Tannic acid inhibits lipopolysaccharide-induced cognitive impairment in adult mice by targeting multiple pathological
Rahim Ullah1, Gowhar Ali2, Abdul Baseer3
1Department of Pharmacy, Faculty of Life Sciences, Sarhad University of Science and Information Technology, Peshawar, Pakistan; Department of Pharmacy, University of Peshawar, Peshawar 25120, Pakistan.
Abstract:
Tannic acid (TA) is a natural compound present abundantly in fruit such as grapes and green tea. In this study, we have evaluated the therapeutic efficacy of TA against Lipopolysaccharide (LPS)-induced oxidative stress-mediated memory impairment, neuroinflammation, insulin signaling impairment, and Amyloid Beta (Aβ) deposition in adult male mice. The LPS was administered once per week and TA twice a week to adult male mice for three months consecutively. Behavioral studies were performed using different behavioral models such as balance beam, novel object recognition (NOR), Morris water maze (MWM), and Y-maze tests. The protein expression of different mediators such as TNF-α, p-JNK, pIRS636, BACE1, APP, and Aβ was evaluated through western blot and immunofluorescence staining techniques. Biochemical assays were carried out to assess the antioxidant activities of TA. The computational study was conducted to predict the binding mode of TA with target sites of TNF-α. Behavioral studies showed that the TA-treated mice exhibited gradual memory improvement. TA significantly inhibited BACE1 activity and reduced production and accumulation of Aβ in the hippocampus of mice brains. Moreover, the TA significantly inhibited LPS-induced ROS production and enhanced the glutathione levels. Furthermore, we have shown via the computational method for the first time that TA inhibits LPS-triggered TNF-ὰ and its downstream signaling to reduce AD pathology including memory impairment, neuroinflammation, insulin signaling impairment, and Aβ deposition in adult mice. Taken together our current study demonstrates that TA is a potential candidate for the abrogation of LPS-induced neurotoxicity and AD pathology in rodent's models.
Insights
Tannic acid (TA) effectively combats memory loss, neuroinflammation, and amyloid-beta (Aβ) buildup in mice. This natural compound shows promise for treating Alzheimer
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Lipopolysaccharide (LPS) induces oxidative stress, leading to memory impairment, neuroinflammation, insulin resistance, and amyloid-beta (Aβ) deposition.
- Natural compounds are being investigated for therapeutic potential against neurodegenerative diseases.
Purpose of the Study:
- To evaluate the therapeutic efficacy of tannic acid (TA) against LPS-induced neurotoxicity and Alzheimer's disease (AD) pathology in adult male mice.
- To investigate TA's effects on memory, neuroinflammation, insulin signaling, and Aβ deposition.
Main Methods:
- Mice were treated with LPS and TA for three months.
- Behavioral tests (balance beam, NOR, MWM, Y-maze) assessed memory function.
- Western blot, immunofluorescence, and biochemical assays evaluated protein expression, antioxidant activity, and Aβ levels. Computational studies predicted TA's binding to TNF-α.
Main Results:
- TA treatment improved memory in mice.
- TA significantly inhibited BACE1 activity, reducing Aβ production and accumulation in the hippocampus.
- TA reduced reactive oxygen species (ROS) and increased glutathione levels, indicating antioxidant effects. TA also inhibited LPS-induced TNF-α signaling.
Conclusions:
- Tannic acid demonstrates significant therapeutic efficacy against LPS-induced neurotoxicity and AD pathology in a rodent model.
- TA mitigates memory impairment, neuroinflammation, insulin signaling deficits, and Aβ deposition.
- TA is a potential therapeutic candidate for neurodegenerative conditions like Alzheimer's disease.
