The present study was performed to examine the antihypertensive effect of neferine in hypertensive rats and its relaxant mechanisms in isolated rat thoracic aorta. The antihypertensive effect was evaluated by tail-cuff methods on N^G-nitro-L-arginine methyl ester (L-NAME) (40 mg/kg BW) 4-week hypertensive-induced hypertensive rats. The vasorelaxant effect and its mechanisms were studied by the organ bath technique in the thoracic aorta isolated from normotensive rats. The results indicated that the treatment of neferine (1 mg/kg and 10 mg/kg) markedly decreased the systolic blood pressure (SBP) when compared with the hypertension group (137.75 ± 10.14 mmHg and 132.23 ± 9.5 mmHg, respectively, p < 0.001), without affecting the heart rate. Moreover, neferine (10⁻¹² − 10⁻⁴ M) exhibited concentration-dependent vasorelaxation in endothelium-intact rings (E_max values = 98.95 ± 0.66% and pD₂ = 7.93 ± 0.28) and endothelium-denuded rings (E_max values = 90.61 ± 1.91% and pD₂ = 6.85 ± 0.36). The effects of neferine were reduced by pre-incubation with L-NAME and 1H-[1,2,4]oxadiazolo[4,3-a] quinoxalin-1-one (ODQ) but not with pre-incubation with indomethacin and K⁺channel blockers. Neferine attenuated the contractions induced by phenylephrine and caffeine in a Ca²⁺-free solution and also inhibited in CaCl₂- and phenylephrine-induced contracted rings. Our study suggests that neferine exhibited hypertensive potential, induced vasorelaxation through the endothelium nitric oxide synthase (eNOS)/nitric oxide (NO)/soluble guanylyl cyclase (sGC) pathway and involved the modulation of Ca²⁺ influx through Ca²⁺ channels and intracellular Ca²⁺ release from the sarcoplasmic reticulum.

Sericin-derived oligopeptides obtained from silk cocoons were investigated for the in vivo hypotensive effect and investigated for the underlying mechanism involved in vasodilation in isolated rat thoracic aorta. In normotensive anesthetized rats, oligopeptides induced an immediate and transient hypotensive activity. In rat aortic rings, oligopeptides induced a concentration-dependent vasorelaxation in vessels precontracted with both KCl and phenylephrine (PE) with endothelium-intact or endothelium-denuded rings. In endothelium-intact rings, pretreatment with Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME, 100 µM), an inhibitor of the NO synthase (NOS) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 1 µM), a selective inhibitor of the guanylyl cyclase enzyme, significantly reduced the relaxant effect of oligopeptides. However, indomethacin, an inhibitor of the cyclooxygenase, had no effect on oligopeptides-induced relaxation. In addition, pretreatment with tetraethylammonium (TEA, 5 mM) reduced the maximal relaxant effect induced by oligopeptides. By contrast, relaxation was not affected by 4-aminopyridine (4-AP, 1 mM), glibenclamide (10 µM), or barium chloride (BaCl₂, 1 mM). In depolarization Ca²⁺-free solution, oligopeptides inhibited calcium chloride- (CaCl₂-) induced contraction in endothelium-denuded rings in a concentration-dependent manner. Nevertheless, oligopeptides attenuated transient contractions in Ca²⁺-free medium containing EGTA (1 mM) induced by 1 µM PE, but they were not affected by 20 mM caffeine. It is obvious that potent vasodilation effect of oligopeptides is mediated through both the endothelium and the vascular smooth muscle.

Type I interferons (IFNs-I) are inflammatory cytokines that play an essential role in the pathogenesis of inflammation and autoimmune diseases. Signaling through nucleic acid sensors causes the production of IFNs-I. A stimulator of interferon genes (STING) is a DNA sensor that signals transduction, leading to the production of IFNs-I after their activation. This study aims to determine the anti-inflammatory effects of red rice bran extract (RRBE) on macrophages through the activation of STING signaling. RAW264.7 macrophage cells were stimulated with STING agonist (DMXAA) with and without RRBE. Cells and supernatant were collected. The level of mRNA expression was determined by qPCR, and inflammatory cytokine production was investigated by ELISA. The results indicate that RRBE significantly lowers the transcription of STING and interferon-stimulated genes (ISGs). Moreover, RRBE suppresses the phosphorylation of STING, leading to a decrease in the expression of Irf3, a transcription factor that initiates IFN-I signaling. Our results provide evidence that red rice bran extract may be a protective compound for inflammatory diseases by targeting STING signaling.

This study was conducted to investigate the phytochemical constituents, antioxidant capacity, and anticancer potential of aqueous, ethanolic, and hexane extracts derived from the leaves and stems of Cissampelos pareira L. ( C. pareira L.). Proximate analysis revealed that the stems contained a high fiber content (48.02% ± 0.14%) and carbohydrate content (32.31% ± 0.47%), whereas the leaves exhibited a higher carbohydrate content (53.93% ± 0.02%). Ethanolic extracts of both stems and leaves showed notably high levels of total phenolic and flavonoid compounds. Specifically, the total phenolic content (TPC) was 58.26 ± 2.56 mg GAE/g dry weight (DW) in the stem extract (CPSE) and 95.73 ± 1.76 mg GAE/g DW in the leaf extract (CPLE). The total flavonoid content (TFC) was 27.23 ± 2.89 mg CE/g DW in CPSE and 82.68 ± 4.98 mg CE/g DW in CPLE. Furthermore, the ethanol extract from C . pareira L. leaves exhibited the strongest free radical scavenging activity, with IC ₅₀ values of 55.00 ± 1.93 µg/mL and 25.77 ± 0.38 µg/mL against DPPH and ABTS radicals, respectively. In terms of anticancer activity, the hexane extract from the stem (CPSH) showed the highest inhibitory effects on the proliferation of breast cancer cell lines (MCF‐7 and MDA‐MB‐231), as well as HEK293T cells. Interestingly, the proliferation of normal human dermal fibroblast (NHDF) cells was more effectively inhibited by CPLE. These findings indicate that the ethanol extract of C . pareira L. leaves possesses strong antioxidant properties, while the hexane extract of the stem demonstrates potent anticancer activity. Therefore, both leaf and stem extracts of C . pareira L. hold promise for development as functional foods or dietary supplements due to their diverse and significant biological activities.

Inflammation‐induced dysregulation of microRNAs, particularly miR‐138‐5p, compromises trophoblast cell function and may contribute to pregnancy‐related complications. While Elsholtzia species have been reported to possess therapeutic properties, the anti‐inflammatory effects of Elsholtzia kachinensis Prain (EKP) in trophoblast cells have not been explored. In this study, a 70% ethanolic extract of EKP was fractionated into hexane (HEX), dichloromethane (DCM), ethyl acetate (ETAC), and water (WT) fractions. Each fraction was subjected to phytochemical profiling, antioxidant assessment, and bioactive compound identification by GC–MS and high‐performance liquid chromatography (HPLC). Among them, the ETAC fraction (EKP‐ETAC) showed the highest antioxidant activity, reflected by the lowest IC ₅₀ values in ABTS and DPPH assays, and contained the greatest levels of phenolic and flavonoid compounds. Nontoxic concentrations were determined by an MTT assay. Pretreatment with EKP‐ETAC alleviated lipopolysaccharide (LPS)‐induced impairment of proliferation, migration, and invasion in HTR‐8/SVneo trophoblast cells, while reducing apoptosis, intracellular ROS generation, and inflammatory cytokine expression. Mechanistic analysis revealed that EKP‐ETAC suppressed LPS‐induced upregulation of miR‐138‐5p and restored the expression of FOXC1. The dual luciferase reporter assay confirmed that FOXC1 is a direct target of miR‐138‐5p, mediating the effects of EKP‐ETAC. LC–MS and HPLC analyses identified rosmarinic acid as the predominant bioactive component. These findings suggest that rosmarinic acid‐enriched EKP‐ETAC exerts protective effects on trophoblast cells by mitigating oxidative stress and inflammation through the miR‐138‐5p/FOXC1 axis.

Hydrolyzed collagen (HC) derived from salmon skin is a promising source of bioactive peptides. In this study, the vasorelaxant effects and potential mechanisms of action of HC on isolated rat thoracic aorta rings were investigated using the organ bath technique. The vasorelaxant properties of HC were evaluated using aortic rings from Wistar rats pre-contracted with phenylephrine (PE) or potassium chloride (KCl). HC induced significant vasorelaxation in both endothelium-intact and endothelium-denuded rings, indicating that its mechanism of action was independent of the endothelium and involved direct effects on vascular smooth muscle cells. The vasorelaxant effect of HC was reduced when pre-contraction was induced by tetraethylammonium chloride (TEA). However, the vasodilatory effects of HC were not significantly inhibited by all K⁺ channel blockers, including glibenclamide, barium chloride (BaCl₂), or 4-aminopyridine (4-AP). Additionally, pre-incubation with prazosin, an α-adrenoceptor blocker, significantly reduced the vasorelaxation induced by HC, whereas propranolol, a β-adrenoceptor blocker, had no effect. In addition, HC inhibited CaCl₂-induced contractions induced by both PE and caffeine in a Ca²⁺-free solution. Therefore, HC exhibited the vasorelaxant effects through an endothelium-independent mechanism. The vasodilatory effects of HC were associated with the activation of K_Ca channels, suppression of PE-induced contraction via α₁-adrenergic receptor pathways, and inhibition of CaCl₂-induced contractions by modulating intracellular Ca²⁺ release and extracellular Ca²⁺ influx in vascular cells.