RECENT ADVANCES IN THE NEUROPROTECTIVE EFFECTS OF TRADITIONAL CHINESE MEDICINE: FOCUS ON ACTIVE INGREDIENTS AND MECHANISMS OF ACTION IN ALZHEIMER’S DISEASE
Volume 7, Issue 2, Pp 59-65, 2025
DOI: https://doi.org/10.61784/jpmr3047
Author(s)
YiWen Zhang
Affiliation(s)
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, Guangdong, China.
Corresponding Author
ABSTRACT
Alzheimer's disease (AD) is a senile brain disease characterized by insidious onset and neurodegenerative pathology. According to reports from the World Health Organization, the global population of individuals affected by AD exceeds 55 million, with a new case occurring approximately every three seconds. This number is projected to exceed 150 million by the year 2050. Given the unclear pathogenesis of AD, there are currently no available etiological treatments. Traditional Chinese Medicine (TCM) is known for its multi-target therapeutic approach, which provides several advantages, including a variety of treatment methods, minimal side effects, and the capacity to coordinate effects across multiple targets and pathways. This makes TCM particularly significant for research focused on the prevention and treatment of AD. This paper utilizes TCM as a foundation to review recent research findings regarding its treatment of AD, including ganolearins A–D, ulmoidol (30), Ganoderma lucidum polysaccharide, Ganoderma sinense crude polysaccharide and so on. It identifies newly discovered active ingredients and treatment methods, with the aim of providing a theoretical basis for TCM approaches to AD and serving as a reference for drug development.
KEYWORDS
Alzheimer's disease; Traditional Chinese Medicine; Active ingredient; Mechanism of action; Neuroprotection
CITE THIS PAPER
YiWen Zhang. Recent advances in the neuroprotective effects of traditional Chinese medicine: focus on active ingredients and mechanisms of action in alzheimer's disease. Journal of Pharmaceutical and Medical Research. 2025, 7(2): 59-65. DOI: https://doi.org/10.61784/jpmr3047.
REFERENCES
[1] Cummings J. The National Institute on Aging—Alzheimer's Association Framework on Alzheimer's disease: Application to clinical trials. Alzheimer's & Dementia: The Journal of the Alzheimer's Association, 2019, 15(1): 172–178.
[2] Wu C, Ma D, Chen Y. Association of pulse pressure difference and diabetes mellitus in Chinese people: A cohort study.International Journal of General Medicine, 2021, 14: 6601-6608.
[3] Kamila P, Kar K, Chowdhury S, et al. Effect of neuroinflammation on the progression of Alzheimer’s disease and its significant ramifications for novel anti-inflammatory treatments. IBRO Neuroscience Reports, 2025, 18: 771-82.
[4] Miao Qi, Zhu Renyan, Li Niannian, et al. Progress in traditional Chinese medicine treatment of Alzheimer's Disease. Journal of Shaanxi University of Chinese Medicine, 2024, 47(1): 139-42.
[5] Zhang Tao, Zhao Lei, Zhan Rui, et al. Novel mechanisms of some traditional chinese medicine for the therapy of neurocognitive disorders. Progress In Biochemistry and Biophysics, 2020, 47(8): 729-742.
[6] Erli Fei, Yun Gu. Progress in the prevention and treatment of Alzheimer's disease with traditional Chinese medicine. Chinese Journal of Alzheimer's Disease and Related Disorders, 2025, 8(1): 67-72.
[7] Yuan Fang, Wang Gang. Progress in pharmacotherapy for Alzheimer's disease. Acta Academiae Medicinae Sinicae, 2024, 41(5): 702-708.
[8] Rafii M S, Aisen P S. Amyloid-lowering immunotherapies for Alzheimer disease: current status and future directions. Nature Reviews Neurology, 2025.
[9] Zhang He, Zheng Yan. β Amyloid Hypothesis in Alzheimer’s Disease: Pathogenesis, Prevention,and Management. Acta Academiae Medicinae Sinicae, 2019, 41(5): 702-708.
[10] Wang Guoqing. Advances in the study of Aβoligomers and Alzheimer's disease. Journal of Apoplexy and Nervous Diseases, 2023, 40(7): 579-83.
[11] Guo X, Li H, Yan C, et al. Molecular mechanism of substrate recognition and cleavage by human γ-secretase. Science, 2024, 384(6700): 1091-1095.
[12] Zheng Y F, Song Z Y, Lyu W C, et al. A review of research on A β 1-42 oligomers and Alzheimer's disease. Journal of Regional Anatomy and Operative Surgery, 2016(2): 142-144.
[13] Niu Z, Gui X, Feng S, et al. Aggregation mechanisms and molecular structures of Amyloid-β in Alzheimer's Disease. Chemistry, 2024: 1521-3765.
[14] Zhang P, Song C, Shi J, et al. Endothelium-specific endoglin triggers astrocyte reactivity via extracellular vesicles in a mouse model of Alzheimer's disease. Mol Neurodegener, 2025: 1750-1326.
[15] Azargoonjahromi A. The duality of amyloid-β: its role in normal and Alzheimer's disease states. Molecular Brain, 2024, 17(1).
[16] Zhang X, Hu J, Zhong L, et al. Quercetin stabilizes apolipoprotein E and reduces brain Aβ levels in amyloid model mice. Neuropharmacology, 2016, 108: 179-92.
[17] Benjamin Falcon, Wenjuan Zhang, Alexey G Murzin, et al. Structures of filaments from Pick’s disease reveal a novel tau protein fold. Nature, 2018: 137–140.
[18] Zhang Xin, Zhu Tiantian, Wei Yuting, et al. Research progress on the mechanism of acupuncture intervention in Alzheimer's Disease via regulation of tau protein. Western Journal of Traditional Chinese Medicine, 2025, 38(3): 98-102.
[19] Gaikwad S, Senapati S, Haque M A, et al. Senescence, brain inflammation, and oligomeric tau drive cognitive decline in Alzheimer's disease: Evidence from clinical and preclinical studies. Alzheimers Dement, 2024: 1552-5279.
[20] Arakhamia T, Lee CE, Carlomagno Y, et al. Posttranslational modifications mediate the structural diversity of tauopathy strains. Cell, 2021: 1097-4172.
[21] Wan H L, Hong X Y, Zhao Z H, et al. STAT3 ameliorates cognitive deficits by positively regulating the expression of NMDARs in a mouse model of FTDP-17. Signal Transduction and Targeted Therapy, Cell, 2020, 5(1): 295.
[22] Zeng F X, Zhao R Q, Wang B. Neuroprotective mechanism of exercise on Alzheimer’s Disease: Role of oxidative stress. Chinese Journal of Biochemistry and Molecular Biology, 2025, 41(5): 687-695.
[23] Wen L, Bi D, Shen Y. Complement-mediated synapse loss in Alzheimer's disease: mechanisms and involvement of risk factors. Trends in Neurosciences, 2024: 1878-108X.
[24] Puranik N, Song M. Oxidative stress and the role of immune cells in Alzheimer's Disease: therapeutic implications and future perspectives.CNS neurol disord drug targets, 2025: 1996-3181.
[25] Bodur O C, Hasanoglu Ozkan E, Colak O, et al. Preparation of acetylcholine biosensor for the diagnosis of Alzheimer's disease. Journal of Molecular Structure, 2021, 1223: 129168.
[26] Li W, Pang Y, Wang Y, et al. Aberrant palmitoylation caused by a ZDHHC21 mutation contributes to pathophysiology of Alzheimer’s disease. BMC Med, 2023, 21(1): 223.
[27] Jiang Q W, Tang H D. Case report of a sporadic alzheimer's disease caused by psen2 gene mutation and literature review. Chinese Journal of Alzheimer's Disease and Related Disorders, 2021, 4(4): 302-305.
[28] Bilousova T, Melnik M, Miyoshi E, et al. Apolipoprotein E/Amyloid-β Complex Accumulates in Alzheimer Disease Cortical Synapses via Apolipoprotein E Receptors and Is Enhanced by APOE4. The American Journal of Pathology, 2019, 189(8): 1621-1636.
[29] Millet A, Ledo J H, Tavazoie S F. An exhausted-like microglial population accumulates in aged and APOE4 genotype Alzheimer’s brains. Immunity, 2024, 57(1): 153-170.
[30] Zhou X, Fu A K, Ip N Y. APOE signaling in neurodegenerative diseases: an integrative approach targeting APOE coding and noncoding variants for disease intervention. Current Opinion in Neurobiology, 2021, 69: 58-67.
[31] Imai Y, Meng H, Shiba-Fukushima K, et al. Twin CHCH proteins, CHCHD2, and CHCHD10: Key molecules of Parkinson's Disease, Amyotrophic Lateral Sclerosis, and Frontotemporal Dementia. International Journal of Molecular Sciences, 2019, 20(4): 908.
[32] Tao L Q, Zhang H. Research progress of triterpenoids in the prevention and treatment of Alzheimer's disease. Chinese Bulletin of Life Science, 2024, 36(4): 487-498.
[33] Qi Z, Deng S, Wu Y, et al. The effects of Ganoderma leucocontextum triterpenoids treatment on the D-galactose and aluminum chloride-induced Alzheimer-like pathology in mouse brain. Journal of Ethnopharmacology, 2024: 1872-7573.
[34] Peng X, Luo R, Ran X, et al. Ganoapplins A and B with an unprecedented 6/6/6/5/6-fused pentacyclic skeleton from Ganoderma inhibit Tau pathology through activating autophagy. Bioorganic Chemistry, 2023, 132: 106375.
[35] Peng X R, Luo R C, Qiu, M H, et al. A-ring opening triterpenoid compounds and their pharmaceutical compositions and applications in Ganoderma lucidum, 2024, 01.
[36] Shan X X, Zhou L L, Li D W, et al. Research progress on mechanism of classic famous prescription Kaixin Powder in treatment of Alzheimer's disease. Chinese Traditional and Herbal Drugs, 2023, 54(11): 3685-3695.
[37] Wu Tong. Study on anti-Alzheimer's disease effect and active ingredient screening of triterpene extract of Poria cocos. Changchun University of Chinese Medicine, 2023, 12: R749.16 R285.5.
[38] Lv J L, Shen X Y, Shen X Y, et al. NPLC0393 from Gynostemma pentaphyllum ameliorates Alzheimer's disease‐like pathology in mice by targeting protein phosphatase magnesium‐dependent 1A phosphatase. Phytotherapy Research, 2023, 37(10): 4771-4790.
[39] Xiang Z, Li H J, Shen X Y, et al. Chemical Constituents, Pharmacological Effect, and Product Development of Eucommia ulmoides with Both Medicinal and Edible Values: A Review. Chinese Journal of Experimental Traditional Medical Formulae, 2024, 30(2): 190-202.
[40] Han R, Yuan T, Yang Z, et al. Ulmoidol, an unusual nortriterpenoid from Eucommia ulmoides Oliv. Leaves prevents neuroinflammation by targeting the PU.1 transcriptional signaling pathway. Bioorganic Chemistry, 2021, 116: 105345.
[41] Hu F, Lei Y, Han R, et al. The efficacy and pharmacological mechanism of Guilingji to prevent Alzheimer’s disease. Alzheimer's Research & Therapy, 2025, 17(1): 157.
[42] Wang H L, Fu Y Y, Tie F F. Protective Effects of Genkwanin and Other Flavonoids on Alzheimer's Disease and Its Mechanism. Qinghai Science and Technology, 2023, 30(4): 46-55.
[43] Yan X N, Wang Z, Li R F. Research Progress on the Mechanism of Flavonoids from Ampelopsis grossedentata on Alzheimer’s Disease. Modern Food Science and Technology, 2023, 39(8): 343-51.
[44] Ma X N, Gao P, Wu Y, et al. The ameliorative effects of Vitis vinifera L. Suosuo polysaccharides on Aβ142induced oxidative damage in HT22 cells. Journal of Hainan Medical University, 2024, 30(17): 1304-1312.
[45] Fang D Y, Zhang L, Wu P, et al. Exploring the mechanism of pueraria lobata improving AD based on network pharmacology and experimental validation. Journal of Shenyang Pharmaceutical University, 2025, 42(2): 131-41.
[46] Wang Y T, Xu Y M, Zhang Z B, et al. Effect of Drynaria total flavonoids on the expression of NMDAR1, GluR2 and CaMK Ⅱ in the brain of hydrocortisone model mice. Journal of Hainan Medical University, 2022, 28(24): 1860-1866.
[47] Liu X Y, Shang Y Z. Pharmacological research progress on extracting flavonoids from Scutellaria barbata. Journal of Chengde Medical University, 2021, 38(5): 421-426.
[48] Liu X Y, LI H, Shang Y Z. Effects and regulatory mechanism of Scutellaria barbata flavonoids in inhibiting the neuroinflammation of AD rats induced by composited Aβ. Chinese Journal of Hospital Pharmacy, 2022, 42(12): 1197-203.
[49] Sun H Y, Zhou L Y, Ren L X, et al. Recent progress of neuroprotective mechanisms of luteolin in Alzheimer’s disease. Chinese Pharmacological Bulletin, 2022, 38(12): 1781-1785.
[50] Liu X, Li Y, Wang J, et al. Polysaccharides from Ganoderma lucidum attenuate cognitive impairment in 5xFAD mice by inhibiting oxidative stress and modulating mitochondrial dynamics via the Nrf2/antioxidative axis activation. Metabolic Brain Disease, 2025: 1573-7365.
[51] Wang L, Lu Y, Liu J, et al. Gegen Qinlian tablets delay Alzheimer's disease progression via inhibiting glial neuroinflammation and remodeling gut microbiota homeostasis. Phytomedicine, 2024, 128: 155394.
[52] Ye H X, He Yingxi, Qi Y Q, et al. Effect of Lycium barbarum polysaccharides on learning and memory ability and Tau protein phosphorylation level in brain withAlzheimer's disease and type 2 diabetes mellitus mice. Journal of Shihezi University (Natural Science), 2023, 41(3): 360-366.
[53] Fu J. Study on structural characterization, in vitro digestion and fermentation characteristics of Schisandrae Chinensis Fructus polysaccharides and its mechanism of improving Alzheimer's disease. Jilin University, 2023.
[54] Shah Z, Iqbal A, Badshah SL, et al. Macroalgae polysaccharides enhance brain health by mitigating scopolamine-induced oxidative stress and inflammation via Nrf-2/TLR4/NF-kB Pathways. Journal of Neuroimmune Pharmacology, 2025: 1557-1904.
[55] Campanella C, Pace A A-O, Caruso Bavisotto C A-O, et al. Heat shock proteins in Alzheimer's Disease: Role and targeting. Journal of Neuroimmune Pharmacology, 2025: 1422-0067.
[56] Hajihosseini S, Zakavi SA, Farrokhi Z, et al. A meta-analysis update evaluating the treatment effects of donepezil alone versus donepezil combined with memantine for Alzheimer's disease. IBRO Neuroscience Reports, 2025, 19: 72-82.
[57] Salloway S, Chalkias S, Barkhof F, et al. Amyloid-related imaging abnormalities in 2 Phase 3 studies evaluating aducanumab in patients with early Alzheimer Disease. JAMA Neurology, 2022: 2168-6157.
[58] Xu L, Chen W J, Tian C J, et al. Efficacy and safety of chinese herbal medicines combined with chemical drugs for alzheimer's disease: A systematic review and meta-analysis. World Journal of Traditional Chinese Medicine, 2024, 10(1).
[59] Wang J W, Wei B J. Prevention and treatment of Alzheimer's disease by traditional chinese medicine via regulating ROS: A review. Chinese Journal of Experimental Traditional Medical Formulae, 2024, 30(12): 281-8.
[60] Aktary N, Jeong Y, Oh S, et al. Unveiling the therapeutic potential of natural products in Alzheimer's disease: insights from in vitro, in vivo, and clinical studies. Frontiers in Pharmacology, 2025: 1663-9812.