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Context: Liquid crystalline gel, self-assembled vesicular systems covered with nonionic surfactants, are promising for use in drug delivery. Aims: To develop and evaluate the liquid crystal (LC) systems of a combination of 5-fluorouracil and curcumin for a cervical cancer cell line. Methods: The LC was formulated using water, surfactant, and glycerin. Optimization was carried out by using different surfactants. The formulations were chosen for various studies, such as pH determination, environmental scanning electron microscopy (eSEM), Fourier transform infrared spectroscopy (FTIR) and dissolution study. The synergism of the combination of 5-FU and curcumin on cervical cancer HeLa cell line was then analyzed using CompuSyn software. Results: The formulations with 60% surfactant, the average particle size was in the ranges from 15.68 – 26.35 nm whereas with 40% surfactant, were 11.27 – 21.35 nm. The percentage of dissolution of 5-FU at pH 7 (PBS) A2: 40.23 > B2: 47.39 > X2: 50.36 > Y2: 56.36 compared to at pH 4 (vaginal simulated fluid, VSF) were A2: 36.23 > B2: 43.64 > X2: 45.67 > Y2: 49.01. The percentage of dissolution of curcumin of different formulations were at pH 7 (PBS) A2: 44.85 > B2: 51.36 > X2: 58.61 > Y2: 64.38 compared to at pH 4 (VSF) were A2: 41.03 > B2: 49.37 > X2: 57.85 > Y2: 68.75. Conclusions: The combination of the drugs showed that there was a synergistic effect when it was being administered together. The combination of drugs in LC system had a sustained release as well as it was effective against cervical cancer HeLa cell line.

To investigate the anti-neuroinflammatory properties of Panax ginseng (P. ginseng) root by measuring the levels of nitric oxide (NO), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) in lipopolysaccharide (LPS)-stimulated BV2 microglia cells.Maximal non-toxic dose (MNTD) of methanol extract of P. ginseng root culture on BV2 microglia cells was first determined via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, followed by treatment and LPS stimulation of cells, and the measurement of NO using Griess assay and TNF-α, IL-6, and IL-10 using ELISA assay.The MNTD of P. ginseng root extract was determined to be (587 ± 57) µg/mL. Following that, NO and IL-6 levels were found to be insignificantly reduced by 6.88% and 0.14% respectively in stimulated cells upon treatment with MNTD. Treatment with MNTD yielded similar insignificant result, with only a reduction of 3.58% and 0.08% in NO and IL-6 levels respectively. However, TNF-α and IL-10 levels were significantly downregulated by 15.64% and 34.96% respectively upon treatment with P. ginseng root extract at MNTD.Methanol extract of P. ginseng root culture did not show any significant anti-inflammatory effects on NO and IL-6 levels, but might potentially possess both anti-neuroinflammatory and pro-neuroinflammatory properties through the downregulation of TNF-α and IL-10 respectively.

Curcumin is a hydrophobic compound with good anti-proliferative, anti-oxidative, and anti-cancer properties but has poor bioavailability. Liquid crystals (LC) can accommodate both hydrophilic and hydrophobic drugs. The aim of this study was to formulate and evaluate a novel vaginal drug delivery system for cervical cancer using a curcumin LC system. The curcumin LC system was formulated using surfactant, glycerol, and water together with curcumin. Three types of surfactants were used to optimize the formulation, i.e., Tween 80, Cremphor EL, and Labrasol. The optimized formulations were subjected to physicochemical analysis, and their efficacy was evaluated in HeLa cells. The pH of the formulations was in the range of 3.91&ndash, 4.39. Environmental scanning electron microscopy (ESEM) observations revealed spherical as well as hexagonal micelles. In vitro release of LC curcumin from vaginal simulated fluid (VSF, pH 4.5) showed a release from 20.47% to 87.25%. The IC50 of curcumin in HeLa cells was 22.5 &mu, g/mL, while the IC25 and IC75 were 6.5 &mu, g/mL and 35&mu, g/mL, respectively. The cytotoxicity of the formulations was determined in comparison with liquid crystals without curcumin and pure curcumin by performing a t-test based on a significance level of p less than or equal to 0.05 (p &le, 0.05). The curcumin LC system was able to release the required amount of drug and was effective against the cervical cancer cell line examined.

Background: Clinacanthus nutans (C.nutans) is a plant consumed as a cancer treatment in tropical Asia. Despite the availability of numerous anecdotal reports, evaluation of active anticancer effects has remained elusive. Therefore we here examined antiproliferative, reactive oxygen species (ROS)-inducing and apoptosis mechanisms of whole plant extracts in different cancer cell lines. Methods: Antiproliferative actions of five solvent extracts (hexane, chloroform, ethyl acetate, methanol and water) of C.nutans were tested on non-small cell lung cancer (A549), nasopharygeal cancer (CNE1) and liver cancer (HepG2) cells using MTT assay. The most potent anticancer extract was then assessed by flow cytometry to study cell cycle changes . Intracellular levels of ROS were quantified by DCFH-DA assay. Involvement of the caspase pathway in induction of apoptosis was assessed using caspase assay kits. GC-MS analysis was performed to identify phytoconstituents in the extracts. Results: Hexane and chloroform extracts were antiproliferative against all three cell lines, while the ethyl acetate extract, at 300 μg/mL, was antiproliferative in the CNE1 but not A549 and HepG2 cases. Methanol and water extracts did not inhibit cancer cell proliferation. The most potent anticancer hexane extract was selected for further testing. It induced apoptosis in all three cell lines as shown by an increase in the percentage of cell in sub-G1 phase. Dose-dependent increase in ROS levels in all three cell lines indicated apoptosis to be possibly modulated by oxidative stress. At high concentrations (100 μg/mL), hexane extracts upregulated caspases 8, 9 and 3/7 across all three cell lines. GC-MS analysis of the hexane extract revealed abundance of 31 compounds. Conclusion : Among the five extracts of C.nutans, that with hexane extract demonstrated the highest antiproliferative activity against all three cancer cell lines tested. Action appeared to be via ion of intracellular ROS, and induction of apoptosis via intrinsic and extrinsic caspase pathways.

To date, medicinal plants are the most important resources in the discovery of new drugs. Clinacanthus nutans has been used traditionally in Thailand folk medicine to promote overall well-being. A few biological constituents of C. nutans and their physiological functions have been evaluated in previous studies. However, the mechanisms of action, potency and efficacy of the plant are still not well understood. In this review, the pharmacological properties of C. nutans such as anti-inflammatory effects, anti-proliferation, anti-venom and anti-bacterial activities, and their underlying mechanisms of action are presented and discussed.Keywords: Clinacanthus nutans: Anti-inflammatory, Anti-proliferation, Anti-venom, Anti-bacterial properties

Background: Uncontrolled inflammation may cause serious inflammatory diseases if left untreated. Non-steroidal anti-inflammatory drug (NSAIDs) is commonly used to inhibit pro-inflammatory enzymes, thus, reduce inflammation. However, long term administration of NSAIDs leads to various complications. Medicinal plants are getting more attention as it is believed to be more compatible with human body. One of them is a flavonoid-containing medicinal plants, Strobilanthes crispus which has been traditionally claimed to possess anti-inflammatory and antioxidant activities. Nevertheless, its anti-inflammatory activities are yet to be scientifically documented. Objectives: This study aimed to examine the anti-inflammatory activity of S. crispus by investigating its effects on intracellular oxidative stress and prostaglandin E2 (PGE2) levels. Materials and Methods: In this study, the Maximum Non-toxic Dose (MNTD) of methanol extract of both leaves and stems of S. crispus was first determined using 3-(4,5-dimethylthiazolyl-2)-2,5-diphenytetrazolium Bromide (MTT) assay. The effects of S. crispus extracts at MNTD and half MNTD (½MNTD) on intracellular ROS as well as PGE2 levels in 1.0 µg/mL LPS-stimulated RAW 264.7 macrophages were then be measured using DCFH-DA and a competitive enzyme immunoassay kit, respectively. Results: The MNTD of leaf extract was determined as 700µg/mL while for stem was as low as 1.4µg/mL. When LPS-stimulated RAW 264.7 macrophages were subjected to the MNTD of S. crispus leaf extract, both intracellular ROS and PGE2 levels were significantly reduced. In contrast, stem extract at both MNTD and ½MNTD did not significantly reduce the PGE2 level, but significantly increased the intracellular ROS level. Conclusion: The methanol leaf extract of S. crispus may possess anti-inflammatory properties as it is able to significantly reduce the intracellular ROS and PGE2 levels of LPS-stimulated cells. Nevertheless, further studies such as investigating the interleukin, nitric oxide and cytokine tumor necrosis factor-α (TNFα) levels has to be conducted to further confirm the anti-inflammatory properties of S. crispus., {"references":["M.H. Pan, Y.S. Chiou, M.L. Tsai, and C.T. Ho, \"Anti-inflammatory activity of traditional Chinese medicinal herbs,\" Journal of Traditional and Complementary Medicine, vol. 1, pp. 8-24, Oct 2011.","W.J. Yoon, Y.M. Ham, K.N. Kim, S.Y. Park, N.H. Lee, C.G. Hyun, and W.J. Lee, \"Anti-inflammatory activity of brown alga Dictyota dichotoma in murine macrophage RAW 264.7 cells,\" Journal of Medicinal Plants Research, vol. 3, pp. 001–008, Jan 2009.","H.T. Sorensen, L. Mellemkjaer, W.J. Blot, G.L. Nielsen, F.H. Steffensen, J.K. McLaughlin JK, and J.H. 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Medicinal plants continue to play an important role in modern medications and healthcare as consumers generally believe that most of them cause fewer or milder adverse effects than the conventional modern medicines. In order to use the plants as a source of medicinal agents, the bioactive compounds are usually extracted from plants. Therefore, the extraction of bioactive compounds from medicinal plants is a crucial step in producing plant-derived drugs. One of the bioactive compounds isolable from medicinal plants, orientin, is often used in various bioactivity studies due to its extensive beneficial properties. The extraction of orientin in different medicinal plants and its medicinal properties, which include antioxidant, antiaging, antiviral, antibacterial, anti-inflammation, vasodilatation and cardioprotective, radiation protective, neuroprotective, antidepressant-like, antiadipogenesis, and antinociceptive effects, are discussed in detail in this review.

para‑Phenylenediamine (p‑PD) is a potential carcinogen, and widely used in marketed hair dye formulations. In the present study, the role of the protein tyrosine kinase (PTK)/Ras/Raf/c‑Jun N‑terminal kinase (JNK) and phosphoinositide 3‑kinase (PI3k)/protein kinase B (Akt) pathways on the growth of NRK‑52E cells was investigated. The results demonstrated that p‑PD reduced cell viability in a dose‑dependent manner. The cell death due to apoptosis was confirmed by cell cycle analysis and an Annexin‑V‑fluorescein isothiocyanate binding assay. Subsequent to staining with 2',7'‑dichlorofluorescin diacetate, the treated cells demonstrated a significant increase in reactive oxygen species (ROS) generation compared with the controls. The effects of p‑PD on the signalling pathways were analysed by western blotting. p‑PD‑treated cells exhibited an upregulated phospho‑stress‑activated protein kinase/JNK protein expression level and downregulated Ras and Raf protein expression levels; however, Akt, Bcl‑2, Bcl‑XL and Bad protein expression levels were not significantly altered compared with the control. In conclusion, p‑PD induced apoptosis by a PTK/Ras/Raf/JNK‑dependent pathway and was independent of the PI3K/Akt pathway in NRK‑52E cells.

To test the hypothesis that exogenous purified angiotensin II (ANG) might cause apoptosis of alveolar epithelial cells (AECs) and acute lung injury, male Wistar rats were intratracheally instilled with purified ANG (10 mumol/L), ANG plus the caspase inhibitor ZVAD-fmk (60 mumol/L), ANG plus the ANG receptor AT1 antagonist losartan (LOS, 100 mumol/L) or sterile phosphate-buffered saline (PBS) vehicle alone. Six or 20 h later, the lungs were lavaged in situ for determination of bronchoalveolar lavage (BAL) fluid content of hemoglobin (Hb) and fluorescent (BODIPY)-albumin, a bolus of which was injected intravenously 15 min prior to BAL. Terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) revealed that instillation of ANG, but not PBS alone, increased labeling of fragmented DNA in bronchiolar epithelial cells and in AECs (P0.05) at 6 h post-ANG. Increased TUNEL was abrogated by concurrent instillation of ZVAD-fmk or LOS. Significant increased numbers of caspase-positive cells were observed by anti-caspase 3 immunolabeling after instillation of ANG (P0.01); the same doses of LOS or ZVAD-fmk that blocked TUNEL also blocked the activation of caspase 3 (P0.01). Intratracheal instillation of ANG also remarkably increased BAL BODIPY-albumin (P0.01) and Hb (P0.05), both of which were eliminated by ZVAD-fmk or LOS. These data indicate that exposure of AECs to ANG in vivo is sufficient to induce apoptosis and alveolar epithelial barrier injury mediated by ANG receptor AT1.