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Background  A few bioactivities of constituents from  Gynostemma laxum , which has been collected in Vietnam, have been reported until now. There is no report about the effects of constituents from  G. laxum  although the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-mediated heme oxygenase-1 (HO-1) antioxidant defense system is involved in neuroprotection in the brain. Therefore, we investigated whether quercetin ( 2 ), benzoic acid ( 10 ) and their analogues ( 1 ,  3 – 9  and  11 ) from  G. laxum  have the antioxidant and neuroprotective activities and also their underlying mechanism.    Methods  To examine their neuroprotective and antioxidant activities, oxytosis, total oxidant scavenging capacity (TOSC), 2,7-dichlorofluorescein (DCFDA), dihydroethidium (DHE), antioxidant response element (ARE)-luciferase reporter gene assays, Western blot analysis, real time-PCR, immunocytochemistry and in silico 3D molecular docking simulation were performed.    Results  The study of constituents using chromatographic techniques and spectroscopic analysis showed that  G. laxum  contained an abundance of quercetin ( 2 ), benzoic acid ( 10 ) and their analogues ( 1 ,  3 – 9  and  11 ). Our data demonstrated that quercetin ( 2 ) and its analogue ( 4 ) among the constituents from  G. laxum  showed the strongest neuroprotective effect against oxytosis triggered by the excessive amount of glutamate. Compounds  2 ,  4 ,  6  and  11  exhibited reactive oxygen species (ROS) inhibitory and ARE transcriptional activities in immortalized hippocampal HT22 cell line. Among them, compound  4 , a second active compound, induced Nrf2/HO-1 activation. They were also fit stable onto the Tramtrack and Bric-à-Brac (BTB) domain of Kelch-like ECH-associated protein 1 (Keap1), a known Nrf2 inhibitor protein, based on the results of docking and interaction energies. Overall, these data suggest that –OH and –OCH 3  groups of quercetin and its analogues are responsible for their neuroprotective effect.    Conclusions  In summary, the major constituents of  G. laxum  had strong antioxidant and neuroprotective activities so that they could consider as a natural antioxidant supplement. Furthermore,  G. laxum  might be used beneficially in reducing oxidative complications with the further deep investigation in vivo.    Electronic supplementary material  The online version of this article (doi:10.1186/s13020-017-0136-y) contains supplementary material, which is available to authorized users.

Chemical constituents from a Gynostemma laxum and their antioxidant and neuroprotective activities