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The combination of luteolin and l-theanine improved Alzheimer disease-like symptoms by potentiating hippocampal insulin signaling and decreasing neuroinflammation and norepinephrine degradation in amyloid-β-infused rats.
Nutr Res 2018; 60:116-131NR

Abstract

Luteolin and l-theanine have anti-inflammatory, antioxidant, and possible antidiabetic activities, and they may synergistically protect against dementia. Here, we hypothesized that a combination of luteolin and l-theanine would synergistically act to improve memory function and glucose disturbances in rats infused with amyloid-β, and the mechanisms underlying these actions were investigated. Rats that received an amyloid-β(25-35) infusion into the CA1 region of the hippocampus were fed dextrin (AD-CON), 0.1% luteolin (AD-Lut), 0.2% l-theanine (AD-Thea), or both 0.05% luteolin and 0.1% l-theanine (AD-LuTh) in conjunction with a high-fat diet over 8 weeks. AD-LuTh improved memory function, as determined by water maze and passive avoidance tests, by potentiating the hippocampal insulin signaling and reducing inflammation: Luteolin mainly potentiated insulin signaling via the pAkt➔pGSK➔pTau pathway, and l-theanine primarily reduced tumor necrosis factor-α. In the metabolomics analysis of the hippocampus lysates, the concentration of proline, phenylpyruvic acid, and normetanephrine decreased in the AD-LuTh compared to AD-CON. Norepinephrine contents were lower in the AD-CON than non-AD rats with a high fat diet with 0.2% dextrin, whereas AD-Thea and AD-LuTh inhibited the decrease. Both the AD-Lut and AD-LuTh increased glucose infusion rates and decreased hepatic glucose output under basal and hyperinsulinemic conditions, indicating improved whole-body and hepatic insulin sensitivity. Disturbances in glucose-stimulated insulin secretion during hyperglycemic clamp were most effectively corrected by the AD-Lut and AD-LuTh treatments. In conclusion, the hypothesis of the study was accepted. The combination of luteolin and l-theanine prevented Alzheimer disease-like symptom, possibly by improving hippocampal insulin signaling, norepinephrine metabolisms, and decreasing neuroinflammation. The combination of luteolin and l-theanine may be a useful therapeutic option for preventing and/or delaying the progression of memory dysfunction.

Authors+Show Affiliations

Department of Food & Nutrition, Obesity/Diabetes Center, Hoseo University, 165 Sechul-Ri, BaeBang-Yup, Asan, 336-795, Republic of Korea. Electronic address: smpark@hoseo.edu.Department of Food & Nutrition, Obesity/Diabetes Center, Hoseo University, 165 Sechul-Ri, BaeBang-Yup, Asan, 336-795, Republic of Korea.Department of Food & Nutrition, Obesity/Diabetes Center, Hoseo University, 165 Sechul-Ri, BaeBang-Yup, Asan, 336-795, Republic of Korea.Department of Food Science & Technology, and Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 52828, Republic of Korea.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30527255

Citation

Park, Sunmin, et al. "The Combination of Luteolin and L-theanine Improved Alzheimer Disease-like Symptoms By Potentiating Hippocampal Insulin Signaling and Decreasing Neuroinflammation and Norepinephrine Degradation in Amyloid-β-infused Rats." Nutrition Research (New York, N.Y.), vol. 60, 2018, pp. 116-131.
Park S, Kim DS, Kang S, et al. The combination of luteolin and l-theanine improved Alzheimer disease-like symptoms by potentiating hippocampal insulin signaling and decreasing neuroinflammation and norepinephrine degradation in amyloid-β-infused rats. Nutr Res. 2018;60:116-131.
Park, S., Kim, D. S., Kang, S., & Kim, H. J. (2018). The combination of luteolin and l-theanine improved Alzheimer disease-like symptoms by potentiating hippocampal insulin signaling and decreasing neuroinflammation and norepinephrine degradation in amyloid-β-infused rats. Nutrition Research (New York, N.Y.), 60, pp. 116-131. doi:10.1016/j.nutres.2018.09.010.
Park S, et al. The Combination of Luteolin and L-theanine Improved Alzheimer Disease-like Symptoms By Potentiating Hippocampal Insulin Signaling and Decreasing Neuroinflammation and Norepinephrine Degradation in Amyloid-β-infused Rats. Nutr Res. 2018;60:116-131. PubMed PMID: 30527255.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The combination of luteolin and l-theanine improved Alzheimer disease-like symptoms by potentiating hippocampal insulin signaling and decreasing neuroinflammation and norepinephrine degradation in amyloid-β-infused rats. AU - Park,Sunmin, AU - Kim,Da Sol, AU - Kang,Suna, AU - Kim,Hyun Jin, Y1 - 2018/10/02/ PY - 2018/04/01/received PY - 2018/08/10/revised PY - 2018/09/27/accepted PY - 2018/12/12/entrez PY - 2018/12/12/pubmed PY - 2018/12/12/medline KW - Hippocampus KW - Insulin signaling KW - Memory deficit KW - Metabolomics KW - Norepinephrine SP - 116 EP - 131 JF - Nutrition research (New York, N.Y.) JO - Nutr Res VL - 60 N2 - Luteolin and l-theanine have anti-inflammatory, antioxidant, and possible antidiabetic activities, and they may synergistically protect against dementia. Here, we hypothesized that a combination of luteolin and l-theanine would synergistically act to improve memory function and glucose disturbances in rats infused with amyloid-β, and the mechanisms underlying these actions were investigated. Rats that received an amyloid-β(25-35) infusion into the CA1 region of the hippocampus were fed dextrin (AD-CON), 0.1% luteolin (AD-Lut), 0.2% l-theanine (AD-Thea), or both 0.05% luteolin and 0.1% l-theanine (AD-LuTh) in conjunction with a high-fat diet over 8 weeks. AD-LuTh improved memory function, as determined by water maze and passive avoidance tests, by potentiating the hippocampal insulin signaling and reducing inflammation: Luteolin mainly potentiated insulin signaling via the pAkt➔pGSK➔pTau pathway, and l-theanine primarily reduced tumor necrosis factor-α. In the metabolomics analysis of the hippocampus lysates, the concentration of proline, phenylpyruvic acid, and normetanephrine decreased in the AD-LuTh compared to AD-CON. Norepinephrine contents were lower in the AD-CON than non-AD rats with a high fat diet with 0.2% dextrin, whereas AD-Thea and AD-LuTh inhibited the decrease. Both the AD-Lut and AD-LuTh increased glucose infusion rates and decreased hepatic glucose output under basal and hyperinsulinemic conditions, indicating improved whole-body and hepatic insulin sensitivity. Disturbances in glucose-stimulated insulin secretion during hyperglycemic clamp were most effectively corrected by the AD-Lut and AD-LuTh treatments. In conclusion, the hypothesis of the study was accepted. The combination of luteolin and l-theanine prevented Alzheimer disease-like symptom, possibly by improving hippocampal insulin signaling, norepinephrine metabolisms, and decreasing neuroinflammation. The combination of luteolin and l-theanine may be a useful therapeutic option for preventing and/or delaying the progression of memory dysfunction. SN - 1879-0739 UR - https://www.unboundmedicine.com/medline/citation/30527255/The_combination_of_luteolin_and_l-theanine_improved_Alzheimer_disease-like_symptoms_by_potentiating_hippocampal_insulin_signaling_and_decreasing_neuroinflammation_and_norepinephrine_degradation_in_amyloid-β-infused_rats DB - PRIME DP - Unbound Medicine ER -