A systematic review of ginsenoside biosynthesis, spatiotemporal distribution, and response to biotic and abiotic factors in American ginseng.

American ginseng (Panax quinquefolius) has gained recognition as a medicinal and functional food homologous product with several pharmaceutical, nutritional, and industrial applications. However, the key regulators involved in ginsenoside biosynthesis, the spatiotemporal distribution characteristics of ginsenosides, and factors influencing ginsenosides are largely unknown, which make it challenging to enhance the quality and chemical extraction processes of the cultivated American ginseng. This review presents an overview of the pharmacological effects, biosynthesis and spatiotemporal distribution of ginsenosides, with emphasis on the impacts of biotic and abiotic factors on ginsenosides in American ginseng. Modern pharmacological studies have demonstrated that American ginseng has neuroprotective, cardioprotective, antitumor, antidiabetic, and anti-obesity effects. Additionally, most genes involved in the upregulation of ginsenoside biosynthesis have been identified, while downstream regulators (OSCs, CYP450, and UGTs) require further investigation. Futhermore, limited knowledge exists regarding the molecular mechanisms of the impact of biotic and abiotic factors on ginsenosides. Notably, the nonmedicinal parts of American ginseng, particularly its flowers, fibrous roots, and leaves, exhibit higher ginsenoside content than its main roots and account for a considerable amount of weight in the whole plant, representing promising resources for ginsenosides. Herein, the prospects of molecular breeding and metabolic engineering based on multi-omics to improve the unstable quality of cultivated American ginseng and the shortage of ginsenosides are proposed. This review highlights the gaps in the current research on American ginseng and proposes solutions to address these limitations, providing a guide for future investigations into American ginseng ginsenosides.

AAV11 enables efficient retrograde targeting of projection neurons and enhances astrocyte-directed transduction.

Viral tracers that enable efficient retrograde labeling of projection neurons are powerful vehicles for structural and functional dissections of the neural circuit and for the treatment of brain diseases. Currently, some recombinant adeno-associated viruses (rAAVs) based on capsid engineering are widely used for retrograde tracing, but display undesirable brain area selectivity due to inefficient retrograde transduction in certain neural connections. Here we developed an easily editable toolkit to produce high titer AAV11 and demonstrated that it exhibits potent and stringent retrograde labeling of projection neurons in adult male wild-type or Cre transgenic mice. AAV11 can function as a powerful retrograde viral tracer complementary to AAV2-retro in multiple neural connections. In combination with fiber photometry, AAV11 can be used to monitor neuronal activities in the functional network by retrograde delivering calcium-sensitive indicator under the control of a neuron-specific promoter or the Cre-lox system. Furthermore, we showed that GfaABC1D promoter embedding AAV11 is superior to AAV8 and AAV5 in astrocytic tropism in vivo, combined with bidirectional multi-vector axoastrocytic labeling, AAV11 can be used to study neuron-astrocyte connection. Finally, we showed that AAV11 allows for analyzing circuit connectivity difference in the brains of the Alzheimer's disease and control mice. These properties make AAV11 a promising tool for mapping and manipulating neural circuits and for gene therapy of some neurological and neurodegenerative disorders.

Icariin ameliorates the cognitive function in an epilepsy neonatal rat model by blocking the GluR2/ERK I/II pathway.

The present study was performed to evaluate the protective effects of icariin on cognitive function in a hypoxia-induced neonatal epilepsy rat model. Neonatal epilepsy was induced in rat pups on postnatal day (PD) 20 by induction of hypoxia for 15 minutes. Rats were treated intraperitoneally with icariin at 75 mg/kg 1 hour before the induction of hypoxia. The effects of icariin were examined by estimating seizure stage, cognitive function and parameters of electroencephalography (EEG) in this neonatal epilepsy rat model. Parameters of oxidative stress and expression of proteins were examined in the brain tissue of the neonatal epilepsy rat model by histopathological study and Western blotting analysis, respectively. The results of this study suggest that treatment with icariin ameliorates the changes in seizure stage, number of seizures and parameters of EEG in hypoxia-induced neonatal epilepsy rats. Oxidative stress and apoptosis were decreased in the brain tissue of the icariin treatment group compared to the hypoxia group. Moreover, treatment with icariin ameliorated the altered expression of glutamate ionotropic receptor AMPA type subunit 2 (GluR2) and extracellular receptor kinase (ERK I/II) proteins in the brain tissue of hypoxia-induced epilepsy rats. Histopathological study also showed that icariin treatment improved the histopathology of brain tissue of hypoxia-induced epilepsy rats. In conclusion, the results of the present study suggest that icariin protects against neuronal injury and improves cognitive function in hypoxia-induced neonatal epilepsy rats by modulating the GluR2/ERK I/II pathway.