Melittin, a Potential Natural Toxin of Crude Bee Venom: Probable Future Arsenal in the Treatment of Diabetes Mellitus

Abstract

Since diabetes mellitus (DM) is one of the most common and serious endocrine metabolic disorders, it is important to elucidate novel antidiabetic therapeutic agents from various sources, including natural products. Bee venom (BV) is a complex mixture of proteins, peptides, and low molecular components, and melittin is the main constituent. Melittin is a peptide consisting of 26 amino acids with the sequence GIGAVLKVLTTGLPALISWIKRKRQQ. It has several important biological effects and has a relatively low toxicity. Recent studies using animal models have confirmed that melittin has significant glucose and lipid lowering activities by acting on several mechanistic pathways. The main antidiabetic activity of melittin is increasing insulin secretion via depolarization of pancreatic -cells. Other possible mechanisms may involve stimulation of phospholipase A 2 , increase of glucose uptake, improving lipid profile, and/or reduction of inflammation. This review summarizes the various sources, proteomics, biological roles, adverse effects, and medical applications of melittin and its mechanism of action in combating DM.

Antidiabetic effect of the Egyptian honey bee (Apis mellifera) venom in alloxan-induced diabetic rats

“…Hyperglycemia, hyperlipidemia, hypertension, atherosclerosis, retinopathy, neuropathy, and nephropathy are the major complications of DM (Anfenan, 2014). Due to the undesirable secondary effects of the currently used hypoglycemic medications, there is a need to find another safer antidiabetic traditional medicine (Hossen et al, 2017). Experimentally, Alloxan induced tremendous damage to pancreatic β-cells by generating ROS leading to the induction of diabetes in animals (Rohilla & Ali, 2012).…”

“…Insulin is not the only treatment of DM; there were many known oral medications that help to lower elevated blood glucose levels such as glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase 4 inhibitors (Thakare, Shende, Shirure, & Swami, 2017). Mostly, these drugs have adverse unwanted effects which necessitate the need for new modalities like natural products to replace those (Hossen, Gan, & Khalil, 2017). Great attention has been paid lately to the venomous products of some animals in the development of treatments for many diseases; one of them is DM (Roudbari & Imani, 2012).…”

Design of a Helical-Stabilized, Cyclic, and Nontoxic Analogue of the Peptide Cm-p5 with Improved Antifungal Activity

“…Notably, most AMPs are very hemolytic and toxic to mammalian cells (mellitin, 8 guavanin 2, 9 etc. ), avoiding their use orally; therefore, only topical formulation is possible in the majority of cases (commercial triple antibiotics).…”

An overview of the bioactive compounds, therapeutic properties and toxic effects of apitoxin

“…In the last decade, as result of increasing investigation worldwide, the usefulness of BV has been reported for several diseases and pathologic contexts (Table 2), in studies performed in vitro and in vivo, in animal models or enrolling humans. Among other settings, the effects of BV were demonstrated in multiple sclerosis and Parkinson's disease (Ostrovsky and Ehrlich, 2018), dementia (Silva et al, 2015), atherosclerosis (Lee and Bae, 2016), osteoarthritis (Lee et al, 2012), human immunodeficiency virus (HIV) (Jallouk et al, 2014), periodontitis (Gu et al, 2019), Diabetes mellitus (Hossen et al, 2017) and rheumatoid arthritis (Son et al, 2007;Brito et al, 2018). The effects of BV and its isolated bioactive compounds have also been described in several types of solid cancer like breast, ovarian, bladder, lung, liver and prostate, as well as on hematologic malignancies (Moga et al, 2018).…”

“…This natural product is a light-yellow liquid, characterized by a bitter taste, pungent smell and a pH ranging from 4.5 to 5.5 (Eze et al, 2016;Hossen et al, 2017). Some studies have described that 88% of BV is water, yet its specific composition varies depending on bee' species and season (Moreno and Giralt, 2015).…”