TGP, derived from the dried root of Paeonia lactiflora Pall, encompasses active components like paeoniflorin, hydroxypaeoniflorin, and paeoniflorin. Known for its anti-inflammatory, immunomodulatory, antithrombotic, and hepatoprotective properties, TGP plays a crucial role in curbing autoimmune responses, thereby upholding immune tolerance within the body (101, 102). Lin et al. observed that TGP significantly curtails Th17-related cytokines like IL-17 and TNF-α in rats afflicted with UC while elevating Treg-related cytokines such as TNF-β, and IL-10, among others. This suggests that TGP mitigates intestinal mucosal damage in UC by orchestrating cytokine production, quelling the effector attributes of Th17 cells, and enhancing Treg responses (103). Basic research has revealed that paeoniflorin restores the balance of Th17/Treg, inhibits the activation of the NF-κB signaling pathway, reduces oxidative stress, suppresses the secretion of inflammatory factors such as IL-17, TNF-α, and ICAM, while simultaneously promoting the expression of autophagy-related factors such as LC3BII and Beclin1, thus ameliorating UC (104–106). Paeoniflorin also aids in improving TNBS-induced colitis by modulating the Th17/Treg balance mediated by DCs (107).

Mangiferin and neomangiferin (Figure 3) are present in Anemarrhena asphodeloides and mango pistils (from the Anacardiaceae family), commonly utilized in herbal remedies and functional foods to address inflammation, asthma, and pain management (108–110). Mangiferin exhibits antioxidants, analgesics, anti-inflammatories, and effects on colitis and diabetes (111–113). Neomangiferin, more hydrophilic than mangiferin, benefits osteoporosis and lipid issues (110, 114). In vitro studies indicate that neomangiferin restores the balance of Th17/Treg cell populations by downregulating IL-17 and RORγt expression while upregulating IL-10 and FOXP3 expression, ameliorating colitis (115). Meanwhile, mangiferin modulates innate immunity by inhibiting TLR4-NF-κB/MAPK signaling, particularly IRAK1 phosphorylation, exhibiting anti-colitis effects (116). In a TNBS-induced colitis mouse model, mangiferin significantly reduced colon shortening and myeloperoxidase activity, potentially by impeding Th17 cell differentiation, decreasing TNBS-induced IL-17 expression, promoting Treg cell differentiation, and enhancing TNBS-inhibited IL-10 expression. Additionally, mangiferin inhibited spleen cell differentiation into Th17 cells in vitro while promoting Treg cell differentiation. This may involve downregulating RORγt and IL-17 expression, inhibiting STAT3 activation in spleen cells, upregulating Foxp3 and IL-10 expression, and enhancing STAT5 activation (117). Overall, in both in vitro and in vivo settings, mangiferin has demonstrated its ability to mitigate inflammation by modulating the differentiation of adaptive immune-related T cells.

Timosaponin AIII (Figure 3), derived from Anemarrhena asphodeloides rhizomes and serving as sarsasapogenin, exhibits anti-inflammatory properties (118). Lim et al. identified that both timosaponin AIII and its metabolite sarsasapogenin effectively inhibited NF-κB and MAPK activation, as well as the phosphorylation of IRAK1, TAK1, and IκBα in LPS-stimulated macrophages. These compounds not only suppressed Th17 cell differentiation in the colonic lamina propria but also facilitated Treg cell differentiation. Additionally, timosaponin AIII and sarsasapogenin impeded the differentiation of splenic CD4+ T cells into Th17 cells in vitro (119).

Oleanolic acid (Figure 3) and its derivatives, natural pentacyclic triterpenoids extensively present in various plants, offer a range of preventive and therapeutic benefits across conditions such as UC, multiple sclerosis, and metabolic disorders (120–123). Research highlights the remarkable inhibitory prowess of a potent synthetic triterpene analog derived from oleanolic acid in interrupting cellular inflammatory pathways. Oleanolic acid showcases its inhibitory impact on induced nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 in macrophages (124). This compound also deters DSS-induced Th17 cell differentiation and lowers the expression of RORγt and IL-17 in the colon and colonic lamina propria concurrent with an upsurge in Treg cell differentiation markers, notably Foxp3 and IL-10 (125). These outcomes suggest that oleanolic acid holds promise in ameliorating inflammatory conditions like colitis by curtailing Th17 cell differentiation while enhancing Treg cell development.

The indigenous Nian hill tribes of Vietnam have traditionally harnessed the therapeutic potential of Panax vietnamensis Ha & Grushv., attributing it with significant anti-fatigue, life-preserving, and anti-inflammatory properties (126, 127). Notably rich in follistol saponins, particularly machonoside R2 (Figure 3), this plant showcases antistress, antidepressant, and anxiolytic effects (128). Lee et al. discovered that majonoside R2 can be metabolized into ocolitoll (Figure 3) through gut microbiota (129). Ocolitoll inhibited the TNBS-induced physiological damage, including colon shortening, increased macroscopic scores, heightened myeloperoxidase activity, and elevated production of nitric oxide and prostaglandin E2. Additionally, ocolitoll effectively suppressed Th17 cell differentiation triggered by TNBS within the colonic lamina propria, while modulating the expression levels of key markers such as T-bet, RORγt, IL-17, and IL-23. Concurrently, Treg cell differentiation was significantly enhanced, accompanied by increased expression of Foxp3 and IL-10. These findings suggest that oral administration of majonoside R2 leads to its conversion into ocolitoll through gut microbiota metabolism, thereby rebalancing the Th17/Treg ratio and offering relief in inflammatory conditions like colitis (129).

Centella asiatica (L.) Urb. is a perennial herb acclaimed for its bioactive compounds, which include glycosides such as madecassoside (Figure 3) and asiaticoside, alongside their corresponding aglycones asiatic acid and asiatic acid (130–132). Within investigations concerning collagen-induced arthritis in rats, the madecassoside was observed to play a crucial role in rebalancing Th17/Treg cell populations (133). Remarkably, a study revealed that oral administration of madecassic acid resulted in decreased proportions of Th17 cells, accompanied by reduced expression levels of pivotal markers like RORγt, IL-17A, IL-17F, IL-21, and IL-22, while concurrently increasing Treg cell counts and enhancing the expression of Foxp3 and IL-10 in the colons of mice with colitis (134). Interestingly, under Th17 polarized conditions, madecassic acid exhibited inhibitory effects on ACC1 expression and promoted the transition of Th17 cells to Treg cells, without impacting Treg cell differentiation under Treg-polarized conditions. Overall, the conversion of madecassoside to madecassic acid elucidates a regulatory mechanism involving the PPARγ/AMPK/ACC1 pathway, aimed at restoring the Th17/Treg balance to potentially mitigate conditions such as UC (134).

Curcumin (Figure 3), a naturally occurring non-toxic compound extracted from Curcuma longa L., possesses a myriad of biological properties, including anti-inflammatory, anti-infective, anticoagulant, and immunomodulatory actions (135, 136). Curcumin can reduce nitric oxide levels, myeloperoxidase activity, and TNF-α, inhibiting NF-κB activation to exert its anti-inflammatory effects, while providing protective benefits through antioxidative pathways in the treatment of DSS-induced colitis (137–139). Wei et al. observed that curcumin elevated the anti-inflammatory cytokine IL-10 while reducing pro-inflammatory cytokines like IL-23 to modulate the balance of Treg/Th17, thereby ameliorating DSS-induced colitis (140).

Derived from Scutellaria baicalensis Georgi, baicalin (Figure 3) is a flavonoid compound deeply entrenched in TCM for its versatile therapeutic properties, including anti-inflammatory, antibacterial, anti-allergic, and anti-cancer activities (141). Recent research underscores baicalin’s profound impact on TNBS-induced colitis, showcasing remarkable reductions in disease severity indicators like disease activity index, macroscopic and microscopic scores, while simultaneously ameliorating weight loss and colon shortening (142). Intriguingly, the salutary effects of baicalin appear intertwined with the modulation of Th17 and Treg cell dynamics. Treatment with baicalin notably dampened the population of Th17 cells, along with suppressing Th17-associated cytokines (IL-17 and IL-6) and repressing RORγt expression. Moreover, baicalin demonstrated the potential to enhance Treg cell numbers, elevate Treg-linked cytokines such as TGF-β and IL-10, and boost the expression of FOXP3 (142).

The primary constituents of Glycyrrhizae radix Et Rhizoma include Glycyrrhizin and flavonoids like liquiritigenin and isoliquiritigenin (Figure 3), along with their aglycones. Studies have shown that both Glycyrrhizae radix Et Rhizoma and isoliquiritigenin, a component thereof, possess the ability to impede NF-kB activation induced by LPS and the activation of the NLRP3 inflammasome (143–145). Notably, Glycyrrhizin aids in mitigating tissue inflammation by diminishing reactive oxygen species (ROS) production by neutrophils (146). In addition, Guo et al. uncovered that isoliquiritigenin and naringin facilitate the generation of Treg cells, both in laboratory settings and in live subjects. This observation suggests that the enhancement of regulatory T-cell development could serve as the fundamental mechanism behind the long-standing therapeutic efficacy of Glycyrrhizae radix Et Rhizoma, suggesting these two potent molecules as valuable resources in combatting autoimmune and inflammatory disorders (147).

Berberine (Figure 3), an alkaloid isolated from Rhizoma Coptidis, exhibits many biological functions and has been used in the treatment of diarrhea, gastroenteritis, diabetes, hyperlipidemia, and UC (148). Studies have shown that berberine can improve the balance of Treg/Th17 in DSS-induced UC model, and also reduce the diversity of intestinal microbiota, affecting the relative abundance of Desulfovibrio, Eubacterium and Bacteroides (149). Tang et al. found that berberine can regulate the expression of various inflammatory factors, proteins and miRNAs through the miR-31-5p-Th17/Treg immune network axis, and exert a therapeutic effect on TNBS/ethanol-induced UC (150).

Parthenolide (Figure 3), a sesquiterpene lactone extracted from Tanacetum balsamita branches, demonstrates robust bioactivity encompassing potent anticancer, anti-inflammatory, and antibacterial effects (151). Liu et al. reveal that mice treated with parthenolide exhibited marked improvements in colonic inflammation, accompanied by reductions in body weight, colon length, disease activity index, histological scores, and colonoscopy scores (152). Parthenolide exerts selective actions by increasing Treg cell levels while decreasing the proportion of colonic Th17 cells, thus enhancing the Treg/Th17 equilibrium crucial for intestinal stability. To validate this microbiota-dependent mechanism, experiments involving gut microbiota depletion and fecal microbiota transplantation (FMT) were conducted. The findings suggest that parthenolide substantially boosts the concentration of short-chain fatty acids in mice with colitis by regulating gut microbiota, specifically targeting short-chain fatty acid-associated bacteria such as Alloprevotella, Rikenella, and Fournierella, subsequently fostering Treg/Th17 balance (152).

Polydatin (Figure 3) is a natural component extracted from the dried rhizome of Polygonum cuspidatum Sieb. et Zucc., which has anti-fibrosis, anti-tumor, anti-atherosclerotic disease, anti-hepatitis, and prevention of multiple organ ischemia–reperfusion injury and other activities (153). Liu et al. found that Polydatin significantly alleviated DSS and TNBS-induced colitis in mice, and significantly reduced the proportion of Th17 cells in the spleen and mesenteric lymph nodes (154). Mechanistic studies have shown that polydatin can relieve colitis by directly binding to STAT3-specific inhibitory signal transducers and STAT3 phosphorylation activators, leading to the reduction of Th17 cells. These findings provide new insights into the anti-colitis effects of Polydatin, which may be a promising drug candidate for the treatment of IBD (154).

Resveratrol (Figure 3), a naturally derived active compound present in grapes, peanuts, and various plant sources, exhibits a diverse array of biological functions, including immunomodulation, anti-inflammatory properties, antioxidant effects, anti-angiogenic activity, and mitigation of tissue damage (155, 156). Notably, resveratrol showcases remarkable therapeutic potential in addressing UC (UC) by diminishing neutrophil exudation, thwarting adhesion molecules, and fine-tuning cytokine levels (157, 158). Clinical investigations underscore the efficacy of anti-inflammatory interventions in managing UC patients. Yao et al. found that resveratrol may restore Treg/Th17 equilibrium, elevate TGF-β1 and IL-10 concentrations, reduce IL-6 and IL-17 levels, and inhibit the hypoxia-mTOR-HIF-1α-Th17 as well as IL-6-STAT3-HIF-1α-Th17 pathways (159). Additionally, Gu et al. observed that resveratrol can rectify the Treg/Th17 immune imbalance and curb intestinal inflammatory responses in UC cases, highlighting its promising immunomodulatory properties (160).

Dihydromyricelin is a dihydroflavonol flavonoid compound, which has various pharmacological effects such as anti-oxidation, anti-tumor, anti-inflammation, anti-alcohol and liver protection, anti-pathogenic microorganisms and blood lipid regulation (161). Li et al. found that Dihydromyricelin may restore the balance of Treg/Th17 in peripheral blood and reduce the expression of MMP9 in colon tissue, so as to alleviate DSS-induced UC in mice (162).

Derived from daphne coumadin, DAPH is a coumarin derivative renowned for its robust anti-inflammatory and antioxidant characteristics, commonly employed in combatting inflammatory ailments (163–165). DAPH demonstrates the capacity to impede T h17 cell differentiation while fostering Treg cell maturation, thereby fostering immune equilibrium and ameliorating inflammation (166, 167). Previous research indicates that DAPH can shield against intestinal inflammatory disorders in a rat model of TNBS-induced colitis, with its intestinal anti-inflammatory efficacy linked to its antioxidant profile (165). A novel investigation reveals that this compound substantially boosts the population of gut microbiota capable of producing short-chain fatty acids (SCFAs), a shift associated with bolstering Treg development and diminishing the differentiation of pro-inflammatory T cells into h17 cells, ultimately quelling UC (168).

Stigmasterol (Figure 3), a phytosterol renowned for its anti-inflammatory, antioxidant, and antitumor attributes, and its positive impacts on metabolism (169, 170), serves as a key active component in traditional Chinese herbal mixtures utilized for managing inflammatory bowel disease (IBD) (171, 172). Prior investigations unveiled stigmasterol’s capacity to notably diminish cyclooxygenase-2 (COX-2) expression levels, leading to enhanced colonic inflammation scores and amelioration of colitis symptoms. Treatment with stigmasterol was shown to rebalance the Treg/Th17 equilibrium and induce alterations in gut microbiota composition in a colitis model induced by DSS. Moreover, stigmasterol treatment amplified the generation of short-chain fatty acids (SCFAs) by gut microbiota, particularly boosting butyrate production. Researchers hypothesized that stigmasterol might rectify the Treg/Th17 cell imbalance by activating PPARγ via butyrate, thus offering therapeutic benefits in addressing IBD concerns (173).

Citrus flavonoids, like psilocybin and tangeretin, are naturally occurring compounds found abundantly in the rinds of citrus fruits, particularly Citrus species (174). These compounds boast a spectrum of biological activities encompassing anti-inflammatory, anticancer, hypolipidemic, anti-obesity, and neuroprotective effects (175–179). They demonstrate efficacy in ameliorating dermal responses by mitigating histamine effects and triggering the activation of transcription factors NF-κB and AP-1 via protein kinase C pathways (180, 181). In UC, tangeretin effectively suppresses TNF-α, IL-12, and IL-23 expression, alongside NF-κB activation in lipopolysaccharide-stimulated dendritic cells. Moreover, Tangeretin impedes the differentiation of Th1 and Th17 cells induced by TNBS, restraining the expression of T-bet, RORγt, interferon-γ, IL-12, IL-17, and TNF-α, while concurrently promoting the differentiation of Treg cells suppressed by TNBS, upregulating Foxp3 and IL-10 expression levels (182).

Andrographolide (Figure 3), an therapeutic agent with clinical efficacy in treating bronchitis, tonsillitis, and bacillary dysentery (183, 184), has garnered attention in recent research for its ability to modulate macrophage activation, suppress Th1/Th17 immune responses, and diminish MAPK and NF-κB signaling pathways, beneficial for managing conditions like acute colitis and lung injuries (185, 186). Noteworthy findings indicate that andrographolide sulfonate notably ameliorated TNBS-induced symptoms including weight loss, myeloperoxidase activity, colon shortening, and colonic inflammation, while reducing the expression of pro-inflammatory cytokines at both mRNA and protein levels. Moreover, andrographolide sulfonate impeded the infiltration of CD4+ T cells and the differentiation of Th1 (CD4+ IFN-γ+) and Th17 (CD4+ IL17A+) subsets. Studies illustrated that andrographolide sulfonate successfully mitigated TNBS-induced colitis in mice through the inhibition of Th1/Th17 immune responses (187).

Astragaloside IV (Figure 3), a triterpene saponin derived from Astragalus membranaceus (Fisch.) Bge., is renowned for its wide-ranging beneficial effects, spanning antioxidant, cardioprotective, anti-inflammatory, antiviral, antibacterial, antifibrotic, antidiabetic, and immunomodulatory properties (188). Notably, in models of experimental colitis triggered by DSS and TNBS, astragaloside IV demonstrated the ability to modulate macrophage polarization via the STAT signaling pathway and influence energy metabolism, thereby effectively mitigating intestinal inflammation (189, 190). Furthermore, astragaloside IV exhibited the capacity to lower levels of key pro-inflammatory cytokines such as myeloperoxidase, TNF-α, IL-1β, IL-6, and nitric oxide in vitro (191). Recent research findings underscored that astragaloside IV not only ameliorated clinical symptoms associated with DSS-induced colitis but also significantly enhanced ulcer repair, reduced inflammatory cell infiltration and inflammation indices, and regulated the expression of inflammatory cytokines within colon tissues. Of significant note, early administration of astragaloside IV was found to restore Th17/Treg cell balance in mice with acute colitis, inhibiting Th17 responses while promoting Treg cell responses in cases of recurrent colitis (192, 193).

Astragalus polysaccharide, the primary bioactive compound derived from Astragalus membranaceus (Fisch.) Bge, showcases a diverse array of biological properties encompassing antiviral, antitumor, anti-aging, anti-radiation, anti-stress, and antioxidant activities (194, 195). In the context of DSS-induced colitis, Astragalus polysaccharides exhibited therapeutic effects by impeding the NF-κB and NRF2/HO-1 signaling pathways (196, 197). Recent investigations unveiled that these polysaccharides enhanced the survival rates, disease activity indices, body weight fluctuations, colon lengths, body weights, and mitigated colonic histopathological damage in a mouse model of UC. Notably, Astragalus polysaccharides orchestrated the expression levels of inflammatory cytokines (IL-2, IL-6, IL-12p70, IL-23, TNF-ɑ, and TGF-β1) in the colon tissues of colitis-afflicted mice. Moreover, Astragalus polysaccharide significantly upregulated Tfh10 and Tfr populations while downregulating Tfh1, Tfh17, and Tfh21. Additionally, these polysaccharides elevated Treg cell levels along with pertinent nuclear transcription factor Foxp3 and cytokine IL-10 expression in colitis models. In essence, Astragalus polysaccharide holds promise in alleviating UC by rebalancing the Tfh/Treg cell equilibria (198).

Derived from Epimedium brevicornu Maxim, icariin (Figure 3) is a natural flavonoid glucoside recognized for its diverse pharmacological attributes (199), spanning antioxidant, antidepressant, and anti-inflammatory properties (200, 201). Oral intake of icariin markedly decelerates disease advancement and mitigates pathological alterations in colitis conditions, and effectively curbs the generation of pro-inflammatory cytokines and the activation of p-p65, p-STAT1, and p-STAT3 within colon tissues (202). Further investigations unveiled the dose-dependent capacity of icariin to impede the proliferation and activation of T lymphocytes, along with lowering pro-inflammatory cytokine levels in stimulated T cells. Moreover, icariin administration was shown to suppress the phosphorylation of STAT1 and STAT3, pivotal transcription factors associated with Th1 and Th17 responses, within CD4+ T cells (202). Collectively, these outcomes underscore the potential of icariin as a viable therapeutic option for addressing IBD.

Hailing from green tea, EGCG (Figure 3) stands as a natural compound with a spectrum of beneficial attributes including antibacterial, anti-inflammatory, antitumor, antioxidant, and anti-aging properties (203, 204). Notably, research highlights its capacity to modulate the immune system, showcasing potential in the realm of autoimmune disease treatment (205, 206). EGCG interventions led to decreased IL-6 and IL-17 release, alongside the adjustment of Treg/Th17 ratios within mouse spleens. Concurrently, elevated plasma levels of IL-10 and TGF-β1 were observed, while the expression of HIF-1α and STAT3 proteins in the colon was curtailed. These findings hint at EGCG’s potential in ameliorating experimental colitis in mice by stifling IL-6 release and orchestrating the Treg/Th17 equilibrium in vivo (39).

Within the realm of herbal medicine lies Arctigenin (Figure 3), a bioactive dibenzylbutyrolactone lignan renowned for its array of properties. Its repertoire spans antimicrobial, anti-inflammatory, and immune-modulating capabilities, with a recent surge of interest stemming from its antitumor prowess (20, 207, 208). Deemed an ERβ agonist in a recent investigation, Arctigenin exhibits a moderate affinity for ERβ, initiating the dissociation of the ERβ/HSP90 complex, enhancing ERβ phosphorylation for nuclear translocation, and elevating transcriptional activity levels. Through ERβ activation, Arctic Aglycon impedes mTORC1 function by disrupting ERβ-constrained-mTOR complex interaction. Intriguingly, the absence of ERβ effectively annulled Arctigenin-induced suppression of Th17 cell differentiation, hinting at ERβ as a prime candidate for Arctigenin’s target protein. This regulatory mechanism obstructs mTORC1 activation, hence thwarting Th17 cell differentiation and the progression of colitis (209).

Emerging from the breakdown of glucosinolate in cruciferous vegetables, DIM is a natural compound known for inhibiting inflammatory responses in select mouse inflammation models (Figure 3) (210, 211). Recent investigations have spotlighted DIM’s protective role in inflammation mitigation, showcased by its ability to curb NF-κB activation, stifle prostaglandin E2 production, and modulate antioxidant levels (212, 213). A novel study underscored how DIM administration assuaged experimental colitis, suggesting its influence on the downstream signaling pathways of AhR could reduce Th2/Th17 cells while bolstering Treg populations. Demonstrating therapeutic efficacy in animal models of UC, DIM’s capability to suppress Th2/Th17 cells and boost Tregs positions it as a promising therapeutic avenue for UC patients (214).

Artemisinins (Figure 3), derived from Artemisia annua L., encompass a collection of sesquiterpene trioxanes lauded for their therapeutic potential (215, 216). Dihydroartemisinin (DHA), an artemisinin derivative, emerges as a robust immunomodulator with diverse applications. Studies indicate the efficacy of DHA and its derivatives in managing autoimmune conditions, such as experimental autoimmune encephalomyelitis (EAE) (217) and collagen-induced arthritis (218). Yan et al. discovered that DHA inhibited Th1, Th17, Th9, and Th22 cell populations in TNBS- or OXA-induced colitis, while enhancing Tregs (219). Remarkably, DHA induced HO-1 production, promoted CD4+ T cell apoptosis, and restored the Th17/Treg balance, effects that were blocked by the HO-1 inhibitor Sn-protoporphyrin IX. Overall, these results suggest that DHA has the potential to serve as a novel therapeutic agent for managing inflammatory bowel disease (IBD) or Th17/Treg immune modulation (219).

Derived from the green walnut shell of Juglans regia L., juglone (Figure 3) stands out as a pivotal naphthoquinone compound recognized for its manifold properties (220, 221). Recent investigations have highlighted juglone’s anti-inflammatory prowess, showcasing efficacy in conditions like hepatitis, neuroinflammation, and allergic pulmonary fibrosis (222, 223). Juglone has been shown to improve the disease activity index and pathological features of UC, significantly reducing the protein levels of IL-6, TNF-α, and IL-1β, while enhancing IL-10 expression (224). Moreover, Juglone induces changes in microbial diversity and gut microbiota composition, promoting the ratio of Firmicutes to Bacteroidetes and the abundance of Actinobacteria, while inhibiting the levels of Proteobacteria (224). This compound also inhibits the protein levels of IL-6, STAT3, and RORγt, thereby enhancing FOXP3 expression. Additionally, Juglone impedes the progression of Th17 cells and promotes the generation of Tregs, essential for maintaining the Th17/Treg balance (224). These findings suggest that Juglone can protect mice from UC by shaping the dynamics of gut microbiota and restoring the balance of Th17/Treg.

Nelumbo nucifera Gaertn. is used in TCM for fever, diarrhea and bleeding (225). Nuciferine, an alkaloid containing an aromatic ring, is the main bioactive component derived from Nelumbo nucifera Gaertn. (226). Studies reveal nuciferine’s potential in counteracting high-fat diet-induced obesity in mice through gut microbiota modulation (227, 228), mitigating inflammation triggered by fructose or uric acid in HK-2 cells, among other beneficial effects (229). In research, nuciferine showcased its efficacy in alleviating symptoms in DSS-induced UC mice, such as mitigating histological damage and colon shortening. Notably, nuciferine played a role in enhancing the Th1/Th2 and Treg/Th17 equilibrium, alongside influencing gut microbiota composition within DSS-induced inflammatory bowel disease (IBD) models (230).

KJL, a TCM formulation deeply rooted in empirical practices, addresses UC by employing a therapeutic approach that involves heat dissipation, spleen fortification, and blood circulation enhancement (231). Noteworthy outcomes in clinical assessments underscore its effectiveness (232). Experimental investigations reveal that KJL can mitigate ulceration, ameliorate pathological tissue damage, and diminish levels of inflammatory markers such as IL-1β, TNF-α, and IL-6 in UC-induced rats (232–234). KJL enhances the levels of blood TGF-β1, IL-2, IL-10, increases colonic Foxp3, STAT5, and IL-2 levels, while decreasing the levels of IL-6, IL-23, IL-17, IL-21 in the blood and inhibiting colonic-related RORγt, STAT3, IL-23, IL-17, and IL-21, thereby restoring the balance of Th17/Treg (235, 236).

BTWT, a prevalent TCM concoction majorly compounded with pulsatilla, has gained substantial traction in UC therapy across China (237–239). Tan et al. discovered that BTWT could downregulate RORγt expression, upregulate Foxp3 expression, increase the proportion of Treg cells in patients, decrease the proportion of Th17 cells, thereby restoring the Th17/Treg balance in the body (240).

With a historical backdrop spanning millennia, FZLZT stands as a stalwart remedy against gastrointestinal maladies, encompassing conditions such as enteritis, diarrhea, and gastritis (241–243). Shedding light on its therapeutic potential, Li et al. unveiled FZLZT’s capacity to ameliorate UC symptoms linked to spleen-kidney yang deficiency, attenuate colonic tissue inflammation in rat models, and facilitate mucosal regeneration within the colon (244). Furthermore, FZZLT bolsters the expression of Treg-associated factors like IL-10, TGF-β1, Foxp3, and STAT5, thereby contributing significantly to the management of UC characterized by spleen-kidney yang deficiency (244).

QCWZT has showcased clinical efficacy in alleviating symptoms of UC and has obtained authorization for further clinical investigations. Research findings underscore its notable capacity to effectively suppress the active phase of UC, exhibiting comparable outcomes to mesalamine (245). Moreover, QCWZT demonstrates the ability to diminish the modified Mayo score in patients grappling with mild to moderate UC, enhance pathological repair, curtail inflammatory cellular infiltration in the intestinal mucosa, promote colonic goblet cell proliferation, elevate mucin MUC2 expression in colonic mucosal tissue, and impede STAT6 expression (245). In a parallel discovery, Sun et al. proposed that QCWZT may modulate the VDR signaling pathway by downregulating miR-675-5p expression, thereby harmonizing the Th17/Treg immune equilibrium in UC, remedying intestinal mucosal barrier impairments, and aiding in UC management (246). Recent investigations have indicated that the bioactive constituents of QCWZT possess the capability to suppress the IL-6-STAT3 pathway, ultimately impeding the differentiation of Th17 lymphocytes, thereby diminishing colonic inflammation (247).

Clinical evaluations have affirmed the therapeutic efficacy of FFKST in managing UC, showcasing a capacity to diminish intestinal mucosal inflammation in afflicted individuals. This herbal formulation has proven instrumental in alleviating abdominal pain and hematochezia symptoms (248). Primarily constituted of active components like matrine, gallic acid, indigo, notoginsenoside R1, ginsenoside Rb1, and glycyrrhizic acid, FFKST has demonstrated inhibitory properties at a molecular level across various UC models. Matrine, for instance, mitigated colitis manifestations and curbed inflammatory cytokine expression of IFN-γ and IL-17 in TNBS-induced colitis within IL-10-deficient mice (249). Oxymatrine, when tested in a UC model, ameliorated intestinal damage by modulating T cell-secreted inflammatory cytokines and inhibiting NF-κB activation (250, 251). Moreover, researchers noted significant enhancements in colitis symptoms and pathological mitigation in mice treated with FFKST, alongside notable effects on immune modulation through the regulation of Th17/Treg cell balance in DSS-induced colitis models (252, 253).

Originally documented in the ancient text Jingui Yaolüe, DHMDT emerges as a viable solution for intestinal abscesses (254). Discoveries by Luo et al. unveiled the remarkable efficacy of DHMDT in mitigating pathological alterations in UC-afflicted mice. This included the restoration of colon length, amelioration of weight loss, and tissue repair in conjunction with inflammation reduction. Additionally, DHMDT precipitated a shift in gut microbiota composition, enhancing alpha diversity while notably elevating Firmicutes and Actinobacteria populations and diminishing Proteobacteria and Bacteroidetes numbers. Noteworthy was the substantial augmentation of butyrate-producing Butyricoccus elongatum colonies and the restoration of short-chain fatty acid levels in the gut. DHMDT also fostered an improved Th17 cell/Treg cell ratio in mesenteric lymph nodes and a decline in various inflammatory cytokines like IL-6, TNF-α, IFNγ, IL-10, IL-17A, IL-21, and IL-22 within the colon (255).

Utilized clinically for acute enteritis, chronic diarrhea, and bacillary dysentery, GQT harbors a diverse array of potent bioactive compounds like berberine, baicalin, and puerarin. Recent studies suggest that these constituents possess the ability to modulate T cell differentiation individually, offering promise in mitigating T cell-associated inflammatory disorders across various animal models (256–258). Hu et al. reported significant symptom relief in UC-afflicted mice following GQT treatment, alongside noteworthy inhibition of myeloperoxidase activity. Notably, the administration of GQT led to a substantial decrease in pro-inflammatory factors like IL-1β, TNF-α, and IL-6. This herbal formulation facilitated the infiltration of Treg and Th17 cells into the colon while concurrently reducing the expression of inflammatory mediators such as TGF-β1 and IL-17. Through the suppression of IL-6/JAK2/STAT3 signaling, GQT is postulated to restore Treg and Th17 cell equilibrium within colon tissue, ultimately easing DSS-induced UC symptoms (259). Wang et al. additionally observed that modified GQT modulates the Treg/Th17 balance and effectively addresses DSS-triggered acute experimental colitis in mice by reshaping the gut microbiota composition (260).

In a study by Tian et al., it was observed that when SLBZS was administered in conjunction with standard therapy, patients exhibited significantly lower rates of colonoscopic congestion, edema, erosion, and ulcers compared to those in the control group. This indicates the potential benefits of this combined approach in aiding the restoration of intestinal mucosal integrity in individuals with UC. The purported efficacy of SLBZS on mucosal repair appears connected to its capability to address Th17/Treg imbalances and temper inflammatory responses in UC patients. Notably, the post-treatment recurrence rate in the observation group was notably lower than in the control group, underscoring the potential role of SLBZS in rectifying immune irregularities among patients (261). The therapeutic mechanisms of SLBZS in UC management could entail modulating the expression levels of RORγt/FoxP3 and rectifying the Th17/Treg immune imbalance. Furthermore, Qi et al. highlighted that SLBZS’s protective influence in UC rats might also be linked to adjusting the RORγt/FoxP3 expression levels and correcting Th17/Treg immune discrepancies (262).

Extracts from Panax ginseng C. A. Mey. contain essential components like ginsenosides Rb1, Rb2, Re, and Rg1, utilized in TCM to address conditions such as inflammation, cancer, and diabetes (263, 264). These ginsenosides are known for their anti-inflammatory properties and immune-regulating abilities (265–267). For instance, ginsenoside Rb1 undergoes gut microbiota metabolism to produce 20-O-(β-D-glucopyranosyl)-20(S)-protopanaxadiol (compound K), which has demonstrated suppressive effects on LPS-induced inflammation by targeting IRAK1 in macrophages and enhancing outcomes in TNBS-induced colitis models in mice (268).

In the realm of ginsenoside research, ginsenoside Re, belonging to the prototalol-type ginsenosides, was found effective in ameliorating TNBS-induced colitis by impeding the LPS-TLR4 binding on macrophages, thus showcasing its potential as an anti-colitis agent (249). Recent investigations unveiled that oral administration of ginsenosides Rg1, Rh1, or 20(S)-protopanaxadiol could counter TNBS-induced colon narrowing, suppress myeloperoxidase activity, and alleviate the expression of pro-inflammatory cytokines like IL-1β, IL-17, and TNFα. Additionally, these compounds exhibited the capability to hinder NF-κB activation, restore the Th17/Treg balance disrupted by TNBS, and revive the expression of key regulatory molecules like IL-10 and Foxp3. In vitro studies indicated their ability to inhibit Th17 cell differentiation, with 20(S)-protopanaxadiol showcasing the most potent anti-inflammatory effects, followed by Rh1. The transformation of ginsenoside Rg1 into 20(S)-protopanaxadiol by ginsenoside Rh1 and F1 unveiled a potential route for therapeutic benefits (269).

These metabolites, particularly 20(S)-protopanaxadiol, were found effective in ameliorating inflammatory conditions like colitis by impeding LPS-TLR4 interaction on macrophages and restoring Th17/Treg balance. Long et al. further highlighted the potential of ginsenoside Rg1 in mitigating DSS-induced UC in mice by modulating the Treg/Th9 cell equilibrium (270).

Originating from the Jin and Yuan Dynasties, SYT represents a traditional Chinese medicinal formula known for its therapeutic benefits in managing UC (271). Recent investigations have shed light on its potential mechanisms, including the regulation of immune factors within immune cells, inflammation inhibition, and mitigation of oxidative stress (272–274). In a study conducted by Lu et al., it was observed that SYT led to a significant reduction in serum IL-17 levels and an increase in serum IFN-γ and IL-27 levels among rats afflicted with gastroenteric fever-type UC. This suggests that the therapeutic efficacy of SYT could be attributed to the modulation of serum IL-17 levels alongside elevated concentrations of IL-27 and IFN-γ (275).

Our previous research has highlighted the effectiveness of SYT in UC treatment, indicating a possible mechanism of action linked to the restoration of Treg/Th17 balance through the inhibition of HIF-1α (22). Furthermore, findings by Yao et al. unveiled that SYT exhibited significant relief of intestinal symptoms in UC patients characterized by damp-heat syndrome in the large intestine. By fostering intestinal mucosa recovery and enhancing patient quality of life, SYT was shown to regulate the Th17/Treg cell balance effectively (276).