Modulating nasal barrier function and tissue remodeling in inflammatory diseases: the role of ginseng and its bioactive compounds

ABSTRACT

Ginseng, a well-known herbal supplement, is widely recognized for its pharmacological properties, including anti-inflammatory, antioxidant, and immune-modulatory effects. This review explores the potential therapeutic benefits of ginseng, particularly its active compounds, ginsenosides, in promoting nasal mucosa health. The nasal mucosa plays a crucial role in respiratory defense, acting as a barrier to pathogens and particulate matter, while also orchestrating immune responses. Ginseng’s bioactive compounds have shown promise in modulating inflammation, reducing oxidative stress, and enhancing immune functions, which could be beneficial in conditions such as allergic rhinitis, chronic rhinosinusitis, and viral infections. Histological studies highlight the impact of ginseng on nasal mucosal cells, particularly in regulating immune responses and promoting tissue resilience. Research demonstrates that ginseng can reduce inflammation in the nasal passages by inhibiting pro-inflammatory cytokines and pathways like NF-κB, while enhancing the activity of immune cells such as natural killer cells and macrophages. Furthermore, ginseng’s antioxidant properties help protect nasal tissue from oxidative damage, which is common in chronic nasal conditions. Although promising, the evidence base is still developing, with many studies limited by small sample sizes and variations in ginseng preparations. Further clinical trials are needed to substantiate ginseng’s efficacy, optimal dosage, and delivery methods for treating nasal conditions. This review provides insights into the potential of ginseng as a complementary therapeutic approach for enhancing nasal mucosa health and improving respiratory outcomes.

GRAPHICAL ABSTRACT

1. Introduction

Ginseng, a well-known herbal supplement used in both traditional and modern medicine, primarily comes from two main varieties: Panax ginseng (Asian ginseng) and Panax quinquefolius (American ginseng). Asian ginseng has historically been used in Eastern medicine, believed to boost energy and reduce fatigue, while American ginseng is more common in North America and is often used for its purported calming effects.¹

Both species contain active compounds known as ginsenosides, which are triterpene saponins thought to have pharmacological properties including antioxidant, anti-inflammatory, and immune-modulatory effects. Over 100 types of ginsenosides have been identified, each with varying biological activities. For instance, Panax ginseng tends to have higher concentrations of specific ginsenosides like Rb1, Rb2, and Rg1, which have been associated with effects on the central nervous system and potential benefits in immune response and metabolic health.^2–4

Recent studies highlight the importance of these compounds, exploring their effects on stress response, blood glucose regulation, and even potential therapeutic roles in managing certain cancers and cardiovascular conditions. Different extraction and analysis methods, such as HPLC and UPLC, have advanced understanding of ginsenoside content and allowed for more standardized formulations in both varieties of ginseng, supporting its use in diverse medicinal applications.²

The nasal mucosa, the lining of the nasal cavity, is a critical component of the respiratory system, serving both as a physical barrier and an immune defense. It consists of a mucous membrane populated by ciliated epithelial cells, mesenchymal cells, goblet cells, and various immune cells, including macrophages and dendritic cells. The nasal mucosa’s structure and function make it essential for trapping and clearing airborne pathogens, allergens, and particulate matter. The mucus produced by goblet cells captures these particles, while cilia work to move them out of the respiratory tract, helping to prevent infection and inflammation.^5–8

Beyond being a physical barrier, the nasal mucosa plays a vital immunological role. It houses immune cells that recognize and respond to pathogens, triggering both innate and adaptive immune responses. For example, dendritic cells in the nasal mucosa can present antigens to immune cells, stimulating a targeted response against specific pathogens. This immune function is especially crucial in the context of respiratory infections and conditions like allergies, where the nasal passages are frequently exposed to environmental irritants and microbes’ health is thus vital for overall respiratory health, as compromised nasal function can lead to infections, chronic inflammation, and conditions like allergic rhinitis and sinusitis. Healthy nasal mucosa supports the immune system and helps manage inflammatory responses, reducing the risk of allergic and infectious issues that can exacerbate or trigger respiratory diseases.^9,10

The purpose of this review is to analyze and synthesize the current body of research on ginseng’s potential effects on the nasal mucosa and its role in promoting nasal health. This review explores how these effects may benefit conditions characterized by inflammation, infections, and immune dysregulation in the nasal mucosa. At the molecular level, the interactions of proteins and small molecules are pivotal in maintaining cellular homeostasis and modulating pathological processes.^11–14 Understanding these mechanisms in the context of ginseng’s bioactive compounds could provide valuable insights into their therapeutic potential across various tissues.

The focus will be on evaluating evidence from both in vitro and clinical studies that explore how ginseng and its components may aid in reducing inflammation, mitigating immune responses to allergens, and promoting overall nasal tissue resilience. This analysis will help clarify ginseng’s therapeutic potential as a complementary or alternative approach in managing nasal conditions, offering insights into potential applications for individuals with allergic rhinitis, sinusitis, and other nasal inflammatory conditions.

2. Pharmacological properties of ginseng

Ginsenosides, the active compounds found in Panax ginseng, have been extensively studied for their anti-inflammatory effects. These compounds modulate various inflammatory pathways by inhibiting the release of pro-inflammatory cytokines like IL-6 and TNF-α, both of which are pivotal in the inflammatory response. Ginsenosides also exert their effects by suppressing the nuclear factor kappa B (NF-κB) signaling pathway, a critical regulator of inflammation. NF-κB plays a central role in the transcriptional activation of inflammatory genes, and its inhibition by ginsenosides results in reduced expression of inflammatory mediators.^9,15 Studies have shown that ginsenosides, particularly Rb1, Rg1, and Rd, demonstrate potent anti-inflammatory properties by interfering with these pathways, providing potential therapeutic applications for inflammatory diseases (Figure 1).^15–17

Figure 1.

Mechanisms of ginsenosides in Panax ginseng. The illustration highlights the primary actions of ginsenosides in Panax ginseng, including anti-inflammatory effects through the inhibition of pro-inflammatory cytokines (IL-6, tnf-α), antioxidant properties by reducing reactive oxygen species (ROS) to protect against oxidative stress, and immune support by enhancing immune cell activity to bolster the body’s defense against pathogens. These mechanisms emphasize the potential of ginsenosides in managing inflammation, oxidative damage, and immune responses.

Ginseng, particularly its bioactive compounds known as ginsenosides, is widely recognized for its antioxidant properties, which play a significant role in mitigating oxidative stress. In conditions such as chronic rhinitis and nasal infections, oxidative stress in the nasal mucosa can lead to inflammation and tissue damage. Ginsenosides have been shown to reduce the production of reactive oxygen species (ROS) and enhance the activity of endogenous antioxidant enzymes, such as superoxide dismutase (SOD) and catalase, thereby protecting cells from oxidative damage. These antioxidant effects are beneficial in alleviating the symptoms of respiratory disorders by reducing inflammation and promoting tissue repair in the nasal mucosa. Studies suggest that ginseng’s antioxidant properties may contribute to the modulation of inflammatory pathways, offering a protective role in diseases characterized by oxidative damage, including chronic rhinitis and sinusitis.^11,15,16 Ginseng’s ability to counteract oxidative stress underscores its potential therapeutic application in managing conditions involving oxidative injury in the upper respiratory tract (Figure 1).

Ginseng, particularly through its active constituents, ginsenosides, has been shown to modulate immune responses, enhancing the activity of various immune cells, including natural killer (NK) cells, macrophages, and T lymphocytes. Research has demonstrated that ginseng can stimulate NK cell activity, which is crucial for the body’s defense against viral infections, including those affecting the nasal mucosa. Additionally, ginseng has been found to enhance macrophage function, promoting phagocytosis and the production of cytokines that help coordinate the immune response. These effects are particularly relevant in combating nasal pathogens such as bacteria and viruses, where an effective immune response is essential. Studies have also highlighted that ginseng can improve the mucosal immune response in the respiratory system by increasing the secretion of immunoglobulins and enhancing the barrier function of the nasal mucosa, thus improving the body’s ability to ward off infections.^18–20 Ginseng’s immune-modulatory effects offer significant therapeutic potential for enhancing immune defense mechanisms, particularly in the nasal mucosa, where pathogens frequently invade (Figure 1).

3. Effects of ginseng on nasal conditions

3.1. Ginseng for allergic rhinitis

Ginseng, particularly its active compounds known as ginsenosides, has gained attention for its therapeutic potential in managing allergic rhinitis (AR), a condition characterized by inflammation and immune dysregulation in the nasal mucosa. Both preclinical and clinical studies suggest that ginseng may alleviate common AR symptoms, such as nasal congestion, itching, and sneezing, by reducing the production of pro-inflammatory cytokines like IL-4 and TNF-α and inhibiting inflammatory pathways such as NF-κB.²¹ Among the various forms of ginseng, Korean red ginseng (KRG) has shown particular promise in alleviating allergic inflammation. Studies in murine models suggest that KRG reduces levels of key Th2 cytokines IL-4 and IL-5, which mediate the allergic response. Additionally, KRG treatment led to lower serum IgE levels and fewer eosinophils in nasal tissues compared to controls, indicating that KRG can suppress the allergic response by inhibiting Th2 cytokine activation. This positions KRG as a potential treatment for allergic rhinitis, with ginsenosides Rg1 and Rb1 contributing to its anti-allergic effects through mechanisms similar to glucocorticoids.²²

Supporting this, a randomized, double-blind, placebo-controlled study by Jung et al. (2011) demonstrated that ginseng supplementation significantly improved AR symptoms, including nasal congestion and sneezing, by modulating immune responses and reducing histamine release.²³ In addition to KRG, fermented red ginseng (fRG) has also shown therapeutic promise for allergic rhinitis. Kim et al. (2019) found that fRG inhibited IL-4 expression in mast cells and suppressed IL-4 and IL-5 production in models of allergic rhinitis. Further in vivo studies revealed that fRG reduced eosinophil infiltration, mast cell activation, and Th2 cell accumulation, while alleviating nasal allergy symptoms. Additionally, fRG was found to modulate the gut microbiota, increasing populations of beneficial bacteria like Bacteroidetes and Actinobacteria while reducing Firmicutes levels, which correlated with a reduction in pro-inflammatory cytokines. These findings suggest that fRG alleviates AR symptoms by both modulating immune responses and influencing gut microbiota composition.²⁴ Further reinforcing these findings, clinical studies of KRG have demonstrated improvements in allergic rhinitis symptoms. In a study of 60 patients, KRG treatment resulted in significant reductions in total serum IgE, serum IL-4 levels, and eosinophil counts, similar to the effects of antihistamines.²⁵ These findings suggest that KRG can modulate allergic inflammatory responses and may offer a beneficial treatment for allergic rhinitis.

Beyond KRG and fRG, ginsenoside Rg1, another bioactive compound derived from ginseng, has been shown to reduce the production of thymic stromal lymphopoietin (TSLP) in allergic rhinitis (AR) models, specifically in ovalbumin (OVA)-induced AR mice. TSLP is a critical cytokine that drives allergic inflammation by activating immune cells, including dendritic cells, which play a central role in the allergic response. By inhibiting TSLP, Rg1 may help modulate immune responses, thereby reducing the severity of allergic inflammation and improving AR symptoms. This suggests that Rg1 could be a promising natural agent for managing AR, particularly in models where allergic inflammation is induced by OVA²⁶

Interestingly, ginsenoside Rg3 has recently emerged as a promising therapeutic candidate for AR. While ginsenoside Rg3 has been well-studied for its effects on allergic lower airway diseases, its impact on allergic upper airway diseases, particularly AR, has only recently been explored. Recent studies in ovalbumin (OVA)-induced AR mouse models have demonstrated that Rg3 can alleviate inflammation, oxidative stress, and nasal symptoms associated with AR. This suggests that Rg3 may be an effective natural agent in modulating the progression of AR. In these studies, female mice were used based on prior research indicating that allergic airway inflammation is more pronounced in females than in males after OVA challenge, ensuring the reproducibility and relevance of the findings.²⁷

Gene expression analyses in these studies revealed several key molecular players involved in the pathogenesis of AR. Among the downregulated genes, COL1A1 and COL3A1 were identified, both of which are implicated in airway remodeling and inflammation, particularly in the context of allergic airway diseases. Interestingly, COL1A1 has also been linked to severe asthma models, further suggesting that its regulation could play a critical role in managing AR. On the other hand, the upregulated genes in response to Rg3 treatment, such as DNASE1, HMOX1, and KLF15, highlight mechanisms for oxidative stress reduction and inflammatory modulation. DNASE1 has been associated with reduced oxidative stress and enhanced disintegration of neutrophil extracellular traps (NETs), indicating a protective role in AR pathology. Similarly, HMOX1 and KLF15 are critical regulators of oxidative stress and inflammation, providing further evidence of Rg3‘s therapeutic potential.

Metabolic analysis of AR models treated with Rg3 revealed key metabolites such as glutathione, stearidonic acid, α-linolenic acid, and β-retinol, all of which contribute to AR progression and the beneficial effects of Rg3. Glutathione, a well-known antioxidant, was upregulated, suggesting its role in protecting airway epithelial cells from oxidative damage. Stearidonic acid and α-linolenic acid, both polyunsaturated fatty acids, were found to reduce inflammation, supporting the hypothesis that Rg3 may modulate lipid metabolism to combat AR. Additionally, β-retinol, with its established anti-inflammatory effects, was shown to enhance oxidative stress responses, potentially via the Nrf2/HMOX1 pathway. These findings underscore the hypothesis that Rg3’s therapeutic effects in AR are mediated by a combination of gene regulation and metabolic alterations, including the modulation of Nrf2, a key regulator of antioxidant responses.²⁷

Moreover, recent research has focused on the therapeutic potential of other ginseng-derived compounds, such as PNS-R1, an active component from Panax notoginseng. This compound has demonstrated promising effects in alleviating AR symptoms by targeting mitochondrial dysfunction and apoptosis pathways. PNS-R1 showed similar effects to dexamethasone (Dex), a conventional treatment for AR, by inhibiting key inflammatory markers such as IL-4, IL-6, IL-13, and TNF-α, while also regulating Th1/Th2 imbalance. Additionally, PNS-R1 reduced epithelial cell apoptosis in nasal mucosa and alleviated mitochondrial damage in IL-13-treated human nasal epithelial cells (HNEPCs). PNS-R1‘s effects were linked to the regulation of mitochondrial dynamics, specifically by inhibiting Drp1-mediated mitochondrial fission and promoting mitochondrial fusion via upregulation of MFN2. This regulation helped reduce the production of ROS and mtROS, known contributors to mitochondrial dysfunction and inflammation in AR. Further investigation revealed that PNS-R1’s protective effects are mediated through the AMPK/Drp1 signaling pathway. By activating AMPK, PNS-R1 regulated Drp1 phosphorylation and mitochondrial fission, which in turn reduced ROS production and prevented the loss of mitochondrial membrane potential (MMP). Moreover, PNS-R1 inhibited TXNIP/NLRP3 inflammasome activation, a key regulator of inflammation in AR. This inhibition of mitochondrial fission and ROS production led to reduced NLRP3 inflammasome activation and inflammatory cytokine secretion, suggesting that PNS-R1 alleviates AR by modulating mitochondrial function and inflammatory responses. These findings highlight the growing therapeutic potential of ginseng compounds like KRG and PNS-R1 for managing allergic rhinitis. By targeting key inflammatory pathways and mitochondrial dynamics, ginseng-based treatments offer a promising avenue for alleviating AR symptoms and regulating immune responses (Table 1). Further studies are needed to fully elucidate the molecular mechanisms underlying these effects, but the roles of AMPK/Drp1 and TXNIP/NLRP3 pathways suggest significant potential for AR treatment.²⁸

Table 1.

Key studies on ginseng for allergic rhinitis.

Key Compounds	Mechanisms	Findings	Type of Study	References
Ginsenosides (e.g., Rg1, Rb1)	Comparable to glucocorticoids in inflammation modulation	Ginseng reduces pro-inflammatory cytokines like IL-4 and TNF-α; inhibits NF-κB pathway.	Preclinical and Clinical Review	22
Ginsenosides (e.g., Rg1, Rb1)	Suppresses Th2 cytokine activation; reduces allergic inflammation.	Korean red ginseng (KRG) reduces Th2 cytokines (IL-4, IL-5), serum IgE, and eosinophils.	Murine Model	22
General ginseng extract	Histamine reduction, immune modulation.	Ginseng supplementation improved AR symptoms; modulated immune response, reduced histamine.	Clinical Trial (RCT)	23
fRG, unspecified ginsenosides	Alters gut microbiota, reduces pro-inflammatory cytokines.	Fermented red ginseng (fRG) inhibits IL-4/IL-5, reduces eosinophils, modulates gut microbiota.	Murine Model + Clinical Insights	24
KRG	Anti-inflammatory, similar to antihistamines.	KRG reduces serum IgE, IL-4, and eosinophils.	Clinical Study	25
Rg3	Nrf2/HMOX1 pathway activation, gene and metabolic modulation (glutathione, lipid metabolism).	Rg3 alleviates AR symptoms by reducing oxidative stress, inflammation, and modulating genes.	Murine Model	27
PNS-R1	AMPK/Drp1 signaling, TXNIP/NLRP3 inflammasome inhibition.	PNS-R1 targets mitochondrial dysfunction; inhibits IL-4, IL-6, IL-13, TNF-α, and ROS.	Preclinical Studies	28

Table 1. Therapeutic Potential of Ginseng in Allergic Rhinitis Management. This figure illustrates the key mechanisms and therapeutic effects of ginseng and its bioactive compounds, such as ginsenosides (e.g., Rg1, Rb1, Rg3) and PNS-R1, in alleviating allergic rhinitis (AR). The mechanisms include modulation of inflammatory cytokines (IL-4, IL-5, IL-13, TNF-α), reduction of oxidative stress via Nrf2/HMOX1 pathway activation, and suppression of mitochondrial dysfunction through AMPK/Drp1 signaling. Korean red ginseng (KRG) and fermented red ginseng (fRG) demonstrate significant anti-inflammatory effects, including reductions in serum IgE, eosinophil infiltration, and mast cell activation. Additionally, fRG modulates gut microbiota composition, which correlates with decreased pro-inflammatory cytokines. PNS-R1 specifically targets mitochondrial dynamics, inhibiting Drp1-mediated mitochondrial fission and TXNIP/NLRP3 inflammasome activation. These findings support the potential of ginseng-based therapies in reducing AR symptoms such as nasal congestion, sneezing, and itching while offering novel insights into molecular and metabolic pathways involved in AR pathogenesis.

3.2. Therapeutic potential of ginseng and its ginsenosides in modulating inflammation and EMT in chronic rhinosinusitis and nasal polyps

Based on its active components, particularly ginsenosides, ginseng has shown potential as a therapeutic approach for managing allergic rhinitis (AR) and chronic rhinosinusitis (CRS), both of which are characterized by persistent inflammation of the nasal and sinus mucosa. These conditions are often exacerbated by bacterial colonization, and in the case of CRS, the presence of nasal polyps may further complicate the clinical picture. Given its anti-inflammatory and immunomodulatory effects, ginseng may help alleviate symptoms such as nasal congestion, sinus pressure, headache, and nasal polyp swelling. This is achieved through the reduction of key inflammatory cytokines like TNF-α, IL-4, and IL-6, which play central roles in the pathogenesis of CRS and AR^24,29

One specific ginsenoside, G-F1, has shown effectiveness in alleviating eosinophilic inflammation in a murine model of eosinophilic CRS (ECRS) by enhancing natural killer (NK) cell activity. NK cells, which typically induce eosinophil apoptosis, are often impaired in patients with severe inflammatory diseases, leading to persistent inflammation. G-F1 offers a novel therapeutic approach by boosting NK cell function, which could be especially beneficial for patients unresponsive to conventional corticosteroid treatments like dexamethasone.³⁰ Notably, G-F1 operates through a distinct mechanism: while dexamethasone reduces IL-1β production by macrophages, G-F1 enhances IFN-γ production by NK cells, highlighting its unique mode of action. Both G-F1 and dexamethasone reduce eosinophilic inflammation and Th2 cytokines (e.g., IL-4, IL-13), but via different cellular pathways, offering valuable insights into G-F1’s potential for treating eosinophilic inflammation in CRS and similar disorders. The safety profile of G-F1 is favorable, with no systemic toxicity observed in mice even at higher doses. Additionally, G-F1 was effective when administered intranasally at much lower doses, suggesting its potential for targeted delivery to the sinonasal mucosa, thereby enhancing therapeutic outcomes. These doses were similar to those used for treating allergic rhinitis in humans, supporting G-F1’s potential as a safe and effective treatment for CRS.³⁰ Beyond its anti-inflammatory properties, ginseng, particularly through red ginseng (KRG) and its ginsenoside Rg3, may also play a role in modulating epithelial-to-mesenchymal transition (EMT), a process involved in tissue remodeling in CRS. Exposure to Asian dust (ASD) was shown to induce EMT in nasal epithelial cells, characterized by decreased E-cadherin expression and increased fibronectin production. Red ginseng and Rg3 inhibit ASD-induced EMT by suppressing TGF-β1 production and reducing fibronectin expression, likely through the inhibition of inflammatory pathways such as ERK, p38, and mTOR. These findings suggest that KRG and Rg3 may offer therapeutic benefits in managing ASD-induced inflammation and EMT, especially when applied topically to the sinonasal mucosa. However, the pharmacokinetics of KRG remain poorly understood, and further research is necessary to assess its bioavailability and safety.³¹ Moreover, ginsenoside Rg1 has shown potential in modulating the fibrotic processes associated with nasal polyps, a common manifestation of CRS. Rg1 inhibits TGF-β1-induced myofibroblast differentiation and extracellular matrix (ECM) production in nasal polyp-derived fibroblasts by specifically inhibiting the ERK1/2 signaling pathway. This mechanism reduces ECM components like fibronectin and collagen, providing a novel therapeutic approach for managing nasal polyp formation. These findings suggest that Rg1’s targeted action on the ERK/AP-1 signaling axis could be beneficial for controlling fibrosis in nasal tissues and other TGF-β1-associated conditions.³²

In summary, ginseng, particularly its ginsenosides Rg1, Rg3, and G-F1, plays a significant role in modulating inflammation, fibrosis, and EMT in CRS and nasal polyps.^30–32 By modulating immune responses, ginseng may also enhance the effectiveness of immunological therapies, such as monoclonal antibodies targeting IL-4, IL-5, and IgE, which have shown success in treating both AR and CRS, particularly in patients with nasal polyps.^10,33 These findings support their potential as effective therapeutic agents for managing chronic sinus conditions (Table 2). Further research is necessary to explore their clinical applications, refine the understanding of their mechanisms, and establish their safety and efficacy for widespread use in CRS and related inflammatory disorders.

Table 2.

Therapeutic potential of ginseng and ginsenosides in CRS and Nasal Polyps.

Key Compounds	Findings	Mechanisms	Type of Study	References
G-F1	G-F1 reduces eosinophilic inflammation; boosts NK cell function; no systemic toxicity.	Enhances NK cell activity; distinct mechanism vs. dexamethasone.	Murine Model + Dosing Insights	30
Korean red ginseng (KRG), Rg3	KRG and Rg3 prevent ASD-induced EMT; reduce TGF-β1 and fibronectin.	Inhibition of EMT pathways (TGF-β1, ERK, mTOR).	Cell Culture Study	31
Rg1	Rg1 reduces fibrotic ECM components (e.g., collagen, fibronectin) in nasal polyps.	Inhibition of TGF-β1-induced fibrosis via ERK/AP-1 signaling.	Cell Culture Study	32

Table 1. Therapeutic Potential of Ginseng and Ginsenosides in Chronic Rhinosinusitis (CRS) and Nasal Polyps. This table summarizes key findings on the anti-inflammatory, immunomodulatory, and antifibrotic effects of ginseng and its active ginsenosides in the management of CRS and nasal polyps. Mechanisms of action include modulation of inflammatory cytokines (e.g., TNF-α, IL-6), enhancement of natural killer (NK) cell activity by G-F1, inhibition of epithelial-to-mesenchymal transition (EMT) via TGF-β1 and ERK/mTOR pathways by Korean red ginseng (KRG) and Rg3, and suppression of fibrosis through ERK/AP-1 signaling by Rg1.

3.3. Therapeutic potential of ginseng and ginsenosides in respiratory viral infections: anti-inflammatory and barrier-protective effects

Ginseng, particularly its active compounds called ginsenosides, has shown promise in enhancing the body’s resistance to viral and bacterial infections, including respiratory viruses like rhinovirus (HRV) and influenza.³⁴ Ginsenosides, such as those found in Korean Red Ginseng (KRG), have been demonstrated to inhibit viral replication and modulate immune responses, positioning ginseng as a potential therapeutic agent for managing viral respiratory infections.^35,36 KRG was shown to reduce HRV replication and inflammatory cytokine production, including IL-6 and IL-8, in primary human nasal epithelial (HNE) cells by modulating key signaling pathways, including NF-κB and MAP kinases.³⁷ These pathways play a crucial role in the inflammatory response to HRV infection. Specifically, KRG inhibited the activation of NF-κB p65 and reduced the phosphorylation of IκBα and MAP kinases like JNK and c-Jun, suggesting its potential to suppress inflammation and viral replication. Furthermore, ginsenoside Re, a bioactive compound in ginseng, was shown to protect tight junctions in HNE cells infected with HRV 16 by reducing reactive oxygen species (ROS) production and preventing phosphatase inactivation. HRV 16 infection disrupts tight junction integrity by downregulating proteins such as ZO-1, claudin-1, E-cadherin, and occludin, but ginsenoside Re restored the expression of these proteins, thereby protecting the epithelial barrier. This study highlights the protective antiviral and anti-inflammatory effects of ginsenoside Re, providing evidence for its therapeutic potential in managing HRV-induced inflammation and epithelial barrier dysfunction.^37,38 These findings suggest that ginseng may offer both prophylactic and therapeutic benefits in respiratory infections, particularly those involving viral pathogens that target the nasal mucosa (Figure 1).

4. Histological evidence supporting ginseng’s effects

4.1. Potential therapeutic effects of Korean Red Ginseng on ciliary dysfunction in allergic rhinitis and nasal polyps

Ciliary dysfunction plays a pivotal role in the pathophysiology of allergic rhinitis and CRSwNP, both of which are characterized by chronic inflammation in the upper airway. In allergic rhinitis, the immune response to allergens triggers inflammation of the nasal mucosa, which impairs ciliary function and disrupts mucociliary clearance. This dysfunction hinders the effective removal of allergens, pathogens, and irritants from the nasal passages, leading to a cycle of persistent inflammation and further ciliary damage.³⁹ Similarly, nasal polyps, often a consequence of chronic allergic inflammation, contribute to the formation of edema and inflammation in the nasal passages, resulting in mucosal prolapse that obstructs airflow and exacerbates ciliary dysfunction. The presence of these polyps intensifies mucosal inflammation, further compromising ciliary ability to clear mucus and pathogens. This can result in persistent nasal congestion, difficulty breathing, and an increased susceptibility to infections, underscoring the critical role of cilia in respiratory health.^40,41

Beyond the localized effects of ciliary dysfunction, recent evidence suggests that airway Type-2 inflammation, which underlies both allergic rhinitis and CRSwNP, may have systemic implications. Type-2 inflammation has been associated with multiorgan involvement, indicating that upper airway diseases should not be viewed in isolation but rather as part of a broader inflammatory network affecting respiratory and immune function. Addressing this inflammation holistically could be key to improving disease outcomes.⁴² In this context, recent studies suggest that Korean Red Ginseng (Panax ginseng Meyer) may have potential benefits for improving ciliogenesis and ciliary function. Its anti-inflammatory and immunomodulatory properties may help mitigate ciliary damage and restore mucociliary clearance, offering a promising therapeutic approach for managing chronic airway inflammation.^40,41

Recognized for its immune-boosting and antimicrobial properties, Korean Red Ginseng is commonly used both as an herbal remedy and a health supplement. In investigating the effects of ginseng’s bioactive components on chloride (Cl−) secretion, research has shown that Korean Red Ginseng aqueous extract (RGAE) stimulates sustained Cl− secretion in wild-type (WT) and cystic fibrosis transmembrane conductance regulator-deficient (CFTR−/−) mouse nasal epithelial cells (MNSE), surpassing forskolin-induced CFTR-mediated secretion. Interestingly, RGAE’s effects were largely independent of CFTR, pointing to the involvement of alternative chloride channels, particularly TMEM16A (a calcium-activated chloride channel or CaCC). Even in the absence of CFTR, RGAE robustly stimulated Cl− secretion, suggesting that CaCCs and potentially SLC26A9 are key mediators of this effect.⁴³

Further analysis identified specific ginsenosides – Rb1, Rg1, and Rg3—as contributors to RGAE’s effects, with Rg3 being the most potent. However, even when combined, these ginsenosides accounted for only about 30% of RGAE’s chloride transport effect, indicating that other, unidentified components of the ginseng extract may be involved. One such component is gintonin, a glycolipoprotein derived from ginseng, which has been shown to activate CaCCs through G-protein-coupled signaling pathways. Despite its potential, gintonin’s contribution to RGAE’s effects in this study appears minimal, likely due to its low concentration in the extract.^4,43,44

Patch-clamp experiments further demonstrated that while RGAE had a minimal direct effect on TMEM16A, it enhanced chloride secretion when combined with uridine triphosphate (UTP), suggesting that RGAE may influence TMEM16A expression or channel conductance. These findings imply that RGAE could enhance mucociliary clearance (MCC) without exacerbating airway hyper-responsiveness, a common issue in allergic diseases. In addition to its potential therapeutic applications for conditions like allergic rhinitis and asthma, RGAE may hold promise as a mutation-independent treatment approach for cystic fibrosis (CF), as it improves chloride secretion and mucociliary transport in CF models⁴³ (Figure 2).

Figure 2.

The diagram illustrates the protective effects of a ginseng plant-based intervention on the nasal epithelium against various environmental challenges. The nasal epithelium is shown to be exposed to external insults, including allergens (depicted as yellow circles), and pathogens such as bacteria and viruses. These factors can disrupt the integrity of the epithelium, which consists of goblet cells responsible for mucus secretion and ciliated cells that facilitate mucus clearance. The application of a ginseng plant-based extract, represented by the image of a ginseng plant, helps restore the health of the nasal epithelium. This intervention enhances mucus production, stabilizes the epithelial barrier, and promotes ciliary activity, mitigating the damage caused by allergens and pathogens. As a result, the nasal epithelium regains its functionality, leading to improved mucociliary clearance, enhanced pathogen defense, and relief from nasal symptoms. The figure underscores the pathway from environmental challenges to intervention and recovery, highlighting the potential therapeutic benefits of the plant-based extract.

Despite these encouraging results, the study’s in vitro design presents several limitations. Further in vivo studies in human sinonasal or bronchial cells, as well as CF animal models, are necessary to confirm the therapeutic effects of RGAE and clarify its underlying mechanisms. Further exploration into the role of alternative chloride channels and the precise molecular pathways activated by RGAE is also warranted to better understand its potential for improving airway epithelial cell function in both cystic fibrosis and chronic rhinosinusitis.⁴⁵

5. Safety considerations and local adverse effects of topical ginseng in nasal applications

Ginseng is widely acknowledged for its therapeutic properties and is generally safe for most individuals when used appropriately. However, some users may experience side effects, including gastrointestinal discomfort, headaches, and fluctuations in blood pressure, particularly among those with preexisting conditions or who are on medications affecting blood pressure. These side effects are usually mild and transient but can impact the long-term use of ginseng, especially when applied over extended periods or at higher doses. Patients should be mindful of these potential effects, particularly when using ginseng in chronic treatments or as part of broader therapeutic regimens.^46,47

Topical application of ginseng, such as in nasal sprays or other local formulations, may introduce additional concerns. Nasal application can potentially cause local irritation or allergic reactions, particularly in individuals with sensitive mucous membranes or a history of allergic rhinitis. Symptoms such as burning, stinging, or redness in the nasal passages are more likely in these cases. Although allergic reactions are uncommon, there is still the possibility of swelling or increased inflammation. As with any nasal treatment, it is important to monitor for adverse effects and adjust the usage accordingly to minimize the risk of irritation or sensitization.⁴⁸

6. Challenges and gaps in understanding Ginseng’s therapeutic potential

Despite the promising effects of ginseng on nasal health observed in both preclinical and clinical studies, there are several notable limitations within the current body of research. One significant gap is the lack of large-scale, well-designed human trials. Many of the existing studies have small sample sizes, often fewer than 100 participants, which limits the ability to generalize their findings. For example, trials examining ginseng’s impact on conditions such as allergic rhinitis and chronic rhinosinusitis may be subject to biases or lack the statistical power needed for robust conclusions.^23,49 Additionally, a considerable portion of the research has been conducted in animal models, which, while providing useful insights, may not always accurately reflect human physiological responses due to species differences in metabolism and immune function.^23,49 Another challenge arises from the variation in ginseng preparations used across studies, making it difficult to establish optimal dosages or determine the most effective formulation. To strengthen the evidence, base for ginseng’s efficacy in treating nasal health conditions, further randomized controlled trials (RCTs) with larger, more diverse human populations and standardized ginseng preparations are needed. These studies should also explore long-term safety, dosage regimens, and the underlying mechanisms of action to better assess the full therapeutic potential of ginseng for nasal conditions.

7. Limitations of the study

A key limitation of this study is its narrative review design, which, unlike systematic reviews, does not adhere to a predefined methodology for literature selection. As a result, there is a potentially higher risk of selection bias, as studies were included based on relevance and availability rather than through a structured and comprehensive search strategy. Additionally, the variability in ginseng preparations, dosages, and study designs among the reviewed articles makes it challenging to draw definitive conclusions regarding its therapeutic effects on nasal mucosa health. The heterogeneity of these studies may limit the generalizability of the findings, particularly in the absence of standardized formulations and clinical guidelines. Another notable limitation is the scarcity of human clinical data in this field. While preclinical and animal studies provide valuable mechanistic insights, the lack of large-scale, well-controlled human trials hinders the ability to translate these findings into clinical practice. Further research, particularly randomized controlled trials, is needed to validate ginseng’s efficacy and determine optimal dosing regimens for its potential therapeutic applications in nasal inflammatory diseases.

8. Conclusion

In conclusion, ginseng has shown considerable promise in improving nasal health through its anti-inflammatory, immune-modulating, and symptom-relieving properties. Research indicates that ginsenosides help reduce inflammation in the nasal mucosa by inhibiting pro-inflammatory cytokines and pathways such as NF-κB, making it a potential therapeutic agent for conditions like allergic rhinitis, chronic rhinosinusitis, and upper respiratory infections. Additionally, ginseng’s ability to enhance immune function – boosting natural killer cell activity and supporting mucosal immunity – further underscores its role in managing nasal conditions and preventing infections. Despite these promising findings, the current body of research is limited by small sample sizes, variations in ginseng formulations, and a lack of long-term studies in humans. Future research should focus on identifying which specific ginsenosides are most effective, determining optimal dosages, and exploring alternative delivery methods, such as nasal sprays or inhaled forms, to improve bioavailability and efficacy. Furthermore, large-scale randomized controlled trials are needed to substantiate ginseng’s role in ENT (ear, nose, and throat) medicine, particularly for patients with chronic rhinitis or those seeking complementary therapies for nasal health. With further investigation, ginseng-based treatments could become a valuable addition to the therapeutic arsenal for nasal conditions, offering a natural approach to managing inflammation and enhancing immune responses in the nasal mucosa.

Funding Statement

Funding Information: Open access funding provided by Università degli Studi Magna Graecia di Catanzaro within the CRUI-CARE Agreement.

Disclosure statement

The author of this manuscript assert that she does not have any competing financial, professional, or personal interests that could have influenced the work reported in this paper. The research presented in this manuscript was conducted independently and without external influence.

Author contributions

Conceptualization, G.L.P., N.L. (Nadia Lobello) and E.C.; writing – original draft preparation, E.C.; writing – review and editing, E.C., N.L. (Nadia Lobello), G.L.P. and N.L.; visualization, C.P., M.P.; funding acquisition, N.L., G.L.P. and C.P. All authors have read and agreed to the published version of the manuscript.