Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, and colorectal cancer (CRC) represent two of the most significant gastrointestinal health challenges worldwide. In 2023, CRC ranked as the third most commonly diagnosed cancer globally, accounting for approximately 10% of all cancer cases and standing as the second leading cause of cancer-related death. Projections suggest that global CRC incidence will reach 3.2 million new cases annually by 2040.
The relationship between IBD and CRC is clinically important: persistent intestinal inflammation dramatically increases a patient's long-term risk of developing colorectal malignancy. Chronic mucosal inflammation, alterations in the gut microbiota, and a heightened oxidative stress environment collectively create conditions that promote adenoma formation and progression toward carcinoma, making IBD both a disease in its own right and a precancerous risk state.
Current standard therapies for CRC include surgical resection, chemotherapy (primarily 5-fluorouracil-based regimens), and radiotherapy in select cases. While these treatments have improved survival rates, they are associated with substantial side effects, variable efficacy, and an increasing problem of drug resistance. Similarly, long-term IBD management with corticosteroids, immunosuppressants, and biologics carries risks of hepatic toxicity, hyperglycemia, and immune suppression.
These limitations have prompted growing interest in plant-derived bioactive compounds as complementary or preventive approaches. Traditional medical systems worldwide have relied on medicinal plants for gastrointestinal complaints for centuries, and modern pharmacological research is now systematically validating many of these ancestral practices with rigorous experimental methods.
Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are normal byproducts of cellular metabolism, but when their production overwhelms the body's antioxidant defenses, a state of oxidative stress results. In the intestinal mucosa, this redox imbalance drives lipid peroxidation, DNA damage, and protein oxidation, all of which contribute to the initiation and perpetuation of IBD-related inflammation.
Oxidative DNA damage is not merely a bystander effect of inflammation but an active contributor to carcinogenesis. Persistent ROS exposure can introduce mutations in tumor suppressor genes such as p53 and oncogenes like KRAS, activate transcription factors including NF-kB and STAT3, and disrupt signaling pathways that normally restrain uncontrolled cell growth. This creates a direct mechanistic bridge between chronic gut inflammation and the development of colon cancer.
Beyond ROS, chronic activation of inflammatory pathways produces elevated levels of cytokines such as TNF-alpha, IL-6, and IL-1 beta. These cytokines drive continuous immune cell recruitment, epithelial barrier dysfunction, and stromal remodeling. In the long term, this inflammatory milieu promotes angiogenesis, suppresses immune surveillance of early cancer cells, and accelerates tumor invasion and metastasis.
Dietary factors are also key modulators of gut oxidative stress. High saturated fat intake has been strongly linked to increased oxidative DNA damage and elevated CRC risk. Conversely, diets rich in antioxidants from fruits, vegetables, and plant foods are consistently associated with lower IBD severity and reduced colorectal cancer risk, providing the biological rationale for studying plant extract therapeutics in this context.
This review compiles and critically analyzes data from over a decade of published research on plant extracts and isolated natural compounds tested for their protective effects against IBD and colon cancer. Databases searched included PubMed, Web of Science, Science Direct, SCOPUS, and Google Scholar, with the search restricted to English-language publications from 2015 to 2025.
Eligibility required studies to include specific experimental data on plant extract effects in in vitro cell models, in vivo animal models, or ex vivo tissue preparations. Articles were assessed for biochemical characterization of the plant extracts, clear reporting of doses used, and documented mechanistic findings rather than purely descriptive results.
The resulting dataset for IBD covers more than 40 studies examining 55 different medicinal plant species, while the colon cancer section compiles data from over 50 experimental studies across 71 plant species. This breadth reflects the extensive preclinical literature exploring plant-derived therapeutics for gut diseases, spanning herbs, fruits, roots, bark, and marine species from diverse global traditions.
Key outcome measures assessed across studies included effects on pro-inflammatory cytokine levels (TNF-alpha, IL-6, IL-1 beta), antioxidant enzyme activity (SOD, CAT, GPx), epithelial barrier integrity markers (tight junction proteins such as ZO-1 and occludin), cell viability and proliferation, apoptosis induction, and cell cycle arrest in cancer cell models.
Across the IBD studies reviewed, plant extracts consistently demonstrated the ability to reduce intestinal inflammation through several complementary mechanisms. Most extracts suppressed the production of key pro-inflammatory cytokines including TNF-alpha, IL-6, and IL-1 beta, while simultaneously enhancing activity of protective antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx).
A particularly important finding was the ability of several plant extracts to restore intestinal epithelial barrier integrity. Extracts from Lycium ruthenicum, Artemisia argyi, Lindera aggregata, and Achyrocline satureioides increased expression of tight junction proteins including ZO-1, occludin, and claudin-1. Because a leaky intestinal barrier is a primary driver of chronic gut inflammation, these barrier-protective effects have direct therapeutic relevance for IBD management.
Polyphenols and flavonoids emerged as the most consistently active chemical classes across the IBD studies. These compounds, found abundantly in berries, tea, citrus fruits, and many traditional medicinal herbs, appear to act through multiple simultaneous pathways rather than a single target. This polypharmacological profile may actually make them more suitable for a multifactorial disease like IBD than single-target drugs, which often drive resistance.
Traditional medicine precedents were validated in multiple cases. For example, Phaseolus vulgaris (Fagiola di Venanzio, an Italian bean variety) extracts effectively attenuated interleukin-1 beta-induced inflammation in intestinal cell models, reducing COX-2 expression and prostaglandin E2 levels. These results confirm that traditional food-based remedies contain pharmacologically active compounds with measurable anti-inflammatory effects at relevant concentrations.
In the colon cancer section of the review, plant extracts from 71 species demonstrated significant anticancer activity. The dominant mechanisms were apoptosis induction through either mitochondrial or caspase-dependent pathways, and inhibition of cancer cell proliferation through cell cycle arrest at the G0/G1 or G2/M phases. These mechanisms directly target the fundamental processes that distinguish cancer cells from normal cells.
Several key signaling pathways were identified as recurring targets of plant-derived anticancer compounds. These included NF-kB (a master inflammatory and survival regulator), JNK (a stress-activated kinase), the Wnt/beta-catenin pathway (frequently dysregulated in colon cancer), and the PI3K/Akt/mTOR pathway (which governs cell growth and survival). The ability of plant compounds to modulate these pathways at multiple nodes represents a distinct advantage over targeted therapies that inhibit only a single step.
Compounds from Origanum majorana (marjoram), Rhus coriaria (sumac), Artemisia annua (sweet wormwood), and Gnetum montanum were particularly effective, demonstrating suppression of tumor proliferation and metastatic invasion while activating tumor suppressor genes including p53 and Bax. Several extracts also showed synergy with conventional chemotherapy agents like 5-fluorouracil, suggesting potential for combination regimens that reduce chemotherapy doses while maintaining efficacy.
Plant-derived compounds tested against colorectal cancer cell lines including HT-29, HCT-116, SW-480, Caco-2, and RKO demonstrated selective cytotoxicity: killing cancer cells at concentrations that were non-toxic to normal colon epithelial cells. This selectivity is a critical feature for any candidate therapeutic compound and supports continued development of plant-based anticancer agents.
Polyphenols are the most extensively studied class of plant anticancer and anti-inflammatory compounds. They include phenolic acids, stilbenes (such as resveratrol), and hydroxycinnamic acid derivatives. Polyphenols exert their effects through direct free radical scavenging, modulation of inflammatory enzyme activity including COX-2 and iNOS, and epigenetic regulation of gene expression. Their high bioavailability from dietary sources makes them particularly relevant for preventive strategies.
Flavonoids, a major subclass of polyphenols, include quercetin, kaempferol, luteolin, and anthocyanins from berries and dark-colored fruits. In colon cancer models, flavonoids have been shown to induce cell cycle arrest, inhibit the PI3K/Akt pathway, downregulate anti-apoptotic proteins like Bcl-2, and upregulate pro-apoptotic factors like Bax. In IBD models, they reduce myeloperoxidase activity, suppress NLRP3 inflammasome activation, and protect gut barrier proteins.
Terpenes and alkaloids constitute additional biologically active classes. Terpenoids such as betulinic acid and ursolic acid have demonstrated potent pro-apoptotic effects in colorectal cancer through mitochondrial membrane disruption. Alkaloids including berberine (found in multiple traditional medicinal plants) have shown broad anti-inflammatory effects and inhibition of cancer cell migration and invasion through multiple pathways including NF-kB and STAT3 suppression.
The diversity of active compound classes and their overlapping mechanisms of action suggest that whole plant extracts, which contain multiple compound classes simultaneously, may be more effective in complex disease settings than isolated single compounds. This concept aligns with traditional medicine practices that typically use whole plant preparations rather than purified active ingredients, and supports the investigation of standardized multi-compound formulations.
The breadth of preclinical evidence reviewed in this paper strongly supports the biological plausibility of plant-derived compounds as complementary tools for IBD management and CRC prevention or treatment. However, translating these findings to clinical benefit requires addressing several key gaps: most studies rely on cell lines rather than patient-derived organoids, and in vivo models often use supraphysiological doses that may not be achievable in humans.
Bioavailability remains a major challenge for plant compounds, many of which are rapidly metabolized, poorly absorbed, or extensively converted by gut bacteria before reaching target tissues. Future formulation strategies including nanoencapsulation, liposomal delivery, and microbiome-mediated activation may be necessary to achieve therapeutically relevant concentrations at the intestinal mucosa and in tumor tissue.
The integration of traditional herbal knowledge with modern biomedical science represents a valuable and cost-effective drug discovery framework. Many traditional plants used for gut ailments across cultures contain compound classes that overlap with those identified in modern high-throughput screening campaigns, suggesting that centuries of empirical use have effectively pre-screened the natural world for biologically active molecules.
Plant-based compounds represent not only potential therapeutic agents but also a foundation for developing functional foods and nutraceuticals aimed at reducing colorectal cancer risk in the general population. Given the strong epidemiological data linking high fruit, vegetable, and polyphenol intake with reduced CRC risk, strategies that increase dietary intake of these compounds at a population level may have substantial public health impact beyond individual treatment settings.
This comprehensive review demonstrates that plant extracts and their bioactive constituents exert multiple complementary protective effects relevant to both IBD and colorectal cancer. The consistency of anti-inflammatory, antioxidant, barrier-protective, and pro-apoptotic effects across dozens of independent studies from different research groups provides strong support for the therapeutic potential of plant-derived compounds in gut disease.
The finding that numerous plant compounds selectively target cancer cells while sparing normal colon epithelium is particularly encouraging from a safety standpoint. This selectivity, if confirmed in clinical settings, would make plant-based agents suitable candidates for chemopreventive use in high-risk populations including IBD patients, where long-term tolerable interventions are especially needed.
Polyphenols and flavonoids stand out as the most promising compound classes based on current evidence, given their widespread availability, extensive preclinical data, and favorable safety profiles from decades of dietary consumption research. However, terpenes and alkaloids from less-studied traditional plants also warrant further investigation, particularly for cases where standard therapies have failed.
The body of evidence reviewed here supports a growing paradigm shift: rather than viewing natural compounds as alternatives to conventional medicine, the field is moving toward an integrative approach where plant-derived agents are developed alongside and in combination with established therapies. This integration, guided by rigorous mechanistic understanding and clinical testing, holds the greatest promise for improving outcomes in the significant global population affected by IBD and colorectal cancer.