The application of Panax notoginseng with a focus on its anti-inflammatory effect: a narrative review

Introduction

Panax notoginseng (P. notoginseng) is a plant native to Yunnan Province in southern China. Similar to Panax ginseng, it belongs to the Panax genus and has been widely used for medicinal purposes. Due to its geographical distribution, P. notoginseng is referred to as “Southern notoginseng”, while P. ginseng, which grows in northeastern China, is known as “Northern ginseng”. Traditionally, P. notoginseng has been classified as a medicinal herb that acts on the circulatory system. It has been used to maintain cardiovascular homeostasis due to its dual properties of promoting blood circulation and stopping bleeding (1).

In recent years, extensive research has demonstrated that P. notoginseng possesses a wide range of pharmacological effects. As of 2018, studies have reported that P. notoginseng not only improves cardiovascular diseases but also exerts beneficial effects on cancer, liver disease, neurodegenerative disorders, inflammatory diseases, diabetes, acute injuries, wound healing, hyperlipidemia, and osteoporosis (1). Moreover, ongoing studies continue to apply P. notoginseng to various pathological models, further expanding our understanding of its therapeutic potential.

Both P. ginseng and P. notoginseng belong to the same genus and share similar bioactive components. Their primary constituents include polysaccharides and ginsenosides. The ginsenosides present in P. notoginseng are largely similar to those in P. ginseng, both predominantly composed of dammarane-type triterpenoid saponins. Major constituents include ginsenosides Rb1, Rg1, Rc, Rd, Re, Rf, Rh1, and Rg, while notoginsenoside R1 (NR1) is unique to P. notoginseng. Among these, Rb1, Rg1, and NR1 are considered principal bioactive markers and are commonly used for quality control (2).

However, despite these compositional similarities, P. ginseng and P. notoginseng have distinct pharmacological applications. P. ginseng is classified as an adaptogen and is primarily used to maintain overall physiological homeostasis, whereas P. notoginseng is well-known for improving cardiovascular resistance and enhancing liver function. These differences are largely attributed to variations in the content of their bioactive components. According to a 2020 study, P. notoginseng contains approximately 15% ginsenosides and 1% polysaccharides, whereas P. ginseng contains about 4% ginsenosides and 29% polysaccharides (3). This suggests that the primary effects of P. notoginseng stem from its high ginsenoside content, whereas P. ginseng exhibits a synergistic effect between ginsenosides and polysaccharides. Notably, polysaccharides, which are abundant in P. ginseng, play a crucial role in maintaining immune system homeostasis.

While P. ginseng and P. notoginseng share many compositional features, P. notoginseng possesses distinctive pharmacological activities primarily attributable to its higher ginsenoside content. Specifically, P. notoginseng is recognized for improving blood circulation, protecting cardiovascular and hepatic systems, and modulating inflammatory responses. In this review, we focus on the therapeutic potential of P. notoginseng—particularly its anti-inflammatory actions mediated by ginsenosides that contribute to cardiovascular and liver homeostasis. While several pharmacological mechanisms have been identified, this paper focuses on reviewing the therapeutic effects of P. notoginseng, particularly in relation to the anti-inflammatory properties of its key bioactive components, the ginsenosides. We present this article in accordance with the Narrative Review reporting checklist (available at https://atm.amegroups.com/article/view/10.21037/atm-25-69/rc).

Methods

We conducted a narrative review to investigate the anti-inflammatory mechanisms underlying the traditionally recognized pharmacological effects of P. notoginseng, with a particular focus on its cardiovascular, hepatic, and metabolic activities.

A structured literature search was performed across PubMed, Web of Science, Scopus, and Google Scholar on December 20, 2024, covering publications from January 2010 to July 2024. Search terms included combinations of MeSH terms and free-text keywords such as “Panax notoginseng”, “inflammation”, “anti-inflammatory”, “cardiovascular”, “liver”, “hepatoprotective”, “dyslipidemia”, “diabetes”, “diabetic vascular”, “gut”, and “gut microbiome”.

Studies were included if they were published in English, represented original research or narrative reviews, investigated anti-inflammatory mechanisms in relation to known pharmacological effects of P. notoginseng, particularly in cardiovascular, hepatic, or metabolic models.

We excluded commentaries, conference abstracts, and studies lacking mechanistic detail.

Two authors independently screened the titles and abstracts of retrieved articles and selected those that aligned with the study hypothesis. In cases of disagreement, consensus was reached through discussion. Preference was given to studies that provided mechanistic evidence linking anti-inflammatory pathways—to therapeutic outcomes attributed to P. notoginseng (Table 1).

Anti-inflammatory effects of P. notoginseng

Inflammation is a biological response of vascularized living tissues to injury. It occurs due to microbial infection, physical or chemical factors, necrotic tissue, or immune-based reactions, leading to irreversible cellular damage. During inflammation, antigen-presenting cells and lymphocytes are recruited, vascular permeability increases, and inflammatory mediators such as interleukin (IL)-2, IL-4, and interferone (IFN)-γ are secreted, further attracting neutrophils, macrophages, and lymphocytes. A key process in initiating and sustaining inflammation is the activation of nuclear factor-κB (NF-κB) (4).

Immune cells release reactive oxygen species (ROS), lysozymes, prostaglandins, leukotrienes, and inflammatory markers such as IL-1, IL-12, and tumor necrosis factor (TNF)-α, which amplify the inflammatory response and may cause collateral tissue damage. P. notoginseng extracts and their active compounds demonstrate distinct anti-inflammatory effects by directly inhibiting inflammatory proteins and dephosphorylating kinases involved in intermediate inflammatory signaling. Most inflammatory responses are driven by the activation of genes associated with NF-κB translocation into the nucleus (5).

Ginsenosides such as Rb1, Compound K, and Re inhibit the activation of IL-1 receptor-associated kinase-1 (IRAK-1), thereby suppressing IκB kinase (IKK)-β phosphorylation and preventing the degradation of IκBα. This maintains the NF-κB-IκBα complex, preventing NF-κB nuclear translocation. Additionally, Re reverses IRAK-1 phosphorylation and reduces the binding ability of lipopolysaccharides (LPS) to toll-like receptor (TLR)4 in peritoneal macrophages, effectively blocking inflammation (6).

Compound K and Rb1 reduce nitric oxide (NO) and prostaglandin E2 (PGE2) production, while Rd and Rh1 inhibit cyclooxygenase (COX-2) and inducible nitric oxide synthase (iNOS), linking their effects to NF-κB regulation in murine macrophages (7). P. notoginseng selectively alters costimulatory molecules such as CD40 and CD86 in dendritic cells, independent of LPS-induced NF-κB p65 activation, thus preventing excessive dendritic cell activation (8).

Rg1, PPT, and Rh1 metabolites enhance TLR4 activation via IRAK- and transforming growth factor β (TGF-β)-activated kinase 1 (TAK-1)-dependent mechanisms (9). Rg1 inhibits NF-κB activation by modulating mitogen-activated protein kinase (MAPK) phosphorylation in a glucocorticoid receptor (GR)-dependent manner, like dexamethasone (10). Furthermore, NR1, Rg1, and Re’s primary metabolites, panaxatriol-type saponins, block NF-κB-related COX-2 expression by inhibiting IκBα phosphorylation in LPS-induced RAW264.7 cells (11). The inhibitory effects of Rb1 on NF-κB activation, IL-8, and PGE2 production were found to be associated with transient receptor potential vanilloid 1 signaling, demonstrating superior efficacy compared to chemical antagonists (12).

The anti-inflammatory effects of P. notoginseng on chronic diseases suggest that its activity is not limited to the regulation of NF-κB but may also be mediated through immune system modulation. The water extract of P. notoginseng and its saponins (PNS) effectively inhibited apoptosis and the excessive production of NO and PGE2 in peritoneal macrophages exposed to inflammatory stimuli in mice. In RAW264.7 cells, P. notoginseng reduced the expression of co-stimulatory molecules such as CD86 and CD40 induced by LPS while having no effect on TLR4 or CD14. This was associated with the induction of adhesion molecules in vascular endothelial cells, promoting hematopoiesis.

Ginsenosides Rb1 and Rg1 were found to induce the expression of CD86 and CD40, thereby promoting dendritic cell maturation and enhancing sustained stimulatory interactions with T cells to generate adaptive immunity. Additionally, Rb1 and Rg1 directly inhibited the growth of Th1 and Th17 cells while promoting regulatory T cells, alleviating experimental autoimmune encephalomyelitis. Rg1 and its metabolites restored the Th17/Treg balance and suppressed Th17 cell differentiation. Furthermore, PNS and NR1 were observed to activate immune responses in infected endothelial cells by reducing the secretion of Th2-type cytokines (IL-4 and IL-10) and increasing the production of Th1 cytokines (IL-2) (13). This indicates that P. notoginseng does not regulate the immune system unidirectionally but rather suppresses excessive activation while supporting normal immune function.

Moreover, Rg1 was found to protect against lung damage in sepsis, an extreme inflammatory response, by inhibiting the secretion of TNF-α, IL-10, and IL-6. This effect was attributed to the activation of the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) pathway (14). Ginsenoside Rd also alleviated experimental autoimmune encephalomyelitis by regulating the expression of IFN-γ and IL-4 in the cerebral cortex and splenic cells, promoting Th2 differentiation while preventing the reduction of brain-derived neurotrophic factor and nerve growth factor in the cerebral cortex (15). Additionally, NR1 was observed to inhibit the inflammatory response and pyroptosis of nucleus pulposus cells in the intervertebral disc. These effects were found to be mediated through the inactivation of the NF-κB and NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome pathways (16).

Overall, extracts of P. notoginseng and its major active components, ginsenosides, alleviated excessive immune responses associated with inflammation while supporting the normal functioning of immune cells under physiological conditions.

The impact of the anti-inflammatory effects of P. notoginseng on the cardiovascular system

Research on P. notoginseng extracts and ginsenosides has been actively conducted regarding their effects on promoting blood circulation while simultaneously protecting the cardiovascular system. The anti-inflammatory effects of P. notoginseng may help enhance blood circulation and protect the circulatory system (17). The factors influencing blood circulation can be broadly categorized into the heart, blood vessels, and the internal environment of the blood. P. notoginseng enhances blood circulation without causing significant cardiovascular side effects, suggesting that it primarily improves the internal environment of the blood through its anti-inflammatory actions rather than by altering heart rate or vascular tone. Inflammation is intricately involved in blood circulation in various ways:

• Inflammation increases vascular permeability (18). Uncontrolled immune responses lead to the recruitment of immune cells from surrounding tissues. This process increases vascular permeability, allowing inflammatory mediators to accumulate and attract additional immune cells. If capillary permeability increases excessively, small leaks can occur in tightly woven vascular structures, thereby impairing blood circulation.
• Inflammation promotes foam cell formation and accumulation in blood vessels (19). Chronic inflammation elevates oxidative stress and increases oxidized LDL levels. Simultaneously, inflammatory responses cause an influx of macrophages into blood vessels. These infiltrated macrophages engulf oxidized LDL, transforming into foam cells that accumulate in the vascular walls. The buildup of foam cells narrows the vascular lumen, reduces elasticity, and sustains inflammation, ultimately contributing to atherosclerosis (20). Persistent vascular inflammation not only drives atherosclerotic plaque formation but also increases the likelihood of plaque rupture and subsequent thrombosis, which can result in major cardiovascular events such as myocardial infarction, ischemic stroke, and venous thromboembolism. Therefore, the anti-inflammatory effects of P. notoginseng may play a crucial role in mitigating inflammation-associated cardiovascular risks.
• Inflammation facilitates thrombosis (21). Inflammation is an immune response that neutralizes external pathogens. When immune responses become dysregulated, excessive immune activation occurs, promoting non-specific blood clot formation, or thrombosis. Unlike normal hemostasis, which occurs in response to bleeding, inflammation-induced thrombosis can arise from excessive immune responses. In severe cases, systemic inflammatory responses, such as sepsis, may cause disseminated thrombosis, leading to ischemia and multi-organ failure. Given the close relationship between blood circulation and inflammation, the anti-inflammatory effects of P. notoginseng ginsenosides, once distributed in the bloodstream, can significantly improve circulation. Moreover, as inflammation plays both direct and indirect roles in the pathogenesis of cardiovascular diseases such as heart disease and stroke, P. notoginseng ginsenosides are expected to exert beneficial effects in these conditions.

According to a 2021 study, NR1 restored the blood-brain barrier (BBB) in a stroke model by modulating the caveolin1/matrix metalloproteinase (MMP)2/9 pathway (22). Additionally, PNS were found to protect endothelial cells in cerebral microvasculature, with antioxidant effects mediated through PI3K)/Akt/nuclear factor erythroid 2-related factor 2 (Nrf) pathway activation. Furthermore, Rg1 was reported to prevent endothelial cell damage caused by foam cells (23).

A 2017 review paper summarized multiple mechanisms by which PNS suppress atherosclerosis (24). According to this study, PNS restores vascular permeability compromised by inflammatory immune cell infiltration, prevent oxidized LDL-induced foam cell formation, and inhibit thrombosis. Individual ginsenosides, including Rg1, Rg3, Rh1, and Rk1, have demonstrated anticoagulant effects, and synergistic interactions among them have also been reported (25).

One key distinction to note is that the antiplatelet effects of P. notoginseng differ from those of aspirin. While aspirin irreversibly inhibits COX-1 to prevent clot formation, P. notoginseng operates through a different mechanism. A 2021 clinical study found that co-administration of P. notoginseng with aspirin enhanced the antithrombotic effect while mitigating aspirin-induced gastrointestinal side effects (26). This suggests that P. notoginseng exerts anticoagulant effects through mechanisms distinct from aspirin.

Moreover, as previously mentioned, inflammation is a key contributor to thrombosis, and thus the anti-inflammatory properties of P. notoginseng may also contribute to thrombolysis. A 2022 clinical study confirmed that P. notoginseng administration reduced thrombus formation in stroke patients, primarily by inhibiting the TLR4/MyD88/NF-κB pathway, which is closely linked to inflammatory responses (27).

Taken together, these findings suggest that the ginsenosides in P. notoginseng play a crucial role in maintaining cardiovascular health by safely modulating inflammation-induced vascular changes, including increased vascular permeability, foam cell accumulation, and thrombosis formation. Furthermore, no reports indicate that P. notoginseng increases bleeding tendency, further supporting its safety (2).

Hepatoprotective effects of P. notoginseng

Inflammasomes are multimeric protein complexes that are activated in response to pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs). These complexes regulate inflammatory responses and programmed cell death, playing a crucial role in liver diseases. Chronic liver conditions such as hepatitis, non-alcoholic fatty liver disease (NAFLD), and fibrosis involve excessive inflammasome activation, particularly of the NLRP3 inflammasome (28).

PNS have demonstrated significant hepatoprotective effects in NAFLD mice (high-fat diet-induced obese mice and obesity-prone Lep^ob mice), primarily through anti-fibrotic and anti-inflammatory mechanisms. Mice were treated with 800 mg/kg of PNS for 8 weeks. PNS have been shown to inhibit liver fibrosis by reducing collagen accumulation, modulating inflammatory cytokines (e.g., TNF-α, TGF-β1, and IL-6), and maintaining the balance of anti-fibrotic cytokines like IL-10 (29).

In the CCl₄-induced liver injury model, Rb1 administration began two weeks before CCl₄ exposure and continued for a total of seven weeks. Ginsenoside Rb1 significantly inhibited hepatic collagen deposition and reduced plasma alanine aminotransferase (ALT) levels. Additionally, it suppressed PGE2 and tissue inhibitor of metalloproteinases-1, mitigating both inflammation and fibrosis (30).

Rg1 has shown potential in preventing alcohol-induced liver damage by modulating the NF-κB pathway via GR signaling. This pathway plays a crucial role in regulating inflammatory cytokine expression, and its inhibition by Rg1 was associated with reduced liver damage (31).

PNS have also been found to prevent liver damage induced by acetaminophen overdose through the restoration of thioredoxin-1, an important antioxidant enzyme. This restoration reduced the levels of ALT, TNF-α, and pro-caspase-12, indicating protection against inflammation-mediated liver injury (32).

Lipid-lowering effects of P. notoginseng

P. notoginseng has demonstrated potential for preventing and treating cardiovascular diseases by regulating lipid metabolism and reducing inflammation related to hyperlipidemia.

Study reported in 2011 has shown that treatment of P. notoginseng with diet (0.25–1%, for 4 weeks) lowers total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) levels while increasing high-density lipoprotein cholesterol (HDL-C) levels, thereby improving lipid profiles. These effects are mediated through the inhibition of hepatic 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase), a key enzyme in cholesterol biosynthesis. Additionally, P. notoginseng modulates antioxidant enzymes such as glutathione peroxidase and superoxide dismutase, reducing lipid peroxidation markers such as malondialdehyde (33).

In a poloxamer-407-induced hyperlipidemic rat model, Panax notoginseng extract (40 mg/kg) significantly reduced TC and TG levels, while LDL-cholesterol reduction was observed only in the atorvastatin group. Unlike atorvastatin, which lowers cholesterol through HMG-CoA reductase inhibition, P. notoginseng appeared to modulate lipid metabolism through alternative mechanisms that remain to be fully elucidated (34).

These findings indicate that the anti-inflammatory and lipid-lowering effects of P. notoginseng are closely interconnected. Hyperlipidemia leads to increased ROS production and elevated inflammatory cytokines such as TNF-α and IL-6, which contribute to vascular inflammation and atherosclerosis. By inhibiting NF-κB signaling and modulating lipid metabolism, P. notoginseng prevents cholesterol accumulation, suppresses foam cell formation, and maintains vascular integrity.

Moreover, P. notoginseng increases HDL-C levels while reducing LDL-C levels, thereby reducing vascular inflammation and preventing foam cell formation, which is a critical factor in the progression of atherosclerosis (24,33). It also enhances the activity of antioxidant enzymes, mitigating oxidative stress-induced vascular damage.

Anti-diabetic and vascular protective effects of P. notoginseng

Inflammation plays a crucial role in the development of insulin resistance, activating signaling pathways that impair glucose metabolism. The NF-κB and JNK signaling pathways are key mediators of inflammation-induced metabolic dysregulation, particularly in obesity and metabolic disorders (35).

NF-κB signaling promotes the production of pro-inflammatory cytokines such as TNF-α and IL-6, which further perpetuate chronic inflammation. This inflammatory response inhibits insulin receptor substrate-1 (IRS-1) activation, impairing insulin signaling and leading to insulin resistance. Similarly, JNK signaling phosphorylates the serine residues of IRS-1, disrupting its interaction with insulin receptors and exacerbating metabolic dysregulation. These processes are particularly active in adipose tissue, where macrophage infiltration and inflammatory cytokine secretion contribute to systemic metabolic disturbances (35).

A 2019 study demonstrated that PNS activate the IRS1-PI3K-AKT signaling pathway, enhancing glucose transporter (GLUT)4 translocation and improving glucose uptake in skeletal muscles. PNS also reduced TNF-α and IL-6 expressions, suggesting that its anti-inflammatory effects restore insulin signaling and improve glucose metabolism. Additionally, PNS reduced ROS production, exerting antioxidant effects that alleviated metabolic stress (36).

Several ginsenosides have shown anti-diabetic effects. Ginsenosides Rb1 and Rg1 promote glucose-stimulated insulin secretion and reduce triglyceride accumulation. Ginsenoside Re has demonstrated hypoglycemic effects in ob/ob mice, while Rb1 has been reported to improve insulin resistance in KK-Ay diabetic mouse models (37).

Rb1 has also been identified as an anti-obesity and anti-hyperglycemic agent. In a study where Rb1 was administered for four weeks, high-fat diet-induced obese mice showed reduced food intake, inhibited weight gain, decreased fat accumulation, and increased energy expenditure. Additionally, fasting blood glucose levels significantly decreased, and glucose tolerance improved (38).

Similarly, ginsenoside Re demonstrated anti-diabetic and anti-obesity effects in ob/ob mice and high-fat diet-fed C57BL/6J mice, reducing blood glucose and triglyceride levels while preventing hepatic steatosis. Re also inhibited hepatic gluconeogenesis by activating the AMPK (AMP-activated protein kinase) pathway, enhancing GLUT4 expression and promoting glucose uptake in adipocytes and skeletal muscle cells (39).

The most important mechanism in the pathogenesis of diabetes is insulin resistance, which is closely related to the inflammatory response. P. notoginseng or its active components, ginsenosides, which have clear anti-inflammatory effects, have been found to successfully manage blood glucose levels and improve related factors.

Gut homeostasis modulation by P. notoginseng

The maintenance of intestinal homeostasis is closely related to the inflammatory response (40). When harmful bacteria in the gut proliferate, the activity of beneficial bacteria is relatively suppressed. The toxins produced by harmful bacteria increase intestinal inflammation, which weakens the tight junctions of intestinal epithelial cells and allows microbial products to enter the systemic circulation (40). A 2014 study demonstrated that P. notoginseng exerts anti-inflammatory and anti-cancer effects in colitis and colorectal cancer models. Using azoxymethane and dextran sulfate sodium-induced colitis models, researchers found that P. notoginseng extract significantly reduced disease activity index (DAI) scores, mitigated colon shortening, and improved histological damage. Additionally, P. notoginseng suppressed iNOS and COX-2 expression, reducing inflammatory markers (41).

PNS were also found to alleviate colitis-associated colorectal cancer (CAC) by suppressing immune cell infiltration, reducing tumor burden, and maintaining intestinal epithelial structure. This effect was attributed to the inhibition of the indoleamine 2,3-dioxygenase-1 pathway, which regulates Treg cell differentiation and macrophage accumulation in the tumor microenvironment (42).

PNS increase beneficial bacteria such as Akkermansia muciniphila and Bifidobacterium while reducing pathogenic bacteria, thereby maintaining gut microbial balance. P. notoginseng also interacts with gut microbiota to enhance its bioactivity. Saponins from P. notoginseng are metabolized by gut bacteria into bioactive compounds such as Compound K, which exhibits anti-inflammatory, immunomodulatory, and anti-cancer effects (43,44).

Conclusions

This paper aims to explain the phamacological effects of P. notoginseng based on its anti-inflammatory properties. The cardiovascular benefits of P. notoginseng, particularly its ability to improve blood circulation, were found to be largely attributable to its suppression of vascular inflammation. Rather than directly influencing heart rate or vascular diameter, P. notoginseng maintained cardiovascular homeostasis by reducing vascular resistance through its anti-inflammatory effects. Similarly, its ability to enhance liver function and improve blood lipid levels was also linked to its suppression of inflammatory responses in the liver, which in turn inhibited lipid synthesis caused by inflammation.

Moreover, insulin resistance, the key pathological mechanism of diabetes, was also associated with inflammation, and the anti-inflammatory effects of P. notoginseng were found to be effective in managing diabetes. Additionally, P. notoginseng contributed to intestinal homeostasis no 11t only by directly alleviating intestinal inflammation but also by regulating gut microbiota composition.

While P. notoginseng belongs to the same genus as P. ginseng and shares similar bioactive components, their composition ratios differ. P. ginseng contains a high amount of polysaccharides in addition to ginsenosides, making it commonly used as an adaptogen. In contrast, P. notoginseng has minimal polysaccharides but contains approximately two to three times more ginsenosides than P. ginseng, allowing it to serve as a potent therapeutic agent for physiological modulation.

Clinical trials of P. notoginseng preparations, such as Xuesaitong and Sanchitongshu, have typically employed doses ranging from 120 to 600 mg per day of standardized total saponins, administered for 4 to 12 weeks, mainly in patients with ischemic stroke, coronary heart disease, or unstable angina (26,45-49). Across these studies, P. notoginseng demonstrated a favorable safety profile, with only mild and transient adverse events—most commonly gastrointestinal discomfort or mild constipation—and no treatment-related serious events were reported.

Pharmacokinetic data indicate that ginsenosides Rb1, Rg1, and R1 are absorbed slowly, achieving plasma concentrations in the nanomolar to low micromolar range with elimination half-lives of 30–50 hours, suggesting potential for accumulation during long-term dosing. Ginsenosides are primarily metabolized via CYP3A4 and excreted hepatobiliarily (50). Although P. notoginseng generally shows negligible influence on most cytochrome P450 enzymes, isolated ginsenosides such as Rg3, Rh2, and R1 have demonstrated P-glycoprotein inhibition, potentially increasing the bioavailability of co-administered drugs such as aspirin, digoxin, or ritonavir (51-55).

Regarding toxicity, both acute and subchronic studies report excellent tolerance: oral administration of P. notoginseng powder at up to 7.5 g/kg/day for 90 days in rats produced no observable adverse effects, and only very high in vitro concentrations (>70 µg/mL) exhibited developmental toxicity in zebrafish models (56,57). Human studies have not identified any hepatotoxic or nephrotoxic outcomes (45-49). Collectively, these data suggest that P. notoginseng, at clinically used doses, is safe and well-tolerated, though vigilance is advised when co-administered with drugs metabolized through CYP3A4 or transported by P-glycoprotein. Research on the fundamental mechanisms underlying the effects of natural substances provides valuable insights into their pharmacological properties and potential therapeutic applications. Although the existing clinical evidence for P. notoginseng remains largely confined to cerebrovascular and cardiovascular disorders (2), accumulating preclinical findings demonstrate that its core pharmacological actions—particularly the suppression of pro-inflammatory cytokines and modulation of NF-κB and related signaling pathways—are mechanistically relevant to a much broader spectrum of diseases. Building upon this foundation, further translational and clinical investigations, including rigorous pharmacological and toxicological evaluations, are warranted to validate and extend the therapeutic potential of P. notoginseng to metabolic, hepatic, and gastrointestinal disorders. The present review provides a conceptual and mechanistic framework for such future studies, highlighting that the diverse biological activities of P. notoginseng are fundamentally rooted in its anti-inflammatory properties.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://atm.amegroups.com/article/view/10.21037/atm-25-69/rc

Peer Review File: Available at https://atm.amegroups.com/article/view/10.21037/atm-25-69/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-25-69/coif). S.H. and D.Y. are Representatives (CEOs) of Pharm Friends Co., Ltd. S.K. is an Employee of Pharm Friends Co., Ltd. All authors report that they are each with professional training in pharmacognosy, contributed to this manuscript exclusively from an academic and scholarly standpoint. They respectfully confirm that the content of this review was developed independently of any commercial interests. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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