment) are effective against CCH-induced chronic cerebral ischemia, while Reduced_L was ineffective. The mechanisms of the protection are related to transcriptome regulation in the hippocampus, and modulation of CCH-disrupted gut dysbiosis.

Hua‐Feng‐Dan is a Chinese medicine in the treatment of epilepsy and neurodegeneration. The prior studies demonstrated its protection against neuroinflammation, dopaminergic neuron loss, and in the treatment of ischemic stroke, but its anticonvulsive efficacy against epilepsy remains elusive. The aim of this study was to examine antiepileptic effects of Hua‐Feng‐Dan recipes and the mechanism of protection. Pentylenetetrazol (PTZ)‐induced kindling mouse model (35 mg/kg, ip on alternate days × 10) was used to evaluate the antiepileptic effects of Hua‐Feng‐Dan recipes. Mice were given original, reduced, and nonfermented Hua‐Feng‐Dan via feed at clinical dose (0.5 g/kg) and diazepam was used as a positive control. The seizure scores were recorded after each PTZ injection. At the end of the experiments, the brain and colon content were collected for RNA‐Seq and 16S rRNA‐Seq, respectively, followed by bioinformatics and qPCR verification. Hua‐Feng‐Dan recipes were effective against PTZ‐induced seizures, with original the best and half of reduced (0.25 g/kg) ineffective. PTZ‐induced aberrant gene expressions in the brain were ameliorated by Hua‐Feng‐Dan recipes to various extents. Ingenuity Pathway Analysis of differentially expressed genes revealed that PTZ‐altered canonical pathways and upstream regulators were attenuated by Hua‐Feng‐Dan treatments. qPCR verified the expression of early immediate genes, proinflammatory mediators, transporters and apoptosis genes. PTZ‐disrupted gut microbiome was also ameliorated by Hua‐Feng‐Dan recipes, and the modulation of Lachnospiraceae and ASV230 was consistent with the literature. Hua‐Feng‐Dan recipes were effective against PTZ‐induced kindling mice. The mechanisms appeared to be related to the modulation of brain gene expression and gut microbiota. Hua‐Feng‐Dan (HFD) recipes were effective against PTZ‐induced seizures in mice. HFD ameliorated abnormal brain gene expressions in PTZ kindling mice via RNA sequencing (RNA‐seq). IPA of DEGs revealed improved canonical pathways and upstream regulators. 16S rRNA‐seq showed microbiome modulation by HFD in PTZ kindling mice. qPCR verified selected brain genes and bacterial ASVs.

Traditional Chinese medicine (TCM) has been used in the treatment of vascular cognitive impairment and dementia caused by chronic cerebral hypoperfusion (CCH) in patients for hundreds of years. Ethnopharmacological researches have been conducted in recent years to elucidate their therapeutic effects on cognitive deficits and potential mechanisms in animal models. This manuscript critically reviewed recent 5-year experimental researches from PubMed on the topic, including 11 TCM formulae, 8 herb extracts, and 21 pure compounds extracted from TCM, including polyphenols, flavonoids, alkaloids, terpenoids, saponins, iridoid glycosides, glucosides, and others in rodent CCH models, using bilateral common carotid artery occlusion (BCCAO, 2VO), bilateral common carotid artery stenosis (BCAS), and unilateral common carotid artery occlusion (UCCAO). The underlying mechanisms are multiple, including the maintenance of blood brain barrier and endothelium integrity, the increase in cerebral blood flow, the amelioration of white matter lesions, the modulation of microglia M1/M2 phenotype, the scavenge of reactive oxidative oxygen species and reduction of proinflammatory factors, the maintenance of mitochondrial function, the inhibition of apoptosis, ferroptosis and pyroptosis, and the promotion of neuronal regeneration and angiogenesis through the regulation of gene/protein expressions, including the Toll, NF-κB, MAPK, PPARγ, and/or Nrf2 pathways. These mechanisms are not mutually exclusive, rather they play an integrated role to fortify the multi-components, multi-targets feature of TCM in the treatment of CCH and human vascular cognitive impairments.

This study examined the effects of _Musa paradisiaca_ L. (MP) stem juice on PTZ-induced seizures in rats. Studying the pharmacological basis of this traditional remedy against seizures is meritorious. The study determined the major phytochemical ing...

Excessive manganese (Mn) exposure produces neurotoxicity with mitochondrial damage. Mitophagy is a protective mechanism to eliminate damaged mitochondria to protect cells. The aim of this study was to determine the dose-response of Mn-induced mitochondria damage, the expression of mitophagy-mediated protein PINK1/Parkin and mitophagy in dopamine-producing SK-N-SH cells. Cells were exposed to 0, 300, 900, and 1500 μM Mn²⁺ for 24 h, and ROS production, mitochondrial damage and mitophagy were examined. The levels of dopamine were detected by ELISA and neurotoxicity and mitophagy-related proteins (α-synuclein, PINK1, Parkin, Optineurin, and LC3II/I) were detected by western blot. Mn increased intracellular ROS and apoptosis and decreased mitochondrial membrane potential in a concentration-dependent manner. However, at the low dose of 300 μM Mn, autophagosome was increased 11-fold, but at the high dose of 1500 μM, autophagosome was attenuated to 4-fold, together with decreased mitophagy-mediated protein PINK1/Parkin and LC3II/I ratio and increased Optineurin expression, resulting in increased α-synuclein accumulation and decreased dopamine production. Thus, Mn-induced mitophagy exhibited a novel biphasic regulation: at the low dose, mitophagy is activated to eliminate damaged mitochondria, however, at the high dose, cells gradually loss the adaptive machinery, the PINK1/Parkin-mediated mitophagy weakened, resulting in neurotoxicity.