NRICM101 in combatting COVID-19 induced brain fog: Neuroprotective effects and neurovascular integrity preservation in hACE2 mice

Amidst growing concerns over COVID-19 aftereffects like fatigue and cognitive issues, NRICM101, a traditional Chinese medicine, has shown promise. Used by over 2 million people globally, it notably reduces hospitalizations and intubations in COVID-19 patients. To explore whether NRICM101 could comba...

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Main Authors: Cher-Chia Chang, Yea-Hwey Wang, Jiin-Cherng Yen, Chia-Ching Liaw, Keng-Chang Tsai, Wen-Chi Wei, Wen-Fei Chiou, Chun-Tang Chiou, Kuo-Tong Liou, Yuh-Chiang Shen, Yi-Chang Su
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Journal of Traditional and Complementary Medicine
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Online Access:http://www.sciencedirect.com/science/article/pii/S2225411024000841
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author Cher-Chia Chang
Yea-Hwey Wang
Jiin-Cherng Yen
Chia-Ching Liaw
Keng-Chang Tsai
Wen-Chi Wei
Wen-Fei Chiou
Chun-Tang Chiou
Kuo-Tong Liou
Yuh-Chiang Shen
Yi-Chang Su
author_facet Cher-Chia Chang
Yea-Hwey Wang
Jiin-Cherng Yen
Chia-Ching Liaw
Keng-Chang Tsai
Wen-Chi Wei
Wen-Fei Chiou
Chun-Tang Chiou
Kuo-Tong Liou
Yuh-Chiang Shen
Yi-Chang Su
author_sort Cher-Chia Chang
collection DOAJ
description Amidst growing concerns over COVID-19 aftereffects like fatigue and cognitive issues, NRICM101, a traditional Chinese medicine, has shown promise. Used by over 2 million people globally, it notably reduces hospitalizations and intubations in COVID-19 patients. To explore whether NRICM101 could combat COVID-19 brain fog, we tested NRICM101 on hACE2 transgenic mice administered the S1 protein of SARS-CoV-2, aiming to mitigate S1-induced cognitive issues by measuring animal behaviors, immunohistochemistry (IHC) staining, and next-generation sequencing (NGS) analysis. The study revealed that S1 protein-administered mice displayed marked signs of brain fog, characterized by reduced learning, memory, and nesting abilities. However, NRICM101 treatment in these animals ameliorated all these cognitive functions. S1 protein administration in mice induced notable inflammation, leading to the death of neurons (NeuN+) and neural stem cells (DCX+) in hACE2 transgenic mice. This was accompanied by heightened microglia activation (IBA1+/CD68+), increased cytokine production (IL1β, IL6), induction of neutrophil extracellular traps (NET), inflammation (NLRP3, CD11b), and platelet (CD31, vWF) and complement (C3) activation, ultimately damaging neurovasculature and disrupting the blood-brain barrier (B.B.B.). Administration of NRICM101 effectively alleviated all these pathological changes. In conclusion, NRICM101 has the potential to prevent COVID-19-associated brain fog by bolstering neurovascular integrity and protecting neurons and neural stem cells. This is achieved by the inhibition of S1 protein-induced complement activation, which in turn leads to the prevention of damage to the neurovasculature and the subsequent death of neurons.
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spelling doaj-art-8a0e8ff98d814b80879fc2a8d2c7d12d2024-12-18T08:49:01ZengElsevierJournal of Traditional and Complementary Medicine2225-41102025-01-011513650NRICM101 in combatting COVID-19 induced brain fog: Neuroprotective effects and neurovascular integrity preservation in hACE2 miceCher-Chia Chang0Yea-Hwey Wang1Jiin-Cherng Yen2Chia-Ching Liaw3Keng-Chang Tsai4Wen-Chi Wei5Wen-Fei Chiou6Chun-Tang Chiou7Kuo-Tong Liou8Yuh-Chiang Shen9Yi-Chang Su10Institute of Pharmacology, School of Medicine, National Yang Ming Chiao Tung University, Taipei City, 112304, TaiwanNational Taipei University of Nursing and Health Science, Taipei City, 112303, TaiwanInstitute of Pharmacology, School of Medicine, National Yang Ming Chiao Tung University, Taipei City, 112304, TaiwanNational Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei City, 112026, Taiwan; Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, 807378, TaiwanNational Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei City, 112026, Taiwan; Program in Medical Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei City, 110301, TaiwanNational Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei City, 112026, TaiwanNational Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei City, 112026, TaiwanNational Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei City, 112026, TaiwanNational Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei City, 112026, Taiwan; Department of Medicine, Mackay Medical College, New Taipei City, 25245, Taiwan; Department of Chinese Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei City, 114202, Taiwan; Corresponding author. Division of Clinical Chinese Medicine, National Research Institute of Chinese Medicine, Ministry of Health and Welfare, No. 155-1 Li-Nong Street, Section 2, Taipei City, 112026, Taiwan.National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei City, 112026, Taiwan; National Taipei University of Nursing and Health Science, Taipei City, 112303, Taiwan; Corresponding author. Division of Clinical Chinese Medicine, National Research Institute of Chinese Medicine, Ministry of Health and Welfare, No. 155-1 Li-Nong Street, Section 2, Taipei City, 112026, Taiwan.National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei City, 112026, Taiwan; Corresponding author. National Research Institute of Chinese Medicine, Ministry of Health and Welfare, No. 155-1 Li-Nong Street, Section 2, Taipei, 112026, Taiwan.Amidst growing concerns over COVID-19 aftereffects like fatigue and cognitive issues, NRICM101, a traditional Chinese medicine, has shown promise. Used by over 2 million people globally, it notably reduces hospitalizations and intubations in COVID-19 patients. To explore whether NRICM101 could combat COVID-19 brain fog, we tested NRICM101 on hACE2 transgenic mice administered the S1 protein of SARS-CoV-2, aiming to mitigate S1-induced cognitive issues by measuring animal behaviors, immunohistochemistry (IHC) staining, and next-generation sequencing (NGS) analysis. The study revealed that S1 protein-administered mice displayed marked signs of brain fog, characterized by reduced learning, memory, and nesting abilities. However, NRICM101 treatment in these animals ameliorated all these cognitive functions. S1 protein administration in mice induced notable inflammation, leading to the death of neurons (NeuN+) and neural stem cells (DCX+) in hACE2 transgenic mice. This was accompanied by heightened microglia activation (IBA1+/CD68+), increased cytokine production (IL1β, IL6), induction of neutrophil extracellular traps (NET), inflammation (NLRP3, CD11b), and platelet (CD31, vWF) and complement (C3) activation, ultimately damaging neurovasculature and disrupting the blood-brain barrier (B.B.B.). Administration of NRICM101 effectively alleviated all these pathological changes. In conclusion, NRICM101 has the potential to prevent COVID-19-associated brain fog by bolstering neurovascular integrity and protecting neurons and neural stem cells. This is achieved by the inhibition of S1 protein-induced complement activation, which in turn leads to the prevention of damage to the neurovasculature and the subsequent death of neurons.http://www.sciencedirect.com/science/article/pii/S2225411024000841COVID-19NRICM101Traditional Chinese medicineBrain fogNeurovasculature disruptionComplement &NET activation
spellingShingle Cher-Chia Chang
Yea-Hwey Wang
Jiin-Cherng Yen
Chia-Ching Liaw
Keng-Chang Tsai
Wen-Chi Wei
Wen-Fei Chiou
Chun-Tang Chiou
Kuo-Tong Liou
Yuh-Chiang Shen
Yi-Chang Su
NRICM101 in combatting COVID-19 induced brain fog: Neuroprotective effects and neurovascular integrity preservation in hACE2 mice
Journal of Traditional and Complementary Medicine
COVID-19
NRICM101
Traditional Chinese medicine
Brain fog
Neurovasculature disruption
Complement &NET activation
title NRICM101 in combatting COVID-19 induced brain fog: Neuroprotective effects and neurovascular integrity preservation in hACE2 mice
title_full NRICM101 in combatting COVID-19 induced brain fog: Neuroprotective effects and neurovascular integrity preservation in hACE2 mice
title_fullStr NRICM101 in combatting COVID-19 induced brain fog: Neuroprotective effects and neurovascular integrity preservation in hACE2 mice
title_full_unstemmed NRICM101 in combatting COVID-19 induced brain fog: Neuroprotective effects and neurovascular integrity preservation in hACE2 mice
title_short NRICM101 in combatting COVID-19 induced brain fog: Neuroprotective effects and neurovascular integrity preservation in hACE2 mice
title_sort nricm101 in combatting covid 19 induced brain fog neuroprotective effects and neurovascular integrity preservation in hace2 mice
topic COVID-19
NRICM101
Traditional Chinese medicine
Brain fog
Neurovasculature disruption
Complement &NET activation
url http://www.sciencedirect.com/science/article/pii/S2225411024000841
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