Journal Articles

Permanent URI for this collectionhttps://mro.massey.ac.nz/handle/10179/7915

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Author: search.filters.author.Singh HSubject: search.filters.subject.inflammation

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    The Leptospermum scoparium (Mānuka)-Specific Nectar and Honey Compound 3,6,7-Trimethyllumazine (LepteridineTM) That Inhibits Matrix Metalloproteinase 9 (MMP-9) Activity
    (MDPI (Basel, Switzerland), 2023-11-09) Lin B; Nair S; Fellner DMJ; Nasef NA; Singh H; Negron L; Goldstone DC; Brimble MA; Gerrard JA; Domigan L; Evans JC; Stephens JM; Merry TL; Loomes KM
    3,6,7-trimethyllumazine (Lepteridine™) is a newly discovered natural pteridine derivative unique to Mānuka (Leptospermum scoparium) nectar and honey, with no previously reported biological activity. Pteridine derivative-based medicines, such as methotrexate, are used to treat auto-immune and inflammatory diseases, and Mānuka honey reportedly possesses anti-inflammatory properties and is used topically as a wound dressing. MMP-9 is a potential candidate protein target as it is upregulated in recalcitrant wounds and intestinal inflammation. Using gelatin zymography, 40 μg/mL LepteridineTM inhibited the gelatinase activities of both pro- (22%, p < 0.0001) and activated (59%, p < 0.01) MMP-9 forms. By comparison, LepteridineTM exerted modest (~10%) inhibition against a chromogenic peptide substrate and no effect against a fluorogenic peptide substrate. These findings suggest that LepteridineTM may not interact within the catalytic domain of MMP-9 and exerts a negligible effect on the active site hydrolysis of small soluble peptide substrates. Instead, the findings implicate fibronectin II domain interactions by LepteridineTM which impair gelatinase activity, possibly through perturbed tethering of MMP-9 to the gelatin matrix. Molecular modelling analyses were equivocal over interactions at the S1' pocket versus the fibronectin II domain, while molecular dynamic calculations indicated rapid exchange kinetics. No significant degradation of synthetic or natural LepteridineTM in Mānuka honey occurred during simulated gastrointestinal digestion. MMP-9 regulates skin and gastrointestinal inflammatory responses and extracellular matrix remodelling. These results potentially implicate LepteridineTM bioactivity in Mānuka honey's reported beneficial effects on wound healing via topical application and anti-inflammatory actions in gastrointestinal disorder models via oral consumption.
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    Bioactive Yoghurt Containing Curcumin and Chlorogenic Acid Reduces Inflammation in Postmenopausal Women
    (MDPI (Basel, Switzerland), 2022-11-02) Ahmed Nasef N; Thota RN; Mutukumira AN; Rutherfurd-Markwick K; Dickens M; Gopal P; Singh H; Garg ML; Bordoni A
    Menopause is marked by a gradual and permanent decrease of estrogen from the ovaries, leading to metabolic and physiological changes in the body. Combined with increased body mass index, postmenopausal women have elevated systemic inflammation and metabolic disturbances leading to increased risk of developing chronic diseases. A bioactive coconut yoghurt containing curcumin and chlorogenic acid was developed with the potential to target inflammatory processes. In this randomized crossover study, healthy postmenopausal women with a BMI of 25-40 were recruited to consume 125 g of either the bioactive or placebo yoghurt. Blood samples were collected at baseline, 30 min, and 1, 2, 3 and 4 h postprandially. Plasma inflammatory markers (TNFα and IL6) and metabolic markers (triglycerides, insulin and glucose) were measured. Participants had significantly lower plasma TNFα Cmax after consumption of the bioactive yoghurt compared to placebo (mean difference = 0.3 pg/mL; p = 0.04). Additionally, plasma TNFα was significantly lower postprandially compared to baseline after consumption of the bioactive yogurt but not the placebo. No differences were observed in the metabolic markers measured. Conclusions: The bioactive yoghurt fortified with curcumin and chlorogenic acid has the potential to reduce inflammatory mediators; however, a larger and longer-term study is required to confirm these findings.