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 NG-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 (Emax values = 98.95 ± 0.66% and pD2 = 7.93 ± 0.28) and endothelium-denuded rings (Emax 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.
Turmeric oil (TO) exhibits various biological activities with limited therapeutic applications due to its instability, volatility, and poor water solubility. Here, we encapsulated TO in chitosan/alginate nanocapsules (CS/Alg-NCs) using o/w emulsification to enhance its physicochemical characteristics, using poloxamer 407 as a non-ionic surfactant. TO-loaded CS/Alg-NCs (TO-CS/Alg-NCs) were prepared with satisfactory features, encapsulation efficiency, release characteristics, and cytotoxicity against breast cancer cells. The average size of the fabricated TO-CS/Alg-NCs was around 200 nm; their distribution was homogenous, and their shapes were spherical, with smooth surfaces. The TO-CS/Alg-NCs showed a high encapsulation efficiency, of 70%, with a sustained release of TO at approximately 50% after 12 h at pH 7.4 and 5.5. The TO-CS/Alg-NCs demonstrated enhanced cytotoxicity against two breast cancer cells, MDA-MB-231 and MCF-7, compared to the unencapsulated TO, suggesting that CS/Alg-NCs are potential nanocarriers for TO and can serve as prospective candidates for in vivo anticancer activity evaluation.
Crinum asiaticum is a perennial herb widely distributed in many warmer regions, including Thailand, and is well-known for its medicinal and ornamental values. Crinum alkaloids contain numerous compounds, such as crinamine. Even though its mechanism of action is still unknown, crinamine was previously shown to possess anticancer activity. In this study, we demonstrate that crinamine was more cytotoxic to cervical cancer cells than normal cells. It also inhibited anchorage-independent tumor spheroid growth more effectively than existing chemotherapeutic drugs carboplatin and 5-fluorouracil or the CDK9 inhibitor FIT-039. Additionally, unlike cisplatin, crinamine induced apoptosis without promoting DNA double-strand breaks. It suppressed cervical cancer cell migration by inhibiting the expression of positive regulators of epithelial-mesenchymal transition SNAI1 and VIM. Importantly, crinamine also exerted anti-angiogenic activities by inhibiting secretion of VEGF-A protein in cervical cancer cells and blood vessel development in zebrafish embryos. Gene expression analysis revealed that its mechanism of action might be attributed, in part, to downregulation of cancer-related genes, such as AKT1, BCL2L1, CCND1, CDK4, PLK1, and RHOA. Our findings provide a first insight into crinamine’s anticancer activity, highlighting its potential use as an alternative bioactive compound for cervical cancer chemoprevention and therapy.
Ultraviolet-B (UVB) exposure is one of the primary extrinsic factors causing skin photoaging. It stimulates inflammatory responses and arrests the cell cycle. Matrix metalloproteinase-1 (MMP-1) secreted by keratinocytes is one of the important extracellular matrixes to attenuate UVB-induced skin aging via collagen degradation. Curcuma aromatica (CA) and Curcuma comosa (CC), the herbaceous plants in the Zingiberaceae family, are commonly used in Thai traditional women’s medicines. The present work was aimed to investigate the potential of the CA and CC extracts and their isolated compounds to attenuate UVB-induced MMP-1 and cell cycle arrest in HaCaT keratinocytes. Total phenolic contents and antioxidant capacities of the extracts were determined. CC extract contains more phenolic components and provides more potent antioxidant activities than CA extract. HaCaTs were pretreated with the extracts or their isolated constituents 1–4 for 24 h and then repeatedly exposed to UVB at 100 mJ/cm2 10 times. Both extracts and compounds 1–4 effectively reduce UVB-induced MMP-1 levels in HaCaT cells and restore cell cycle arrest. This is the first report on the potential of CA and CC extracts in reducing UVB-induced MMP-1 expression and regulating cell proliferation in HaCaT cells. Thus, CA and CC extracts might be used as alternative natural agents to prevent UVB-induced skin photoaging.