Neuroprotective effects of Gynostemma pentaphyllum (Jiaogulan): Mechanisms, active compounds, and therapeutic potential

Neurodegenerative diseases such as Alzheimer’s and Parkinson’s involve oxidative stress, inflammation, and neuronal loss, with limited therapeutic options. Gynostemma pentaphyllum (Jiaogulan), a traditional Chinese medicinal herb rich in gypenosides, has demonstrated neuroprotective potential through antioxidant, anti-inflammatory, and neurogenic activities. This review synthesizes data from phytochemical, in vitro, in vivo , and limited clinical studies investigating the neuroprotective effects of Jiaogulan. Sources were selected from experimental models of oxidative stress, neuroinflammation, and neurodegeneration, focusing on mechanistic pathways, active compounds, and therapeutic relevance. Evidence indicates that Jiaogulan mitigates neuronal injury via multiple mechanisms, including activation of Nrf2/ARE signaling, inhibition of NF-κB/MAPK pathways, modulation of BDNF and PI3K/Akt signaling, protection against mitochondrial dysfunction, and acetylcholinesterase inhibition. Most available human studies evaluate the systemic antioxidant, anti-inflammatory, and metabolic effects of G. pentaphyllum . While these outcomes are not direct neurological endpoints, they are biologically relevant to neuroprotection, given the established links between systemic inflammation, oxidative stress, and neurodegenerative processes. Limited clinical data suggest improvements in oxidative stress, inflammation, and cognitive outcomes, with favorable safety profiles. The multi-target pharmacological profile of Jiaogulan aligns with the complex pathophysiology of neurodegenerative disorders. However, gaps remain regarding compound-specific mechanisms, pharmacokinetics, bioavailability, and large-scale clinical validation. Standardization of extracts and advanced delivery approaches may enhance translational potential. Gynostemma pentaphyllum represents a promising natural neuroprotective agent. With further mechanistic studies and well-designed clinical trials, Jiaogulan could emerge as a novel therapeutic candidate for the prevention and management of neurodegenerative diseases. Neuroprotective Effect of Gynostemma pentaphyllum (Jiaogulan): Mechanism, active compounds, and therapeutic use