SUMMARY Aim: Herbal products are complex mixtures of organic chemicals that may come from any raw or processed part of a plant, including leaves, stems, flowers, roots, and seeds. Medicinal plants and herbal medicines account for a significant percentage of the pharmaceutical market. The present study aimed to assess the prevalence of herbal products and their indications in Al-Taif area, Kingdom of Saudi Arabia (KSA). Methods: A cross-sectional survey about the use of herbal medicines was conducted. Four hundred eighty respondents through private and hospital pharmacies filled the questionnaire. Questions about trade names, dosage forms, active ingredients and indications of the herbal pharmaceutical products were considered. Results: The present study revealed that natural product drugs had a noticeable share in the pharmaceutical market in Al-Taif area. Natural cough products represent the highest percent used by Al-Taif area populations. Conlusion: Herbal medicine represents an important part in pharmacies. Many patients prefer to use herbal medicine because of its safety and fewer side effects.

NULL

NULL

NULL

NULL

Peptides were designed based on the identified structural motif of the most potent antioxidant peptides derived from barley protein. Six peptides contained the effective pentapeptide QPYPQ with appended Gln and Pro residues and the other peptides possessed higher hydrophobicity. The peptides have the repetitive sequences of Q, P and Y to investigate the contribution of vicinal residues to their antioxidant capacity. Antioxidant activity of the synthetic peptides was evaluated in chemical and cellular models. Free radical scavenging assays demonstrated the positive role of QP and PY pairs in stabilizing the peptide radicals. Cellular models revealed that repetitive peptide sequences effectively inactivate lipid hydroperoxides and intracellular reactive oxygen species. Peptides with alternating residues were also found effective in inhibition of amyloid fibril formation. These results verified that in addition to the chemical structure of individual side chains, the combined effects of the vicinal residues are also important in antioxidant activity of the whole peptide.

β-Peptides made from L-aspartic acid monomers form a new class of β3-peptides. Here we report the first three-dimensional NMR solution structure of a β3-hexapeptide (1) from L-aspartic acid monomers in 2,2,2-trifluoroethanol (TFE). We show that 1 forms a right-handed 14-helical structure in TFE. α-peptides from naturally occurring L-amino acids adopt a right-handed α-helix whereas β3-peptides formed from β3-amino acids derived from naturally occurring L-amino acids form left-handed 14-helices. The right-handed 14-helical conformation of 1 is a better mimic of α-peptide conformations. Using the NMR structure of 1 in TFE, we further study the conformation of 1 in water, as well as two similar β3-peptides (2 and 3) in water and TFE by molecular dynamics (MD) simulations. NMR and MD results suggest loss of secondary structure of 1 in water and show that it forms a fully extended structure. 2 and 3 contain residues with oppositely charged side chains that engage in salt-bridge interactions and dramatically stabilize the 14-helical conformation in aqueous media.

The specific targeting ability of novel breast cancer targeting peptides as ligands coupled to polymeric micelles was evaluated in the present study. In this context, engineered breast cancer cell targeting peptides, denoted as peptide 11 (RGDPAYQGRFL) and peptide 18 (WXEAAYQRFL), were compared with the lead 12-mer p160 peptide and cyclic RGDfK peptide. All four peptides were conjugated individually to poly(ethylene oxide)-b-poly(caprolactone) (PEO-b-PCL) diblock polymeric micelles to obtain targeted carrier systems PM11, PM18, PM 160, and PM c-RGD. Physical blending of the peptides 11 and 18 with PEO-b-PCL was also done to yield combination micelles, comPM11 and comPM18. The structural confirmation of polymer was carried out using 1H NMR and MALDI-TOF, and the size distribution and zeta potential of the micelles were determined using dynamic light scattering. Lipophilic cyanine fluorescent probe DiI was physically incorporated in the polymeric micelles to imitate the hydrophobic drug loaded in the micellar core. The cellular uptake of DiI-loaded peptide-containing polymeric micelles by MDA-MB-435, MDA-MB-231, and MCF7 breast cancer cell lines, as well as HUVEC and MCF10A noncancerous cells, were analyzed using flow cytometry and confocal microscopy techniques. Modification of polymeric micelles with peptide 11 or 18 led to an increase in micellar uptake specifically in breast cancer cells compared to p160, c-RGD modified, or naked micelles. The peptide–micelle combinations (comPM11 and comPM18) displayed better uptake by the cells compared to the covalently conjugated PM11 and PM18 micelles; however, the combinations were less selective toward cancer cells. The results point to a potential for peptides 11- and 18-micelle conjugates as attractive platforms for improved performance of a wide range of chemotherapeutic drugs and/or imaging agents in cancer therapy and diagnosis.

The use of peptides as drugs in pharmaceutical applications is hindered by their susceptibility to proteolysis and therefore low bioavailability. β-Peptides that contain an additional methylene group in the backbone, are gaining recognition from a pharmaceutical stand point as they are considerably more resilient to proteolysis and metabolism. Recently, we reported two new classes of β-peptides, β3- and β2-peptides derived from l-aspartic acid and l-diaminopropionic acid, respectively. Here, we report the proteolytic stability of these β-peptidic compounds and a mixed α /β-peptide against three enzymes (pronase, trypsin and elastase), as well as, human serum. The stability of these peptides was compared to an α-peptide. Peptides containing β-linkages were resistant to all conditions. The mixed α /β-peptide, however, exhibited proteolysis in the presence of trypsin and pronase but not elastase. The rate of degradation of the mixed α /β-peptide was slower than that would be expected for an α-peptide. In addition, these β-peptides were not toxic to HeLa and COS-1 cell lines as observed by MTT cytotoxicity assay. These results expand the scope of mixed α /β-peptides containing β-amino acids or small β-peptide fragments as therapeutic peptides.

Peptides containing the Asn-Gly-Arg (NGR) motif are known to bind CD13 isoforms expressed in tumor vessels and have been widely used for tumor targeting. Residues flanking the NGR sequence play an important role in modulating the binding affinity and specificity of NGR for the CD13 receptor. Herein, we have used a rapid, easy, and reliable peptide array–whole cell binding assay for screening a library of NGR peptides with different flanking residues. A peptide array consisting of forty-five NGR containing peptides was synthesized on a cellulose membrane, followed by screening against CD13 positive (HUVEC and HT-1080) and CD13 negative cell lines (MDA-MB-435 and MDA-MB-231). The library screening led to the identification of five cyclic and acyclic NGR peptides that display higher binding (up to 5-fold) to CD13 positive cells with negligible binding to CD13 negative cell lines when compared to the lead sequence cyclic CVLNGRMEC. Peptides with high binding affinity for the CD13 positive cells also showed improved in vitro cellular uptake and specificity using flow cytometry and fluorescence microscopy. Interestingly, the identified peptides resemble the NGR sequences present in the human fibronectin protein. These NGR peptides are promising new ligands for developing tumor vasculature targeted drugs, delivery systems and imaging agents with reduced systemic toxicity.