Therapeutic effects of a lipid transfer protein isolated from Morinda citrifolia L. (noni) seeds on irinotecan-induced intestinal mucositis in mice

Abstract

This work aimed to evaluate the activity of a lipid transfer protein isolated from Morinda citrifolia L. seeds, McLTP 1 , on the development of intestinal mucositis following irinotecan administration. McLTP 1 (0.5, 2 and 8 mg/kg, i.v.) was injected into mice 1h before irinotecan administration (75 mg/kg, i.p.; 4 days), and then for additional 6 days. Seven days after the rst dose of irinotecan, diarrhea was assessed and the intestine was removed for histological evaluation, assessment of intestinal over-contractility, measurement of myeloperoxidase (MPO), glutathione (GSH), malondialdehyde (MDA), proin ammatory cytokines and chemokine (IL-1, IL-6, and KC levels -a murine homolog of human IL-8 chemokine), analysis of cyclooxygenase 2 (COX-2), nuclear factor kappa B (NF-κB) and nitric oxide synthase (iNOS) expression. At the two highest doses, McLTP 1 administration decreased mortality and diarrhea. McLTP 1 (8 mg/kg, i.v.) signi cantly prevented irinotecan-induced intestinal damage and led to a reduction in overcontractility of the intestinal muscle (p < 0.05). Moreover, McLTP 1 decreased the MPO, IL-1β, IL-6, and KC levels signi cantly by 74.7%, 42%, 92.9%, and 95.9%, respectively. Also, the expression of COX-2, NF-κB, and iNOS was reduced. Pretreatment with McLTP 1 (8mg/kg; i.v.) signi cantly reduced the MDA level and increased the duodenum homogenates' GSH level. Our study provides a potential new therapeutic for preventing irinotecan-induced mucositis, improved clinical parameters, reduced in ammation, and oxidative damage.

Uroprotective effect of a protein isolated from seed ofMorinda citrifolia(McLTP1) on hemorrhagic cystitis induced by ifosfamide in mice

“…Ifosfamide increased tissue MPO levels, which were significantly reduced after treatment with McLTP1 at doses of 10 and 20 mg/kg. Our findings are in line with previous studies, in which McLTP1 (8mg/kg) reduced MPO activity in the duodenum of mice subjected to intestinal mucositis by irinotecan [42]. In fact, previous research with other models of inflammation has already shown that polysaccharides from Morinda citrifolia are able to attenuate classic signs of inflammation such as edema in a model of experimental colitis induced by acetic acid [46].…”

“…Previous studies with McLTP1 described in the literature already show its anti-inflammatory and antioxidant activity in different preclinical models of nociception, intestinal mucositis by irinotecan, antimicrobial and protective activity on sepsis, nephro and gastroprotective. Therefore, the protein was considered a potential uroprotector to be investigated [42][43][44][45].…”

McLTP1, a lipid transfer protein isolated from noni seeds induces effective healing of superficial burns

“…Aiming to verify results of histologic analysis, the inflammatory profile of burn wounds and treatments with silver sulfadiazine and McLTP1 was evaluated. MPO activity, a marker of neutrophil presence, was increased after 3 days of burn, in according with other protocols 31 . Indeed, neutrophils are the more abundant cells after 48 hours of burns 43 .…”

“…McLTP1 is a lipid transfer protein isolated from Noni seeds that has been demonstrating anti-inflammatory, antinociceptive and antioxidant effects 29,30,31,32 . Recently, this protein showed an in vitro antibacterial effect in Sthaphylococcus aureus and Staphylococcus epidermidis 33 , predominant bacteria in secondary skin infections 34,35 .…”