Combined Extract of Vitis vinifera L. and Centella asiatica Synergistically Attenuates Oxidative Damage Induced by Hydrogen Peroxide in Human Umbilical Vein Endothelial Cells

Abstract

Endothelial cell injury caused by oxidative stress is a critical factor in the initial stage of vascular diseases. Thus, identification of more effective antioxidants is a promising strategy to protect against endothelial cell injury. Recently, synergistic effects between phytochemicals have received renewed attention for their role in the treatment of various diseases. Vitis vinifera L. and Centella asiatica are well-known medicinal plants with various biological effects. However, the combination of the two has not previously been studied. Here, we investigated the effects of V. vinifera L. leaf and C. asiatica extract combination (VCEC), a standardized herbal blend comprising V. vinifera L. leaf extract (VE) and C. asiatica extract (CE), for its antioxidant activity and for the protection of endothelial cells against hydrogen peroxide (H2O2)-mediated oxidative damage in human umbilical vein endothelial cells (HUVECs). VCEC showed higher antioxidant activity than VE or CE in oxygen radical antioxidant capacity assays. In HUVECs, VCEC significantly suppressed increases in the production of intracellular reactive oxygen species, decreased levels of nitric oxide and vascular endothelial-cadherin, and increased endothelial hyperpermeability triggered by H2O2. Treatment with VE or CE alone ameliorated HUVEC injury in a pattern similar to VCEC, although their effects were significantly weaker than VCEC. Overall, VCEC exhibited a substantial synergistic effect on protecting endothelial cells against oxidative damage through its antioxidant activity. Therefore, VCEC could be developed as a potential agent for reducing the risk of vascular diseases related to oxidative stress.

Synergistic Effects of Natural Product Combinations in Protecting the Endothelium Against Cardiovascular Risk Factors

“…The combined activities were generally higher than each monotherapy although no statistical analysis was shown. 56 …”

“…Additionally, three herbal combinations, including Vitis vinifera L. - Centella asiatica , Olea europaea L. - Hibiscus sabdariffa L. and Phikud Navakot mixture, demonstrated a greater ROS inhibitory effect against H 2 O 2 compared to their single components. 56 , 57 , 59 …”

“…is a traditional medicinal plant used for wound-healing and scar management, partially attributed to its anti-inflammatory and antioxidant properties. A study from Jeon et al (2020) showed that a mixture of V. vinifera L. leaf and C. asiatica ethanolic extract (3:1) reduced ROS production and decreased nitric oxide level in HUVECs. This contributed to the enhanced integrity of the endothelial tight junction against oxidative damage (H 2 O 2 ).…”

“…The combined activities were generally higher than each monotherapy although no statistical analysis was shown. 56 Nalinratana et al (2014) investigated the synergistic effect of the nine herbal ingredients in a Thai herbal preparation, Phikud Navakot (see Table 1 for the full ingredients) which is indicated for circulatory disorders. Phikud Navakot was extracted in 50% ethanol or water, and the extracts were examined in a H 2 O 2 induced-oxidative stress model using human endothelial ECV304 cells.…”

“…Additionally, three herbal combinations, including Vitis vinifera L. -Centella asiatica, Olea europaea L. -Hibiscus sabdariffa L. and Phikud Navakot mixture, demonstrated a greater ROS inhibitory effect against H 2 O 2 compared to their single components. 56,57,59 Oxidative stress induces ROS expression, leading to oxidative modification or crosslinking of cysteine residues within kelch-like ECH-associated protein 1 (Keap1), which results in the dissociation of Keap 1 from Nrf2 and permits the translocation of Nrf2 from cytoplasm into the nucleus. 86 Nrf2 in the nucleus binds to antioxidant response elements (ARE), thereby activating the transcription of many genes encoding antioxidant proteins including HO-1, NAD(P)H dehydrogenase [quinone] 1 and SOD.…”