Irradiation from diverse sources is ubiquitous and closely associated with human activity. Radiation therapy (RT), an important component of the multiple radiation origins, contributes significantly to oncotherapy by killing tumor cells. On the other hand, RT can also cause some undesired normal tissue injuries that afflict numerous cancer patients. Although many promising radioprotective agents are emerging, few of them have entered the market successfully due to various limitations. At present, the most accepted hypothesis for the radiation-caused injury involves reactive oxygen species (ROS) generation. Superoxide dismutase (SOD), the unique enzyme responsible for the dismutation of superoxide radicals, is expected to occupy an indispensable position in the treatment of ROS-mediated tissue injuries originating from exposure to radiation. This review focuses on the mechanism of radioprotection by SOD at the tissue or organ level, cellular level, and molecular level, respectively, in order to provide references for further investigation of radiation injury and development of new radioprotectors.
Epilepsy is the most common chronic neurological disorder of the brain. For several decades different kinds of medications have been used to treat epilepsy. Even though many surgical advances has been made and implemented, medications remain the basis of treatment. The search for noble antiepileptic drugs (AEDs) with more selective activity and lower toxicity continues to be an area of intensive investigation in medicinal chemistry. Additionally, drug resistance is an important clinical problem in epilepsy and is associated with an increased risk of morbidity and mortality. This review intends to present a comprehensive overview on AED in particular along with discussion on some aspects of associated drug resistance and combination therapy.
Geranium nepalense Sweet is a common Chinese herbal medicine and has been used as influenza, dysentery, antiphlogistic and analgesic tonic, hemostatic, stomachic, and antidiabetic drugs. The anti-inflammatory effects of G. nepalense on tetradecanoyl phorbol acetate (TPA)-induced mouse ear edema were studied in this work. The results showed that ethyl acetate fraction of the water extract of G. nepalense possessed significant activity at 2.5 g/kg (p < 0.01) with aspirin as a positive control (0.6 g/kg). Six polyphenolic compounds, including three flavonoids, i.e. kaempferol, kaempferol-7-O-β-D-glucopyranoside, and quercetin-7-O-α-rhamnopyranoside, and two tannins, i.e. pyrogallol and gallic acid, and one lignin, i.e. epipinoresinol, were isolated and characterized from ethyl acetate fraction. The isolation of polyphenols provides a clue for beneficial effects of G. nepalense in the demonstrated anti-inflammatory activity.
The synthesis and structure-activity relationship (SAR) study of a series of 2-(substituted benzylidene)-7-(4-fluorophenyl)-5-(furan-2-yl)-2H-thiazolo[3,2-a]pyrimidin-3(7H)-one (4a-4j) derivatives as anticancer agents are described. This series of thiazolopyrimidines were synthesized by the reaction of 7-(4-fluoro phenyl)-5-(furan-2-yl)-2H-thiazolo[3,2-a] pyrimidin-3(7H)-one (3) with appropriate substituted aldehydes in the presence of anhydrous sodium acetate and glacial acetic acid. Their structures were confirmed by IR, 1H-NMR, mass, and elemental analyses. These novel thiazolopyrimidine derivatives were screened for their anticancer activity on the U937 human histocytic lymphoma cell line by 3-(4,5-dimethyl thiazole-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay. The comparison of anticancer activity of thiazolopyrimidine was performed considering their structures. This study was done using 2-(substituted benzylidene)-7-(4-fluorophenyl)-5-(furan-2-yl)-2Hthiazolo[3,2-a]pyrimidin-3(7H)-one (4a-4j) as a basic model, showing that i) presence of a hydrogen donor/acceptor domain [thiazolo[3,2-a]pyrimidin-3(7H)-one] on the thiazolopyrimidine ring; ii) presence of a hydrophobic [(4-fluorophenyl)] aryl ring system on the thiazolopyrimidine ring; iii) presence of an electron donor moiety [5-(furan-2-yl)] on the thiazolopyrimidine ring; iv) ortho and para substitution of the distal aryl ring [2-(substituted benzylidene)] function strongly influenced anticancer activity. Among these compounds (4a-4j) para substituted derivatives 4c, 4e, 4f, 4g, 4h, and 4j showed significant anticancer activity.
Herbal medicines have traditionally been used worldwide for the prevention and treatment of liver disease with fewer adverse effects. The leaves of the Syzygium jambos (SJL) plant were chosen and studied for their antioxidant activity in vitro and hepatoprotective activity in vivo. The antioxidant activity of the ethanol extract was examined in vitro using a 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay, reducing capacity, total phenol, total flavonoid content, and total antioxidant capacity. The extract had significant dose-dependent antioxidant activity in all in vitro experiments. IC50 values of SJL and ascorbic acid (standard) were found to be 14.10 and 4.87 μg/mL, respectively, according to a DPPH radical scavenging assay. Hepatoprotective activity of the plant extract was evaluated in a rat model of carbon tetrachloride (CCl4)-induced liver damage. CCl4 significantly altered serum marker enzymes, total bilirubin, total protein, and liver weight. The extract caused these values to return to normal in rats with CCl4-induced liver damage that were given SJL. This indicated the hepatoprotective potential of SJL and was comparable to use of the standard drug silymarin. Thus, the present study revealed that SJL may have antioxidant and hepatoprotective activity.
One hundred and twenty four plant extracts were evaluated for their antimicrobial activity against four pathogenic bacteria (Staphylococcus aureus (ATCC 8095), Salmonella enteritides (ATCC 13076), Escherichia coli (ATCC 25922), and Listeria monocytogenes (ATCC 15313)) and Candida albicans yeast (ATCC 10231) using the disk diffusion and broth microdilution methods. Of the plant extracts, fourteen exhibited antimicrobial activity against two or more of the five microorganisms tested. Only the methanol extract of Lagerstroemia indica leaves exhibited antimicrobial activity against all pathogenic bacteria and C. albicans yeast that were tested. Purification of the methanol extract of L. indica leaves using antimicrobial assay-guided isolation yielded one pure active compound. The chemical structure of the isolated active compound was found to be '4-methoxy apigenin-8-C-β-D-glucopyranoside; cytisoside according to detailed spectroscopic analysis of its nuclear magnetic resonance and mass spectrometry data. The compound exhibited antimicrobial activity against C. albicans (minimum lethal concentration (MLC): 32 μg/mL), S. aureus (MLC: 16 μg/mL), S. enteritides (MLC: 16 μg/mL), E. coli (MLC: 16 μg/mL), and L. monocytogenes (MLC: 16 μg/mL). The present study found that the methanol extract of L. indica leaves holds great promise as a potential source of beneficial antimicrobial components for different applications.
Cell-wall skeleton prepared from Mycobacterium bovis BCG (BCG-CWS) is known as a potent adjuvant and has been shown to possess antitumor activity in many non-clinical and clinical studies. As there are no approved BCG-CWS formulations for cancer therapy, we investigated the potential for cancer immunotherapy of SMP-105, our originally produced BCG-CWS. For optimizing SMP-105 emulsion, we compared the effects of drakeol- and squalane-based SMP-105 emulsions on IFN-γ production in rats and evaluated their ability to induce skin reaction in guinea pigs. Both emulsions had the same activity in both experiments. We selected squalane as base material and produced two types of squalane-based formulations (vialed emulsion and pumped emulsion) that can easily be prepared as oil-in-water emulsions. Although the vialed emulsion showed the same pattern of distribution as a usual homogenized emulsion, the pumped emulsion showed more uniform distribution than the other two emulsions. Whereas both emulsions enhanced strong delayed type hypersensitivity (DTH) reaction in a mouse model, the pumped emulsion induced slightly smaller edema. Data on oil droplet size distribution suggest that few micrometer oil droplet size might be appropriate for oil-in-water microemulsion of SMP-105. The antitumor potency of SMP-105 emulsion was stronger than that of some of the launched toll-like receptor (TLR) agonists (Aldara cream, Picibanil, and Immunobladder). Aldara and Picibanil showed limited antitumor effectiveness, while Immunobladder had almost the same effect as SMP-105 at the highest dose, but needed about 10 times the amount of SMP-105. These findings first indicate that SMP-105 has great potential in cancer immunotherapy.
Sacrificing model animals is required for developing effective drugs before being used in human beings. In Japan today, at least 4,210,000 mice and other mammals are sacrificed to a total of 6,140,000 per year for the purpose of medical studies. All the animals treated in Japan, including test animals, are managed under control of "Act on Welfare and Management of Animals". Under the principle of this Act, no person shall kill, injure, or inflict cruelty on animals without due cause. "Animal" addressed in the Act can be defined as a "vertebrate animal". If we can make use of invertebrate animals in testing instead of vertebrate ones, that would be a remarkable solution for the issue of animal welfare. Furthermore, there are numerous advantages of using invertebrate animal models: less space and small equipment are enough for taking care of a large number of animals and thus are cost-effective, they can be easily handled, and many biological processes and genes are conserved between mammals and invertebrates. Today, many invertebrates have been used as animal models, but silkworms have many beneficial traits compared to mammals as well as other insects. In a Genome Pharmaceutical Institute's study, we were able to achieve a lot making use of silkworms as model animals. We would like to suggest that pharmaceutical companies and institutes consider the use of the silkworm as a model animal which is efficacious both for financial value by cost cutting and ethical aspects in animals' welfare.