VERBENA OFFICINALIS

Experiments conducted at the University of Hong Kong (China) have demonstrated the neuroprotective effect of Verbena Officinalis extracts. The studies were conducted in vitro on neurons of the cerebral cortex of rats. The in vitro cultured neurons were treated with an aqueous extract of the plant followed by various toxins such as β-amyloid 25–35 (25 μM for 24 h), tunicamycin (1 μg/mL for 16 h), dithiothreitol (0.5 and 1.0 mM for 16 h), hydrogen peroxide (50 μM for 16 h), and UV radiation (32 kJ/cm 2 for 2 h). The cells were then washed with a new medium. Cell lysates were subjected to a caspase activity assay. Cytotoxic activity was determined based on the level of lactate dehydrogenase (LD) in the harvested media. Measurements of the LD level showed that a verbena herb extract at a concentration of 100 μg/mL reduced the mortality of nerve cells exposed to β-amyloid (Aβ) by 9.1 % and dithiothreitol by 9.8 % (0.5 mM DTT) and 29.6 % (1.0 mM DTT). However, the extract did not protect against the effects of tunicamycin, H2O2 , and UV radiation, which may indicate a weaker effect of the extract against the agents directly damaging DNA. Colorimetric caspase-3-like and caspase-2-like activity assays were used to measure the effect of a verbena extract in doses of 25 to 150 μg/mL. The V. officinalis extract already significantly reduced Aβ-triggered activity at a dose of 75 mg/mL by 1.4 times compared to control conditions. This activity was dose dependent. The results obtained prove that extracts from V. officinalis can potentially be used in the prevention of neurodegenerative diseases, with particular emphasis on Alzheimerʼs disease. Verbenalin, hastatoside, aucubin, swertiamarine, acetoside, isoacteoside, jionoside D, cistanoside F, acacetin-7-O-rutinoside, apigenin-7-O-glucoside, glucosyl-6-pedalitin, and acacetin were used to molecular docking. Verbenalin, swertiamarin, and jionoside D have a good binding effect with NLRP3, which may play a role in the treatment of AD by reducing inflammation. Phenylethanoid glycosides including acetoside  and isoacteoside have good docking effects with NLRP3 and BACE1, which may reduce the inflammatory response and inhibit Aβ deposition. Apigenin-7-O-glucoside  and glucosyl-6-pedalitin were higher than positive drugs in molecular docking with NLRP3, BACE1, and AChE. Acacetin-7-O-rutinoside has a good binding effect on all four protein targets, which is better than that of apigenin-7-O-glucoside, glucosyl-6-pedalitin. Acacetin also has multi-target effects. 

Aqueous extracts from Verbena Officinalis have been reported to decrease Aβ-induced neurotoxicity such as neurite shorting and DNA condensation in primary cortical neurons. In a recent study, human neuroblastoma SH-SY5Y cells treated with verbenalin showed neuroprotective properties against Aβ-induced cytotoxicity. Verbenalin,was shown to reduce both the intracellular and extracellular expression of APP, which is a precursor to Aβ. Furthermore, verbenalin markedly reduced Aβ 42 in SweAPP/N2a cells. Numerous investigations have demonstrated that the hippocampus and amygdala, as well as other structures of the medial temporal lobe show significant atrophy as AD progresses. Verbenalin reduced the expression of Aβ and tau in the hippocampus of AD animal models, which was consistent with the results of the in vitro assays. Taken together, these findings suggest that verbenalin can be used as an adjuvant therapy for AD owing to its ability to improve AD pathology associated with Aβ and tau.

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