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<p>Brain-gut disorder is a worldwide health problem that affects the quality of life in Parkinson’s disease (PD) patients. PD is well-documented to be associated with clinical symptoms of gastrointestinal dysfunction. However, there are limited effective preventive and therapeutic strategies for brain-gut disorders. We, therefore, investigated the gastroprotective mechanisms of methanol extract of <i>Zingiber officinale</i> (MEZO) following systemic exposure to rotenone (ROT) toxicity in mice in the current study. Male Swiss mice were grouped into five (<i>n</i> = 8): normal control (received DMSO and sunflower oil; <i>per os</i>), ROT control (injected with ROT 2.5&#xa0;mg/kg in DMSO-sunflower oil at alternate days to induce PD-associated gastrointestinal dysfunctions; <i>i.p</i>), MEZO (50 and 100&#xa0;mg/kg; <i>per os</i>), and LD-CD (10&#xa0;mg/kg; <i>per os</i>) for 28&#xa0;days. MEZO and LD-CD groups received ROT injection 30&#xa0;min prior to treatment. Serum dopamine and α-synuclein (α-syn) were measured. Ileal acetylcholinesterase (AChE) level, oxidative stress markers, inflammatory mediators, and histopathology were evaluated. MEZO treatment enhanced the ileal endogenous antioxidant enzymes (reduced glutathione, glutathione-s-transferase, and superoxide dismutase) by attenuating the redox imbalances after ROT exposure in a dose-dependent effect. Of MEZO treatment, 50&#xa0;mg/kg increased serum dopamine level and decreased ileal AChE level after ROT lesioning. MEZO (50 and 100&#xa0;mg/kg) treatment markedly suppressed serum α-synuclein aggregation and gastro-inflammatory mediators, associated with ROT lesioning. Ileal epithelial injury after ROT injection was associated with decreased ileal occludin expression and histoarchitectural alterations in the crypt and villi. Meanwhile, MEZO (50 and 100&#xa0;mg/kg) treatment improved the ileal occludin immunoreactivity and the histoarchitecture of the gut. Overall, our findings suggest that MEZO has a potential gastroprotective effect against ileal oxidative damage and inflammation as a characteristic non-motor gut dysfunction in PD.</p>

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Systemic exposure to rotenone toxicity induces gastro-inflammatory damage in mice: protective response of Zingiber officinale Roscoe extract

  • 期刊论文

  • 发表日期：

    2025年2月21日

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  • Olusegun G. Adebayo,
  • Emmanuel U. Modo,
  • Blessing Ogechukwu Orji,
  • Joseph Chimezie,
  • Iheanyichukwu Wopara,
  • Adebimpe V. Masanwoola,
  • Ichipi-Ifukor Patrick Chukwuyenum,
  • Benjamin Oritsemuelebi,
  • Iria Kelly Esezobor

摘要

Brain-gut disorder is a worldwide health problem that affects the quality of life in Parkinson’s disease (PD) patients. PD is well-documented to be associated with clinical symptoms of gastrointestinal dysfunction. However, there are limited effective preventive and therapeutic strategies for brain-gut disorders. We, therefore, investigated the gastroprotective mechanisms of methanol extract of Zingiber officinale (MEZO) following systemic exposure to rotenone (ROT) toxicity in mice in the current study. Male Swiss mice were grouped into five (n = 8): normal control (received DMSO and sunflower oil; per os), ROT control (injected with ROT 2.5 mg/kg in DMSO-sunflower oil at alternate days to induce PD-associated gastrointestinal dysfunctions; i.p), MEZO (50 and 100 mg/kg; per os), and LD-CD (10 mg/kg; per os) for 28 days. MEZO and LD-CD groups received ROT injection 30 min prior to treatment. Serum dopamine and α-synuclein (α-syn) were measured. Ileal acetylcholinesterase (AChE) level, oxidative stress markers, inflammatory mediators, and histopathology were evaluated. MEZO treatment enhanced the ileal endogenous antioxidant enzymes (reduced glutathione, glutathione-s-transferase, and superoxide dismutase) by attenuating the redox imbalances after ROT exposure in a dose-dependent effect. Of MEZO treatment, 50 mg/kg increased serum dopamine level and decreased ileal AChE level after ROT lesioning. MEZO (50 and 100 mg/kg) treatment markedly suppressed serum α-synuclein aggregation and gastro-inflammatory mediators, associated with ROT lesioning. Ileal epithelial injury after ROT injection was associated with decreased ileal occludin expression and histoarchitectural alterations in the crypt and villi. Meanwhile, MEZO (50 and 100 mg/kg) treatment improved the ileal occludin immunoreactivity and the histoarchitecture of the gut. Overall, our findings suggest that MEZO has a potential gastroprotective effect against ileal oxidative damage and inflammation as a characteristic non-motor gut dysfunction in PD.