Amino acid-mPEGs: Promising excipients to stabilize human growth hormone against aggregation.

Objectives: Today, the non-covalent PEGylation methods of protein pharmaceuticals attract more attention and possess several advantages over the covalent approach. In the present study, Amino Acid-mPEGs (aa-mPEGs) were synthesized, and the human Growth Hormone (hGH) stability profile was assessed in their presence and absence. Materials and Methods: aa-mPEGs were synthesized with different amino acids (Trp, Glu, Arg, Cys, and Leu) and molecular weights of polymers (2 and 5 KDa). The aa-mPEGs were analyzed with different methods. The physical and structural stabilities of hGH were analyzed by SEC and CD spectroscopy methods. Physical stability was assayed at different temperatures within certain intervals. Molecular dynamics (MD) simulation was used to realize the possible mode of interaction between protein and aa-mPEGs. The cell-based method was used to evaluate the cytotoxicity. Results: HNMR and FTIR spectroscopy indicated that aa-mPEGs were successfully synthesized. hGH as a control group is known to be stable at 4 °C; a pronounced change in monomer degradation is observed when stored at 25 °C and 37 °C. hGH:Glu-mPEG 2 kDa with a molar ratio of 1:1 to the protein solution can significantly increase the physical stability. The CD spectroscopy method showed that the secondary structure of the protein was preserved during storage. aa-mPEGs did not show any cytotoxicity activities. The results of MD simulations were in line with experimental results. Conclusion: This paper showed that aa-mPEGs are potent excipients in decreasing the aggregation of hGH. Glu-mPEG exhibited the best-stabilizing properties in a harsh environment among other aa-mPEGs.

Achillea spp.: A comprehensive review on its ethnobotany, phytochemistry, phytopharmacology and industrial applications.

The genus Achillea genus houses more than 100 species, a number of them are popularly used in traditional medicine for spasmodic gastrointestinal, gynecological and hepatobiliary disorders, hemorrhages, pneumonia, rheumatic pain, inflammation, wounds healing etc. Members of the genus contain a wide variety of volatile and non-volatile secondary metabolites, including terpenes, polyphenols, flavonoids and others. Multiple studies have assessed the biological effects and other aspects of Achillea spp. In a number of preclinical studies, Achillea plants and their essential oils have demonstrated promising antibacterial properties against a number of human and plant pathogens. Besides, the plants have displayed strong antioxidative and potent anti-proliferative and anticancer properties in various cellular and animal models. Achillea plants have widely been used as food preservative in food industry. Clinical studies have indicated its potential against multiple sclerosis (MS), irritable bowel syndrome (IBS), ulcerative colitis, episiotomy wound, primary dysmenorrhea, oral mucositis etc. The present work focuses to provide a brief overview on folk knowledge, phytochemistry, biological activity and applications of Achillea plants. There is a close relationship between the traditional ethnobotanical usage and pharmacological and clinical data from different Achillea spp. The application of Achillea plants and their extracts seems to be a promising alternative for antimicrobial and antioxidant purposes in food, pharmaceutical and cosmetic industries.

Phenolic compounds, saponins and alkaloids on cancer progression: emphasis on p53 expression and telomere length.

Telomere length is correlated with cell proliferation, and cancer cells are characterized by an uncontrolled cell cycle. Being apoptosis one of the checks and balances incorporated into cells cycle, due to its characteristics, cancer cells are able to overcome this process. In particular, the tumour suppressor protein p53 loss or inactivation can lead to activation of telomerase enzyme, which can make cells unable to detect DNA damages that spurs apoptosis. Some bioactive compounds, in particular phenolic compounds, saponins and alkaloids have revealed good abilities to affect p53 expression and indirectly control the telomere length. In this sense, this review gives a key emphasis to the ability of these compounds in blocking cancer progression by acting on p53 expression and controlling telomere length. As main findings, phenolic compounds, saponins and alkaloids interfere with cancer progression by stimulating p53 expression, which can cause pro-apoptotic onset and restrict the anti-apoptotic activity, in addition to preventing telomerase enzyme activity.