The pathophysiology of cardiovascular diseases is complex and may involve oxidative stress-related pathways. Eriodictyol is a flavonoid present in citrus fruits that demonstrates anti-inflammatory, anti-cancer, neurotrophic, and antioxidant effects in a range of pathophysiological conditions including vascular diseases. Because oxidative stress plays a key role in the pathogenesis of cardiovascular disease, the present study was designed to verify whether eriodictyol has therapeutic potential. Upregulation of heme oxygenase-1 (HO-1), a phase II detoxifying enzyme, in endothelial cells is considered to be helpful in cardiovascular disease. In this study, human umbilical vein endothelial cells (HUVECs) treated with eriodictyol showed the upregulation of HO-1 through extracellular-regulated kinase (ERK)/nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathways. Further, eriodictyol treatment provided protection against hydrogen peroxide-provoked cell death. This protective effect was eliminated by treatment with a specific inhibitor of HO-1 and RNA interference-mediated knockdown of HO-1 expression. These data demonstrate that eriodictyol induces ERK/Nrf2/ARE-mediated HO-1 upregulation in human endothelial cells, which is directly associated with its vascular protection against oxidative stress-related endothelial injury, and propose that targeting the upregulation of HO-1 is a promising approach for therapeutic intervention in cardiovascular disease.

Jin Z, et al. Korean J Physiol Pharmacol. 2014 Apr;18(2):149-153. http://dx.doi.org/10.4196/kjpp.2014.18.2.149

Oxaliplatin is a third-generation platinum-based chemotherapeutic drug widely used in colorectal cancer treatment. Although potent against this tumor, it can induce cold and mechanical allodynia even after a single injection. The currently used drugs to attenuate this allodynia can also cause unwanted effects, which limit their use. Bee venom acupuncture (BVA) is widely used in Korean medicine to treat pain. Although the effect of BVA on oxaliplatin-induced neuropathic pain has been addressed in many studies, its action on dorsal root ganglia (DRG) neurons has never been investigated. A single oxaliplatin injection (6 mg/kg, intraperitoneally) induced cold and mechanical allodynia, and BVA (0.1 and 1 mg/kg, subcutaneous, ST36) dose-dependently decreased allodynia in rats. On acutely dissociated lumbar 4–6 DRG neurons, 10 min application of oxaliplatin (100 μM) shifted the voltage-dependence of sodium conductance toward negative membrane potentials in A- but not C-fibers. The resting membrane potential remained unchanged, but the action potential threshold decreased significantly compared to that of the control (p < 0.05). However, 0.1 μg/mL of BVA administration increased the lowered action potential threshold. In conclusion, these results suggest that BVA may attenuate oxaliplatin-induced neuropathic pain by altering the action potential threshold in A-fiber DRG neurons.

The cytotoxic drugs used in chemotherapy often are accompanied by nausea and vomiting. Despite use of antiemetic drugs, chemotherapy-induced nausea and vomiting (CINV) remains a significant side effect for cancer patients and is associated with serotonin type3 receptor (5-HT3R) activation in the brain stem. Farnesol and nerolidol are sesquiterpene alcohols found in essential oils of plants such as rose, citronella, and lemon grass and used as anti-mite parapheromones. Medicinal plants often are effective in treating gastrointestinal disorders including CINV, although the mechanism of action remains unclear. In the current work, the antiemetic efficacy of the naturally occurring racemic mixture of farnesol (m-farnesol) and nerolidol (m-nerolidol) against cisplatin CINV was tested using the pica behavior of rats. Animals treated with m-farnesol or m-nerolidol consumed smaller amount of kaolin than saline treated control animals. This result is consistent with antiemetic efficacy of farnesol and nerolidol. Unexpectedly, m-farnesol but not m-nerolidol treated animals consumed more food and lost less body weight than controls. Thus, farnesol effectively reduced appetite suppression and weight loss induced by cisplatin. In separate experiments, isomers of farnesol and nerolidol were tested on 5-HT-induced responses of acutely isolated nodose neurons with patch-clamp methods. All of the tested constituents inhibited 5-HT3R-mediated current in a non-competitive manner. Thus, both of the farnesol and nerolidol may exert antiemetic efficacy by inhibiting 5-HT signaling in cranial visceral afferents resulting in interruption of emetogenic signaling. However, nerolidol failed to suppress cisplatin-induced anorexia and weight loss suggesting that additional mechanisms may contribute.