---
title: "Ginseng and Ginsenosides in Inflammatory Bowel Disease: Mechanisms, Preclinical Evidence, and Chal"
id: "frontiers-in-immunology-11-therapeutic-potential-of-ginseng-and-its-bioactive-compounds-in-inflammatory"
canonical_url: "https://medichelpline.com/clinical-feed/frontiers-in-immunology-11-therapeutic-potential-of-ginseng-and-its-bioactive-compounds-in-inflammatory"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "Frontiers in Immunology"
source_url: "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1878839"
published_at: "2026-08-10T00:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Ginseng and Ginsenosides in Inflammatory Bowel Disease: Mechanisms, Preclinical Evidence, and Chal
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/frontiers-in-immunology-11-therapeutic-potential-of-ginseng-and-its-bioactive-compounds-in-inflammatory
- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** Frontiers in Immunology
- **Source URL:** [Original Journal Publication](https://www.frontiersin.org/articles/10.3389/fimmu.2026.1878839)
- **Published At:** 2026-08-10T00:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- Inflammatory bowel disease (IBD), including **ulcerative colitis** (UC) and Crohn’s disease (CD), is a chronic immune-mediated condition marked by persistent intestinal inflammation, epithelial barrier disruption, and symptoms such as abdominal pain and bloody diarrhea. - Global IBD burden is rising; the 2017 GBD estimated ~6.8 million cases and more recent data show increasing incidence and prevalence through 2023. In the U.S., CDC estimates 2.4–3.1 million affected and substantial healthcare costs. - Conventional IBD therapies include corticosteroids, 5-ASA, immunosuppressants, anti-TNF agents, anti-integrin drugs, IL-12/23 and IL-23 inhibitors, JAK inhibitors, and S1P modulators; limitations include adverse effects, incomplete responses, immunogenicity, cost, and safety concerns. - Ginseng has long traditional use and contains bioactive constituents—most notably **ginsenosides**—which have anti-inflammatory, immunomodulatory, antioxidant, barrier-supporting, and microbiota-modulating properties demonstrated in vitro and in vivo. - Ginsenosides are glycosylated triterpenoid saponins classified mainly as dammarane-type (protopanaxadiol and protopanaxatriol groups), with additional minor ocotillol- and oleanane-type compounds; structural diversity influences pharmacology. - Mechanisms implicated in IBD pathogenesis include epithelial barrier breakdown, dysregulated innate and adaptive immune responses, altered cytokine production and signaling, and gut microbiota dysbiosis. - Ginseng and ginsenosides have shown protective effects in experimental colitis models via inhibition of inflammatory signaling, modulation of cytokine production, regulation of immune cell activity, reinforcement of epithelial integrity, and alteration of gut microbiota. - Major obstacles to clinical translation include limited well-designed human trials, low oral bioavailability of ginsenosides, variable intestinal uptake dependent on gut microbiota metabolism, interindividual and interspecies pharmacokinetic variability, structural and product differences, and inconsistent therapeutic outcomes. - Enhancing bioavailability and addressing pharmacokinetic variability are highlighted as key priorities for future research to validate therapeutic potential in human IBD. - Most available evidence in the reviewed literature derives from UC models; extrapolation to CD should be cautious. Detailed clinical recommendations were not reported in the source.
## Clinical Analysis & Structured Key Points
Frontiers | Therapeutic potential of ginseng and its bioactive compounds in inflammatory bowel disease: current evidence and future directions REVIEW article Front. Immunol. , 10 August 2026 Sec. Inflammation Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1878839 Published in Frontiers in Immunology Inflammation 7 impact factor 11.3 citescore Part of a Research Topic Pharmacological Advances in Inflammatory Bowel Disease: Mechanisms, Biomarkers, and Therapeutic Strategies Submission open 12k views 13 articles Editor & Reviewers Edited by S W Shuai Wu Reviewed by C F Changhao Fu L X Liuwei Xie Outline Figures and Tables Figure 1 View in article Figure 2 View in article Figure 3 View in article Table 1 Classification of ginsenosides. View in article Table 2 Overview of preclinical evidence on ginseng-derived compounds in experimental IBD models, emphasizing their protective roles through various mechanisms. View in article REVIEW article Front. Immunol. , 10 August 2026 Sec. Inflammation Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1878839 Therapeutic potential of ginseng and its bioactive compounds in inflammatory bowel disease: current evidence and future directions M I Minarul Islam 1 I P Il-Ho Park 2 * K S Ki Sung Kang 3 * 1. Department of Food Science and Biotechnology, Gachon University, Seongnam, Republic of Korea 2. College of Pharmacy, Sahmyook University, Seoul, Republic of Korea 3. College of Korean Medicine, Gachon University, Seongnam, Republic of Korea See more Article metrics View details Abstract Inflammatory bowel disease (IBD) is a group of chronic immune-mediated inflammatory disease characterize by persistent inflammation of the gastrointestinal tract that can substantially impact quality of life. Due to the inconsistencies and adverse effects associated with conventional therapies, there is an increasing demand for safer and more reliable treatment alternatives for IBD. The pathogenesis of IBD involves multiple factors, including the overactivation of signaling pathways, elevated pro-inflammatory cytokine levels, dysbiosis of the gut microbiota, and activation of immune cells. Traditionally, ginseng has been used as both a dietary component and a therapeutic agent, its bioactive constituents (ginsenosides and their derivatives) have demonstrated potential therapeutic effects in preclinical IBD models. Numerous studies have shown that ginsenosides may ameliorate experimental colitis through multiple mechanisms, including the inhibition of inflammatory signaling pathways, regulation of cytokine production, modulation of immune cell activity, and alteration of the gut microbiota. However, clinical studies investigating the use of ginsenosides in the treatment of IBD are extremely limited. In this review, we provide a comprehensive overview of IBD pathology and highlight the therapeutic potential of ginseng and its derivatives, particularly ginsenosides, as emerging therapeutic option, along with their current challenges and prospects. Graphical Abstract 1 Introduction Inflammatory bowel disease (IBD) encompasses ulcerative colitis (UC) and Crohn’s disease (CD), both of which are chronic and recurrent inflammatory conditions of the gastrointestinal tract characterized by persistent intestinal inflammation, disruption of the epithelial barrier, and symptoms such as abdominal pain and bloody diarrhea ( 1 , 2 ). Although its precise etiology is unknown, IBD is believed to stem from a complex interplay of genetic predisposition, immune system dysfunction, environmental influences, and gut microbiome imbalances. These processes result in heightened intestinal permeability, increased immune cell infiltration, altered T-cell and macrophage activity, and microbial dysbiosis—characterized by decreased short-chain fatty acid (SCFA)–producing bacteria and increased pro-inflammatory microbes—thus perpetuating chronic intestinal inflammation ( 3 , 4 ). The 2017 Global Burden of Disease (GBD) study estimated that approximately 6.8 million individuals worldwide (95% uncertainty interval: 6.4–7.3 million) were affected by IBD, underscoring its significant global impact ( 5 ). Recent GBD data (up to 2023) have shown a continuing global increase in both the incidence and prevalence of IBD, with the age-standardized incidence escalating from 12.3 per 100,000 in 1990 to 25.6 per 100,000 in 2023, and the overall prevalence increasing from approximately 396 to 523 per 100,000 during the same time period ( 6 ). According to the Centers for Disease Control and Prevention (CDC), IBD affects an estimated 2.4–3.1 million individuals in the United States (U.S.), with variations in burden across demographic groups. In 2018, total annual healthcare expenses for IBD in the U.S. were approximately $8.5 billion, underscoring its substantial health and economic effects ( 7 ). The incidence of IBD has steadily increased in the Western world during the twentieth century. Although it has leveled off in certain areas, it continues to rise among specific groups, including pediatric-onset cases. Currently, IBD affects approximately 0.5% of the population in Western nations, with more than 1 million cases in the U.S. and 2.5–3.0 million in Europe. Although previously rare in developing regions, IBD has rapidly emerged in newly industrialized nations in Asia, South America, and the Middle East, where its incidence is increasing significantly. Due to its persistent nature and low mortality, IBD exhibits “compounding prevalence,” resulting in a continuous and exponential increase in the worldwide disease burden ( 8 ). Treatment for IBD has traditionally relied on corticosteroids, aminosalicylates, and immunosuppressive medications. Corticosteroids such as hydrocortisone, prednisolone, and budesonide are used to induce remission by decreasing inflammation via the inhibition of the NF-κB pathway; however, prolonged use is associated with various side effects, such as weight gain, swelling, acne, increased appetite, insomnia, dyspepsia, and mood changes ( 9 ). Aminosalicylate derivatives, such as Olsalazine, Balsalazide, and Sulfasalazine, are frequently recommended for mild to moderate UC but are less effective in CD. These agents act by blocking NF-κB, reducing oxidative stress, and altering arachidonic acid metabolism, thereby reducing the production of inflammatory substances such as prostaglandins and leukotrienes. Consequently, 5-ASA reduces intestinal inflammation and protects epithelial cells. Nonetheless, 5-ASA treatment has been associated with negative effects, such as pancreatitis, heart toxicity, liver and kidney damage, sexual issues, gastrointestinal problems, and skin reactions ( 10 ). Immunosuppressants, particularly anti-TNF medications such as Infliximab, Adalimumab, Certolizumab pegol, and Golimumab have improved IBD management by providing more precise anti-inflammatory effects. These agents reduce inflammation by inhibiting tumor necrosis factor (TNF) signaling and restricting immune cell infiltration ( 11 ). However, some patients may not initially respond to treatment, others may lose their response over time, and repeated therapies may result in immunogenicity, highlighting the importance of patient selection ( 12 , 13 ). Current IBD treatments encompass anti-integrin agents (like vedolizumab, natalizumab) which block leukocyte migration, IL-12/23 and IL-23 inhibitors (focusing on p40 or p19 units) that reduce inflammatory cytokine signaling, JAK inhibitors (such as tofacitinib, upadacitinib) that disrupt intracellular cytokine pathways, and S1P receptor modulators (for example, ozanimod, etrasimod) that control lymphocyte movement ( 14 – 16 ). Despite advancements in these therapies for IBD, issues like insufficient response, side effects, high expenses, and long-term safety worries underscore the necessity for additional and alternative treatment options. Hence, there is an urgency for alternative therapeutic approaches with greater effectiveness and minimal side effects to complement the existing IBD treatments. Ginseng could be a potential therapeutic agent for IBD owing to its strong anti-inflammatory and immunomodulatory effects. In vitro , and in vivo studies have revealed that ginseng can reduce intestinal inflammation by influencing immune cell differentiation, inhibiting inflammatory cytokine production, and modulating key inflammatory signaling pathways ( 17 – 20 ). Ginseng also play a role in maintaining immune balance, strengthening the intestinal barrier, and rehabilitating the gut microbiota ( 21 – 23 ). Ginseng and its bioactive compounds exhibit diverse biological and pharmacological activities, including anti-inflammatory, immunomodulatory, and antioxidant effects ( 24 , 25 ). Moreover, traditionally valued as a medicinal herb, ginseng has been widely used and scientifically investigated for the treatment of various conditions, including diabetes mellitus, fatigue, tumors, ulcers, hypertension, stress, and neurological diseases, such as Alzheimer’s, Parkinson’s, and Huntington’s diseases ( 26 – 32 ). Ginseng contains numerous bioactive compounds, including ginsenosides, polysaccharides, peptides, fatty acids, polyacetylenes, and gintonin. Ginsenosides are considered the most significant and active of these components, with over 100 varieties recognized to date. These substances demonstrate notable anti-inflammatory effects and have displayed beneficial effects in a range of inflammatory conditions ( 33 – 35 ). Therefore, ginsenosides, considered the main bioactive compounds, are thought to contribute to its health benefits and pharmacological effects of ginseng. However, despite their encouraging preclinical results, their clinical application is impeded by low oral bioavailability, inadequate intestinal uptake, and reliance on metabolism mediated by complex gut microbiota. In addition, variability in pharmacokinetics across individuals and species, differences in structure, and variability between products lead to inconsistent therapeutic results. The scarcity of well-designed clinical evidences also restricts the validation of their effectiveness in human IBD ( 36 – 39 ). Therefore, enhancing the bioavailability of ginsenosides is an important and utmost attention for future IBD research. In this review, we aim to explore the role of ginseng and its derivatives in IBD management and provide a theoretical basis for the development of prospective therapeutic strategies and potential approaches to overcome existing limitations. Most of the evidence covered in this review derived from UC models; hence, the impacts of ginseng and its bioactive components should be interpreted mainly within the framework of UC. 2 Methods To find pertinent research on the therapeutic potential of ginseng and its bioactive constituents in inflammatory bowel disease (IBD), a thorough literature search was carried out. Combinations of keywords like “ginseng,” “Panax species,” “ginsenosides,” “ginseng polysaccharides,” “bioactive compounds,” “IBD,” “Crohn’s disease,” “ulcerative colitis,” “colitis,” “inflammation,” “gut microbiota,” “ginsenosides and ginseng alleviate IBD,” and “intestinal barrier” were used to retrieve published articles from databases such as PubMed, Scopus, Web of Science, and Google Scholar. Studies that focused on IBD pathogenesis, structure and characteristics of ginseng, the mechanisms of action, anti-inflammatory properties, immune regulation, gut microbiota modulation, and intestinal protective benefits of substances derived from ginseng were chosen. An overview of the present knowledge and therapeutic potential of ginseng in IBD was produced by analyzing and summarizing the collected evidences. 3 Chemistry and classification of ginsenosides Ginsenosides are distributed throughout the ginseng plant, including in the roots, leaves, stems, flowers, and fruits. Their composition and content vary according to the ginseng species and plant parts ( 40 ). Ginsenosides are saponins, which are glycosylated triterpenoids featuring a hydrophobic aglycone framework with approximately 30 carbon atoms and one or more hydrophilic sugar units, including glucose, rhamnose, xylose, and arabinose. These sugar moieties are often linked to specific carbon sites (primarily C-3, C-6, and C-20), which enhances their structural diversity and biological roles ( 41 – 43 ). Ginsenosides are mainly categorized into dammarane- and oleanane-type saponins based on their chemical structures and aglycone frameworks ( Table 1 ). Dammarane-type ginsenosides comprise the bulk and are categorized into protopanaxadiol (PPD) and protopanaxatriol (PPT) groups, based on the location and quantity of hydroxyl groups and connected sugars. Other minor types include ocotillol-type ginsenosides with distinct epoxy ring structures and oleanane-type ginsenosides with pentacyclic structures, which are found in smaller quantities ( 44 – 46 ). The structural differences among these categories, particularly the changes in the aglycone backbone and sugar chains, are crucial for influencing the pharmacological effects and therapeutic potential of ginsenosides ( 47 ) ( Figure 1 ). Table 1 Category Backbone Examples Protopanaxadiol Dammarane Rb1, Rb2, Rb3, Rc, Rd, Rg3, Rh2, Rs Protopanaxatriol Dammarane Re, Rf, Rg1, Rg2, Rh Oleanolic acid Pentacyclic triterpenoid Ro Ocotillol Five-membered epoxy ring at C20 F11, RT2, RT4, RT5 Classification of ginsenosides. Figure 1 Schematic representation of the chemical structure of different ginsenosides. 4 Mechanistic basis of IBD pathogenesis The intestinal mucosa maintains stability with luminal contents through the intestinal barrier, composed of epithelial, microbial, chemical, and immune components. This selective barrier facilitates nutrient uptake while regulating the entry of pathogens, toxins, and antigens, thus preserving immune balance. Disruption of barrier integrity increases intestinal permeability, allowing harmful agents to penetrate the mucosa and trigger inflammatory reactions ( 48 – 51 ). Although genetic predisposition and environmental factors may contribute to disease development, the disruption of the epithelial barrier and subsequent immune activation are considered central events in the onset and progression of IBD ( 52 ). Its pathogenesis involves intricate interactions between intestinal endothelial and immune cells, abnormal cytokine production and signaling pathways, and disruption of the gut microbiome, resulting in persistent immune activation and chronic intestinal inflammation ( Figure 2 ). Figure 2 Mechanistic insights into the pathogenesis of inflammatory bowel disease (IBD). The development of IBD is driven by complex interactions among intestinal barrier disruption, dysfunctional immune cell differentiation, dysregulated cytokine production and signaling pathways, and gut microbiota alterations. These factors collectively lead to sustained immune activation and chronic intestinal inflammation. (↓: Decrease; ↑: Increase) (Created with Biorender.com ). 4.1 Intestinal epithelial cells (IECs) The intestinal epithelium consists of a single cell layer that lines the intestinal tract, creates a physical barrier, and is crucial for preserving barrier integrity and immune balance ( 53 ). The specialized IECs, such as absorptive, goblet, enteroendocrine, Paneth, M, cup, and tuft cells, play roles in mucus secretion, antimicrobial defense, immune regulation, and interaction with the underlying immune system ( 54 ). The integrity of the epithelial barrier is maintained by tight junctions, mucus layers, and antimicrobial peptides that regulate intestinal permeability and block microbial invasion ( 55 ). In IBD, breakdown of epithelial integrity, including altered tight junctions, increased apoptosis of IECs, and dysfunctional differentiation of epithelial cell types, results in enhanced intestinal permeability and irregular immune activation ( 56 , 57 ). Pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and interferon-γ (IFN-γ), also enhance epithelial apoptosis and compromise barrier function ( 58 – 60 ). Consequently, epithelial damage facilitates the entry of microbes into the mucosa, triggering the immune response and leading to ongoing inflammation, establishing intestinal epithelial dysfunction as a key factor in IBD development ( 61 , 62 ). 4.2 Intestinal immune cells Dysregulated immune responses in the digestive system are a hallmark of IBD. Innate immunity provides the first-line defense through pattern recognition receptors (PRRs) and consists of IECs, Paneth cells, macrophages, (Dendritic cells) DCs, neutrophils, monocytes, (Innate lymphoid cells) ILCs, and (Natural killer cells) NK cells, which block pathogens while maintaining tolerance for commensal microbiota ( 63 ). Nonetheless, alterations in this immune equilibrium cause heightened inflammatory responses that contribute to chronic intestinal inflammation and develop IBD ( 64 ). In UC, activated neutrophils accumulate in the intestinal mucosa and promote inflammation by secreting neutrophil extracellular traps and reactive oxygen species via enzymes, such as myeloperoxidase. This results in epithelial damage, crypt abscess formation, and ulceration ( 65 , 66 ). In IBD, NK cells show metabolic impairment with diminished mitochondrial function and decreased mTORC1 activity, even though pro-inflammatory IL-17A and TNF-α production is elevated. They additionally control neutrophil-driven inflammation through the inhibitory receptor NKG2A ( 67 , 68 ). ILCs are crucial for intestinal immunity, barrier maintenance, and tissue repair. Nonetheless, the imbalance among ILC subsets contributes to disease development. Elevated ILC1 levels lead to inflammation via cytokines such as IFN-γ, reduced ILC3 levels weaken the intestinal barrier protection usually provided by IL-22, and altered ILC2 activity may either worsen inflammation or aid epithelial repair ( 69 ). In IBD, DCs transition from tolerogenic to pro-inflammatory states. Typically, intestinal CD103 + DCs sustain immune tolerance by producing IL-10 and facilitating the differentiation of Foxp3 + regulatory T cells (Tregs) ( 70 ). In IBD, the number of pro-inflammatory DCs increases, whereas that of the tolerogenic subsets decreases. These DCs exhibit increased expression of toll-like receptor 2 (TLR2) and TLR4, triggering NF-κB signaling and generating cytokines, such as IL-12, IL-23, and TNF, which enhance Th1 and Th17 responses and contribute to chronic intestinal inflammation ( 71 , 72 ). In healthy subjects, intestinal macrophages promote immune tolerance by exhibiting robust phagocytic activity and releasing anti-inflammatory cytokines such as IL-10, which bolster Treg responses and maintain gut homeostasis ( 73 ). In IBD, this equilibrium is disrupted, leading to the accumulation of pro-inflammatory macrophages, particularly M1 macrophages. These cells produce elevated levels of inflammatory mediators, including TNF-α, IL-6, IL-1β, and IL-23, which enhance Th1 and Th17 immune responses and intensify intestinal inflammation ( 74 , 75 ). Additionally, increased levels of CD14 + and TREM-1 + macrophages boost cytokine release and inflammatory signaling, leading to chronic mucosal inflammation and tissue injury ( 76 , 77 ). Adaptive immune cells, such as T helper cells (Th1, Th2, Th17, and Th9) and B cells, play an important role in the pathogenesis of IBD. Unlike innate immunity, adaptive immunity is specific, long-lasting, and capable of immune memory. However, it develops slowly and with greater precision. CD8 + T cells contribute to IBD pathogenesis through distinct functional subsets. Cytotoxic CD8 + T cells (Tc1) and IL-17–producing CD8 + T cells (Tc17) promote inflammation by secreting IFN-γ and TNF-α, resulting in IEC injury, whereas tissue-resident memory CD8 + T cells (Trm) may exert context-dependent regula
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