Developmental toxicity, antioxidant, and marker enzyme assessment of swertiamarin in zebrafish (Danio rerio).

A secoiridoid glycoside called swertiamarin has been widely used as a herbal medicine for many decades. In particular, swertiamarin from the Enicostema axillare herb has been used as a multipurpose drug to treat innumerable health problems. As this medicine is consumed orally, its toxicity level should be determined. To examine the safety of this compound, toxicology work was done in zebrafish, and this is the first report to describe swertiamarin toxicity in zebrafish. Zebrafish embryos were used in this swertiamarin toxicity study, and morphological changes were observed. Further, the compound was also studied in adult zebrafish to determine the impact of the compound on the fish liver. Enzyme profiling with superoxide dismutase, glutathione peroxidase, catalase, reduced glutathione levels, glutathione S-transferase, lactate dehydrogenase, glutamic oxaloacetic transaminases, lipid peroxidation, Na+ /K+ -ATPase, and glutamic pyruvic transaminases) was evaluated (p ≤ 0.05). Results suggest that swertiamarin is a safe drug only at a low concentration (40 µM). This study also shows that even herbal medicinal compounds may be toxic to humans at higher dosages. Hence, irrespective of whether a drug is synthetic or natural, it needs to be tested for its toxicity before use in humans.

Repellency Assessment of Nepeta cataria Essential Oils and Isolated Nepetalactones on Aedes aegypti.

There is an increased need for improved and affordable insect repellents to reduce transmission of rapidly spreading diseases with high mortality rates. Natural products are often used when DEET cannot be afforded or accessed and when consumers choose not to use a synthetic repellent. The essential oils from two newly bred Nepeta cataria (catnip) plants representing two different chemotypes and their respective isolated nepetalactone isomers were evaluated as mosquito repellents against Aedes aegypti mosquitoes that transmit the Zika and Dengue virus in a one choice landing rate inhibition assay. A dose response curve was generated for each treatment and a time course analysis of repellency was performed over 24 hours with a N. cataria essential oil sample. The results indicate that all essential oil samples and their respective purified nepetalactone isomers were able to achieve greater than 95% repellency. Between two and four hours, the ability to repel more than 95% of the mosquitoes diminished. At the lowest concentrations tested, the nepetalactones and crude essential oil samples were more effective than DEET at reducing the number of mosquito landings.

Asperlin Stimulates Energy Expenditure and Modulates Gut Microbiota in HFD-Fed Mice.

Asperlin is a marine-derived, natural product with antifungal, anti-inflammatory and anti-atherosclerotic activities. In the present study, we showed that asperlin effectively prevented the development of obesity in high-fat diet (HFD)-fed mice. Oral administration of asperlin for 12 weeks significantly suppressed HFD-induced body weight gain and fat deposition without inhibiting food intake. Hyperlipidemia and liver steatosis were also substantially ameliorated. A respiratory metabolism monitor showed that asperlin efficiently increased energy expenditure and enhanced thermogenic gene expression in adipose tissue. Accordingly, asperlin-treated mice showed higher body temperature and were more tolerant of cold stress. Meanwhile, asperlin also increased the diversity and shifted the structure of gut microbiota. Oral administration of asperlin markedly increased the relative abundance of Bacteroidetes, leading to a higher Bacteroidetes-to-Fimicutes ratio. The HFD-induced abnormalities at both phylum and genus levels were all remarkably recovered by asperlin. These results demonstrated that asperlin is effective in preventing HFD-induced obesity and modulating gut microbiota. Its anti-obesity properties may be attributed to its effect on promoting energy expenditure.

Cytotoxic activity assessment, QSAR and docking study of novel bis-carboxamide derivatives of 4-pyrones synthesized by Ugi four-component reaction.

Fourteen novel bis-carboxamide derivatives of 4-pyrones were designed and synthesized via Ugi four-component reactions of 4-pyrone carbaldehydes, aromatic amines, isocyanides and carboxylic acids. The cytotoxic activity of synthesized derivatives was evaluated against LS180, MCF-7 and HL-60 cell lines using MTT reduction assay. Synthesized compounds demonstrated strong cytotoxic potential in HL-60 cell line. Compound 12n was the most potent derivative with IC50 values of 16.1, 9.1 and 13.8 µM in LS180, MCF-7 and HL-60 cells, respectively. The results of MLR-QSAR study indicated that topological property of these derivatives directly influenced the cytotoxic potential in HL-60 cell line. Docking study of compounds, conducted for ATP binding site of Src tyrosine kinase, demonstrated the key H-bond interaction with Met 347 of the hinge region.

Induction of caspase-9, biochemical assessment and morphological changes caused by apoptosis in cancer cells treated with goniothalamin extracted from Goniothalamus macrophyllus.

Goniothalamin, a natural compound extracted from Goniothalamus sp. belonging to the Annonacae family, possesses anticancer properties towards several tumor cell lines. This study focused on apoptosis induction by goniothalamin (GTN) in the Hela cervical cancer cell line. Cell growth inhibition was measured by MTT assay and the IC50 value of goniothalamin was 3.2 ± 0.72 µg/ml. Morphological changes and biochemical processes associated with apoptosis were evident on phase contrast microscopy and fluorescence microscopy. DNA fragmentation, DNA damage, caspase-9 activation and a large increase in the sub-G1 and S cell cycle phases confirmed the occurrence of apoptosis in a time-dependent manner. It could be concluded that goniothalamin show a promising cytotoxicity effect against cervical cancer cells (Hela) and the cell death mode induced by goniothalamin was apoptosis.

Effect of extracted housefly pupae peptide mixture on chilled pork preservation.

The peptide mixture from housefly pupae has broad spectrum antimicrobial activity but has not previously been reported as a food preservative. In this study, the preservation effects of a housefly pupae peptide mixture, nisin, and sodium dehydroacetate (DHA-S) on the number of mesophilic aerobic bacteria (MAB), total volatile basic nitrogen (TVB-N), and pH value of chilled pork were compared. All results showed that a good preservation effect was observed among 3 treatments with the peptide mixture of housefly pupae, nisin, and DHA-S and that there was no significant difference among them. These results indicate that housefly peptide mixture has a great potential as a food preservative. The results of scanning electron microscope and transmission electron microscopy suggest that the primary mechanism of housefly pupae peptide mixture may be bacterial cytoplasmic membrane lysis and pores induced in the membranes. Practical Applications: Peptide mixture extracted from housefly pupae using low-cost and simple method has broad spectrum antimicrobial activity. According to the effect on chilled pork preservation, extracted housefly peptide mixture has a great potential as a food preservative.

Analysis of swertiamarin in Swertia herb and preparations containing this crude drug by capillary electrophoresis.

Swertia herb (florescent whole plantof Swertia japonica, Gentianaceae) has long been utilized as a folk medicine in Japan. It is often blended in general gastroenteric drugs as a bitter stomachic. Swertiamarin, a bitter secoiridoid glycoside, is the representative constituent of this crude drug and Swertia herb is normally evaluated by the swertiamarin content. To date, papers have described the discrimination of Swertia herbs from other bitter crude drugs, estimation of swertiamarin and seasonal variation in swertiamarin content using thin-layer chromatography, while other papers have reported quantitative determination of swertiamarin using high-performance liquid chromatography (HPLC). In our previous papers, we reported analyses of the constituents of some crude drugs using capillary electrophoresis (CE). To aid in the evaluation of crude drugs, we succeeded in our attempt to separate and determine the quantity of swertiamarin in Swertia herb. Subsequently, we applied the same analytical condition to estimate the swertiamarin contents in Japanese pharmacopoeia stomachic preparations, in OTC gastroenteric drugs and in OTC hair tonics containing Swertia herb.

Protease inhibitors: where are they now?

AIDS: Protease inhibitors block HIV by binding with its protease enzyme and it is hoped that they will be more potent and less toxic than nucleoside analogs. The companies Hoffmann-La Roche, Merck, Abbott, Searle, Agouron, Kyoto and Upjohn all have tested protease inhibitors in human trials. The drugs include L-524, ABT-538, AG- 1343, saquinavir, SC-52151, and SC-55389a. The protease inhibitors from Merck, Roche, and Abbott have shown higher anti-viral activity than any previous anti-HIV drug. Vertex, Burroughs Wellcome, and Kissei have conducted animal studies of VX-478, which shows promise in inhibiting the virus, with no toxicity. Other companies developing protease inhibitors include DuPont-Merck, Ciba-Geigy, Hoechst-Bayer, Nippon Mining, Parke-Davis, and Smith-Kline Beecham. Companies increasingly are combining protease inhibitors with nucleoside analogs, mainly AZT, in their large-scale efficacy studies in an effort to produce a strong and sustained anti-HIV effect. Potential cross-resistance to many of these compounds remains a major research issue. It is likely that at least one of the three leading companies in the field -- Merck, Abbott, or Roche -- will file for Food and Drug Administration approval in 1995. The National Drug Development Task Force is expected to announce the creation of a new task force on protease inhibitors.^ieng