Current Status of Plant-Based Bioactive Compounds as Therapeutics in Alzheimer’s Diseases

Abstract

Alzheimer’s disease (AD) is a common central neurodegenerative disease disorder characterized primarily by cognitive impairment and non-cognitive neuropsychiatric symptoms that significantly impact patients’ daily lives and behavioral functioning. The pathogenesis of AD remains unclear and current Western medicines treatment are purely symptomatic, with a singular pathway, limited efficacy, and substantial toxicity and side effects. In recent years, as research into AD has deepened, there has been a gradual increase in the exploration and application of medicinal plants for the treatment of AD. Numerous studies have shown that medicinal plants and their active ingredients can potentially mitigate AD by regulating various molecular mechanisms, including the production and aggregation of pathological proteins, oxidative stress, neuroinflammation, apoptosis, mitochondrial dysfunction, neurogenesis, neurotransmission, and the brain-gut microbiota axis. In this review, we analyzed the pathogenesis of AD and comprehensively summarized recent advancements in research on medicinal plants for the treatment of AD, along with their underlying mechanisms and clinical evidence. Ultimately, we aimed to provide a reference for further investigation into the specific mechanisms through which medicinal plants prevent and treat AD, as well as for the identification of efficacious active ingredients derived from medicinal plants.

Graphical abstract

Keywords

Alzheimer’s disease / medicinal plants / neuroprotection / cognitive function / neuroinflammation

1. Introduction

Alzheimer’s disease (AD) is a progressive neurodegenerative condition characterized by cognitive deficits, behavioral abnormalities, and impaired social functioning, posing a significant global health threat to older adults and ranking as the fifth leading cause of death worldwide [1, 2]. According to a national cross-sectional study in 2020, approximately 9.83 million people aged 60 and above in China were affected by AD [3]. As the global population ages, the incidence, disability, and mortality rates of AD continue to rise annually, promising a growing burden on individuals, families, and societies in the future [4]. Clinical study has identified amyloid-\beta (A\beta) plaque deposition and hyperphosphorylated Tau protein as primary hallmarks of AD pathology [5]. In addition, numerous studies have demonstrated that oxidative stress, inflammatory responses, programmed cell death (such as apoptosis, autophagy, and ferroptosis), and disturbances in intestinal flora contribute significantly to structural and functional abnormalities in AD progression [6, 7].

Currently, the drugs used in the treatment of AD primarily consist of cholinesterase inhibitors and N-methyl-D-aspartate antagonists [8], which can only partially improve the symptoms of patients, but do not reverse disease progression, and prolonged use can lead to various adverse effects. Additionally, surgical interventions used in clinical management are both risky and costly [9]. Hence, there is a critical need to further investigate the pathogenesis of AD and develop effective strategies for its prevention and treatment.

In traditional medical practices, numerous medicinal plants and their active ingredients have been recommended for enhancing cognitive function and alleviating symptoms of AD [10, 11], such as cognitive impairment, memory loss, spatial awareness deficits, depression, and dementia. Bioactive compounds derived from medicinal plants are noted for their low incidence of adverse effects and high effectiveness [12]. In recent years, a large number of scholars have carried out studies on active ingredients from medicinal plants for treating AD and elucidating their associated mechanisms [13, 14], thereby establishing experimental foundations for AD treatment using medicinal plants. Notably, Huperzine-A derived from Huperzia serrata has been clinically employed in the treatment of patients with AD [15, 16]. These findings underscored the potential of medicinal plants to offer novel perspectives and strategies for addressing AD in contemporary society.

Currently, there have been a scarcity of reviews focusing on plant-based bioactive compounds for the prevention and treatment of AD. This review provided a comprehensive overview of the current pathogenesis of AD. Furthermore, it summarized recent research on active ingredients derived from medicinal plants targeting AD through global and local databases such as PubMed, Web of Science, and China National Knowledge Infrastructure. The review examined the mechanisms and clinical efficacy of these compounds, aiming to inform the clinical application of medicinal plants in the treatment of AD and provide a theoretical basis for the development of new drugs to combat this disease.

2. Research Methodology

This review article was conducted using electronic databases such as PubMed, Google Scholar, Springer Link, Science Direct, Cochrane Library, Embase, Web of Science, and Scopus. All published data till the year 2024 have been taken into consideration. The following search keywords were used in the search of materials for this study: “medicinal plants”, “active ingredients”, “bioactive compounds”, “polyphenols”, “flavonoids”, “alkaloids”, “terpenes”, “polysaccharides”, “quinones”, “glycosides”, “volatile oils”, “biological activity”, “pharmacological activities”, “Alzheimer’s disease”, “amyloid \beta”, “tau protein”, and other similar keywords in combination with words such as traditional Chinese medicine, Clinical trials, botanical description, toxicity, human health, and nutritional composition. All articles addressing these principal keywords were considered when available in the English language, and in peer-reviewed journals, whether published as review or research articles. Papers were reviewed in their entirety if their abstract mentioned that the article presented any potential relevance to the inclusion criteria. Articles were excluded based on title, abstract, or full text because of their lack of pertinence to the issue concerned. Articles were excluded if they were letters, comments, and not available for access to the full article.

3. Etiology and Pathophysiology of AD

Although AD was first reported by the German physician Alois Alzheimer more than 100 years ago [17], the precise mechanisms underlying its onset and progression remain unclear. Currently, the primary pathological feature of AD has been recognized as the deposition of extracellular amyloid \beta (A\beta) plaques [18]. A\beta is produced and released through the abnormal cleavage of amyloid precursor protein by \beta-secretase 1 and \gamma-secretase enzymes [19, 20]. Clinical studies have shown that A\beta plaques can penetrate blood vessels and disrupt the blood supply to the brain [21, 22]. Additionally, research has demonstrated that A\beta plaques can damage neurons and trigger activation of microglia and astrocytes [23], leading to increased production of free radicals and influx of Ca²⁺ ions, which exacerbate neuronal apoptosis [24]. It has also been observed that A\beta can enhance the formation of advanced glycation end products on neuron surfaces and stimulate the release of pro-inflammatory cytokines, contributing to impaired neuronal function and eventual cell death [25].

Furthermore, the formation of A\beta plaques typically coincides with additional pathological changes primarily affecting pyramidal neurons and their structural integrity [26]. These changes are induced by increased phosphorylation of tau protein [27], which aggregates into polymers known as tau tangles. Under normal physiological conditions, tau protein plays a crucial role in stabilizing microtubules and facilitating their polymerization to maintain cytoskeletal integrity [28]. Functionally, microtubules are essential for the transport of cellular proteins and enzymes necessary for normal neuronal function [29].

Increasing evidence has observed hyperphosphorylation of tau protein in the brain tissue of patients with AD [30], which in turn leads to the formation of intracellular neurofibrillary tangles, contributing to neuronal degeneration and eventual cell death. At a molecular level, cyclin-dependent kinase 5 (CDK5) can be activated by elevated levels of Ca²⁺ ions within neuronal cells. This activation accelerates microtubule depolymerization, causes cytoskeletal abnormalities, triggers microglial activation, and inflammation, and ultimately impairs neuronal function and leads to apoptotic cell death [31, 32].

Recent studies have also confirmed that viral infections [33], mitochondrial dysfunction [34], abnormalities in insulin signaling [35], imbalance in intestinal flora [36], excitotoxicity from amino acids [37], and deficits in cholinergic function [38] are closely associated with the progression of AD. These processes contribute to the aggregation of A\beta plaques, neuroinflammation, oxidative stress, neuronal death, and insulin resistance. Moreover, these factors collectively increase the permeability of the blood-brain barrier, thereby accelerating the pathological advancement of AD.

4. The Therapeutic Effect of Plant-Based Bioactive Compounds on AD and Its Potential Mechanisms

Through extensive research into the pathogenesis of AD, traditional Chinese medicine (TCM) has demonstrated unique therapeutic advantages in AD treatment due to its multi-component, multi-target approach, and emphasis on whole-body integrity [39]. Increasingly, a study has highlighted that medicinal plants and their primary bioactive constituents characterized by diverse structures, exert protective effects against neurodegenerative diseases [40]. The mechanisms by which plant-based bioactive compounds prevent AD are illustrated in Fig. 1 and detailed in Table 1 (Ref. [41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112]). Meanwhile, the majority of Chinese AD patients have incorporated medicinal plants and herbal formulations into their diagnostic and treatment regimens [113, 114]. This review aimed to consolidate research progress on natural plant components in the treatment of AD, providing a reference for identifying safe and effective small molecules for AD treatment.

4.1 Polyphenols

Polyphenols are widely found in grapes, Salvia miltiorrhiza, tea, Gastrodia elata, and other medicinal plants. Modern pharmacological study has confirmed that polyphenolic compounds have a variety of biological activities [115], including antitumor, antioxidant, anti-inflammation, and anti-oxidative stress properties. Importantly, increasing study has confirmed the anti-AD potential of polyphenolic compounds [116], with their mechanisms summarized in Table 1. For example, proanthocyanidins, a type of polyphenolic compound, possess a spectrum of biological activities that impede the onset and progression of AD [117, 118], including anti-inflammatory effects, improvement of insulin resistance, and anti-oxidative stress properties. Resveratrol, capable of crossing the blood-brain barrier, exerts neuroprotective effects by reducing glial activation, amyloid precursor protein levels, and plaque formation [119], and by modulating gut microbiota composition [120] in AD treatment. Research by Fasina et al. [45] has demonstrated that gastrodin enhances memory function in AD mouse models by targeting the “gut microbiota-brain” axis, attenuating neuroinflammation, and preserving intestinal barrier integrity. Other studies have indicated that pterostilbene possesses neuroprotective properties against AD through its anti-inflammatory activities and mitigation of mitochondria-dependent apoptosis [43, 44]. Additionally, ferulic acid has been shown to ameliorate AD progression by reducing the accumulation of A\beta peptide and tau protein hyperphosphorylation [121]. In conclusion, polyphenolic compounds represent promising therapeutic agents for AD treatment due to their multifaceted mechanisms.

4.2 Flavonoids

Flavonoids, secondary metabolites widely found in medicinal plants, exhibit various pharmacological activities beneficial to human health [122], including their role in treating AD (Table 1). Previous studies have demonstrated that compounds like nobiletin [72] and luteolin [73] exert anti-AD effects by inhibiting oxidative stress, mitochondrial dysfunction, and neuroinflammation. Sun et al. [61] have shown that rutin mitigates AD progression by reducing tau aggregation, neuroinflammation, and tau oligomer-induced cytotoxicity. Icariin [123] and genistein [57] have been found to ameliorate memory impairment in AD mouse models by suppressing endoplasmic reticulum stress. Quercetin-3-O-Glucuronide, a type of active flavonol glucuronide, exhibits anti-neuroinflammatory effects in AD by modulating the gut microbiota-brain axis, as evidenced by its ability to reduce short-chain fatty acids and address gut microbiota dysbiosis [59]. Overall, flavonoids possess a diverse array of biological activities that can prevent the development and progression of AD.

4.3 Alkaloids

Alkaloids, a class of nitrogen-containing basic organic compounds widely found in medicinal plants, exert protective effects against AD by suppressing inflammation, oxidative stress, and neuronal apoptosis (Table 1). Matrine, a natural quinolizidine alkaloid isolated from Sophora flavescens, reduces proinflammatory cytokines and A\beta deposition, alleviating memory deficits in AD transgenic mice by inhibiting the A\beta/receptor for advanced glycation end product (RAGE) pathway [124]. Similarly, oxymatrine demonstrates anti-neuroinflammatory effects in an A\beta_1-42-induced AD rat model by inhibiting nuclear factor-\kappaB (NF-\kappaB) and mitogen-activated protein kinase (MAPK) pathways [76], suggesting it as a potential candidate for the treatment of AD. Research by Li et al. [77] has shown that isorhynchophylline reduces A\beta deposition, tau hyperphosphorylation, and neuroinflammation, while improving cognitive deficits in AD mice by inactivating the c-Jun N-terminal kinase (JNK) pathway. Berberine, a natural isoquinoline alkaloid derived from Rhizoma coptidis, suppresses the formation of A\beta plaques, tau protein hyperphosphorylation, and neuronal loss in the brains of AD mice by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway [86]. Furthermore, a recent study highlights that palmatine, a natural alkaloid found in various plants, enhances cognitive function and restores mitochondrial function in AD mouse models [125].

4.4 Terpenes

Terpenoids, a diverse group of organic compounds found in medicinal plants, are increasingly recognized for their potential in treating various diseases [126, 127]. Their preventive and therapeutic effects on AD have garnered significant attention (Table 1), owing to their remarkable biological activities, such as anti-inflammatory, antioxidant, and anti-apoptotic properties. Huperzine-A, a natural sesquiterpene alkaloid derived from Huperzia serrata, demonstrates a neuroprotective effect in AD by reducing A\beta accumulation, preserving mitochondrial function, and maintaining Fe²⁺ homeostasis [128]. Paeoniflorin, commonly found in Paeoniaceae plants, improves cognitive function and mitigates neuronal ferroptosis in AD mice through inhibition of the P53 pathway [102]. Administration of geniposidic acid attenuates AD progression by enhancing cognitive function, reducing A\beta accumulation, neuronal apoptosis, and neuroinflammation [93]. Patchouli alcohol, a bioactive tricyclic sesquiterpene from Pogostemonis herba, exerts neuroprotective effects against AD by suppressing A\beta plaque deposition, tau protein hyperphosphorylation, neuroinflammation, and gut dysbiosis via inhibition of the CCAAT/enhancer-binding protein \beta/asparagine endopeptidase (C/EBP\beta/AEP) pathway [129]. Ginkgolide B, a terpene lactone derived from Ginkgo biloba leaves, prevents AD progression by inhibiting NLRP3 (Nod-like receptor family, pyrin domain containing 3) inflammasome activation and improving learning and memory impairments [96]. Tanshinone IIA, a fat-soluble component of Salvia miltiorrhiza, protects against AD by enhancing A\beta transport [130], reducing tau phosphorylation, oxidative stress, and neuroinflammation [91, 131]. Celastrol, a friedelane-type triterpene from Tripterygium wilfordii, activates transcription factor enhancer bindings (EBs) to suppress phosphorylated tau aggregates, thereby improving memory and cognitive deficits in AD mouse models [100]. A recent study has shown that catalpol rescues cognitive deficits in AD by preventing A\beta plaque formation and neuroinflammation [103].

4.5 Polysaccharides

Currently, plant polysaccharides have been gaining significant global attention due to their versatile biological activities, including antioxidation, anti-inflammation, and anti-oxidative stress properties, coupled with minimal side effects [132]. Particularly noteworthy are their potential roles in mitigating risk factors associated with AD [133] (Table 1), such as modulation of neuroplasticity, promotion of neurogenesis, normalization of neurotransmission, and suppression of neuroinflammation. For instance, Angelica polysaccharides have been shown to alleviate AD progression by reducing inflammation, oxidative stress, neuronal apoptosis, and improving memory impairment [107]. Polysaccharides from Coptis chinensis protect A\beta-induced neurotoxicity, reduce phosphorylated tau protein, and mitigate oxidative stress in AD rat models [105]. Zhou et al. [106] reported that polysaccharides from Lycium barbarum act as a novel therapeutic agent for AD by reducing A\beta plaque deposition and improving cognitive functions. In D-galactose-induced mouse models, polysaccharides from Polygonatum sibiricum exhibit anti-oxidative stress and anti-inflammatory effects against AD [112]. Additionally, polysaccharides from Cistanche deserticola have been shown to improve cognitive function by restoring homeostasis in the gut microbiota-brain axis [111].

4.6 Others

In addition to the previously mentioned compounds isolated from medicinal plants for the prevention of AD, various other plant-based bioactive compounds have shown therapeutic potential against AD. Studies have highlighted that quinones such as sennoside A [134], rhein [135], and shikonin [136], phenylpropanoids, including magnolol [137] and forsythoside A [138], glycosides such as tenuifolin [139] and ginsenoside compound K [140], and volatile oils from plants like Acorus tatarinowii Schott [141], Rosmarinus officinalis and Mentha piperita oils [142], alleviate AD progression through antioxidant, anti-inflammatory, and anti-apoptotic activities. Furthermore, several medicinal plants have demonstrated potential in preventing or treating AD, including Moringa oleifera [143], Rosmarinus officinalis [144], Nardostachys jatamansi [145], and Tinospora cordifolia [146]. For example, plant-derived alkaloids [147, 148], polyphenols [149], flavonoids [150, 151], saponins [152, 153], alkaloids [154], terpenes [155], and essential oils [156, 157] showed multi-targeted activity against acetylcholinesterase, butyrylcholinesterase, tyrosinase, monoamine oxidase, and pancreatic lipase, which helped to prevent the occurrence and development of AD. However, the functional roles of these plant-based bioactive compounds in the treatment of AD remain poorly understood, with limited knowledge of their mechanisms. In conclusion, plant-based bioactive compounds exhibit multi-target and versatile biological activities in experimental AD studies, suggesting their potential as therapeutic agents for AD treatment in clinical settings.

5. Clinical Trials of Medicinal Plants for AD Management and Challenges

Accumulating evidence indicates that medicinal plants offer a wide range of pharmacological effects in AD, with beneficial efficacy demonstrated in vitro cell models and animal experiments. Gul et al. [158] have reported that Huperzine-A acts as an acetylcholinesterase inhibitor, improving cognition and task-switching abilities in patients with AD. Moreover, ongoing clinical studies are exploring the safety and efficacy of medicinal plant decoctions and injections for the treatment of AD (Table 2). A randomized controlled clinical trial found that Di-Tan decoction is a safe method for treating AD and improving cognitive symptoms [159]. Another study demonstrated that a medicinal plant formula was beneficial for cognitive improvement in AD patients by reducing A\beta plaque deposition [160]. Recently, Huanglian Jiedu decoction has been found to reduce inflammation and oxidative stress in AD patients by regulating lipid and glutamic acid metabolism [161]. Furthermore, clinical trials have indicated that the Jiannao Yizhi formula’s efficacy and safety in treating AD are comparable to Western medicine (donepezil) [162]. Meanwhile, Western medicines are expensive and have side effects. A study in Australia showed that EGb 761® (a standardized extract from Gingkgo biloba) treatment improved the activities of daily living deterioration by 22.3 months in patients with AD, and EUR 531 for one additional therapy success (defined as improvement in clinician’s global judgment) with EGb 761® while cholinesterase inhibitors require between EUR 3849 and EUR 14,224 [163]. A randomized controlled trial (NCT00391833) showed that AD patients treated with Panax ginseng powder (4.5 g/day) for 12 weeks, the cognitive subscale of the Alzheimer’s Disease Assessment Scale and the Mini-Mental State Examination score began to show improvements. Moreover, Chinese medicinal plants’ adjunctive therapy could improve cognitive impairment and enhance immediate response and quality of life in AD patients [12, 164]. Based on these findings, plant-based bioactive compounds present a promising alternative for AD, offering diverse therapeutic benefits.

However, it is also necessary to explore the several challenges of translating preclinical findings into clinical applications. The biggest challenge to plant-based drug delivery into the brain is circumventing the blood-brain barrier, which prevents the entry of numerous potential therapeutic agents. Another challenge is related to approval of the drug for commercialization because enough resources are unavailable. Since some compounds cannot be synthesized in a semi-synthetic manner or by growing or engineering the plant artificially, this will increase the product’s dependency on natural resources. As per the reports, nearly 25,000 plants will go extinct, which imposes an ethical issue for extracting bioactive compounds from plants. In addition, there is still a lack of sufficient clinical data and their mechanisms of action. Finally, plant-based bioactive compounds have solubility & absorption, intellectual property, absence of drug-likeness, and purity issues.

6. Current Status of Plant-Based AD Treatments in Different Countries

Medicinal plants have been used for thousands of years and have been broadly used in clinical practice in China and several other Asian countries (such as Japan and Korea) [165], and Chinese people have a wealth of clinical experience in medicinal plants. Currently, medicinal plants account for more than 40% of China’s pharmaceutical market [166]. Meanwhile, the world health organization (WHO) stated that about 80% of the world population depends on medicinal plants to satisfy healthcare requirements [167, 168]. For example, Evalvulus alsinoides, Centella asiatica, Myristica fragrans, Andrographis paniculata, Nardostachys jatamansi, and Nelumbo nucifera widely used in Indian traditional medicine systems for cognitive enhancement were known for their acetylcholinesterase inhibitory activity [169]. Lobbens et al. [170] reported that a total of 29 ethanolic extracts from European traditional medicine plants served as new drug candidates for the treatment of AD by inhibition of acetylcholinesterase and amyloidogenic activities. Kumar et al. [171] found that medicinal plants from the Australian rainforest possessed anti-AD activity by suppressing neuroinflammation. In the West Africa region, over 10,000 medicinal plants have been utilized in curing neurodegenerative diseases [172], such as Pyllanthus amarus, Crysophyllum albidum, Rauwolfia vomitora, Abrus precatorius. A clinical study confirmed that administration with ninjin’yoeito (NYT), a traditional Japanese medicine (Kampo medicine), improved impairments and depressive states in twelve AD patients [173]. Meanwhile, Ginkgo biloba extract (EGb 761®) was registered as an ethical drug in Western countries and has been widely used in clinical therapy to treat AD [174]. Galantamine (Razadyne®) serves as a selective competitive and reversible inhibitor of acetylcholinesterase and has received regulatory approval in 29 countries [175], such as Sweden, Austria, United States, Europe, and other countries. Rivastigmine (Exelon®) was approved to treat mild to moderate AD in over 40 countries in North and South America, Asia, and Europe [176]. Currently, the U.S. Food and Drug Administration has approved tacrine (Cognex®), donepezil (Aricept®), galantamine, memantine, and rivastigmine for the treatment of AD patients in clinical [177, 178]. Taken together, medicinal plant-based bioactive compounds exhibited their powerful roles in the management of AD progression and helped to relieve the symptoms related to AD.

7. Conclusions and Future Directions

With increasing research into the pathogenesis of AD, the role of medicinal plants in its treatment has advanced significantly in recent years. TCM has been particularly prominent in treating various diseases, including AD, and offers a new perspective in the modern era for both the prevention and treatment of coronavirus disease 2019 (COVID-19). This review underscored that plant-based bioactive ingredients can prevent and manage AD through multiple mechanisms, including reducing the production and aggregation of pathological proteins, enhancing their degradation, antioxidative and anti-inflammatory activities, improving mitochondrial function and energy metabolism, regulating intestinal flora, inhibiting neuronal apoptosis, and promoting neurogenesis. Clinical trials have demonstrated the efficacy and safety of medicinal plants in alleviating the symptoms of AD. However, the treatment of AD with medicinal plant-based bioactive ingredients still faces some challenges that must be addressed. (1) With the rapid development of science, there is a need to elucidate the physiological functions and mechanistic explanations of medicinal plants against AD using network pharmacological approaches and multi-omics techniques, such as nutrigenomics, metabolomics, proteomics, gut microbial macrogenomics, and immunomics. (2) Further validation of the metabolic, toxicity, and pharmacokinetic profiles of medicinal plants in clinical trials for AD is essential. (3) Research on active ingredients from medicinal plants is limited by unstable chemical structures, low bioavailability, and susceptibility to oxidation. Consideration of strategies like liposome embedding or nanoparticle formulation may mitigate these challenges. (4) Many active compounds from medicinal plants cannot effectively cross the blood-brain barrier to reach the brain. Exploring how plant-based bioactive compounds that regulate intestinal flora based on the “brain-gut microbiota” axis can mitigate AD is warranted.

Due to the synergistic effects, systematic analytical tools must be developed to study the multi-component, multi-rule, and multi-target characteristics of TCM. Network-based approaches in medicinal plants use computational algorithms to elucidate the underlying mechanisms of bioactive compounds and identify the underlying synergistic effects. Moreover, the development of network pharmacology diminishes the cost, reduces the risk, and saves time in researching new bioactive compounds for the treatment of various diseases, including AD [179]. Researchers can use these tools and experimental knowledge to determine effective substances in medicinal plants for AD. For example, Wu et al. [180] presented a novel algorithm based on entropy and random walk with the restart of the heterogeneous network was proposed for predicting active ingredients for AD and screening out the effective TCMs for AD, and results showed that the top 15 active ingredients may act as multi-target agents in the prevention and treatment of AD, Danshen, Gouteng and Chaihu were recommended as effective TCMs for AD, Yiqitongyutang was recommended as effective compound for AD. Recent studies have proved that integrating network pharmacology and experimental verification to reveal the potential pharmacological ingredients and mechanisms of different medicinal plants (Paeonia lactiflora [181], Acoritataninowii rhizome [182], Ginkgo biloba [183], Panax ginseng [184], Corydalis rhizome [185]) in curing AD, and TCM decoction (Erjingwan [186], Jin-Si-Wei [187], Guhan Yangshengjing [188], and Tian-Si-Yin [189]). Therefore, using network pharmacology to discover the relationship between medicinal plants, AD, and cellular responses was easily achievable.

In conclusion, medicinal plants exhibit promising anti-AD effects and serve as essential active agents for treating neurodegenerative diseases. In addition to experimental studies, bioinformatics approaches provide valuable insights into the mechanisms by which plant-based bioactive compounds exert their therapeutic effects on AD. Incorporating molecular docking studies, molecular dynamics simulations, quantitative structure-activity relationship models, network pharmacology, and genomics/transcriptomics analyses can significantly enhance our understanding of the multi-target effects and potential efficacy of these compounds. Integration of these bioinformatics methods could validate experimental findings and guide the development of novel therapeutic strategies for AD. This review synthesized the current understanding of AD’s pathogenesis, systematically analyzed and explored the mechanisms of medicinal plants in preventing AD, and reviewed their clinical trial outcomes. The aim was to offer a scientific and comprehensive reference for the treatment of AD with medicinal plants, enhancing the utilization and development of TCM resources.

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