Neuroprotective and Antiherpetic Properties of Polyphenolic Compounds from Maackia amurensis Heartwood

Abstract

In this study, we isolated a new isoflavanostilbene maackiapicevestitol (1) as a mixture of two stable conformers 1a and 1b as well as five previously known dimeric and monomeric stilbens: piceatannol (2), maackin (3), scirpusin A (4), maackiasine (5), and maackolin (6) from M. amurensis heartwood, using column chromatography on polyamide, silicagel, and C-18. The structures of these compounds were elucidated by NMR, HR-MS, and CD techniques. Maksar® obtained from M. amurensis heartwood and polyphenolics 1–6 possessed moderate anti-HSV-1 activity in cytopathic effect (CPE) inhibition and RT-PCR assays. A model of PQ-induced neurotoxicity was used to study the neuroprotective potential of polyphenolic compounds from M. amurensis. Maksar® showed the highest neuroprotective activity and increased cell viability by 18% at a concentration of 10 μg/mL. Maackolin (6) also effectively increased the viability of PQ-treated Neuro-2a cells and the value of mitochondrial membrane potential at concentrations up to 10 μΜ. Maksar® and compounds 1–6 possessed higher FRAP and DPPH-scavenging effects than quercetin. However, only compounds 1 and 4 at concentrations of 10 μM as well as Maksar® (10 μg/mL) statistically significantly reduced the level of intracellular ROS in PQ-treated Neuro-2a cells.

Polyphenols from Maackia amurensis Heartwood Protect Neuronal Cells from Oxidative Stress and Prevent Herpetic Infection

“…Compounds 8 and 12 increased the viability of Neuro-2a cells at a concentration of 1 µM. Maackin ( 9) did not show significant activity in this test (Figure 4c), which was in accordance with the data obtained using a paraquat (PQ)-induced neurotoxicity model [22]. Resveratrol also did not cause any increase in the viability of 6-OHDA-treated Neuro-2a cells.…”

“…The treatment of Vero cells with maackin (9) and scirpusin A (13) before infection (pretreatment of cells) had a weak effect on HSV-1 replication (IC 50 70.3 and 47.2 µg/mL, SI 3.8 and 4.2, respectively) (Table 4). A moderate inhibition of virus replication was observed after simultaneous treatment of cells with the virus and the tested polyphenols [22]. The application of polyphenols after virus adsorption and penetration to cells (treatment of infected cells) also had a moderate effect on HSV-1 replication (Table 4).…”

“…The 50% cytotoxic concentrations (CC 50 ) of the studied compounds were in the range of 120-300 µg/mL (Table 2). We previously reported that stilbenes 9-11, 13, and 14 possessed anti-HSV-1 activity when added to Vero cells simultaneously with the virus [22]. This method of exposure of the virus and cells to polyphenols was used to study the ability of the compounds to prevent the penetration of virus to cells.…”

“…In order to study the mechanism of action of these compounds, two additional schemes of treatment of the virus and Vero cells with polyphenols were applied: the compounds were added before virus infection (pretreatment of cells) and after penetration of the virus into host cells (treatment of infected cells). The fourth method of exposure where the virus and polyphenols were added to cells simultaneously (simultaneous treatment) was previously described by us in [22]. The anti-HSV-1 activity of polyphenols was assessed using the cytopathic effect inhibition (CPE) assay.…”

“…Maksar ® was shown to possess antiviral and neuroprotective properties, but it was unclear which individual compounds were responsible for these activities [11,22]. Recently, we started the study of antiherpetic and neuroprotective properties of polyphenols from M. amurensis in order to identify the most active compounds [22].…”