As our global population ages, the treatment of neurodegenerative diseases is critical to our society. In recent years, researchers have begun to study the role of biologically active chemicals from plants and herbs to gain new inspiration and develop new therapeutic drugs. Ginseng (Panax ginseng C.A. Mey.) is a famous Chinese herbal medicine with a variety of pharmacological activities. It has been used to treat various diseases since ancient times. Extensive research over the years has shown that ginseng has potential as a neuroprotective drug, and its neuroprotective effects can be used to treat and prevent neurological damage or pathologically related diseases (such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, depression symptoms, and strokes). Moreover, evidence for the medicinal and health benefits of ginsenoside, its main active ingredient, in the prevention of neurodegenerative diseases is increasing, and current clinical results have not reported any serious adverse reactions to ginseng. Therefore, we briefly review the recent research and development on the beneficial effects and mechanisms of ginseng and its main active ingredient, ginsenoside, in the prevention and treatment of neurodegenerative diseases, hoping to provide some ideas for the discovery and identification of ginseng neuroprotection.

Panax notoginseng (Sanqi), a traditional Chinese medical drug which has been applied to medical use for over four centuries, contains high content of dammarane-type tetracyclic triterpenoid saponins. A number of stereoisomeric dammarane-type saponins exist in this precious herb, and some are particularly regarded as “biomarkers” in processed notoginseng. Contemporary researches have indicated that some saponin stereoisomers may show stereospecific pharmacological activities, such as anti-tumor, antioxidative, anti-photoaging, anti-inflammatory, antidiabetic, and neuro-protective activities, as well as stereoselective effects on ion channel current regulation, cardiovascular system, and immune system. The current review provides a comprehensive overview of chemical compositions of raw and processed P. notoginseng with a particular emphasis on saponin stereoisomers. Besides, the pharmacological and pharmacokinetic researches, as well as determination and biotechnological preparation methods of stereoisomeric saponins in notoginseng are discussed extensively.

A novel family of cinnamic acid derivatives has been developed to be multifunctional cholinesterase inhibitors against AD by fusing N-benzyl pyridinium moiety and different substituted cinnamic acids. In vitro studies showed that most compounds were endowed with a noteworthy ability to inhibit cholinesterase, self-induced Aβ (1–42) aggregation, and to chelate metal ions. Especially, compound 5l showed potent cholinesterase inhibitory activity (IC₅₀, 12.1 nM for eeAChE, 8.6 nM for hAChE, 2.6 μM for eqBuChE and 4.4 μM for hBuChE) and the highest selectivity toward AChE over BuChE. It also showed good inhibition of Aβ (1–42) aggregation (64.7% at 20 μM) and good neuroprotection on PC12 cells against amyloid-induced cell toxicity. Finally, compound 5l could penetrate the BBB, as forecasted by the PAMPA-BBB assay and proved in OF1 mice by ex vivo experiments. Overall, compound 5l seems to be a promising lead compound for the treatment of Alzheimer’s diseases.

To explore the pharmacokinetic properties of icariin (ICA) and icariside II (ICA II) following intragastric and intravenous administration in rats, a rapid and sensitive method by using ultra-performance liquid chromatography–tandem mass spectroscopy (UPLC-MS/MS) was developed and validated for the simultaneous quantification of ICA and ICA II in rat plasma. The quantification was performed by using multiple reaction monitoring of the transitions m/z 677.1/531.1 for ICA, 515.1/369.1 for ICA II and 463.1/301.1 for diosmetin-7-O-β-d-glucopyranoside (IS). The assay showed linearity over the concentration range of 1.03–1032 ng/mL, with correlation coefficients of 0.9983 and 0.9977. Intra- and inter-day precision and accuracy were within 15%. The lower limit of quantification for both ICA and ICA II was 1.03 ng/mL, respectively. The recovery of ICA and ICA II was more than 86.2%. The LC-MS/MS method has been successfully used in the pharmacokinetic studies of ICA and ICA II in rats. The results indicated that 91.2% of ICA was transformed into ICA II after oral administration by rats, whereas only 0.4% of ICA was transformed into ICA II after intravenous administration. A comparison of the pharmacokinetics of ICA and ICA II after oral administration revealed that the C_max and AUC_0–t of ICA II were 3.8 and 13.0 times higher, respectively, than those of ICA. However, after intravenous administration, the C_max and AUC_0–t of ICA II were about only 12.1% and 4.2% of those of ICA. These results suggest that ICA and ICA II have distinct pharmacokinetic properties, and the insights obtained facilitate future pharmacological action studies.