Synthesis, characterization, and anti-cancer activity of new chalcone derivatives containing naphthalene and fluorine moieties.

In recent years, chalcones and their derivatives have become the focus of global scientists due to increasing evidence reported towards their potency in antitumor and anti-cancer. Here, the chalcones designed and synthesized in our present study were derived from the derivatives of naphthaldehyde and acetophenone. Both these precursors have been reported in demonstrating a certain degree of anticancer property. Also, the substituents on these precursors such as hydroxyl, methoxy, prenyl, and chloro were shown able to enhance the anticancer efficiency. Hence, it is the interest of the current study to investigate the anticancer potential of the hybrid molecules (chalcones) consisting of these precursors with different alkoxy substituents and with or without the fluorine moiety. Two series of chalcone derivatives were designed, synthesized, and characterized using the elemental analysis, IR, 1 H and 13 C NMR spectroscopy, subsequently evaluated for their anti-cancer activity. Interestingly, the results showed that the fluorinated chalcones 11-15 exhibited stronger cytotoxic activity towards the breast cancer cell lines (4T1) compared to non-fluorinated chalcone derivatives. Remarkably, the selectivity index obtained for these fluorinated chalcones derivatives against the breast cancer 4T1 cell line was higher than those exhibited by cisplatin, which is one of the most frequently deployed chemotherapy agents in current medical practice. These findings could provide an insight towards the potential of fluorinated chalcones being developed as an anti-cancer agent with moderate activity towards breast cancer cell and low inhibition of fibroblast cell at a concentration of 100 µM.

Wound Healing Property of Curcuminoids as a Microcapsule-Incorporated Cream.

Curcuminoids have been used for the management of burns and wound healing in traditional Chinese medicine practices but the wide application of curcuminoids as a healing agent for wounds has always been a known problem due to their poor solubility, bioavailability, colour staining properties, as well as due to their intense photosensitivity and the need for further formulation approaches to maximise their various properties in order for them to considerably contribute towards the wound healing process. In the present study, a complex coacervation microencapsulation was used to encapsulate curcuminoids using gelatin B and chitosan. This study also focused on studying and confirming the potential of curcuminoids in a microencapsulated form as a wound healing agent. The potential of curcuminoids for wound management was evaluated using an in vitro human keratinocyte cell (HaCaT) model and the in vivo heater-inflicted burn wound model, providing evidence that the antioxidant activities of both forms of curcuminoids, encapsulated or not, are higher than those of butylated hydroxyanisole and butylated hydroxytoluene in trolox equivalent antioxidant capacity (TEAC) and (2,2-diphenyl-1-picryl-hydrazyl-hydrate) (DPPH) studies. However, curcuminoids did not have much impact towards cell migration and proliferation in comparison with the negative control in the in vitro HaCaT study. The micoencapsulation formulation was shown to significantly influence wound healing in terms of increasing the wound contraction rate, hydroxyproline synthesis, and greater epithelialisation, which in turn provides strong justification for the incorporation of the microencapsulated formulation of curcuminoids as a topical treatment for burns and wound healing management as it has the potential to act as a crucial wound healing agent in healthcare settings.

Anticancer mechanisms of Strobilanthes crispa Blume hexane extract on liver and breast cancer cell lines.

Cancer is a major public health concern not only in developed countries, but also in developing countries. It is one of the leading causes of mortality worldwide. However, current treatments may cause severe side effects and harm. Therefore, recent research has been focused on identifying alternative therapeutic agents extracted from plant-based sources in order to develop novel treatment options for cancer. Strobilanthes crispa Blume is a plant native to countries including Madagascar and Indonesia. It has been used as an anti-diabetic, diuretic and laxative in traditional folk medicine. Furthermore, S. crispa has potential in treating cancer, as evidenced in previous studies. In the present study, the cytotoxic and apoptotic activities of S. crispa crude extracts were investigated in liver and breast cancer cell lines. Hexane, ethyl acetate, chloroform, methanol and water extracts prepared from the leaves, and stems of S. crispa were evaluated for their cytotoxicity on HepG-2 and MDA-MB-231 cells using an MTT assay. The anti-proliferative properties of stem hexane (SH) extract on both cell lines were analysed using cell doubling time determination and cell cycle analysis, while the apoptogenic properties was determined through the detection of caspase-8. Among the extracts tested, SH extract exhibited the lowest half maximal inhibitory concentrations in both the cell lines. The SH extract induced morphological changes in HepG-2 and MDA-MB-231 cells, and significantly delayed cell population doubling time. Furthermore, it altered cell cycle profile and significantly increased caspase-8 activity in HepG-2 cells, but not in MDA-MB-231 cells. In conclusion, the SH extract of S. crispa possesses potent anticancer properties and may be a suitable chemotherapeutic target.

In Vitro Evaluation of Novel Phenytoin-Loaded Alkyd Nanoemulsions Designed for Application in Topical Wound Healing.

Phenytoin-loaded alkyd nanoemulsions were prepared spontaneously using the phase inversion method from a mixture of novel biosourced alkyds and Tween 80 surfactant. Exposure of human adult keratinocytes (HaCaT cells) for 48 h to alkyd nanoemulsions producing phenytoin concentrations of 3.125-200 µg/mL resulted in relative cell viability readings using tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide of 100% confirming nontoxicity and suggesting cell proliferation activity. Phenytoin-loaded alkyd nanoemulsions generally resulted in higher mean cell viability compared with equivalent concentration of phenytoin solutions, suggesting that the nanoemulsions provided a controlled-release property that maintained the optimum phenytoin level for keratinocyte growth. HaCaT cell proliferation, measured by 5-bromo-2-deoxyuridine uptake, was found to increase following exposure to increasing phenytoin concentration from 25 to 50 µg/mL in solution or encapsulated in nanoemulsions but declined at a drug concentration of 100 µg/mL. An in vitro cell monolayer wound scratch assay revealed that phenytoin solution or nanoemulsions producing 50 µg/mL phenytoin concentration resulted in 75%-82% "scratch closure" after 36 h, similar to medium containing 10% fetal bovine serum as a cell growth promoter. These findings indicate that phenytoin-loaded alkyd nanoemulsions show potential for promoting topical wound healing through enhanced proliferation of epidermal cells.

Cytotoxic and apoptogenic effects of Strobilanthes crispa Blume extracts on nasopharyngeal cancer cells.

The chemotherapeutic agents used to treat nasopharyngeal cancer (NPC) exhibit low efficacy. Strobilanthes crispa Blume is widely used for its anticancer, diuretic and anti­diabetic properties. The present study aimed to determine the cytotoxic and apoptogenic effects of S. crispa on CNE­1 NPC cells. A 3­(4,5­dimethylthiazol­2­yl)­2,5 diphenyl tetrazolium bromide assay was used to evaluate the cytotoxic effects of S. crispa against CNE­1 cells. The rate of apoptosis was determined using propidium iodide staining and caspase assays. Ethyl acetate, hexane and chloroform extracts of S. crispa leaves all exhibited cytotoxic effects on CNE­1 cells, at a half maximal inhibitory concentration (IC50) of 119, 123.5 and 161.7 µg/ml, respectively. In addition, hexane, chloroform and ethyl acetate extracts of S. crispa stems inhibited CNE­1 cell proliferation, at a IC50 of 49.4, 148.3 and 163.5 µg/ml, respectively. Flow cytometric analysis revealed an increased proportion of cells in the sub G1 phase and a decreased proportion of cells in the G2/M phase, following treatment with the extracts. However, the extracts did not alter the activities of caspase ­3/7, ­8 and ­9. No cytotoxic effect was observed when the cells were treated with the methanol and water extracts of S. crispa stems and leaves. In conclusion, the S. crispa extracts were cytotoxic against CNE­1 cells and these extracts were able to induce apoptosis, independent of caspase activation.

Edible bird's nest ameliorates oxidative stress-induced apoptosis in SH-SY5Y human neuroblastoma cells.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting the senile population with manifestation of motor disability and cognitive impairment. Reactive oxygen species (ROS) is implicated in the progression of oxidative stress-related apoptosis and cell death of the midbrain dopaminergic neurons. Its interplay with mitochondrial functionality constitutes an important aspect of neuronal survival in the perspective of PD. Edible bird's nest (EBN) is an animal-derived natural food product made of saliva secreted by swiftlets from the Aerodamus genus. It contains bioactive compounds which might confer neuroprotective effects to the neurons. Hence this study aims to investigate the neuroprotective effect of EBN extracts in the neurotoxin-induced in vitro PD model. METHODS: EBN was first prepared into pancreatin-digested crude extract and water extract. In vitro PD model was generated by exposing SH-SY5Y cells to neurotoxin 6-hydroxydopamine (6-OHDA). Cytotoxicity of the extracts on SH-SY5Y cells was tested using MTT assay. Then, microscopic morphological and nuclear examination, cell viability test and ROS assay were performed to assess the protective effect of EBN extracts against 6-OHDA-induced cellular injury. Apoptotic event was later analysed with Annexin V-propidium iodide flow cytometry. To understand whether the mechanism underlying the neuroprotective effect of EBN was mediated via mitochondrial or caspase-dependent pathway, mitochondrial membrane potential (MMP) measurement and caspase-3 quantification were carried out. RESULTS: Cytotoxicity results showed that crude EBN extract did not cause SH-SY5Y cell death at concentrations up to 75 µg/ml while the maximum non-toxic dose (MNTD) of water extract was double of that of crude extract. Morphological observation and nuclear staining suggested that EBN treatment reduced the level of 6-OHDA-induced apoptotic changes in SH-SY5Y cells. MTT study further confirmed that cell viability was better improved with crude EBN extract. However, water extract exhibited higher efficacy in ameliorating ROS build up, early apoptotic membrane phosphatidylserine externalization as well as inhibition of caspase-3 cleavage. None of the EBN treatment had any effect on MMP. CONCLUSIONS: Current findings suggest that EBN extracts might confer neuroprotective effect against 6-OHDA-induced degeneration of dopaminergic neurons, particularly through inhibition of apoptosis. Thus EBN may be a viable nutraceutical option to protect against oxidative stress-related neurodegenerative disorders such as PD.