Determination of the anticancer activity of standardized extract of Centella asiatica (ECa 233) on cell growth and metastatic behavior in oral cancer cells.

Background and purpose: The anticancer drugs used for oral cancer treatment present many disadvantages, such as low solubility, low permeability, and poor bioavailability. However, the anticancer activity of ECa 233 has not been widely studied. Therefore, the anticancer activity of ECa 233 was investigated in this study. Experimental approach: MTT assay was carried out to determine cell viability. Characterizations of cell apoptosis were monitored using DAPI and FDA staining and Hoechst 33258 and AO staining. Confirmation of the apoptosis-induced KON cells was done using annexin V-FITC staining, and ROS generation was determined by DCFDA staining. Cell death and the cell cycle arrest activity of ECa 233 were demonstrated by a flow cytometer. The anti-migration and anti-invasion properties of ECa 233 were examined. The anti-proliferative of ECa 233 was investigated. Cellular uptake of ECa 233 was measured by TEER values. The pharmacokinetics of ECa 233 were estimated using the pkCSM web server. Findings/Results: ECa 233 decreased the KON cell viability. Morphological analysis showed the KON cells' loss of cell stability and structure, disorganized nucleus and cytoplasm, and induced cell death. ECa 233 acted as a cell cycle arrest in the G0/G1 phase and reduced the migration and invasion ability in KON cells. TEER values significantly increased in KON cells, which decreased cell colony and multicellular spheroid formations. The pharmacokinetic profiles of the main components are of interest for future usage. Conclusion and implication: ECa 233 can be used as an alternative therapy as well as a medicinal plant selected for sensitizing oral cancer cells to chemotherapy.

New Approach for Preparing Solid Lipid Nanoparticles with Volatile Oil-Loaded Quercetin Using the Phase-Inversion Temperature Method.

Quercetin (QCT), a natural flavonoid, is of research interest owing to its pharmacological properties. However, its pharmacokinetic limitations could hinder its widespread therapeutic use. Nanocarriers, especially solid lipid nanoparticles (SLNs), might overcome this constraint. This study aimed to investigate QCT-loaded SLNs prepared via a new approach using a volatile oil. The phase-inversion temperature method was used to incorporate rosemary oil (RMO) into SLNs prepared using solid lipids possessing different chemical structures. Among the solid lipids used in the formulations, trilaurin (TLR) exhibited the smallest particle size and good stability after a temperature cycling test. SLNs prepared with a ratio of RMO to TLR of 1:3 could load QCT with an entrapment efficiency of >60% and drug loading of ~2% w/w. The smallest particle size was achieved using the polyoxyethylene-hydrogenated castor oil RH40, and the particle size depended on the concentration. The drug-release profile of QCT_TLR exhibited prolonged biphasic release for >24 h. QCT_TLR was a safe formulation, as indicated by a cell viability percentage of >75% at <2% v/v. In a computer simulation, the system with RMO enabled smaller sized SLNs than those without RMO. This new discovery shows great promise for producing SLNs via the phase-inversion temperature method with incorporation of volatile oil, particularly for delivering compounds with limited water solubility.

Impact of Fixed Oil on Ostwald Ripening of Anti-Oral Cancer Nanoemulsions Loaded with Amomum kravanh Essential Oil.

Recently, essential oil from Amomum kravanh (AMO) was reported to exert anti-oral cancer effects. Although it was more effective after being loaded into nanoemulsions, AMO without an Ostwald ripening inhibitor was unable to form stable nanoemulsions because of the Ostwald ripening phenomenon. In this study, we examined the influence of Ostwald ripening inhibitors, such as fixed oils and polyethylene glycol 4000 (PEG 4000), on nanoemulsion properties prepared by a phase inversion temperature method. Several fixed oils, including virgin coconut oil (VCO), palm oil (PMO), olive oil (OLO), and PEG 4000, were evaluated, and their Ostwald ripening inhibitory effects were compared. The results suggest that the type and ratio of AMO:fixed oils influence the formation and characteristics of nanoemulsions. PEG 4000 was unable to produce nanoemulsions; however, stable nanoemulsions with small droplet sizes were observed in preparations containing OLO and VCO at an AMO:fixed oil ratio of 80:20, which may be the result of specific molecular interactions among the components. Using an MTT assay, we demonstrated that the AMO:OLO (80:20) nanoemulsion produced the most significant cytotoxic effect on oral cancer cells with a percentage of 99.68 ± 0.56%. Furthermore, the AMO:OLO 80:20 nanoemulsion inhibits metastasis and induces oral cancer cell death through the intrinsic apoptosis pathway. In conclusion, AMO nanoemulsion with anti-oral cancer activity was successfully produced by varying the amount and type of fixed oils. In the future, this discovery may lead to the development of stable nanoemulsions employing additional volatile oils.

High dilutions of homeopathic remedies induce relaxation of rat aorta precontracted with noradrenalin

BACKGROUND Homeopathic potencies have been reported to produce alteration of contraction in isolated rat ileum in an organ bath. Potentized homeopathic drugs like Lycopus V and Aurum met are used for the treatment of hypertension. AIM The purpose of this study is to see whether Lycopus V 30 CH and Aurum met 30 CH could produce relaxation of isolated rat aorta in the organ bath. METHODS The aorta of rats were dissected out, placed in Krebs-Henseleit solution, cleared of connective tissue and endothelium and cut into 2-2.5 mm long rings. The rings were fixed in organ baths with the upper end connected by a string to an isometric transducer which was finally attached through a data acquisitation equipment to a computer. Aurum met 30 CH Lycopus V 30 CH, and their medium 90% ethanol were added separately to the bathing fluid containing the aorta rings which were precontracted with noradrenalin (NA). RESULTS Both the drugs produced significant relaxation of the aorta (p<0.001) precontracted with NA (10-7 M). The control did not show any marked effect on the NA induced contraction of aorta. CONCLUSION A potentised drug is thought to be specifically structured water which can transform the water structure in the bathing fluid and the isolated tissue immersed in the fluid into its own form. This in turn produces the observed relaxation. Both Lycopus V 30 CH and Aurum met 30 CH are effective in reducing NA induced contraction of rat aorta. Drugs can directly act on the isolated rat aorta without any system of influence. KEY WORDS High dilution drug, isolated aorta, hypertension, noradrenalin.

Introdução e objetivo: Segundo alguns estudos, diluições homeopáticas alteram a contratilidade de íleo isolado de rato, em banho de órgãos. Os medicamentos homeopáticos como Aurum metallicum Lycopus virginicus são usados no tratamento da hipertensão. O objetivo deste estudo foi determinar se Lycps 30 cH e Aur 30 cH podem induzir o relaxamento da aorta isolada de ratos, em banho de órgãos. Métodos: A aorta foi dissecada e, livre de tecido conjuntivo e endotelio, foi colocada em solução de Krebs-Henseleit, sendo seccionada em anéis de 2 a 2,5 cm de comprimento. Os anéis foram fixados em banho de órgãos, a extremidade superior ligada por um cabo a um transdutor isométrico, por sua vez ligado a dispositivos de registro de dados em um computador. Aur 30 cH, Lycps 30 cH e etanol 90%, foram adicionados separadamente ao líquido do banho contendo os anéis de aorta previamente contraídas pela noradrenalina (NA) ou norpinefrina (NE). Resultados: Os dois medicamentos testados induziram relaxamento significativo (p <0,001), do preparada de aorta contraída por NA (10-7 M), enquanto que a solução de controle não produziu efeitos significativos. Conclusão: Ambas as drogas foram usadas em diluições homeopáticas demasiado elevadas para admitir a presença de moléculas da substância original. Assim, o mecanismo farmacológico tradicional envolvendo as moléculas da droga e receptores no músculo liso da aorta deve ser descartado. Embora reconhecidamente diferente, o mecanismo envolvido permanece desconhecido. Lycps 30 e Aur 30 CH mostraram-se eficazes na redução da contratilidade da aorta de ratos, induzida por NA. As drogas podem agir diretamente na aorta isolada de ratos sem influência sistêmica.