Ginger Is a Potential Therapeutic for Chronic Toxoplasmosis

Abstract

Background:Toxoplasma gondii (T. gondii) is an opportunistic parasite that causes serious diseases in humans, particularly immunocompromised individuals and pregnant women. To date, there are limited numbers of therapeutics for chronic toxoplasmosis which necessitate the discovery of effective and safe therapeutics. In the present study, we aimed to evaluate the antitoxoplasmosis potential of ginger extract in mice with experimentally induced chronic toxoplasmosis. Results: Treatment with ginger extract significantly reduced cysts count in the brains of T. gondii-infected mice with a marked alleviation of edema and inflammation, and a reversal of neuronal injury. Moreover, ginger extract treatment reduced inflammation in liver and lungs and protected hepatocytes from infection-induced degeneration. Consistently, apoptosis was significantly mitigated in the brains of ginger extract-treated mice compared to infected untreated animals or spiramycin-treated animals. Methods: Four groups of Swiss albino mice (10 mice each) were used. The first group was not infected, whereas 3 groups were infected with Me49 T. gondii strains. One infected group remained untreated (infected untreated), whereas the other two infected groups were treated with either ginger extract (250 mg/kg) or spiramycin (positive control; 100 mg/kg), respectively. The therapeutic potential of ginger extract was evaluated by calculation of the parasite burden in infected animals, and examination of the infected tissues for reduced pathologic changes. Conclusions: Our results showed for the first time that ginger extract exhibited marked therapeutic effects in mice with chronic T. gondii infection which indicates that it can be used as a safe and effective treatment for chronic toxoplasmosis.

Keywords: T. gondii; brain; cysts; ginger; liver; lung; toxoplasmosis; treatment.

Figure 1

Ginger extract treatment significantly reduced cysts count in brains of infected mice. Total number of cysts was counted in brain homogenates of infected untreated, sprimaycin-treated, and ginger extract-treated mice (5 mice/group). Data are expressed as means with error bars representing SD and were analyzed using ANOVA. Asterisk (*) indicates a significant difference in the numbers of cysts in treated groups compared to the infected untreated group (p = 0.001), and “ns” indicate insignificant difference.

Figure 2

Treatment with ginger extract reversed pathological changes in brains of T. gondii-infected mice. Sections of mice brains of different groups were stained with H & E and imaged at 100× and 400× magnification. (A) Representative image (100×) of brain tissue section of uninfected mice showing uniform brain tissue. (B) Higher magnification (400×) of (A) showing uniform normal neurons (black arrows) and glial tissue (red arrows). (C) Representative image (100×) of brain tissue section of infected untreated mice with clear T. gondii cyst (black arrow). (D) Higher magnification (400×) of (C) showing brain edema (black arrows) and chronic inflammatory cell infiltrate (arrowheads), and red neurons (red arrows). (E) Representative image (100×) of brain sections of spiramycin-treated mice. (F) Higher magnification (400×) of (E) illustrating uniform neurons (black arrows), mild edema (arrowheads), proliferating glial cells (red arrows), and a red neuron (blue arrow). (G) Representative image (100×) of brain tissue sections of infected ginger extract-treated mice showing degenerated cyst (black arrow). (H) Higher magnification (400×) of (G) clearly demonstrating uniform neurons (black arrows), absence of red neurons, significantly reduced edema (arrowheads), reduced inflammatory cellular infiltration (blue arrows), and marked proliferation of glial cells (red arrows).

Figure 3

Ginger extract treatment protected the liver of T. gondii-infected mice against infection- induced pathologies. (A) Representative image of liver tissue sections of uninfected mice stained with H&E showing normal hepatocytes and portal tract (black arrow). (B) Representative image of liver tissue sections of infected untreated mice with clear lobular inflammation (black arrow), vascular congestion (red arrows) and degeneration of hepatocytes (arrow heads). (C) Representative image of liver tissue sections of spiramycin-treated mice showing lytic necrosis (black arrow), inflammation (red arrow), and hydropic hepatocytes degeneration. (D) Representative image of liver tissue sections of ginger extract-treatment showing uniform preserved hepatocytes, mild lobular inflammation (black arrow), and no vascular congestion. All images were taken at 400× magnification.

Figure 4

Ginger-extract-treatment mitigated inflammation and reduced thickness of alveolar septa in lungs of T. gondii-infected mice. (A) Representative image of lung tissue sections of uninfected mice stained with H&E showing uniform alveolar tissue with normal alveolar septa (black arrows). (B) Representative image of lung tissue sections of T. gondii-infected untreated mice showing significant thickening of alveolar septa with significant inflammatory infiltrate (red arrows) and edema (black arrows). (C) Representative image of lung tissue sections of infected mice treated with spiramycin showing thickened alveolar septa and chronic inflammatory cells (black arrows). (D) Representative image of lung tissue sections of infected mice treated with ginger extract showing alveolar septa with reduced thickening and inflammation (black arrows). All images were taken at 400× magnification.

Figure 5

Treatment with ginger extract reduced caspase-3 levels in brain cells of T. gondii-infected mice. IHC representative images of brain tissue sections stained for caspase-3 showing low levels in uninfected mice (A), and higher levels in infected untreated mice (B). Treatment with spiramycin (C) or ginger extract (D) reduced neuronal caspase-3 levels compared to infected untreated mice. All images were taken at 400× magnification.

Figure 6

Treatment with ginger extract significantly reduced the number of caspase-3 positive cells in brains of T. gondii-infected mice. The mean number of caspase-3-positive cells/HPF in the brain tissue sections of each group of mice was calculated and compared. Asterisks (*) indicate a significant difference; p < 0.05.