Peptide 401

Anti-inflammatory property of 401 (MCD-peptide), a peptide from the venom of the bee Apis mellifera (L.)

1 Peptide 401, a potent mast cell degranulating factor from bee venom, substantially inhibited the oedema provoked by subplantar injection of carrageenin or intra-articular injection of turpentine in the rat. The ED(50) of 401 was c. 0.1 mg/kg. The anti-inflammatory effect was assessed by measurement of the increased (125)I-albumin content of an injected site in comparison with an uninjected contralateral site.2 Peptide 401 also suppressed the increased vascular permeability due to intradermal injection of various smooth muscle spasmogens (histamine, bradykinin, 5-hydroxytryptamine (5-HT), and prostaglandins).3 Other comparable mast cell degranulating agents (48/80 and melittin) showed little evidence of anti-inflammatory activity when tested at comparable dosage on turpentine arthritis and carrageenin oedema.4 The anti-inflammatory effects were not abolished by pretreatment with mepyramine and methysergide, which abolished the increased vascular permeability produced by local injection of 401.5 The anti-inflammatory action of 401 was not affected by regional denervation or pretreatment with phenoxybenzamine, and was reduced but not abolished by adrenalectomy.6 Measurement of skin temperature, fractional extraction of (86)Rb and blood flow in perfused mesentery gave no evidence that the anti-inflammatory action of 401 was due to reduced tissue perfusion.7 It is concluded that 401 may exert its anti-inflammatory action directly by making the vascular endothelium anergic to phlogistic stimuli.

Spectroscopic investigations of peptide 401 from bee venom

The circular dichroism (CD) and ¹ H-nmr properties of peptide 401, a bee venom component with 22 amino acid residues and two disulfide bridges, have been studied under a variety of conditions and compared with those of the structurally related octadecapeptide apamin. The major component of the relatively intense CD signal in the 200-230-nm region in both cases probably arises from the rigid asymmetric ring structures of the disulfide bridges. CD spectra are practically unaffected by pH (in the region 1-7), solvent (water, trifluoroethanol, dioxane/water mixtures), concentration of peptide, or additions of salt (guanidinium chloride, KCl). Temperature changes (in the range 20-59°C) have only a modest influence. For both apamin and peptide 401, reduction of the two disulfide bridges results in a dramatic change of the CD spectrum, which acquires the characteristic form of a random coil. Preliminary ¹ H-nmr data are presented for both the reduced and the oxidized form. Several resonance peaks could be assigned on the basis of the theoretical random-coil spectrum. In the oxidized forms, six slowly exchangeable amide protons could be found in a spectrum taken at low pH, which are ascribed to intramolecular hydrogen bonds. Each of the four protons of the two histidine residues of peptide 401 appears as two distinct resonance peaks in the oxidized form but not in the reduced form. This is interpreted as arising from conformational heterogeneity of peptide 401.

Anti-inflammatory activity of bee venom peptide 401 (mast cell degranulating peptide) and compound 48/80 results from mast cell degranulation in vivo

1. The relationship between the anti-inflammatory activity of the bee venom peptide 401 in the carrageenin-induced oedema of the rat hind paw and its mast cell degranulating activity has been reinvestigated. 2. Mast cell degranulation caused by compound 48/80 (10 mg kg-1) or by allergen challenge in rats sensitized to Nippostrongylus brasiliensis also suppressed rat hind paw oedema in the same test. 3. The anti-inflammatory activities of peptide 401 and compound 48/80 were partially suppressed by pretreatment of rats with mepyramine and methysergide, at doses (2.5 mg kg-1) that completely suppressed skin reactions to these mast cell-derived amines. Pretreatment of rats with compound 48/80 also suppressed the apparent anti-inflammatory actions of peptide 401 and of compound 48/80. 4. Injection of peptide 401 together with carrageenin increased the inflammatory response in the rat hind paw. 5. The anti-inflammatory activity of peptide 401 and of compound 48/80 in the carrageenin-induced swelling of the rat hind paw arises from mast cell degranulation in vivo.

Analytical methods for honeybee venom characterization

The discovery of new drugs has benefited significantly from the development of research in venomics, increasing our understanding of the envenomation processes. It has been previously reported that honeybee venom (HBV) exhibits several pharmacological activities such as anti-inflammatory, antibacterial, antimutagenic, radioprotective, and anticancer activity and may inclusively act as a complementary treatment for SARS-CoV-2. It composition consists mainly on melittin, phospholipase A2, and apamin but other constituents such as hyaluronidase, mast cell degranulating peptide and secapin are also relevant for its bioactivity. However, and because HBV is not officially recognized as a drug, until now, the international community did not establish quality standards for it. To uncover its exact composition, and boost the discovery of HBV-derived drugs, a significant number of techniques were developed. In this review, a relevant overview of the so far published analytical methods for HBV characterization is organized with the aim to accelerate its future standardization. The literature search was performed within PubMed, Google Scholar, and Science Direct by selecting specific documents and exploring HBV evaluation.

Mast cell degranulating (MCD) peptide: a prototypic peptide in allergy and inflammation

The solid phase synthesis of mast degranulating peptide (MCD peptide) raised the possibility of preparing analogs and examining the pharmacology and the proposed role of this peptide as a potential agent in allergy and inflammation. MCD peptide, a cationic 22-amino acid residue peptide with two disulfide bridges, causes mast cell degranulation and histamine release at low concentrations and has anti-inflammatory activity at higher concentrations. Because of these unique immunologic properties, MCD peptide may serve as a useful tool for studying secretory mechanisms of inflammatory cells such as mast cells, basophils, and leukocytes, leading to the design of compounds with therapeutic potential.