Abstract
Many studies have comprehensively examined the venom of Ophiophagus hannah snake. Its venom comprises different compounds exhibiting a wide range of pharmacological activities. In this investigation, four peptide fractions (PFs), ranging from 3 kDa to 10 kDa, isolated from the Vietnamese snake venom of O. hannah were separated by HPLC and investigated for their inhibitory activity on adipogenesis in 3T3-L1 adipocytes. The most effective PF was then further purified, generating two peptides, pOh1 and pOh2. Upon investigation of these two peptides on 3T3-L1 adipocytes, it was revealed that, at 10 μg/mL, pOh2 was able to inhibit the lipid accumulation in 3T3-L1 adipocytes by up to 56%, without affecting cell viability. Furthermore, the pOh2 downregulated the gene expression of important transcription factors C/EBP-α and PPAR-γ. In addition, aP2 and GPDH adipocyte-specific markers were also significantly reduced compared to untreated differentiated cells. Taken together, pOh2 inhibited the expression of key transcription factors C/EBP-α and PPAR-γ and their target genes, aP2 and GPDH, thereby blocking the adipocyte differentiation. In conclusion, this novel class of peptide might have potential for in vivo antiobesity effects.
Highlights
Snakes have a long evolutionary history, and their venoms have evolved to allow them to incapacitate, paralyze, and kill their prey
Data of venom gland transcriptome of Malaysian O. hannah represent 23 protein families related to venom toxic functions, which were dominated by three finger toxins (3FTxs) (84.9%), followed by snake venom metalloproteases (SVMPs, 3.7%), phospholipases A2 (PLA2s, 2.2%), cysteine-rich secretory proteins (CRISPs, 2.1%), Kunitz-type proteinase inhibitors (KUNs, 1.8%), L-amino acid oxidases (LAAOs, 1.5%), and many others that are expressed in less than 1% of abundance [2] in which hyaluronidase, DPPIV, and 5-nucleotidase were not previously reported in the venom gland transcriptome of a Balinese O. hannah [3]
Various compounds from the venom of O. hannah have previously been isolated and characterized, including neurotoxins [4], L-amino acid oxidases [5], metalloproteinases [6], 3FTxs [7], phospholipases A2 (PLA2s) [8, 9], ohanin [10], Kunitz-type protease inhibitors [11], and factor X activator [12]
Summary
Snakes have a long evolutionary history, and their venoms have evolved to allow them to incapacitate, paralyze, and kill their prey. Various compounds from the venom of O. hannah have previously been isolated and characterized, including neurotoxins [4], L-amino acid oxidases [5], metalloproteinases [6], 3FTxs [7], phospholipases A2 (PLA2s) [8, 9], ohanin [10], Kunitz-type protease inhibitors [11], and factor X activator [12]. These compounds, exerting remarkable biological properties, are usually secreted with an aim to reach specific targets including receptors, membranes, and enzymes within the inflicted organism. These toxins make excellent probes for novel pharmacological tools or therapeutic drugs
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