The dermaseptin peptides, mainly derived from the skin secretions of Hylidae frogs, belong to a superfamily of antimicrobial peptides and exhibit diverse antimicrobial and anticancer activities with low cytotoxicity. Here, we reported a novel dermaseptin peptide, from the South American orange-legged leaf frogs, Pithecopus (Phyllomedusa) hypochondrialis, processing the shortest peptide length, namely Dermaseptin-PH. The complementary DNA (cDNA) encoding biosynthetic precursor of Dermaseptin-PH was initially identified by the rapid amplification of cDNA ends PCR (RACE-PCR) technique from the skin secretion. The predicted primary structure was confirmed by a combination of reverse-phase high performance liquid chromatography (RP-HPLC) and MS/MS fragmentation from the skin secretion. Chemically-synthetic Dermaseptin-PH was investigated using a range of bioactivity assessment assays to evaluate the biological activities and cytotoxicity of Dermaseptin-PH. Dermaseptin-PH inhibited the growth of Gram-negative bacteria, Gram-positive bacteria, and pathogenic yeast Candida albicans. In addition, Dermaseptin-PH showed a broad-spectrum of anticancer activities against several cancer cell lines including MCF-7, H157, U251MG, MDA-MB-435S, and PC-3. The potent antimicrobial and anticancer activities of Dermaseptin-PH make it a promising candidate in the discovery of new drugs for clinical applications, and the relatively short sequence of Dermaseptin-PH can provide new insight for the research and structural modification of new peptide drugs.

Antimicrobial peptides (AMPs) can be used as alternative therapeutic agents to traditional antibiotics. These peptides have abundant natural template sources and can be isolated from animals, plants, and microorganisms. They are amphiphilic and mostly net positively charged, and they have a broad-spectrum inhibitory effect on bacteria, fungi, and viruses. AMPs possess significant rapid killing effects and do not interact with specific receptors on bacterial surfaces. As a result, drug resistance is rarely observed with treatments. AMPs, however, have some operational problems, such as a susceptibility to enzymatic (protease) degradation, toxicity in vivo, and unclear pharmacokinetics. However, nanodelivery systems loaded with AMPs provide a safe mechanism of packaging such peptides before they exert their antimicrobial actions, facilitate targeted delivery to the sites of infection, and control the release rate of peptides and reduce their toxic side effects. However, nanodelivery systems using AMPs are at an early stage of development and are still in the laboratory phase of development. There are also some challenges in incorporating AMPs into nanodelivery systems. Herein, an insight into the nanotechnology challenges in delivering AMPs, current advances, and remaining technological challenges are discussed in depth.

The main functions of the abundant polypeptide toxins present in scorpion venoms are the debilitation of arthropod prey or defence against predators. These effects are achieved mainly through the blocking of an array of ion channel types within the membranes of excitable cells. However, while these ion channel-blocking toxins are tightly-folded by multiple disulphide bridges between cysteine residues, there are additional groups of peptides in the venoms that are devoid of cysteine residues. These non-disulphide bridged peptides are the subject of much research interest, and among these are peptides that exhibit antimicrobial activity. Here, we describe two novel non-disulphide-bridged antimicrobial peptides that are present in the venom of the North African scorpion, Androctonus aeneas. The cDNAs encoding the biosynthetic precursors of both peptides were cloned from a venom-derived cDNA library using 3'- and 5'-RACE strategies. Both translated precursors contained open-reading frames of 74 amino acid residues, each encoding one copy of a putative novel nonadecapeptide, whose primary structures were FLFSLIPSVIAGLVSAIRN and FLFSLIPSAIAGLVSAIRN, respectively. Both peptides were C-terminally amidated. Synthetic versions of each natural peptide displayed broad-spectrum antimicrobial activities, but were devoid of antiproliferative activity against human cancer cell lines. However, synthetic analogues of each peptide, engineered for enhanced cationicity and amphipathicity, exhibited increases in antimicrobial potency and acquired antiproliferative activity against a range of human cancer cell lines. These data clearly illustrate the potential that natural peptide templates provide towards the design of synthetic analogues for therapeutic exploitation.

The antidiabetic effects of Ge-Gen-Qin-Lian-Tang decoction (GQD) have been proven clinically. In a pharmacological study conducted on STZ-induced diabetic rats, the constitutive aggregates/sediments of Ge-Gen-Qin-Lian-Tang decoction exhibited stronger hypoglycemic and antioxidant activities compared to the soluble compositions. This study aims to demonstrate the pharmacological properties of aggregates derived from GQD by measuring permeability of the active monomer phytochemicals (e.g., baicalin) in a Caco-2 cell monolayer and determine the cellular viability, intracellular redox status (MDA and SOD), and insulin secretion of pancreatic β-cell line, INS-1, following STZ-induced oxidative stress. The aggregates were separated into three fractions, namely, “MA (microaggregates),” “400 g supernatant,” and “MNA (micro-/nanoaggregates),” by centrifugation at 400 ×g and 15000 ×g, respectively. Aggregates in the sediment increased baicalin absorption, showed little toxicity to β-cells, elevated intracellular SOD levels, and significantly suppressed oxidative damage effects on cellular viability and functions. The “MA” fraction had a larger particle size and provided higher antioxidant cellular protection than “MNA” in vitro, implying that the sediments may be the active components in the herbal decoction. The actions of these micro-/nanoaggregates may provide a new perspective for understanding the antidiabetic effects of herbal decoctions and aid in interpretation of synergistic actions between the multiple components.

The dermaseptin antimicrobial peptide family contains members of 27–34 amino acids in length that have been predominantly isolated from the skins/skin secretions of phyllomedusine leaf frogs. By use of a degenerate primer in Rapid amplification of cDNA ends (RACE) PCR designed to a common conserved domain within the 5′-untranslated regions of previously-characterized dermaseptin encoding cDNAs, two novel members of this peptide family, named dermaseptin-PD-1 and dermaseptin-PD-2, were identified in the skin secretion of the phyllomedusine frog, Pachymedusa dacnicolor. The primary structures of both peptides were predicted from cloned cDNAs, as well as being confirmed by mass spectral analysis of crude skin secretion fractions resulted from reversed-phase high-performance liquid chromatography. Chemically-synthesized replicates of dermaseptin-PD-1 and dermaseptin-PD-2 were investigated for antimicrobial activity using standard model microorganisms (Gram-positive bacteria, Gram-negative bacteria and a yeast) and for cytotoxicity using mammalian red blood cells. The possibility of synergistic effects between the two peptides and their anti-cancer cell proliferation activities were assessed. The peptides exhibited moderate to high inhibition against the growth of the tested microorganisms and cancer cell lines with low haemolytic activity. Synergistic interaction between the two peptides in inhibiting the proliferation of Escherichia coli and human neuronal glioblastoma cell line, U251MG was also manifested.

Amphibian skin secretion has great potential for drug discovery and contributes hundreds of bioactive peptides including bradykinin-related peptides (BRPs). More than 50 BRPs have been reported in the last two decades arising from the skin secretion of amphibian species. They belong to the families Ascaphidae (1 species), Bombinatoridae (3 species), Hylidae (9 speices) and Ranidae (25 species). This paper presents the diversity of structural characteristics of BRPs with N-terminal, C-terminal extension and amino acid substitution. The further comparison of cDNA-encoded prepropeptides between the different species and families demonstrated that there are various forms of kininogen precursors to release BRPs and they constitute important evidence in amphibian evolution. The pharmacological activities of isolated BRPs exhibited unclear structure–function relationships, and therefore the scope for drug discovery and development is limited. However, their diversity shows new insights into biotechnological applications and, as a result, comprehensive and systematic studies of the physiological and pharmacological activities of BRPs from amphibian skin secretion are needed in the future.