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Neuroinflammatory mechanisms in ischemic stroke and phytotherapeutic interventions for enhanced recovery: A review
*Corresponding author: Umar Faruk Saidu, BS Department of Biochemistry and Molecular Biology, Usmanu Danfodiyo University, Sokoto, Nigeria. farouk.saidu@gmail.com
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Received: ,
Accepted: ,
How to cite this article: Suleiman N, Sanusi F, Bulama I, et al. Neuroinflammatory mechanisms in ischemic stroke and phytotherapeutic interventions for enhanced recovery: A review. Am J Pharmacother Pharm Sci 2026:002
Abstract
Stroke is a significant global health challenge, causing substantial mortality and disability worldwide, with its prevalence rising particularly in low- and middle-income countries. This review discusses the role of inflammatory cells in ischemic stroke (IS), the limitations of conventional drugs, and the emerging potential of plant-derived medications. Drawing from extensive research, it highlights recent findings on neuroinflammation and neuroprotective strategies using natural compounds. IS triggers a complex inflammatory response involving microglia, astrocytes, and leukocytes, which significantly contributes to secondary tissue damage; understanding this interplay is crucial for developing effective interventions. Conventional drugs, such as recombinant tissue plasminogen activator and antiplatelet agents, face limitations including a narrow therapeutic window and the risk of hemorrhagic transformation, underscoring the need for alternative approaches. Plant-derived medications show considerable promise due to their neuroprotective effects and ability to modulate inflammatory pathways. Bioactive compounds such as flavonoids and polyphenols offer potent antioxidant and anti-inflammatory properties, which may improve treatment outcomes. Recent research has unveiled their mechanisms of action, which include reducing oxidative stress, neuroinflammation, and promoting neurogenesis, suggesting a strong potential to mitigate neuronal damage and aid post-stroke recovery. Exploring plant-derived medications represents a paradigm shift toward utilizing natural compounds for stroke management. By tapping into the vast pharmacological potential of plants, researchers aim to develop safer and more effective therapies that overcome the limitations of conventional drugs. These advancements offer hope for improving IS management and reducing its global burden. Continued research is crucial to unlock these innovative therapeutic strategies and enhance patient outcomes worldwide.
Keywords
Ischemic stroke
Neuroinflammation
Neuroprotection
Phytotherapy
INTRODUCTION
Ischemic stroke (IS) is one of the most debilitating neurological conditions worldwide. It is characterized by the sudden interruption of blood flow to the brain, leading to neuronal damage and inflammation. Amidst the intricate pathophysiological cascade triggered by ischemia, neuroinflammatory mechanisms play a pivotal role in exacerbating tissue injury and impeding recovery. Stroke refers to an interruption of normal blood flow that causes damage in the brain or spinal cord. This condition presents suddenly and has a multifaceted pathophysiology.[1,2] According to the World Health Organization (WHO’s) global health estimates (2000–2019), it is the second leading cause of disability and death worldwide after ischemic heart disease, responsible for approximately 11% of total deaths.[3]
Stroke is typically classified as either ischemic or hemorrhagic. Approximately 87% of cases are ischemic, making it the most prevalent type worldwide.[4,5] IS occurs due to insufficient cerebral blood flow, depriving the brain of essential nutrients such as glucose and oxygen.[1] Conversely, hemorrhagic stroke results from bleeding into the brain or subarachnoid space, often due to a ruptured blood vessel. This causes increased intracranial pressure.[1]
Stroke risk factors are broadly divided into non-modifiable and modifiable categories. Non-modifiable factors include advancing age, sex, and genetic predisposition.[6] Modifiable factors encompass lifestyle-related contributors and underlying conditions such as atrial fibrillation, hypertension, hyperlipidemia, diabetes, smoking, physical inactivity, poor diet, abdominal obesity, and alcohol consumption.[6] Hypertension is the most significant risk factor, accounting for approximately 54% of strokes globally.[6,7] A recent surge in stroke incidence among young adults has been linked to modifiable risk factors such as hypertension, diabetes, and tobacco and illicit substance use in this demographic.[8]
The WHO estimated in 2020 that the highest burden of stroke falls upon low- and middle-income nations,[3] an assessment aligned with data from the Global Burden of Disease (GBD 2016) study.[9] Furthermore, the incidence of stroke doubled in developing low-income countries during this period. Incidence escalates with age, doubling after the age of 55.[9] However, there is growing concern regarding a 5.7% global surge in stroke occurrences among individuals aged 20–54 from 1990 to 2016, as reported by the GBD study.[9] Notably, younger women face a heightened risk and greater fatality rate compared to older women, attributable to pregnancy-related factors such as preeclampsia and contraceptive or hormonal therapy use.[9]
Africa currently bears one of the highest stroke burdens worldwide, with incidence rates potentially 2–3 times higher than in Western Europe and the USA.[10] This high burden is driven by factors such as the poor diagnosis and management of stroke risk factors such as hypertension, diabetes, and heart disease.[11] Furthermore, the prevalence of conditions such as Chagas disease, sickle-cell disease, and human immunodeficiency virus/acquired immunodeficiency syndrome (AIDS) in Africa increases the population’s stroke risk.[11] Inadequate public health responses and limited access to quality health services and treatment options in many African countries also contribute to the increasing incidence.[11] For example, a case–control study by Sarfo et al. identified a low income (<$1000) as a risk factor for the increasing stroke burden in Ghana and Nigeria.[5]
Amidst this complexity, emerging research sheds light on promising phytotherapeutic interventions aimed at attenuating neuroinflammation and promoting post-stroke recovery.[12] This review explores the intricate interplay between neuroinflammatory mechanisms in IS and the potential of phytotherapeutic strategies to mitigate its detrimental effects, offering new avenues for therapeutic intervention.
PATHOPHYSIOLOGY OF ISCHEMIC STROKE
In the majority of cases, IS occurs due to arterial obstruction, leading to a temporary cessation of blood flow. The sequence of events following the onset of ischemic brain damage begins with the formation of a core of irreversibly damaged necrotic tissue within the affected vascular region. This is followed by the development of late-phase injury in the peri-infarct area, which includes a potentially salvageable region surrounding the core.[13]
Reperfusion is critical to prevent further damage to the ischemic brain tissue; however, the restoration of circulation can paradoxically exacerbate injury.[14] The middle cerebral artery (MCA) is a common site of occlusion in IS. Experimentally, bilateral or unilateral common carotid artery occlusion is often used to induce transient focal cerebral ischemia in rodents,[15] a model relevant due to the increasing clinical incidence of carotid stenosis in acute stroke, which often manifests as unilateral or bilateral carotid artery occlusion.[16] Research into IS and its associated neuronal injuries indicates that oxidative stress (OS) and immune responses are key contributors to the resulting neuronal damage.[17]
Oxidative stress
OS is primarily a disturbance in the balance between the production of reactive oxygen species (ROS) and antioxidant defenses. It is induced in cerebral ischemia mainly through inflammation and reperfusion, which significantly increase ROS production in both the brain and cardiovascular system.[18,19] OS is a primary factor in post-stroke injuries, triggering inflammation, a crucial immune response following stroke.[20] In addition, OS contributes to neuronal apoptosis, excitotoxicity, and compromises blood–brain barrier (BBB) integrity, thereby exacerbating overall brain damage.[21]
The radical nitric oxide (NO) is elevated during brain ischemia. While it plays a role in restoring blood supply and reducing damage, it also encourages the formation of peroxynitrite through its reaction with the superoxide anion. NO further promotes the expression of adhesion molecules and inflammatory mediators, inhibits enzymes necessary for DNA replication, and disrupts cellular iron homeostasis.[22]
Several herbal compounds with antioxidant activities have shown promise in alleviating OS in IS. For instance, research on ligusticum chuanxiong volatile oil demonstrates its ability to mitigate ischemic damage. It reduces cerebral infarction volume and boosts the activity of key antioxidant enzymes, including superoxide dismutase, glutathione peroxidase, and nitric oxide synthase (NOS) in rat models, alongside a notable decrease in malondialdehyde levels.[23]
Necrotic cell death
Ischemic necrosis is a key feature in the pathophysiology of IS. Decreased blood flow subjects neurons in the ischemic core to necrosis. The reduction in blood flow leads to a critical decrease in Adenosine triphosphate (ATP), which is essential for maintaining neuronal membrane potential through the Na+/K+-ATPase pump.[24] During ischemia, the failure of this pump disrupts the regulation of Na+ and K+ concentrations across the neuronal cell membrane. This leads to sodium accumulation, cellular edema, and eventual cellular rupture, resulting in the degradation of nuclei and the release of cellular contents into the extracellular environment.[24] This release of cellular components triggers inflammatory reactions around the dying cell. Furthermore, Ca2+ overload, excessive ROS, and reactive nitrogen species (RNS) formation contribute to mitochondrial swelling, thereby promoting neuronal death.[25]
Neuroinflammation
The pathophysiology of stroke involves a progressive systematic immune response after the initiation of stroke that contributes to neuronal loss as well as tissue repair. The process involves actions of the immune cells, immune mediators, and effector molecules which impact the severity of the stroke and the recovery process.[26] Post-ischemic inflammation accounts for the secondary progression of brain damage and the severity of stroke outcome.[13] The fervent neuroinflammation that occurs following IS through the interaction of inflammatory cells, chemokines, inflammatory cytokines, and the complement system is actively involved in causing BBB damage, leading to hemorrhagic transformation.[27]
A key mechanism in this process involves leukocytes, which are a significant source of matrix metalloproteinase-9 (MMP-9). MMP-9 is instrumental in the initial destruction of the BBB, and in turn, further facilitates leukocyte recruitment, creating a vicious cycle of disruption.[28] The increased number of circulating leucocytes plays a major role by blocking the flow of erythrocytes through the microvasculature and increasing adherence to the endothelium. This causes significant damage to the blood vessels and brain tissues, thereby aggravating neuronal injury and activating proinflammatory factors which lead to the production of ROS, proteases, and MMPs.[28]
This inflammatory cascade is propagated by the sequential invasion of immune cells. Following neutrophils, monocytes adhere to the vessel walls and move toward ischemic regions.[29] Inflammatory mediators such as cytokines, interleukins, and MMPs also contribute majorly to this process by promoting the expression of cell adhesion molecules (CAMs) in the ischemic core, which further AIDS the recruitment of leukocytes.[29] The resulting BBB disruption leads to the migration and infiltration of various inflammatory cells such as macrophages, natural killer cells, T lymphocytes, and polymorphonuclear leukocytes to the ischemic site. Studies have shown that the infiltrating leukocytes and activated microglia elevate cytokines, and some studies have reported that resident neurons and glia also produce cytokines following brain ischemia.[30]
To synthesize these pathophysiological mechanisms, we developed a flowchart illustrating the sequential processes involved in the development and progression of IS [Figure 1]. The flowchart also highlights potential therapeutic entry points for natural compounds that may aid in the management of IS.
- Neuroinflammatory cascade in ischemic stroke pathology and phytotherapeutic interventions. ↑ - Increase; ↓ - Decrease; DAMPs: Damage-associated molecular patterns, ROS: Reactive oxygen species, RNS: Reactive nitrogen species, BBB: Blood–brain barrier, ICAM-1: Intercellular adhesion molecule 1, ATP: Adenosine triphosphate, MMP-9: Matrix metalloproteinase-9, NK: Natural killer, TNF-α: Tumor necrosis factor alpha, IL-1β: Interleukin-1 beta. Core pathological triggers
, secondary damage 
, neuroinflammation 
, and phytotherapy intervention 
.This flowchart illustrates the sequential pathophysiological events triggered by cerebral ischemia. The initial vascular occlusion leads to energy failure (massive ATP depletion), which simultaneously initiates two parallel damaging pathways: OS (characterized by overproduction of ROS and RNS including peroxynitrite) and necrotic cell death (due to Na+/K+ pump failure, cellular swelling, and rupture). These primary insults converge to initiate a self-amplifying neuroinflammatory cascade.
Key convergent steps include (1) release of damage-associated molecular patterns from necrotic neurons, which activate resident microglia and (2) OS directly compromising BBB integrity and promoting neuronal apoptosis and excitotoxicity. Activated microglia produce pro-inflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin-1 beta [IL-1β]), which upregulate adhesion molecules (intercellular adhesion molecule 1, selectins) on endothelial cells, facilitating leukocyte invasion (neutrophils and monocytes). Infiltrated leukocytes release MMP-9, ROS, and additional cytokines, which collectively degrade the basement membrane and tight junctions of the BBB. This disruption permits further influx of inflammatory cells (T-cells, macrophages, natural killer cells), creating a self-perpetuating vicious cycle (emphasized by bold arrows) that amplifies neuroinflammation and leads to hemorrhagic transformation and aggravated brain damage. Phytotherapeutic interventions (highlighted in green) demonstrate potential mechanisms for disrupting this pathological cascade. Scutellaria baicalensis (through baicalein) targets both OS and pro-inflammatory cytokine production; Withania somnifera (ashwagandha) provides anti-apoptotic and anti-oxidant protection; and Buyang Huanwu decoction (BHD) employs a multi-target approach by inhibiting apoptosis, reducing inflammation, and promoting neurogenesis and angiogenesis. The diagram highlights the interconnected nature of these pathways, demonstrating how initial ischemic injury evolves into sustained inflammatory damage through multiple reinforcing feedback loops.
TARGETING NEUROINFLAMMATION IN IS: MANAGEMENT PRACTICE
The management of IS focuses on minimizing neuronal injury by addressing arterial occlusion and facilitating cerebral reperfusion. Acute treatment strategies primarily involve thrombolytic agents to swiftly restore blood flow. However, these agents are effective only within a narrow therapeutic window post-stroke. Once this acute period is surpassed, the risk of irreversible neuronal loss escalates due to the initiation of cell death pathways.[26]
Medical interventions aim to restore blood flow to the affected area and minimize the extent of necrosis. These primarily include thrombolytic therapy to dissolve blood clots, such as the use of recombinant tissue plasminogen activator (rtPA), or mechanical thrombectomy for clot removal.[31] At present, rtPA is the sole Food and Drug Administration-approved thrombolytic agent for IS.[31] Despite its efficacy, rtPA faces significant limitations, notably a constrained therapeutic time window (<4.5 h). Its primary adverse effects include intracerebral bleeding, hemorrhagic transformation, and neurotoxicity.[27] These limitations necessitate the exploration of alternative therapies for stroke management.
Nanomedicine in management of stroke
Recent research trends indicate that nanomedicines can be developed as targeted therapies for stroke and other inflammation-associated cerebrovascular diseases due to their promising anti-inflammatory effects.[32] Yuan et al. discovered that the bioactive nanoparticle anti-inflammatory therapeutic based on tempol-conjugated phenylboronic acid pinacol ester-modified cyclodextrin nanoparticle (ATPCDNP) demonstrates notably enhanced in vivo efficacy resulting from its inflammation-resolving activity.[32] This nanoparticle is derived from loading the anti-inflammatory peptide Ac2-26 onto an active oligosaccharide material, tempolconjugated phenylboronic acid pinacol ester-modified cyclodextrin (TPCD). Previous research also revealed that a synthesized biomimetic Mn3O4 nanoenzyme constrained IS and reduced nervous injury by lowering inflammation levels, prolonging circulation time, and exhibiting potent ROSscavenging activity.[33]
Gut microbiota interventions in management of stroke
Bacteriotherapy, the manipulation of gut microbiota, is gaining increasing attention in stroke research. Its importance lies in the crucial role the gut microbiota plays in modulating the immune system and inflammation.[34,35] Microbiota-focused studies have demonstrated the potential to reverse stroke recovery impairment in elderly mice through post-stroke bacteriotherapy. This approach involves restoring a more youthful gut microbiome by manipulating the immunologic, microbial, and metabolomic profiles.[34,35]
Molecular therapies in management of stroke
Molecular therapeutic approaches encompass various interventions. One strategy is the augmentation of macrophage efferocytosis to address IS, which AIDS in inflammation resolution, brain repair, and the restoration of neurological functions.[36] The intranasal administration of a novel Wnt protein has shown promise in specifically promoting the Wnt/β-catenin signaling pathway. This protein acts as an immunomodulatory agent, ameliorating toxic responses in microglia/macrophages and astrocytes during ischemic brain injury.[36] Another avenue involves angiopoietin-like 4, which enhances post-stroke angiogenesis and neurogenesis by upregulating protein kinase B (AKT) phosphorylation, reducing neuronal death, and inhibiting inflammatory responses.[37] The adoptive transfer of CD3+NK1.1-TCRβ+CD4-CD8- double-negative T cells has demonstrated a significant reduction in infarct volume and improved sensorimotor function following IS.[38] Intranasal administration of small extracellular vesicles (sEVs) carrying brain-derived neurotrophic factor (sEVs) resulted in the upregulation of neuroprotection-related genes, downregulation of inflammation-related genes, and decreased inflammatory cytokine expression and glial response.[24] Similarly, manipulating molecular receptors, such as with the glucagon-like peptide-1 receptor (GLP-1R) agonist exendin-4, protects the BBB and reduces brain inflammation following cerebral ischemia. Notably, GLP-1R is expressed on astrocytes.[39] Furthermore, the complement C3a receptor, known for its regulatory role in inflammation and involvement in neurodevelopment and plasticity, has been targeted through intranasal administration of its agonist to enhance outcomes after IS.[40]
Pharmacological agents in management of IS
Pharmacological interventions utilize agents with anti-inflammatory and/or antioxidant properties for IS management.[41] For instance, combined therapy with chlorpromazine and promethazine has demonstrated efficacy in inhibiting the neuroinflammatory response and activation of the NOD-like receptor protein 3 (NLRP3) inflammasome, conferring neuroprotection after ischemia/reperfusion.[41] Similarly, edaravone dexborneol, which has completed a phase III clinical trial and obtained approval from China’s National Medical Products Administration for treating IS, exhibits the ability to restore redox balance and regulate inflammatory immune responses. This dual action provides neuroprotection in IS.[42]
PHYTOTHERAPY USED IN MANAGEMENT OF NEUROINFLAMMATION IN STROKE
Herbal medicines, primarily derived from plants, represent a valuable reservoir for discovering new therapeutic agents addressing various human ailments. Herbs are often associated with fewer reported side effects compared to allopathic medicine, and they may be suitable for extended periods of use in the context of longstanding health issues such as stroke.[43] Despite the promise, the translation of findings from laboratory animal research to clinical trials has posed a significant challenge for incorporating herbal medicine into stroke treatment.[43]
Various naturally occurring plant-derived compounds have demonstrated efficacy in both preventing and treating stroke [Table 1]. These compounds are not only cost-effective and accessible compared to synthetic alternatives but also often offer enhanced safety and efficacy profiles.[44] Numerous studies have highlighted their potent anti-inflammatory potential, effectively protecting animals from inflammation-associated neurodegenerative diseases, including stroke. Some plant compounds also exhibit vasodilatory properties that can improve blood flow, a crucial factor in stroke recovery. Furthermore, dietary approaches like plant-based diets have been linked to a lower overall risk of stroke.[45] A key therapeutic strategy involves combining these plants into traditional formulations or decoctions that can simultaneously target multiple pathways in stroke pathology [Table 2]. Single plant compounds can exhibit targeted or multi-mechanistic actions. For example, berberine specifically inhibits the pro-inflammatory enzyme cyclooxygenase-2 (COX-2),[46] while Curcuma longa’s curcumin primarily suppresses the NF-kB signaling pathway.[47] Others such as S. baicalensis (through baicalin) and W. somnifera offer broader protection by targeting both OS and inflammation or apoptosis [Figure 1 and Table 1].[48,49] However, traditional formulations or decoctions are designed for multi-systemic intervention by combining several such herbs [Table 2]. BHD demonstrates multi-systemic target, as its formula simultaneously downregulates genes for inflammation and apoptosis while upregulating neurogenesis [Figure 1].[50] Similarly, the NaoXinTong Capsule acts on diverse processes from OS to neurovascularization.[51] This evolution- from single-target molecules to multi-mechanistic plants and finally to synergistic decoctions showcases a strategic shift from isolated interventions to holistic system regulation in managing stroke pathology.
| Plant | Family | Active compound | Outcome | References |
|---|---|---|---|---|
| Berberine | Berbericidaceae | Alkaloid | Anti-inflammatory (↓cyclooxygenase-2, prostaglandin E2); anti-atherosclerotic (↓LDL) | [46] |
| Curcuma longa | Zingiberaceae | Curcumin | Anti-inflammatory | [47] |
| Scutellariabaicalensis(Baikal Skullcap) | Lamiaceae | Baicalin | Anti-apoptotic, antioxidant, anti-inflammatory | [48] |
| Withania somnifera(Ashwagandha) | Solanaceae | Withanolides | Antioxidant; Anti-apoptotic | [49] |
| Garlic | Amaryllidaceae | Organosulfur | Addresses comorbidities (atherosclerosis, hypertension, diabetes) | [52] |
| Panax quinquefolius L. (American Ginseng) | Ginseng | Ginsenosides | Neuroprotective; anxiolytic | [53] |
| Panax ginseng (Ginseng) | Ginseng | Panaxatriol saponins | Pro-angiogenic (↑VEGF, Angiopoietin-1); ↑Cerebral perfusion | [54] |
| Ginkgo biloba | Ginkgoaceae | Ginkgo Biloba Extract | Multi-target alleviation of stroke pathology; clinically safe | [55,56] |
| Clinacanthus nutans | Acanthaceae | Ethanol leaf extract | Anti-inflammatory (↓NF-κB, ↓IL-1β) | [57] |
| Morin | Moraceae | Flavonoid | Antioxidant; Anti-inflammatory (↓proinflammatory cytokines) | [58] |
| Moringa Oleifera | Moringaceae | Crude Extract | Antioxidant (↓ oxidative stress) | [59] |
| Quercetin | Various | Flavonoid | Antioxidant, Anti-apoptotic, Anti-inflammatory, reduces Ca2+overload | [60] |
| Colebrookea oppositifolia | Lamiaceae | Methanolic root extract | Antioxidant (↑SOD, ↓Lipid peroxidation); Anti-inflammatory (↓TNF-α, IL-6, ICAM-1) | [61] |
| Angelica gigas | Apiaceae | Hairy root extract | BBB protectant (↑ZO-1, Occludin; ↓permeability); Pro-angiogenic (↑VEGF) | [62] |
| Cassia obtusifolia | Fabaceae | Cassiae semen | Anti-inflammatory | [63] |
| Arctigenin | Asteraceae | Lignan | Anti-inflammatory (↓Microglial activation, TNF-α, IL-1β) | [64] |
| Cinnamon | Lauraceae | Cinnamon extract | Anti-inflammatory (↓IL-6, TNF-α, MMPs) | [65] |
| Silybum marianum (Milk Thistle) | Asteraceae | Silymarin, Silibinin | Anti-inflammatory (inhibits NF-κB, STAT-1) | [66] |
| Cymbopogon martinii | Graminae | Essential Oil | Neuroprotective; potent antioxidant | [67] |
| Salviae Miltiorrhizae (Danshen) | Lamiaceae | Salvianolic acid A | Antioxidant (inhibits eNOS uncoupling & ONOO-formation) | [68] |
| Herba Leonuri (Motherwort) | Lamiaceae | Leonurine (Alkaloid) | Antioxidant, Anti-apoptotic, protects mitochondrial function | [69] |
| Momordica charantia (Bitter Melon) | Cucurbitaceae | Momordica charantiaPolysaccharide | Antioxidant; inhibits JNK3 signaling | [70] |
| Polygonum multiflorum | Polygonaceae | Emodin | Anti-apoptotic (↑Bcl-2/Bax, p-Akt; ↓Caspase-3) | [71] |
| Mimusops elengi | Sapotaceae | Polyphenolic Compounds | Antioxidant; Anti-inflammatory | [72] |
| Boswellia serrata | Burseraceae | 11-Keto-β-boswellic acid | Antioxidant (activates Nrf2/HO-1 pathway) | [73] |
| Paeonia lactiflora | Paeoniaceae | Paeoniflorin | Anti-apoptotic (↑Bcl-2, ↓Bax); inhibits astrocyte over-activation | [74] |
| Apium graveolens (Celery) | Apiaceae | Not specified | Neuroprotective; Antioxidant; Anti-inflammatory | [75] |
| Uncaria sinensis (Gou Teng) | Rubiaceae | Partially Purified Components | BBB protectant (inhibits MMP-9, protects tight junctions) | [76] |
| Eclipta alba | Asteraceae | Extract | Enhances antioxidant defenses | [77] |
| Brassica rapa L. | Brassicaceae | Functional Monomer | Neuroprotective; Anti-hypoxia | [78] |
| Vitis amurensis | Vitaceae | Methanol Extract | Anti-apoptotic, Antioxidant, Anti-inflammatory (Anti-excitotoxic) | [79] |
| Marine Algae | Various | Phenolics, Carotenoids, Polysaccharides | Antioxidant, Anti-inflammatory, promotes cholesterol homeostasis | [80] |
SOD: Superoxide dismutase, BBB: Blood–brain barrier, ICAM-1: Intercellular adhesion molecule 1, MMP-9: Matrix metalloproteinase-9, TNF-α: Tumor necrosis factor alpha, IL-1β: Interleukin-1 beta. Core pathological triggers, Secondary damage, Neuroinflammation, Phytotherapy intervention, LDL: Low-density lipoprotein, VEGF: Vascular endothelial growth factor, NF-κB: Nuclear factor kappa-light-chain-enhancer of activated B cells. Key: Increase ↑; Decrease ↓
| Decoction/formulation | Origin | Composition | Outcome | References |
|---|---|---|---|---|
| Tongqiao Huoxue Decoction | Traditional Chinese Medicine (TCM) | Radix Paeoniae Rubra, Rhizoma Chuanxiong, Semen Persicae, Flos Carthami, + 5 others | Anti-inflammatory (↓serum TNF-αand IL-6) | [81] |
| Buyang Huanwu Decoction | TCM | Astragalus mongholicus, Angelica sinensis, Paeonia lactiflora, + 4 others | Multi-target. ↓inflammation, apoptosis; ↑neurogenesis, angiogenesis | [50] |
| Mijianchangpu Decoction (MJCPD) | TCM | Contains Suberic acid, epishyobunone, etc. | Neuroprotective | [19] |
| NaoXinTong Capsule (NXT) | TCM | Radix Astragali, Radix Angelicae Sinensis, Radix Paeoniae Rubra, + 4 others | Multi-target. Acts on inflammation, apoptosis, oxidative stress, and neovascularization | [51] |
| Dengzhan Shengmai capsule | TCM | Erigeron breviscapus, Panax ginseng, Ophiopogon japonicus, Schisandra chinensis | Pro-repair (promotes blood circulation, nourishes Yin) | [82] |
| Huang-Lian-Jie-Du-decoction | TCM (Oren-gedoku-to in Japanese) | Berberine+Baicalin+Jasminoidin | Neuroprotective: potent antioxidant (activates Nrf2 pathway) | [83] |
| Qiancao naomaitong mixture | TCM oral liquid | Boschniakia himalaica, Lysimachia barystachys | Anti-apoptotic, Antioxidant, improves neuronal nutrition | [84] |
| Erigeron breviscapus Injection (DZXI/DZSI) | TCM Injection | Extract of Erigeron breviscapus | BBB protectant (↓iNOS and MMP-9 protein expression) | [85,86] |
| HT047 | Herbal Formula | Scutellariabaicalensis, Pueraria lobata | Combats neuroinflammation | [87] |
| Combined extract | Herbal Formula | Oryza sativa, Anethum graveolens | Improves oxidative stress, inflammation, and cerebral blood flow (↑eNOS) | [88] |
| Combined extract | Herbal Formula | Trema orientalis, Bacopa monnieri | Thrombolytic property | [89] |
TNF-α: Tumor necrosis factor alpha, IL-1β: Interleukin-1 beta, BBB: Bood–brain barrier. Key: Increase ↑; Decrease ↓
CONCLUSION
Phytotherapy represents a promising strategic direction for ischemic stroke treatment. It directly addresses critical limitations of current thrombolytics, such as their narrow therapeutic window and reliance on advanced medical infrastructure. By targeting fundamental pathways like neuroinflammation and oxidative stress, herbal medicines offer a viable path toward safer, more accessible, and multi-targeted therapeutic options for a broader global population.
Ethical approval:
Institutional review board approval is not required.
Declaration of patient consent:
Patient’s consent is not required as there are no patients in this study.
Conflicts of interest:
There are no conflicts of interest
Use of artificial intelligence (AI)-assisted technology for manuscript preparation:
The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.
Financial support and sponsorship: Nil.
References
- Pathology, anatomy, and pathophysiology of stroke. Cambridge: Cambridge University Press; 2016:19-54. doi:10.1017/cbo9781316095805.003
- [CrossRef] [Google Scholar]
- Edaravone dexborneol treatment attenuates neuronal apoptosis and improves neurological function by suppressing 4-HNE-associated oxidative stress after subarachnoid hemorrhage. Front Pharmacol. 2022;13:848529. doi: 10.3389/fphar.2022.848529
- [CrossRef] [PubMed] [Google Scholar]
- Global epidemiology of stroke and access to acute ischemic stroke interventions. Neurology. 2021;97(20):S6-S16. doi:10.1212/wnl.0000000000012781
- [CrossRef] [PubMed] [Google Scholar]
- Targeting autophagy in ischemic stroke: From molecular mechanisms to clinical therapeutics. Pharmacol Ther. 2021;225:107848. doi:10.1016/j.pharmthera.2021.107848
- [CrossRef] [PubMed] [Google Scholar]
- Stroke among young West Africans: Evidence from the SIREN (Stroke investigative research and educational network) large multisite case-control study. Stroke. 2018;49(5):1116-1122. doi:10.1161/strokeaha.118.020783
- [CrossRef] [PubMed] [Google Scholar]
- Stroke risk factors, genetics, and prevention. Circ Res. 2017;120(3):472-495. doi:10.1161/circresaha.116.308398
- [CrossRef] [PubMed] [Google Scholar]
- Heart disease and stroke statistics-2019 update: A report from the American heart association. Circulation. 2019;139(10):e56-e528. doi:10.1161/cir.0000000000000659
- [CrossRef] [PubMed] [Google Scholar]
- Epidemiology and risk factors for stroke in young individuals: Implications for prevention. Curr Opin Cardiol. 2021;36(5):565-571. doi:10.1097/hco.0000000000000894
- [CrossRef] [PubMed] [Google Scholar]
- Global burden of mental, neurological, and substance use disorders: An analysis from the global burden of disease study 2010. Disease control priorities In: Mental, neurological, and substance use disorders Vol 4. (3rd ed). United States: The World Bank; 2016. p. :29-40. doi: 10.1596/978-1-4648-0426-7_ch2
- [CrossRef] [PubMed] [Google Scholar]
- Stroke in Africa: Profile, progress, prospects and priorities. Nat Rev Neurol. 2021;17(10):634-656. doi:10.1038/s41582-021-00542-4
- [CrossRef] [PubMed] [Google Scholar]
- A systematic review of the epidemiological and the public health implications of stroke in Sub-Saharan Africa. J Stroke Cerebrovasc Dis. 2024;33(8):107733. doi:10.1016/j.jstrokecerebrovasdis.2024.107733
- [CrossRef] [PubMed] [Google Scholar]
- The role of traditional herbal medicine for ischemic stroke: From bench to clinic-a critical review. Phytomedicine. 2023;109:154609. doi:10.1016/j.pymed/2022.154609
- [CrossRef] [PubMed] [Google Scholar]
- Emerging neuroprotective strategies for the treatment of ischemic stroke: An overview of clinical and preclinical studies. Exp Neurol. 2021;335:113518. doi:10.1016/j.expneurol.2020.113518
- [CrossRef] [PubMed] [Google Scholar]
- Targeting the ischemic penumbra. Stroke. 2011;42(1):S7-11. doi:10.1161/strokeaha.110.596684
- [CrossRef] [PubMed] [Google Scholar]
- Temporary occlusion of common carotid arteries does not evoke total inhibition in the activity of corticospinal tract neurons in experimental conditions. Biomedicines. 2023;11(5):1287. doi:10.3390/biomedicines11051287
- [CrossRef] [PubMed] [Google Scholar]
- Mapping cerebrovascular reactivity impairment in patients with symptomatic unilateral carotid artery disease. J Am Heart Assoc. 2021;10(12):e020792. doi:10.1161/jaha.121.020792
- [CrossRef] [PubMed] [Google Scholar]
- Pathogenic mechanisms following ischemic stroke. Neurol Sci. 2017;38(7):1167-1186. doi:10.1007/s10072-017-2938-1
- [CrossRef] [PubMed] [Google Scholar]
- Oxidative stress in ischemia and reperfusion: Current concepts, novel ideas and future perspectives. Biomark Med. 2017;11(11):11031-1040. doi:10.2217/bmm-2017-0110
- [CrossRef] [PubMed] [Google Scholar]
- Beneficial effects of mijianchangpu decoction on ischemic stroke through components accessing to the brain based on network pharmacology. J Ethnopharmacol. 2022;285:114882. doi:10.1016/j.jep.2021.114882
- [CrossRef] [PubMed] [Google Scholar]
- Neuroinflammation and anti-inflammatory therapy for ischemic stroke. Heliyon. 2023;9(7):e17986. doi:10.1016/j.heliyon.2023.e17986
- [CrossRef] [PubMed] [Google Scholar]
- Pathophysiology of ischemic stroke: Role of oxidative stress. Curr Pharm Design. 2020;26(34):4246-4260. doi:10.2174/138161282666620070813 3912
- [CrossRef] [PubMed] [Google Scholar]
- Nitric oxide-dependent pathways as critical factors in the consequences and recovery after brain ischemic hypoxia. Biomolecules. 2021;11(8):1097. doi:10.3390/biom11081097
- [CrossRef] [PubMed] [Google Scholar]
- Protective effect of salvianolic acid B on isolated heart ischemia/reperfusion injury in rats. China J Chin Mater Med. 2012;37(11):1565-1568. doi:10.4268/cjcmm20120321
- [CrossRef] [Google Scholar]
- Intranasal delivery of BDNF-loaded small extracellular vesicles for cerebral ischemia therapy. J Control Release. 2023;357:1-19. doi:10.1016/j.jconrel.2023.03.033
- [CrossRef] [PubMed] [Google Scholar]
- Cell death mechanisms in stroke and novel molecular and cellular treatment options. Curr Neuropharmacol. 2018;16(9):1396-1415. doi:10.2174/1570159x16666180302115544
- [CrossRef] [PubMed] [Google Scholar]
- Inflammatory responses after ischemic stroke. Semin Immunopathol. 2022;44(5):625-648. doi:10.1007/s00281-022-00943-7
- [CrossRef] [PubMed] [Google Scholar]
- Hemorrhagic transformation after tissue plasminogen activator treatment in acute ischemic stroke. Cell Mol Neurobiol. 2020;42(3):621-646. doi:10.1007/s10571-020-00985-1
- [CrossRef] [PubMed] [Google Scholar]
- Inflammation after ischemic stroke: The role of leukocytes and glial cells. Exp Neurobiol. 2016;25(5):241-251. doi:10.5607/en.2016.25.5.241
- [CrossRef] [PubMed] [Google Scholar]
- Tetraspanin CD9: A key regulator of cell adhesion in the immune system. Front Immunol. 2018;9:863. doi:10.3389/fimmu.2018.00863
- [CrossRef] [PubMed] [Google Scholar]
- Clinical significance of baseline neutrophil-to-lymphocyte ratio in patients with ischemic stroke or hemorrhagic stroke: An updated meta-analysis. Front Neurol. 2019;10:1032. doi:10.3389/fneur.2019.01032
- [CrossRef] [PubMed] [Google Scholar]
- Recycled translation: Repurposing drugs for stroke. Transl Stroke Res. 2022;13(6):866-880. doi:10.1007/s12975-022-01000-z
- [CrossRef] [PubMed] [Google Scholar]
- Targeted treatment of ischemic stroke by bioactive nanoparticle-derived reactive oxygen species responsive and inflammation-resolving nanotherapies. ACS Nano. 2021;15(10):16076-16094. doi:10.1021/acsnano.1c04753
- [CrossRef] [PubMed] [Google Scholar]
- Bioactive nanoenzyme reverses oxidative damage and endoplasmic reticulum stress in neurons under ischemic stroke. ACS Nano. 2021;16(1):431-452. doi:10.1021/acsnano.1c07205
- [CrossRef] [PubMed] [Google Scholar]
- Gut microbiota-derived short-chain fatty acids promote poststroke recovery in aged mice. Circ Res. 2020;127(4):453-465. doi:10.1161/circresaha.119.316448
- [CrossRef] [PubMed] [Google Scholar]
- Gut microbes in cerebrovascular diseases: Gut flora imbalance, potential impact mechanisms and promising treatment strategies. Front Immunol. 2022;13:975921. doi:10.3389/fimmu.2022.975921
- [CrossRef] [PubMed] [Google Scholar]
- Wnt-3a alleviates neuroinflammation after ischemic stroke by modulating the responses of microglia/macrophages and astrocytes. Int Immunopharmacol. 2019;75:105760. doi:10.1016/j.intimp.2019.105760
- [CrossRef] [PubMed] [Google Scholar]
- Angiopoietin-like 4 promotes angiogenesis and neurogenesis in a mouse model of acute ischemic stroke. Brain Res Bull. 2021;168:156-164. doi:10.1016/j.brainresbull.2020.12.023
- [CrossRef] [PubMed] [Google Scholar]
- TCRαβ+NK1.1-CD4-CD8-double-negative T cells inhibit central and peripheral inflammation and ameliorate ischemic stroke in mice. Theranostics. 2023;13(3):896-909. doi:10.7150/thno.80307
- [CrossRef] [PubMed] [Google Scholar]
- The glucagon-like peptide-1 receptor agonist reduces inflammation and blood-brain barrier breakdown in an astrocyte-dependent manner in experimental stroke. J Neuroinflammation. 2019;16(1):242. doi:10.1186/s12974-019-1638-6
- [CrossRef] [PubMed] [Google Scholar]
- Complement C3a treatment accelerates recovery after stroke via modulation of astrocyte reactivity and cortical connectivity. J Clin Investig. 2023;133(10):e162253. doi:10.1172/jci162253
- [CrossRef] [PubMed] [Google Scholar]
- Phenothiazine inhibits neuroinflammation and inflammasome activation independent of hypothermia after ischemic stroke. Mol Neurobiol. 2021;58(12):6136-6152. doi:10.1007/s12035-021-02542-3
- [CrossRef] [PubMed] [Google Scholar]
- Natural history and long-term prognosis of stroke types in urban and rural China: A 9-year prospective study of 0.5 million adults, P2777. Eur Heart J. 2019;40(Supplement_1):ehz748.1094. doi:10.1093/eurheartj/ehz748.1094
- [CrossRef] [Google Scholar]
- Herbal medicine in ischemic stroke: Challenges and prospective. Chin J Integr Med. 2018;24(4):243-246. doi:10.1007/s11655-018-2828-2
- [CrossRef] [PubMed] [Google Scholar]
- Pathophysiology and treatment of stroke: Present status and future perspectives. Int J Mole Sci. 2020;21(20):7609. doi:10.3390/ijms21207609
- [CrossRef] [PubMed] [Google Scholar]
- Quality of plant-based diet and risk of total, ischemic, and hemorrhagic stroke. Neurology. 2021;96(15):e1940-e1953. doi:10.1212/wnl.0000000000011713
- [CrossRef] [PubMed] [Google Scholar]
- Berberine, a herbal metabolite in the metabolic syndrome: The risk factors, course, and consequences of the disease. Molecules. 2022;27(4):1351. doi:10.3390/molecules27041351
- [CrossRef] [PubMed] [Google Scholar]
- Curcumin ameliorates white matter injury after ischemic stroke by inhibiting microglia/macrophage pyroptosis through NF-κB suppression and NLRP3 inflammasome inhibition. Oxid Med Cell Longev. 2021;2021:1-25. doi:10.1155/2021/1552127
- [CrossRef] [PubMed] [Google Scholar]
- Corrigendum to “systematic understanding of the mechanism of baicalin against ischemic stroke through a network pharmacology approach”. Evid Based Complement Alternat Med. 2019;2019:4520704. doi:10.1155/2019/4520704
- [CrossRef] [PubMed] [Google Scholar]
- Withania somnifera improves ischemic stroke outcomes by attenuating PARP1-AIF-mediated caspase-independent apoptosis. Mol Neurobiol. 2014;52(3):1093-1105. doi:10.1007/s12035-014-8907-2
- [CrossRef] [PubMed] [Google Scholar]
- Combined proteomic and metabolomic analyses of cerebrospinal fluid from mice with ischemic stroke reveals the effects of a Buyang Huanwu decoction in neurodegenerative disease. PLoS One. 2019;14(1):e0209184. doi:10.1371/journal.pone.0209184
- [CrossRef] [PubMed] [Google Scholar]
- Overview of therapeutic potentiality of Angelica sinensis for ischemic stroke. Phytomedicine. 2021;90:153652. doi:10.1016/j.phymed.2021.153652
- [CrossRef] [PubMed] [Google Scholar]
- A mini review: Garlic extract and vascular diseases. Neurol Res. 2018;40(6):421-425. doi:10.1 080/01616412.2018.1451269
- [CrossRef] [PubMed] [Google Scholar]
- American ginseng (Panax quinquefolium L.) as a source of bioactive phytochemicals with pro-health properties. Nutrients. 2019;11(5):1041. doi:10.3390/nu11051041
- [CrossRef] [PubMed] [Google Scholar]
- Panaxatriol saponins promotes angiogenesis and enhances cerebral perfusion after ischemic stroke in rats. BMC Complement Altern Med. 2017;17(1):70. doi:10.1186/s12906-017-1579-5
- [CrossRef] [PubMed] [Google Scholar]
- Ginkgo biloba extract as an adjunctive treatment for ischemic stroke. Medicine. 2020;99(2):e18568. doi:10.1097/md.0000000000018568
- [CrossRef] [PubMed] [Google Scholar]
- Similarities and differences between Ginkgo biloba and Panax notoginseng in treatment of ischemic cerebrovascular disease. Zhongguo Zhong Yao Za Zhi. 2020;45(13):3063-3072. doi: 10.19540/j.cnki.cjcmm.20200313.402
- [CrossRef] [Google Scholar]
- Clinacanthus nutans mitigates neuronal death and reduces ischemic brain injury: Role of NF-κB-driven IL-1β transcription. Neuromolecular Med. 2020;23(1):199-210. doi:10.1007/s12017-020-08618-y
- [CrossRef] [PubMed] [Google Scholar]
- Morin protects the blood-brain barrier integrity against cerebral ischemia reperfusion through anti-inflammatory actions in rats. Sci Rep. 2020;10(1):13379. doi:10.1038/s41598-020-70214-8
- [CrossRef] [PubMed] [Google Scholar]
- Moringa oleifera seed extract protects against brain damage in both the acute and delayed stages of ischemic stroke. Exp Gerontol. 2019;122:99-108. doi:10.1016/j.exger.2019.04.014
- [CrossRef] [PubMed] [Google Scholar]
- Effect and mechanisms of quercetin for experimental focal cerebral ischemia: A systematic review and meta-analysis. Oxid Med Cell Longev. 2022;2022:1-13. doi:10.1155/2022/9749461
- [CrossRef] [PubMed] [Google Scholar]
- Characterization and anti-stroke activity of stem extract of Colebrookea oppositifolia Smith. J Biologically Active Prod Nat. 2020;10(3):250-263. doi:10.1080/22311866.2020.1791731
- [CrossRef] [Google Scholar]
- Neuroprotective and cognitive enhancement potentials of Angelica gigas nakai root: A review. Sci Pharm. 2017;85(2):21. doi:10.3390/scipharm85020021
- [CrossRef] [PubMed] [Google Scholar]
- The neuroprotective effects of the seeds of Cassia obtusifolia on transient cerebral global ischemia in mice. Food Chem Toxicol. 2009;47(7):1473-1479. doi:10.1016/j.fct.2009.03.028
- [CrossRef] [PubMed] [Google Scholar]
- Arctigenin protects focal cerebral ischemia-reperfusion rats through inhibiting neuroinflammation. Biol Pharm Bull. 2012;35(11):2004-9. doi:10.1248/bpb.b12-00463
- [CrossRef] [PubMed] [Google Scholar]
- Decreased interleukin 6 and tumor necrosis factor α proteins and metalloproteinase-2,9 levels following cerebral ischemia in cinnamon-treated rats. Avicenna J Pharm Res. 2022;3(1):23-31. doi:10.34172/ajpr.2022.1055
- [CrossRef] [Google Scholar]
- Neuroprotective effects of silymarin on ischemia-induced delayed neuronal cell death in rat hippocampus. Brain Res. 2016;1646:297-303. doi:10.1016/j.brainres.2016.06.018
- [CrossRef] [PubMed] [Google Scholar]
- Bioactivity assessment of essential oils of Cymbopogon species using a network pharmacology approach. Biol Futur. 2022;73(1):107-118. doi:10.1007/s42977-022-00111-w
- [CrossRef] [PubMed] [Google Scholar]
- Salvianolic acid A inhibits calpain activation and eNOS uncoupling during focal cerebral ischemia in mice. Phytomedicine. 2017;25:8-14. doi:10.1016/j.phymed.2016.12.004
- [CrossRef] [PubMed] [Google Scholar]
- Protection against acute cerebral ischemia/reperfusion injury by Leonuri Herba total alkali via modulation of BDNF-TrKB-PI3K/Akt signaling pathway in rats. Biomed Pharmacother. 2021;133:111021. doi:10.1016/j.biopha.2020.111021
- [CrossRef] [PubMed] [Google Scholar]
- Momordica charantia exosome-like nanoparticles exert neuroprotective effects against ischemic brain injury via inhibiting matrix metalloproteinase 9 and Activating the AKT/GSK3β signaling pathway. Front Pharmacol. 2022;13:908830. doi:10.3389/fphar.2022.908830
- [CrossRef] [PubMed] [Google Scholar]
- Emodin from Polygonum multiflorum ameliorates oxidative toxicity in HT22 cells and deficits in photothrombotic ischemia. J Ethnopharmacol. 2016;188:13-20. doi:10.1016/j.jep.2016.04.058
- [CrossRef] [PubMed] [Google Scholar]
- Phytochemical screening and in vitro free radical scavenging activity of hydroalcohol extract of Mimusops elengi L. Root. Rajiv Gandhi Univ Health Sci J Pharm Sci. 2021;11(2):158-161. doi:10.26463/rjps.11_2_3
- [CrossRef] [Google Scholar]
- Aqueous and ethanolic extracts of Boswellia serrata protect against focal cerebral ischemia and reperfusion injury in rats. Phytother Res. 2016;30(12):1954-1967. doi:10.1002/ptr.5701
- [CrossRef] [PubMed] [Google Scholar]
- Paeoniflorin improves functional recovery through repressing neuroinflammation and facilitating neurogenesis in rat stroke model. PeerJ. 2021;9:e10921. doi: 10.7717/peerj.10921
- [CrossRef] [PubMed] [Google Scholar]
- Neuroprotective effects of Apium graveolens against focal cerebral ischemia occur partly via antioxidant, anti-inflammatory, and anti-apoptotic pathways. J Sci Food Agric. 2020;101(6):2256-2263. doi:10.1002/jsfa.10846
- [CrossRef] [PubMed] [Google Scholar]
- Partially purified components of Uncaria sinensis attenuate blood brain barrier disruption after ischemic brain injury in mice. BMC Complement Altern Med. 2015;15(1):157. doi:10.1186/s12906-015-0678-4
- [CrossRef] [PubMed] [Google Scholar]
- Cerebroprotective effect of Eclipta alba against global model of cerebral ischemia induced oxidative stress in rats. Phytomedicine. 2012;19(12):1106-1116. doi:10.1016/j.phymed.2012.07.004
- [CrossRef] [PubMed] [Google Scholar]
- Bioactive compound from the Tibetan turnip (Brassica rapa L.) elicited anti-hypoxia effects in OGD/R-injured HT22 cells by activating the PI3K/AKT pathway. Food Funct. 2021;12(7):2901-2913. doi:10.1039/d0fo03190a
- [CrossRef] [PubMed] [Google Scholar]
- Protective effect of an ethanol extract mixture of Vitis amurensis, Aralia cordata, and Glycyrrhizae radix against ischemia-induced brain injury in rats and excitotoxicity in cultured neurons. J Biomed Transl Res. 2016;17(1):13-19. doi:10.12729/jbtr.2016.17.1.013
- [CrossRef] [Google Scholar]
- Neuroprotective potentials of marine algae and their bioactive metabolites: Pharmacological insights and therapeutic advances. Mar Drugs. 2020;18:347. doi:10.20944/preprints202005.0342.v1
- [CrossRef] [Google Scholar]
- Tongqiao huoxue decoction for the treatment of acute ischemic stroke: A systematic review and meta-analysis. J Ethnoparmacol. 2022;283:114693. doi:10.1016/j.jep.2021.114693
- [CrossRef] [PubMed] [Google Scholar]
- Identification and characterization of chemical constituents in Dengzhan Shengmai Capsule and their metabolites in rat plasma by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. J Chromatogr B. 2019;1108:54-64. doi:10.1016/j.jchromb.2019.01.010
- [CrossRef] [PubMed] [Google Scholar]
- Treatment effects of ischemic stroke by berberine, baicalin, and jasminoidin from huanglian-jie-du-decoction (HLJDD) explored by an integrated metabolomics approach. Oxid Med Cell Longev. 2017;2017:1-20. doi:10.1155/2017/9848594.
- [CrossRef] [PubMed] [Google Scholar]
- The protective effect of qiancao naomaitong mixture on neuronal damage and cerebral ischemia/reperfusion injury. Pharm Biol. 2016;54(10):2304-2311. doi:10.3109/13880209.2016.1155627
- [CrossRef] [PubMed] [Google Scholar]
- Protective mechanism of Erigeron breviscapus injection on blood-brain barrier injury induced by cerebral ischemia in rats. Sci Rep. 2021;11(1):18451. doi:10.1038/s41598-021-97908-x
- [CrossRef] [PubMed] [Google Scholar]
- Pharmacodynamics and mechanisms of Erigeron breviscapus granules in the treatment of ischemic stroke in mice by regulating sphingolipid metabolism based on metabolomics. J Pharm Biomed Anal. 2024;242:116058. doi: 10.1016/j.jpba.2024.116058.
- [CrossRef] [PubMed] [Google Scholar]
- Rationale and design to assess the efficacy and safety of HT047 in patients with acute ischemic stroke. A multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase II trial. Medicine (Baltimore). 2019;98(43):e17655. doi:10.1097/md.0000000000017655
- [CrossRef] [PubMed] [Google Scholar]
- Cerebroprotective effect against cerebral ischemia of the combined extract of oryza sativa and anethum graveolensin metabolic syndrome rats. Oxid Med Cell Longev. 2019;2019:1-19. doi:10.1155/2019/9658267
- [CrossRef] [PubMed] [Google Scholar]
- Effects of organic extracts and their different fractions of five Bangladeshi plants on in vitro thrombolysis. BMC Complement Altern Med. 2015;15(1):128. doi:10.1186/s12906-015-0643-2
- [CrossRef] [PubMed] [Google Scholar]