Inflammation and loss of cholinergic transmission are involved in neurodegenerative diseases, but possible interactions between them within neurons, astrocytes, and microglia have not yet been investigated. We aimed to compare store-operated Ca²⁺ entry (SOCE) in neurons, astrocytes, and microglia following cholinergic dysfunction in combination with (or without) an inflammatory stimulus and to investigate the effects of linalyl acetate (LA) on this process. We used the SH-SY5Y, U373, and BV2 cell lines related to neurons, astrocytes, and microglia, respectively. Scopolamine or lipopolysaccharide (LPS) was used to antagonize the muscarinic receptors or induce inflammatory responses, respectively. The concentration of intracellular Ca²⁺ was measured using Fura-2 AM. Treatment with scopolamine and LPS significantly increased SOCE in the neuron-like cells and microglia but not in the scopolamine-pretreated astrocytes. LA significantly reduced SOCE in the scopolamine-pretreated neuron-like cells and microglia exposed to LPS, which was partially inhibited by the Na⁺-K⁺ ATPase inhibitor ouabain and the Na⁺/Ca²⁺ exchanger (NCX) inhibitor Ni²⁺. Notably, SOCE was significantly reduced in the LPS plus scopolamine-pretreated cells mixed with astrocytes and microglia, with a two-fold increase in the applied number of astrocytes. LA may be useful in protecting neurons and microglia by reducing elevated SOCE that is induced by inflammatory responses and inhibiting the muscarinic receptors via Na⁺-K⁺ ATPase and the forward mode of NCX. Astrocytes may protect microglia by reducing increased SOCE under the conditions of inflammation and a muscarinic receptor blockade.

Acute hyperglycemia induces oxidative damage and inflammation, leading to vascular dysfunction. Ginsenoside Rb₁ (Rb₁) is a major component of red ginseng with anti-diabetic, anti-oxidant and anti-inflammatory properties. Here, we investigated the beneficial effects and the underlying mechanisms of Rb₁ on hypercontraction induced by high glucose (HG) and endothelial dysfunction (ED). The isometric tension of aortic rings was measured by myography. The rings were treated with N^G-nitro-L-arginine methyl ester (L-NAME) to induce chemical destruction of the endothelium, and Rb₁ was added after HG induction. The agonist-induced vasoconstriction was significantly higher in the aortic rings treated with L-NAME + HG50 than in those treated with HG50 or L-NAME (p = 0.011) alone. Rb₁ significantly reduced the hypercontraction in the aortic rings treated with L-NAME + HG50 (p = 0.004). The ATP-sensitive K⁺ channel (K_ATP) blocker glibenclamide tended to increase the Rb₁-associated reduction in the agonist-induced vasoconstriction in the rings treated with L-NAME + HG50. The effect of Rb₁ in the aortic rings treated with L-NAME + HG50 resulted from a decrease in extracellular Ca²⁺ influx through the receptor-operated Ca²⁺ channel (ROCC, 10⁻⁶–10⁻⁴ M CaCl₂, p < 0.001; 10⁻³–2.5 × 10⁻³ M CaCl₂, p = 0.001) and the voltage-gated Ca²⁺ channel (VGCC, 10⁻⁶ M CaCl₂, p = 0.003; 10⁻⁵–10⁻² M CaCl₂, p < 0.001), whereas Rb₁ did not interfere with Ca²⁺ release from the sarcoplasmic reticulum. In conclusion, we found that Rb₁ reduced hyper-vasoconstriction induced by HG and ED by inhibiting the ROCC and the VGCC, and possibly by activating the K_ATP in rat aorta. This study provides further evidence that Rb₁ could be developed as a therapeutic target for ED in diabetes.

Cardiovascular diseases (CVDs) are the leading cause of mortality and a major economic burden worldwide. Various drugs, including antihypertensive, antihyperlipidemic, and antiplatelet agents, are prescribed to treat CVDs, but these agents have side effects, including serious side effects such as bleeding. Therefore, efforts are being made to develop new drugs made of natural substances with relatively weak side effects. Essential oils are natural substances extracted from aromatic plants with biological effects, such as antioxidant and antiinflammatory activities. These oils have therefore long been used in traditional medicines. This chapter reviews the effects of essential oils on CVD-related factors. Essential oils have various effects, including improvements in lipid balance, liver function, and endothelial function; reductions in blood pressure, oxidative stress, thrombosis, and inflammation; promotion of vascular relaxation; and inhibition of diabetes development and angiogenesis. Therefore, essential oils and their active components may be promising therapeutic agents for CVDs. Further studies are needed to clarify their clinical effects and to elucidate their specific mechanisms of activity.

Recent studies showed that Codonopsis lanceolata (CL) has antihypertensive effects. However, to date, no study has examined the effects of CL on vascular tone under a high extracellular K⁺ concentration ([K⁺]_o). Thus, the present study examined the effect of an extract of Codonopsis lanceolata (ECL) on the vascular tension of rat carotid arteries exposed to high [K⁺]_o. We used myography to investigate the effect of an ECL on the vascular tension of rat carotid arteries exposed to high [K⁺]_o and the underlying mechanism of action. In arteries with intact endothelia, the ECL (250 μg/mL) had no effect on vascular tension in arteries exposed to normal or high [K⁺]_o. In contrast, the ECL significantly increased vasorelaxation in endothelium-impaired arteries exposed to a physiologically normal or high [K⁺]_o compared with control arteries exposed to the same [K⁺]_o conditions in the absence of ECL. This vasorelaxing action was unaffected by a broad-spectrum K⁺ channel blocker and an ATP-sensitive K⁺ channel blocker. The ECL significantly inhibited the vasoconstriction induced by Ca²⁺ influx through voltage-dependent Ca²⁺ channels (VDCCs) but not Ca²⁺ influx induced via receptor-operated Ca²⁺ channels or the release of Ca²⁺ from the sarcoplasmic reticulum in the vascular smooth muscle. In summary, our study reveals that the ECL acts through VDCCs in vascular smooth muscle to promote the recovery of vasorelaxation even in arteries exposed to high [K⁺]_o in the context of endothelial dysfunction and provides further evidence of the vascular-protective effects of ECL.