Hepatotoxicity and Mutagenicity assessment during chronic in vivo exposure to aqueous extracts from Peperomia pellucida.

Studies on herbal medicine have exposed some toxic effects on humans. Peperomia pellucida (L.) HBK (P. pellucida) is one of the herbal medicines recommended as an alternative to synthetic medicine for diseases. Studies exist on the pharmacological activities of P. pellucida extracts, but studies on the potential hepatotoxic and mutagenic effects of subchronic administration of P. pellucida aqueous extracts, which is very important knowledge when we venture into alternative medicine, are lacking. In this study, two concentrations (60 mg/kg and 30 mg/kg) of P. pellucida aqueous extracts - decoction and freeze-dried extracts -were administered in vivo to BALB/c mice for nine (9) weeks. Significant differences were observed between the 60 mg/kg freeze-dried extract and the control in terms of mice weight and micronucleus frequency at 7-8 weeks of treatment. Also, no significant differences were found between groups in serum transaminases levels. Generally, there is no sufficient evidence to show that subchronic exposure to P. pellucida aqueous extracts is hepatotoxic though 60 mg/kg concentration may be mutagenic. This study suggests that although the herbal medicine is safe for prolonged consumption, users are advised to take precautions and moderations of its use due to the possibility of potential mutagenic effects.

Conus striatus venom exhibits non-hepatotoxic and non-nephrotoxic potent analgesic activity in mice.

Constant research into the pharmaceutical properties of marine natural products has led to the discovery of many potentially active agents considered worthy of medical applications. Genus Conus, which approximately comprises 700 species, is currently under every researcher's interest because of the conopeptides in their crude venom. Conopeptides have a wide range of pharmacological classes and properties. This research focused on the crude venom of Conus striatus to assess its analgesic activity, mutagenicity, nephrotoxicity, and hepatotoxicity in mice. The crude venom was extracted from the conus snails and the protein concentration was determined using Bradford's method. The analgesic activity of the venom was determined using the hot-plate method and standard IFCC method was used to determine the alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Evaluation of mutagenicity was done using micronucleus assay and the nephrotoxicity of the venom was determined using Kidney Coefficient and serum creatinine concentration. The maximum tolerable dose (MTD) of the crude venom was found to be 75 ppm. The venom exhibited potent analgesic activity even higher than the positive control (Ibuprofen). Most of the analgesic drugs can usually impact damage in the liver and kidneys. However, AST and ALT results revealed that the venom has no adverse effects on the liver. Although the venom increased the incidence of micronucleated polychromatic erythrocytes, making it mutagenic, with MTD concentration's mutagenicity comparable to the positive control methyl methanesulfonate (MMS). The kidney coefficients, on the other hand, showed no significant difference between the treated groups and that of the untreated group. The serum creatinine also showed a concentration-dependent increase; with MTD treated mice got the highest creatinine concentration. However, MTD/2 and MTD/4 showed no significant difference in creatinine levels with respect to the untreated groups. Hence, the nephrotoxicity of the venom was only evident when used at higher concentration. The venom exhibited potent analgesic activity indicated that the C. striatus crude venom extract could have a potential therapeutic component as analgesic drugs that displayed no hepatic damage. This study also suggests that for this venom to be utilized for future medical applications, their usage must be regulated and properly monitored to avoid nephrotoxic effect.

Rapid Endolysosomal Escape and Controlled Intracellular Trafficking of Cell Surface Mimetic Quantum-Dots-Anchored Peptides and Glycopeptides.

A novel strategy for the development of a high performance nanoparticules platform was established by means of cell surface mimetic quantum-dots (QDs)-anchored peptides/glycopeptides, which was developed as a model system for nanoparticle-based drug delivery (NDD) vehicles with defined functions helping the specific intracellular trafficking after initial endocytosis. In this paper, we proposed a standardized protocol for the preparation of multifunctional QDs that allows for efficient cellular uptake and rapid escaping from the endolysosomal system and subsequent cytoplasmic molecular delivery to the target cellular compartment. Chemoselective ligation of the ketone-functionalized hexahistidine derivative facilitated both efficient endocytic entry and rapid endolysosomal escape of the aminooxy/phosphorylcholine self-assembled monolayer-coated QDs (AO/PCSAM-QDs) to the cytosol in various cell lines such as human normal and cancer cells, while modifications of these QDs with cell-penetrating arginine-rich peptides showed poor cellular uptake and induced self-aggregation of AO/PCSAM-QDs. Combined use of hexahistidylated AO/PCSAM-QDs with serglycine-like glycopeptides, namely synthetic proteoglycan initiators (PGIs), elicited the entry and controlled intracellular trafficking, Golgi localization, and also excretion of these nanoparticles, which suggested that the present approach would provide an ideal platform for the design of high performance NDD systems.