Protective effect of epigallocatechin-3-gallate (EGCG) on toxic metalloproteinases-mediated skin damage induced by Scyphozoan jellyfish envenomation

Abstract

Jellyfish stingings are currently raising serious public health concerns around the world. Hence, the search for an effective first aid reagent for the envenomation has been the goal of many investigators in the field. There have been a few previous reports of in vivo as well as in vivo studies suggesting the metalloproteinase activity of scyphozoan jellyfish venom, such as N. nomurai venom (NnV), plays a major role in the pathogenesis. These results have inspired us to develop a metalloproteinase inhibitor as a candidate for the treatment of Scyphozoan jellyfish envenomation. It has been previously demonstrated that the major polyphenol component in green tea, epigallocatechin-3-gallate (EGCG), can inhibit metalloproteinase activity of snake venoms. In fact, plant polyphenols as potential therapeutics have been shown to exert positive effects on neutralizing snake venoms and toxins. In the present study, we found that EGCG significantly inhibits the toxic proteases of NnV in a concentration-dependent manner. Human keratinocyte (HaCaT) and Human dermal fibroblast (HDF) cell culture studies showed that EGCG treatment can protect the cells from NnV-induced cytotoxicity which has been accompanied by the down-regulation of human matrix metalloproteinase (MMP)-2 and -9. Simulated rat NnV envenomation study disclosed that topical treatments with EGCG considerably ameliorated the progression of the dermonecrotic lesions caused by NnV. EGCG also reduced the activitions of tissue MMP-2 and MMP-9, which seem to be crucial players in the dermal toxic responses induced by NnV. Therefore, we propose that EGCG might be an effective therapeutic agent for the treatment of cutaneoous jellyfish symptoms.

Epigallocatechin‐3‐gallate induces autophagy‐related apoptosis associated with LC3B II and Beclin expression of bladder cancer cells

“…EGCG was a well‐known anti‐tumor ingredient which was extracted from green tea (Hwang et al, 2020). Besides, the mechanisms of the anti‐tumor effects (Wei et al, 2020; Zhang et al, 2020), induction of autophagy‐related apoptosis for example (Chen et al, 2020), were well‐studied in many cancers (Kumazoe et al, 2020; Naujokat & McKee, 2020), including bladder cancer (Dettlaff et al, 2017).…”

Proteomic Changes during the Dermal Toxicity Induced by Nemopilema nomurai Jellyfish Venom in HaCaT Human Keratinocyte

“…Jellyfish envenomation can induce local consequences such as erythematous eruption, flaring sensations, edema, and necrosis and generate critical systematic symptoms including cardiovascular discomfort, respiratory impairment and hypovolemic attack [ 2 , 3 , 4 , 5 ]. From our prior findings, we have found that most of the scyphozoan jellyfish venoms are rich in metalloproteinase ingredients, which have a vital role in the pathogenesis of damaged skin tissue in an in vivo model [ 23 , 24 ]. The jellyfish Nemopilema nomurai induce life-threatening effects in human beings and cause many deleterious effects [ 2 ].…”

“…PLTX exposure resulted in severe dermatological distress during Ostreopsis blooms; hence PLTX triggers the cytotoxic effects in vitro [ 22 ]. Our former investigation has shown that the metalloproteinase present in the scyphozoan jellyfish venom predominately mediates dermal toxicity [ 23 , 24 ]. However, the mechanism of dermal toxicity involving NnV effects remain unexplored.…”

Pharmacoinformatic Investigation of Silymarin as a Potential Inhibitor against Nemopilema nomurai Jellyfish Metalloproteinase Toxin-like Protein

“…For example, gallocatechin, isoquercitrin, pinostrobin, and quercetin-3-O-rhamnoside extracted from different plant species have been shown to inhibit the hemorrhagic activity of viperid and elapid venoms, as well as some isolated SVMPs [25][26][27][28]. Likewise, EGCG (belongs to the classes of flavonoids) inhibiting Nemopilema nomurai venom metalloproteinases (NnV-MPs) has been demonstrated [29]. The phenolic nuclei of flavonoids possess the ability to interact with proteins through mechanisms such as hydrogen bonding, hydrophobic interactions, metal chelation, and π-π stacking [30].…”