2 Traditional Chinese Medicine Research Center, Cuixi Academy of Biotechnology, Zhuji, 311800, Zhejiang, China
Author
Correspondence author
Triticeae Genomics and Genetics, 2025, Vol. 16, No. 5
Received: 05 Aug., 2025 Accepted: 25 Sep., 2025 Published: 19 Oct., 2025
Angelica sinensis is a commonly used ingredient in traditional Chinese medicine. Its main function is to promote blood circulation and replenish blood. It is also widely used in regulating the functions of the cardiovascular and cerebrovascular systems. This study focuses on its multi-target mechanism of action in cardiovascular and cerebrovascular diseases, especially the active components, liek polysaccharides, ligustilide and ferulic acid. Research has found that, A. sinensis can exert anti-inflammatory, antioxidant, anti-apoptotic and neural repair effects through pathways, such as PI3K/Akt, MAPK, Nrf2/HO-1, etc., alleviate the damage caused by myocardial and cerebral ischemia-reperfusion, and also enhance vascular endothelial function and the stability of the blood-brain barrier. Animal and cell experiments also suggest that, it can regulate blood lipids, improve the microenvironment and delay aging. Although there is currently a lack of large-scale clinical validation, the existing research foundation provides reliable support for its development into a standardized plant-based drug.
1 Introduction
Angelica sinensis (Oliv.) Diels, an important medicinal herb in traditional Chinese medicine, has been used for treatments, such as "promoting blood circulation" and "replenishing blood" for hundreds of years. Especially for women's health and cardiovascular aspects, its medicinal value is very high (Chen et al., 2013; 2024). In folk and traditional medicine, it is believed that, it can improve insufficient blood supply to the heart and brain, relieve dizziness and fatigue, regulate the condition of blood vessels, and is particularly friendly to some elderly people. Many of these traditional usages are based on experience, but modern pharmacological research has confirmed them.
Modern pharmacological research has found that, A. sinensis contains a wide variety of active ingredients, like volatile oil, organic acids, flavonoids, polysaccharides, coumarin, etc. These substances do not merely "regulate qi and blood". Their scope of action is quite wide - ranging from regulating lipid and lowering blood sugar to inhibiting thrombosis, anti-inflammation and anti-oxidation (Han et al., 2021; Shen et al., 2024). Besides, recent studies have further pointed out that, it also performs well in regulating blood rheology and alleviating ischemic injury, and can affect multiple signaling pathways related to cardiovascular and cerebrovascular protection (Niu et al., 2018; Chen et al., 2024).
Atherosclerosis is the main "cause" of cardiovascular and cerebrovascular diseases. Its development is related to lipid accumulation, damage to vascular endothelium, and chronic inflammation. Oxidative stress and inflammation are two "triggers". Once they break out, they may lead to endothelial dysfunction, followed by problems like hypertension and thrombosis. The Z-ligustilide in A. sinensis has been proven to improve these links. For instance, it can regulate lipid metabolism, protect endothelial cells, and delay or even inhibit plaque formation (Li et al., 2024; Shen et al., 2024).
Cerebral ischemia or myocardial ischemia, in the final analysis, both result from "insufficient blood supply", leading to the necrosis or apoptosis of neurons or myocardial cells. These pathological changes are often accompanied by oxidative stress, inflammatory responses and angiogenesis disorders, making the problem even more complicated. The performance of A. sinensis extract in these aspects is not bad either. For example, it can reduce the infarct area, increase the activity of antioxidant enzymes, and regulate the apoptosis and angiogenesis pathways (Cheng et al., 2017; Niu et al., 2018; Han et al., 2021).
Cardiovascular and cerebrovascular diseases are not simple. It is not a disease that can be solved by a single "target", but rather a process interwoven with multiple factors and paths. Medicinal materials, like A. sinensis, which have complex components and multiple functions, have found their application in multi-target treatment. Combining modern pharmacology with traditional experience, it can be found that it is a potential candidate drug for cardiovascular, and cerebrovascular protection worthy of in-depth development. This study precisely aims to clarify exactly "how it works" and in which pathways it plays a key role, thereby providing new ideas for the treatment of complex vascular diseases.
2 Bioactive Components and Pharmacological Basis of A. sinensis
2.1 Major bioactive components
Polysaccharides, are one of the most abundant and have the greatest pharmacological effects components in A. sinensis. This type of water-soluble macromolecule, is mainly composed of glucose, galactose, arabinose, rhamnose, fucose, xylose and galacturonic acid, and has multiple biological activities, like hematopoiesis, immune regulation, anti-inflammation, anti-oxidation, anti-tumor, liver protection and hypoglycemia (Bi et al., 2021; Tian et al., 2024). Its mechanism of action involves the regulation of inflammation, oxidative stress and pro-fibrotic signaling pathways, and shows broad application prospects in disease prevention and treatment, especially in the intervention of cardiovascular and cerebrovascular diseases (Hou et al., 2021; Nai et al., 2021; Ren et al., 2025).
The volatile oils (ligustilide, butylphthalide etc.), and organic acids (such as ferulic acid) in A. sinensis are also key active ingredients (Lu and Wang, 2025). Ligustilide has anti-inflammatory, neuroprotective and anti-atherosclerotic effects, while ferulic acid is known for its antioxidant, anti-inflammatory and lipid-regulating properties. These components play roles in vascular protection and circulatory health (Yang et al., 2019; Ma et al., 2023; Yan et al., 2023). A. sinensis also contains coumarins (like glabralactone) and phenolic acids, which also exhibit anti-inflammatory, antioxidant and vascular protective activities. Glabralactone can inhibit inflammatory signaling pathways, while phenolic acid substances enhance antioxidant defense, and maintain vascular function (Wei et al., 2016; Choi et al., 2022; Lu and Wang, 2025).
2.2 Pharmacokinetics and tissue distribution
The pharmacokinetic characteristics of the active ingredients in A. sinensis, vary depending on their molecular structure. Polysaccharides, due to their large molecular weight, usually have a low oral bioavailability. But, with the improvement of extraction and formulation processes, their absorption rate and therapeutic potential are constantly increasing. Volatile oils and organic acids, are more easily absorbed and metabolized, and thus can exert pharmacological effects more quickly (Wei et al., 2016; Bi et al., 2021; Nai et al., 2021).
Studies have shown that, the active components of A. sinensis have specific distribution and effects in cardiovascular and cerebrovascular tissues (Niu et al., 2018). This tissue targeting is an important basis for its ability to effectively protect vascular endothelia, reduce ischemic injury, and regulate inflammatory and oxidative stress pathways, related to heart and brain health (Chen et al., 2024; Ren et al., 2025).
2.3 Overview of pharmacological actions
The polysaccharides, volatile oils and coumarin compounds in A. sinensis, all exhibit anti-inflammatory and antioxidant effects. These effects mainly include inhibiting the release of pro-inflammatory cytokines, reducing oxidative stress, and regulating immune responses, thereby jointly protecting blood vessels from damage and alleviating ischemic damage (Hou et al., 2021; Choi et al., 2022).
Due to the synergistic effect of its multiple components, A. sinensis can not only improve blood circulation and prevent thrombosis, but regulate lipid metabolism and protect vascular endothelium (Han et al., 2021; Chen et al., 2024). These mechanisms of action are the theoretical basis for its application in traditional medicine, and as well as the important basis for its recognition, in the prevention and treatment of modern cardiovascular and cerebrovascular diseases (Ren et al., 2025).
3 Multi-Target Effects on Cardiovascular Protection of A. sinensis
3.1 Antioxidant and anti-apoptotic mechanisms
A. sinensis polysaccharides (ASP), can enhance the antioxidant defense capacity of cardiovascular tissues. Studies have shown that, ASP can enhance the activities of key antioxidant enzymes, like superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), while reducing the levels of malondialdehyde (MDA), hydrogen peroxide (H2O2), and reactive oxygen species (ROS). Thereby effectively alleviating oxidative stress in models of hypertension and myocardial ischemia (Niu et al., 2018; Song et al., 2021).
ASP and its combination with other active ingredients of A. sinensis, can inhibit the apoptosis of cardiomyocytes by regulating proteins related to apoptosis. ASP treatment can down-regulate the expression of pro-apoptotic markers (e.g., Bax, cleavage caspase-3 and cleavage caspase-9), and up-regulate the anti-apoptotic protein Bcl-2, thereby reducing cell death in myocardial tissue (Song et al., 2021; Wang et al., 2024). Furthermore, the synergistic effect of ligustilide and active ingredients, like chlorogenic acid, can reduce the ratios of BAX/Bcl-2 and cleaved caspase-3/caspase-3, and provide stronger anti-apoptotic protection after myocardial infarction (Wang et al., 2024).
3.2 Anti-inflammatory and vascular protective roles
A. sinensis and its active components, can inhibit the inflammatory response by suppressing the NF-κB signaling pathway, and reducing the levels of inflammatory factors (IL-1β, IL-6, TNF-α etc.) (Chen et al., 2024; Wang et al., 2024). This anti-inflammatory mechanism is of great significance for reducing myocardial and vascular damage. Animal model studies have confirmed that, it can lower the levels of inflammatory cytokines and improve cardiac function.
A. sinensis extract can also protect vascular endothelial cells from oxidative and inflammatory damage, maintaining the integrity and function of vascular endothelium. This effect is mainly achieved by enhancing the activity of antioxidant enzymes, and regulating signaling pathways, like ERK and eNOS, thereby contributing to maintaining vascular health, and preventing atherosclerosis (Chen et al., 2024).
3.3 Protection against myocardial ischemia-reperfusion injury
ASP can activate pathways, such as AMPK-PGC1α and ATF6, improve mitochondrial function, regulate calcium ion homeostasis, and enhance the folding ability of endoplasmic reticulum proteins. These mechanisms are crucial, for reducing ischemia-reperfusion injury, and maintaining myocardial cell viability (Niu et al., 2018).
The synergistic combination of ASP and their active components, can reduce the infarct area, alleviate myocardial fibrosis, and improve cardiac function after ischemic injury. These effects are coordinated through multiple mechanisms, such as antioxidation, anti-apoptosis and anti-inflammation, thereby showing significant protective effects in myocardial tissue injury (Niu et al., 2018; Song et al., 2021; Wang et al., 2024).
4 Multi-Target Effects on Cerebrovascular Protection of A. sinensis
4.1 Mitigation of cerebral ischemia/reperfusion injury
A. sinensis and its active components, especially polysaccharides and Z-ligustilide, have demonstrated excellent antioxidant effects in models of cerebral ischemia/reperfusion injury. These components can enhance the activities of antioxidant enzymes, like superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX), while reducing oxidative stress markers and neuronal apoptosis levels (Xu et al., 2021; Chen et al., 2024; Shen et al., 2024). Mechanically, it is mainly achieved by inhibiting inflammation, reducing oxidative stress, suppressing apoptosis of nerve cells, promoting cerebral angiogenesis, and activating signaling pathways, such as AKT/mTOR and PINK1/Parkin (Figure 1). Z-ligustilide also can protect neurons by maintaining mitochondrial health, and reducing oxidative damage.
![]() Figure 1 Technological scheme of the thresher of the Tucano 480 combine harvester 1, 2, 3-the accelerator-separator drums of heap, 4-stripper beater, 5-rotary straw walkers; 6-beater drum; 7-undercylinder pan; 8-sieve cleaning; 9-transport board; 10-the hood; 11-the tray; 12-harvester fan (Adopted from Maslov et al., 2022) |
In ischemic events, A. sinensis can maintain the integrity of the blood-brain barrier (BBB) through reducing oxidative and inflammatory damage to endothelial cells. Especially Z-ligustilide, which can inhibit vascular endothelial fibrosis, promote angiogenesis and protect the BBB, thereby jointly limiting secondary brain injury after stroke (Cheng et al., 2017; Shen et al., 2024). Experimental studies have shown that, A. sinensis extract can upregulate the expression of vascular endothelial growth factor A (VEGF-A) and von Willebrand factor (vWF), thereby promoting vascular repair and maintaining BBB stability (Cheng et al., 2017; 2020).
4.2 Regulation of neuroinflammation
A. sinensis can regulate the activation of microglia, and the activation of microglia is a key driver of neuroinflammation in cerebral ischemia. Human participation in the combined application of A. sinensis, can inhibit the activation of NLRP3 inflammasome and pyroptosis of microglia, thereby reducing neuroinflammatory injury and promoting neuronal survival (Hu et al., 2020). Z-ligustilide can also inhibit the activation of microglia and inflammasome pathways, further exerting neuroprotective effects (Shen et al., 2024).
A. sinensis and its active components, can inhibit the release of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, etc.), and down-regulate the NF-κB signaling pathway, thereby reducing neuroinflammatory responses, and improving prognosis in ischemic brain injury (Han et al., 2021; Xu et al., 2021; Chen et al., 2024). These anti-inflammatory effects are one of the core mechanisms, by which A. sinensis limits secondary neuronal damage and promotes recovery.
4.3 Neural repair and regeneration
A. sinensis extract can activate neuronutrition-related signaling pathways, including the p38 MAPK/CREB/BDNF pathway, promoting the expression of brain-derived neurotrophic factor (BDNF) and other growth factors, which are crucial for the survival and repair of neurons after ischemic injury. It is helpful for neurogenesis and functional recovery (Shen et al., 2016; Cheng et al., 2017; 2020).
By up-regulating BDNF and related signals, A. sinensis enhance synaptic plasticity and promote neural regeneration, improving cognitive and neurological functional outcomes after cerebral ischemia (Cheng et al., 2020; Zhao et al., 2023). The volatile oil components of A. sinensis have also been proven to increase the expression of proteins related to synaptic plasticity, further supporting the recovery of cognitive function (Zhao et al., 2023).
5 Mechanistic Pathways of Action in Angelica sinensis
5.1 PI3K/Akt and MAPK pathways
A. sinensis and its active components, like polysaccharides and ferulic acid, could activate the PI3K/Akt pathway, which plays a key role in promoting cell survival and inhibiting apoptosis. This activation enhance the expression of anti-apoptotic proteins, such as Bcl-2, and reduce the levels of pro-apoptotic markers (e.g., Bax, caspase-3), thereby protecting cardiovascular and liver tissue cells from oxidative and inflammatory damage (Du et al., 2023; Lu and Wang, 2025). In ischemic injury and oxidative stress models, PI3K/Akt signaling mediate cell protection and promote tissue repair (Niu et al., 2018; Lu and Wang, 2025).
When returned, it can exert anti-inflammatory and anti-apoptotic effects by regulating the MAPK pathway, containing p38 MAPK. MAPK signal activation can regulate the expression of inflammatory mediators, enhance the resistance of cells to stress-induced apoptosis, and achieve protection for blood vessels and the nervous system (Chen et al., 2022; Huang et al., 2023). In the context of antifungal and angiogenic research, MAPK activation has also been confirmed to mediate cell survival and adaptability (Gao et al., 2023).
5.2 Nrf2/HO-1 and antioxidant regulation
ASP can promote the nuclear translocation of Nrf2, which is a core regulatory factor in antioxidant defense. This process can up-regulate the expression of multiple antioxidant genes, including those encoding superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX), thereby reducing oxidative stress and alleviating cell damage (Du et al., 2023; Ren et al., 2025). The activation of Nrf2 is regarded as a key link for ASP, to exert antioxidant and cytoprotective effects in various tissues.
The downstream target of Nrf2, heme oxygenase-1 (HO-1), can also be upregulated by A. sinensis, thereby enhancing its vascular protective effect. HO-1 has anti-inflammatory, antioxidant and anti-apoptotic effects, can maintain vascular endothelial function, and reduce tissue damage in the cardiovascular and cerebrovascular systems (Ren et al., 2025).
6 Experimental Evidence in Cells and Animals of A. sinensis
6.1 Cell-based studies
A. sinensis polysaccharide (ASP) and ferulic acid, have shown protective effects in various cell models. In endothelial cells and perivascular mesenchymal progenitor cells, ASP can alleviate oxidative stress, promote cell proliferation, and enhance differentiation potential (Niu et al., 2023). In HepG2 cells, ferulic acid improves ethanol induced injury, by regulating the AMPK/ACC and PI3K/AKT pathways, showing cell protective and metabolic regulatory effects (Lu and Wang, 2025). Different ASP grades at different root sites in IPEC-J2 cells, exhibited different anti-inflammatory and antioxidant activities. Some of these grades showed stronger protective effects against LPS-induced inflammation and oxidative stress (Zou et al., 2022).
The results of cell experiments consistently indicated that, ASP and related extracts could down-regulate pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, etc.), while up-regulating the levels of antioxidant enzymes (like SOD, CAT, GPX) (Zou et al., 2022; Niu et al., 2023). These effects are closely related to the inhibition of NF-κB signaling and the enhancement of cellular antioxidant capacity, supporting the anti-inflammatory and antioxidant functions of A. sinensis in in vitro experiments (Zou et al., 2022; Wen et al., 2025).
6.2 Animal model research
Although the direct evidence in myocardial ischemia-reperfusion models is limited, relevant animal studies have shown that, A. sinensis components can protect against tissue damage by reducing oxidative stress and inflammation, and regulating key survival pathways, like PI3K/AKT (Niu et al., 2023; Lu and Wang, 2025). Taking the bone marrow suppression, caused by the chemotherapy drug 5-fluorouracil (5-FU) by ASP as the entry point, Niu et al. (2023) explored its protective effect on perivascular mesenchymal progenitor cells (PMPs) and hematopoietic cells. The results showed that, 5-FU could induce oxidative damage in PMPs, making them prone to adipogenic differentiation, inhibiting osteogenic ability, and reducing the expression of key hematopoietic factors (CXCL12, SCF, Ang-1/Tie2, TPO/MPL, etc.), and adhesion molecules (VCAM-1/VLA-4, ICAM-1/LFA-1). Ultimately, it leads to premature aging of hematopoietic cells. ASP can effectively reverse this process, increase the level of superoxide dismutase (SOD), and reduce the content of lipid peroxidation products (MDA), thereby improving the microenvironmental function of PMPs.
Research has found that, ASP not only directly enhances the antioxidant capacity of PMPs, but provides a healthy microenvironment for hematopoietic cells by improving intercellular signal transduction and adhesion. Meanwhile, ASP can inhibit the excessive activation of the Wnt/β-catenin pathway, induced by 5-FU, down-regulate the expression of aging-related proteins, such as P53, P21 and Cyclin-D1, and delay the stress-induced premature aging of hematopoietic cells (Figure 2). Animal experiments have also shown that, ASP and other extracts can improve hematopoietic function, reduce oxidative burden, and regulate cytokine levels in blood deficiency and tissue injury models (Li et al., 2015; Tian et al., 2024).
![]() Figure 2 Wheat sowing by Super Seeder machine (Adopted from Singla et al., 2025) |
6.3 Pharmacological effects and dose dependence
Comparative studies have found that, different ASP grades and active ingredients, like ferulic acid, phthallactone dimer, show differences in anti-inflammatory, antioxidant and hematopoietic activities (Zou et al., 2022; Lu and Wang, 2025; Tian et al., 2024; Wen et al., 2025). For instance, ASP-H2O showed the strongest blood-nourishing activity, while the effects of other grades were different (Tian et al., 2024).
Dose and time dependencies, have been observed in both cell and animal studies. Higher doses and longer courses of treatment of ASP, or its extracts usually more significantly upregulate antioxidant enzyme activity, inhibit inflammatory markers, and improve functional outcomes (Li et al., 2015; Zhou et al., 2015; Tian et al., 2024). However, the optimal doses for different components and models vary, which suggests that personalized treatment strategies need to be formulated, based on specific circumstances.
7 Case Studies
7.1 A. sinensis polysaccharides in atherosclerosis prevention
Angelica sinensis polysaccharides (ASP) have anti-inflammatory effects, and can regulate lipid metabolism, which are crucial in the prevention of atherosclerosis. Studies have shown that, ASP can down-regulate pro-inflammatory cytokines and inhibit oxidative stress, and these two are precisely the core mechanisms of the occurrence and progression of atherosclerotic lesions (Chen et al., 2024; Ren et al., 2025). Besides, ASP also can improve lipid levels by regulating lipid metabolism-related pathways, thereby reducing plaque formation and lowering vascular inflammation.
By reducing inflammation and oxidative damage, ASP can enhance the stability of atherosclerotic plaques, which is crucial for preventing plaque rupture and subsequent cardiovascular events. Its anti-inflammatory and antioxidant properties not only maintain vascular integrity, but also reduce the risk of complications caused by unstable plaques.
7.2 Volatile oils in ischemic stroke therapy
The volatile oil and its active components (Z-ligustilide and ferulic acid) in A. sinensis, exhibit neuroprotective effects in ischemic stroke models. These components can reduce neuronal apoptosis, inhibit inflammatory responses, and promote angiogenesis and neural regeneration, alleviating cerebral ischemic injury (Han et al., 2021; Chen et al., 2024).
Animal and cell experiments have shown that, A. sinensis can improve cerebral blood flow, promote angiogenesis, and reduce oxidative stress and inflammatory damage by regulating signaling pathways, such as PI3K/Akt, MAPK, and Nrf2, thereby demonstrating neuroprotective effects in cerebral ischemia-reperfusion models. The mechanism of action of A. sinensis, shows multi-target characteristics. It not only alleviates nerve cell damage, but also improves vascular endothelial function, and inhibits platelet aggregation, reducing the volume of cerebral infarction and promoting functional recovery.
A. sinensis, as a traditional Chinese medicine, has been verified in modern pharmacological research, and has the potential to be transformed from the laboratory to clinical practice. This indicates that it can serve as an important candidate for adjuvant drug development, in the treatment of stroke, providing theoretical and experimental basis for future new drug research and development and comprehensive treatment plans (Han et al., 2021).
8 Concluding Remarks
The manifestations of A. sinensis in the cardiovascular and cerebrovascular systems, are indeed not limited to one direction. It can fight inflammation and oxidation, and slow down cell apoptosis and protect nerves, functioning like a versatile agent. Among them, polysaccharides, ligustilide and ferulic acid are regarded as the "main forces". Their effects of improving blood circulation, protecting blood vessels, and promoting the recovery of nerve function have been reflected in many studies. The reason why it can produce so many pharmacological effects lies in the fact that, it does not follow a single path but is the result of the "combined force" of multiple signaling pathways, like the PI3K/Akt, MAPK and Nrf2/HO-1 pathways, which play a supporting role in regulating inflammation and antioxidation. This also explains why it can bring benefits in multiple systems.
But at this stage, our understanding of A. sinensis is still not complete. Although there have been many basic researches and animal experiments, there is still not much evidence that has been truly translated into clinical practice, especially the lack of large-scale and standardized clinical trials. This makes its "position" in the modern medical system somewhat awkward. Moreover, the composition of A. sinensis is too complex, with many active substances, like polysaccharides and phthalonide. However, it is still unclear how they work together and which ones are the key. Issues, such as standardized extraction and component comparison, directly affect its subsequent quality control and safety evaluation.
Where should we go next? Or the combination of many omics could be a breakthrough. If methods such as genomics, transcriptomics, proteomics and metabolomics are used well, they can not only clearly understand how A. sinensis is synthesized and where its functions are, but also help us clarify whether different components are complementary, antagonistic or work independently. The focus of future research should be on developing standardized extracts, identifying core active ingredients, and introducing synthetic biology techniques to enhance their stability and therapeutic efficiency. Only in this way, can A. sinensis truly advance from traditional herbal medicine into the modern evidence-based medical system, and become a more reliable part of treating cardiovascular and cerebrovascular diseases.
Acknowledgments
The authors extend special thanks to Mr. Li for his assistance in organizing the literature during the preparation of this paper. Sincere gratitude is also expressed to the two anonymous peer reviewers for their thorough evaluation of the manuscript.
Conflict of Interest Disclosure
The authors affirm that this research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest.
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