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    Home > Food News > Nutrition News > Antibiotic-Dietary Supplement Combination Improves Cognitive Ability in Mouse Model of Dementia

    Antibiotic-Dietary Supplement Combination Improves Cognitive Ability in Mouse Model of Dementia

    • Last Update: 2022-01-09
    • Source: Internet
    • Author: User
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    Research by scientists from the Graduate School of Medicine at Osaka City University has shown that combining the generic antibiotic rifampicin with the dietary supplement resveratrol, intranasal administration may prevent neurodegenerative diseases (such as Alzheimer's disease) A feasible method
    .
    Their latest report shows that in a five-day course of treatment, the combined drug improved the cognitive function of four different mouse models of neurodegenerative dementia and inhibited the accumulation of oligomers in the brain, including Alzheimer’s.
    Zheimer's disease

    .

    Research leader Dr.
    Takami Tomiyama and his colleagues published their research results in "Frontiers in Neuroscience".
    Mouse preclinical research

    .
    Their conclusion is: "Our discovery provides a feasible way to prevent neurodegenerative dementia by targeting toxic oligomers

    .
    "

    Neurodegenerative dementias include Alzheimer's disease (AD), frontotemporal dementia (FTD) and dementia with Lewy bodies (DLB)
    .
    The author explains that when Parkinson's disease spreads to the cerebral cortex of the brain, it can also cause dementia

    .
    These diseases are characterized by the accumulation of disease-specific amyloid in the brain: A? and tau in AD, tau or TDP-43 in FTD, α-synuclein in DLB and PD," the team continued

    .
    These The protein tends to self-aggregate to form characteristic A? plaques, neurofibrillary tangles with high phosphorylation of tau, and Lewy bodies with phosphorylation of α-synuclein, which can be used for the differential diagnosis of neurodegenerative diseases

    .
    However, the researchers pointed out "There is growing evidence that the real cause of this disease is smaller soluble protein oligomers

    .
    "

    Despite the "active efforts" made by researchers and pharmaceutical companies, there is no effective treatment for neurodegenerative dementia
    .
    "Many drug candidates have been developed, but most of them have failed to show a beneficial effect on patient cognition in clinical trials

    .
    " The author believes that this failure may be due to two main reasons: the late drug treatment.
    And the wrong drug target

    .
    They said: "Treatment should begin before neurodegeneration begins, and the target of the drug should be set on the toxic oligomer

    .
    "

    The newly reported study builds on the team’s previous experiments on mice.
    The experiment found that the imitation antibiotic rifampicin removed oligomers from the brain and improved cognitive function

    .
    "We have previously demonstrated that a well-known antibiotic, rifampicin, inhibits a?, tau, and alpha-nucleoprotein in vitro, and acts as a specific pathological amyloidogenic protein rather than a physiologically assembled protein

    .
    These results indicate that rifampicin is an
    amyloidogenic protein .
    This kind of promising oligomer-targeting medicine and management can prevent early neurodegenerative dementia before neurodegenerative dementia," the scientists said

    .

    However, oral rifampicin is associated with side effects such as liver damage and drug-drug interactions
    .
    These adverse events are believed to occur during the first pass of rifampicin from the intestine to the liver

    .
    In order to avoid this approach, the researchers looked for another alternative route, the intranasal delivery route of rifampicin, which reduces the amount of drug delivered to the liver, but can effectively deliver the drug through the nasal mucosal epithelium.
    To the brain

    .

    The team also wants to identify potential compounds that may help ensure the long-term safety of rifampicin for nasal use
    .
    They explained: "We have studied the literature on compounds with hepatoprotective effects that are contrary to rifampicin, and if possible, we have also studied other clinical effects that rifampicin does not show

    .
    " "Therefore, we chose trans white quinoa Retrol as a candidate ingredient

    .
    "

    Resveratrol is a natural antioxidant in plants and is widely used as a dietary supplement
    .
    Studies have also shown that the compound has anti-inflammatory, anti-diabetic, anti-cancer and neuroprotective effects, and shows that its activity may neutralize the liver toxicity and drug-drug interactions of rifampicin, the author pointed out

    .
    As Toyama said, "In order to combat the negative side effects of the existing drug rifampicin, we are considering combining it with the liver protective effect of resveratrol

    .
    "

    In their latest report, the research team used a fixed dose of rifampicin and resveratrol intranasally injected 5 days a week for 4 weeks to give patients with Alzheimer’s disease, frontotemporal dementia and Lewy small A mouse model of physical dementia
    .
    The results showed that the combination medication improved cognitive function and brain pathology

    .
    The combination therapy suppressed the accumulation of oligomers and restored the levels of synaptophysin-a presynaptic protein that promotes synapses

    .
    "Compared with the use of rifampicin and resveratrol alone, the combined medication significantly improved the cognitive ability of mice, reduced the accumulation of amyloid oligomers, and restored the level of synaptophysin in the hippocampus

    .
    .
    .
    .
    This combination showed a synergistic effect in improving the cognitive ability of mice," the researchers pointed out

    .

    The combination of the generic drug rifampicin and the dietary supplement resveratrol, as well as the use of nasal sprays in the nose, can prevent dementia more safely and effectively
    .

    In addition, an increase in the expression level of brain-derived neurotrophic factor (BDNF) was observed in the hippocampus, which was not observed with rifampicin alone
    .
    "BDNF plays an important role in synapse formation and memory function," the scientists said

    .
    In addition, after taking a fixed dose of compound rifampicin, the liver enzyme levels of the mice remained normal

    .
    These results indicate that the fixed-dose combination is superior to rifampicin alone in terms of safety and effectiveness

    .

    According to the team’s previous research experience, nasal administration of a fixed-dose combination of rifampicin and resveratrol can increase the transfer of the drug to the brain, further improving safety and medicinal effects
    .
    The dose used in this study is 0.
    02 mg rifampicin per mouse per day, or assuming a mouse body weight of 20 g, 1 mg/kg per day

    .
    Professor Toyama said: "Converting the adult body dose based on the human body surface area, it is 0.
    081 mg/kg/day

    .
    Currently, as an antibiotic, the prescribed dose of rifampicin is 10 mg/kg/day.
    Compared with this, we confirmed that, A lower dose is also effective

    .
    "

    Encouragingly, both drugs are cheap
    .
    The research team pointed out: "Rifampicin is now a cheap generic drug, and resveratrol is also very cheap

    .
    " "Therefore, combination drugs can be provided at low cost

    .
    "

    “The number of people with dementia around the world has been increasing, and some sources predict that the number of people with dementia will double every 20 years
    .
    However, there is still no effective treatment for this disease,” the study’s first author , Distinguished lecturer Dr.
    Tomohiro Umeda said

    .
    "Recent studies have shown that the brains of patients with dementia begin to show abnormalities more than 20 years before the onset of disease

    .
    " By studying the new therapeutic purposes of existing drugs in the process of drug repositioning, the research team hopes to diagnose and prevent neurons before they start to die.
    Dementia

    .
    "

    The author admits that further research is needed to determine the appropriate ratio of the two drugs, while conducting pharmacokinetic and general toxicity studies
    .
    Nonetheless, they pointed out, ".
    .
    .
    Rifampicin and resveratrol are widely used, respectively, and are well-known drugs and dietary supplements.
    We believe that the development of combination drugs should not be too challenging.
    It is worth renewing their drugs.
    Positioning

    .
    "

    Medilabo RFP is currently developing a fixed-dose combination of rifampicin and resveratrol nasal spray
    .
    Medilabo RFP is a venture company in the research team's laboratory

    .
    The company is preparing for global clinical trials

    .
    With the support of the Japan External Trade Organization (JETRO), Medilabo RFP established a US subsidiary in Massachusetts in November 2021

    .

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