Combining with UC clinical manifestations, including abdominal pain, diarrhea, mucus pus, bloody stool, and tenesmus, UC belongs to the “diarrhea,” “chronic dysentery,” and “hematochezia” category in TCM(Zhang, 2010). Since UC is a chronic disease with recurrence, “chronic dysentery” can describe UC more precisely. Practitioners of TCM believe that the pathogenetic basis of UC is the deficiency of spleen qi, and the primary triggers include invasion of external evils, internal injury of emotions, improper diet, and stress (He et al., 2012a). The active phase of UC resembles the TCM excessive syndrome, and the primary pathogenesis is the intestinal accumulation of damp-heat and disturbance of qi and blood. The pathogenesis of severe UC is heat-toxic and stagnant heat, and refractory UC with relapse should be blood stasis and turbid phlegm. In remission periods, spleen deficiency is the primary pathogenesis of UC (Liu et al., 2021b). Based on the clinical manifestations and “dialectical treatment” of TCM outcomes, UC is classified into seven subtypes: large intestinal damp-heat syndrome, heat toxin syndrome, spleen deficiency and dampness syndrome, cold-heat complicated syndrome, liver depression and spleen deficiency, spleen and kidney yang deficiency, and yin and blood deficiency syndrome (Zhang et al., 2017). The process for the diagnosis and treatment of UC is shown in Figure 1.

SLBZP is composed of 10 Chinese herbal drugs, including Atractylodes macrocephala Koidz., Poria cocos (Schw.) Wolf, Glycyrrhiza uralensis Fisch., Platycodon grandiflorum (Jacq.) A. DC., Panax ginseng C.A.Mey., Amomum villosum Lour., Dioscorea opposita Thunb., Coix lacryma-jobi L. var. mayuen (Roman.) Stapf, Nelumbo nucifera Gaertn. and Dolichos lablab L., which are mainly targeted at spleen deficiency and dampness syndrome. Additionally, SLBZP is a representative prescription of “supplementing spleen to nourish lung” and can be used to treat cough and asthma caused by lung deficiency. The use of SLBZP is widespread in clinical practice and embraces internal medicine, surgery, and postoperative recovery (Lu et al., 2022). Currently, SLBZP is commonly employed to prevent and treat various diseases including UC, irritable bowel syndrome, diabetic gastroenteropathy, diabetic nephropathy, chronic obstructive pulmonary disease, allergic rhinitis, otitis media, non-alcoholic fatty liver disease (Zhang et al., 2018; Ma et al., 2019; Mao et al., 2021b), and in disease mainly involving digestive system, respiratory system, endocrine system, and skin diseases. As showed as in Figure 2.

SLBZP is modified by Sijunzi Tang and comes from the “Taiping Huimin Hejiju Fang” (Song Dynasty) (Yang, 2018). In this prescription, Atractylodes macrocephala Koidz., Poria cocos (Schw.) Wolf, and Panax ginseng C.A.Mey., are the sovereign drugs, which can strengthen the spleen and eliminate dampness. As minister drugs, Dioscorea opposita Thunb. and Nelumbo nucifera Gaertn can help sovereign drugs strengthen the spleen, tonify the qi, and relieve diarrhea; Coix lacryma-jobi L. var. mayuen (Roman.) Stapf and Dolichos lablab L. can help sovereign drugs strengthen the spleen and excrete dampness. Amomum villosum Lour. and Platycodon grandiflorum (Jacq.) A. DC. are the assistant drugs; the former can enliven the spleen and regulate the stomach, promote qi, and relieve dyspepsia, and the latter can diffuse lung and facilitate qi, regulate waterways, take herbs bottom-up, and supplement spleen to nourish the lung. Glycyrrhiza uralensis Fisch., as the envoy drug, can invigorate the spleen and stomach and coordinate the drug’s actions (Ma et al., 2019). Based on the interactions of these medicines, SLBZP exerts the effects of tonifying the stomach and spleen, eliminating dampness and promoting qi, to achieve the aim of treating disease. Modern pharmacological studies have shown that SLBZP has anti-inflammatory (Sun et al., 2020a), antioxidant (Xiong et al., 2021), and immunomodulatory (Li et al., 2014a) effect. It helps regulate gut microbiota (Mao et al., 2021a) and gastrointestinal motility (Lv et al., 2022) and also has anti-tumor (Chen et al., 2018a) potential. Generally, SLBZP is composed of mixed powders of 10 drugs in definite proportions (Panax ginseng C.A.Mey.: Poria cocos (Schw.) Wolf: Atractylodes macrocephala Koidz.: Dioscorea opposita Thunb.: Dolichos lablab L.: Nelumbo nucifera Gaertn: Coix lacryma-jobi L. var. mayuen (Roman.) Stapf: Platycodon grandiflorum (Jacq.) A. DC.: Glycyrrhiza uralensis Fisch. = 100: 100: 100: 100: 75: 50: 50: 50: 50: 100) and is to be consumed orally 2–3 times a day at a dose of 3–9 g (Ma et al., 2019).

Clinical research has shown that both SLBZP and flavored SLBZP can significantly alleviate the symptoms in UC patients, including diarrhea, abdominal pain, and hematochezia, without significant adverse reactions. Moreover, SLBZP has fewer adverse reactions and better efficacy than chemical drugs. Studies showed that the combined efficacy of SLBZP was significantly higher than sulfasalazine (Ren, 2010; Qin, 2012; Xie et al., 2015). For example, among 150 patients with UC, 75 cases were given SLBZP (treatment group, 1 dose per day, decocted in water, twice daily), while another 75 were treated with sulfasalazine (control group, sulfasalazine, 0.5, 4 times a day), 1 month is a course of treatment, both groups were given medication for 2 courses before reexamination of colonoscopy. The results showed that the total efficiency in treatment group (96.4%) was better than that in control group (80.4%) (Qin, 2012). In another study, 106 cases with UC randomly divided into treatment group (SLBZP, 1 dose per day, decocted in water, twice daily) and control group (sulfasalazine, 1 g, 4 times a day) for 8 weeks. The total effective rate of treatment in the treatment group was higher than the control group, and the recurrence rate in the treatment group was considerably lower than sulfasalazine (Xie et al., 2015). Meanwhile, researchers also compared the efficacy of SLBZP and mesalazine for use in UC(He, 2014; Quan and Tan, 2017; Yang, 2017; Yang et al., 2021). For instance, 48 cases with UC randomly divided into treatment group (SLBZP, according to the prescription powder the herbs and mixed, 6 g each dose, 3 times a day) and control group (mesalazine, 1 g/time, 4 times a day) for 90 days. The total effective rate of treatment in the treatment group (91.67%) was higher than the control group (70.83%) (He, 2014). In addition, flavored SLBZP (1 dose per day, decocted in water, twice daily) could decrease the levels of IL-17, TNF-α, IL-23, CRP, and ESR and increase the levels of IL-10 in UC patients, and these effects were superior to mesalazine (1 g/time, 4 times a day) (Xu, 2021). Furthermore, flavored SLBZP (1 dose per day, decocted in water, twice daily) could promote the growth of probiotics and inhibit the proliferation and colonization of pathogenic bacteria by improving the intestinal microecological environment and protecting intestinal mucosa (Yang et al., 2021). Similarly, several studies indicated that the therapeutical effects of flavored SLBZP (1 dose per day, decocted in water, twice daily) were better than other chemical medicines, including domperidone (Sun and Chen, 2014), sulfamethoxazole and tetracycline combination (Tian and Song, 2015), and norfloxacin (Wang, 2019). The above research showed that SLBZP was superior to chemotherapeutics in improving the pathological changes and clinical manifestations of UC by reducing the inflammatory factors and regulating the balance of gut mucosa. However, there are some differences in the treatment time and dosage form of SLBZP, which may affect the results of the evaluation of therapeutical effects. Meanwhile, the mechanism of action underlying SLBZP monotherapy needs further exploration.

Evidence based medicine (EBM) is the dominant paradigm in assessing the effectiveness of clinical treatments. The processes of EBM mainly contain several steps: 1) pose questions; 2) search relative data; 3) quantitative statistical analysis; 4) systematic evaluation; 5) promote the effective treatment methods and abandon ineffective, or even harmful, treatment methods (Djulbegovic and Guyatt, 2017). Systematic reviews, including a quantitative and qualitative evaluation, are currently considered to be the best evidences. Meta-analyses are the most common form of quantitative evaluation. Compare with traditional literature review, meta-analyses can improve the power of test by summarizing results and increasing sample size, and thus closer to reality (Hernandez et al., 2020). In recent years, several studies had been performed to evaluate the effectiveness and safety of SLBZP in treatment of UC by meta-analyses (Wu et al., 2017; Yang et al., 2018). For example, a meta-analysis conducted by Xiangtao Wen et al., included thirteen randomized controlled trials (RCTs) containing of 659 UC patients treated with SLBZP therapy and 598 patients treated with western medicine. The results showed the effectiveness of SLBZP was higher than that of western medicine (RR = 1.17, 95%CI [1.13, 1.22], p <0.001), could significantly improve time of diarrhea (RR = −12.32, 95%CI [−14.27, −10.37], p < 0.001), abdominal pain (RR = −8.06, 95%CI [−9.88, −6.24], p < 0.001), sepsis (RR = -9.89, 95%CI [−10.77, −9.00], p <0.001), and fever (RR = −8.29, 95%CI [−9.59, −6.98], p <0.001), and significantly decrease the adverse events (RR = 0.06, 95%CI [0.01, 0.40], p = 0.004) (Wen et al., 2017). In addition, another meta-analysis had been conducted by Yin et al., included seventeen RCTs with a total sample of 1263 UC treated with mesalazine (control group) and SLBZP combined with mesalazine (test group) (Yin et al., 2021). Results indicated that the total effective rate of patients in the combination group was higher than that in the mesalazine group (OR = 2.03, 95%CI [1.60, 2.58], p <0.05). And the level of IL-17 (MD = −88.29, 95%CI [-100.37, −76.21], p <0.00001), IL-23 (MD = −115.34, 95%CI [−130.69, -99.99], p <0.00001), TNF-α(MD = −10.64, 95%CI [−11.65, −9.64], p <0.00001), ESR (MD = −8.22, 95%CI [−9.31, −7.12], p <0.00001), and CRP (MD = −6.74, 95%CI [−9.99, −3.48], p <0.00001) in the combination group were significantly lower than those in the mesalazine group. Based on these findings, SLBZP or SLBZP combined with mesalazine proved superior to mesalazine in treating UC, and can also reduce inflammatory factors in UC. However, more large-sample-size double-blind RCTs shall be included to support this conclusion.

The gut mucosal barrier, consisting of mechanical, chemical, immunological, and biological barriers, is an important system of intestinal defense and maintains the integrity of the intestinal barrier and gut homeostasis by isolating the harmful elements. The mechanical barrier includes intestinal mucosa epithelial cells (ICEs) covered with mucosal layer and intercellular tight junctions (with components such as occludin, claudin, and ZO-1) and is the structural foundation for protecting against pathogen invasion and maintaining the intestinal permeability. Intestinal lymph and secretion immune proteins, resident flora, glycoproteins, and digestive juices secreted by ICEs, respectively, are the components of chemical, immunological, and biological barriers. Research has confirmed that mechanical, chemical, immunological, and biological barriers are involved in the pathogenesis of UC (Actis et al., 2014). When the gut mucosa barrier is damaged in UC, many inflammatory factors are produced. These factors can not only induce the apoptosis of ICEs, but can also influence the expression and distribution of tight junction proteins through MLCK and PKC signaling pathways, damage the structure of the mechanical mucosal barrier, and induce intestinal immune response (Actis et al., 2014).

One study found that SLBZP SLBZP (3, 6, 12 g/kg, concentrated water decoction) could help heal the tight junction of UC mice by increasing the expression of colonic components such as occludin, claudin, ZO-1, as well as JAM gene and protein (Liu et al., 2015). Another study showed that the expression levels of occludin in the colonic tissue were significantly downregulated and expression levels of P65, MLCK, MLC2, P-MLC were significantly upregulated in UC mice. Following treatment with sulfasalazine (0.52 g/kg) and SLBZP (7.8, 15.6, 31.2 g/kg, concentrated water decoction), these indicators improved significantly, in particular, high dosage of SLBZP (Liu et al., 2018a). These results indicated that SLBZP downregulates the expression of occludin, claudin, ZO-1, and JAM protein in the colon tissue, thus maintaining the normal permeability of the intestinal mucosa and repairing the intestinal mucosal damage, which may involve inhibition of the MLCK/MLC signaling pathway. Additionally, extracellular matrix degradation can increase intestinal permeability and decrease the barrier function of the intestinal mucosa, which plays an important in the pathogenesis of UC (Kirov et al., 2019). Matrix metalloproteinases (MMPs) are proteolytic enzymes that degrade ECM proteins. The pro-inflammatory factor can stimulate the proteolytic enzymes, and activated MMPs can further aggravate the inflammatory response of the intestinal tract (Bai et al., 2020). MMP-2 and MMP-9 are the major gelatinases among MMPs, which can degrade collagen type IV to prevent cell infiltration and inflammatory proliferation. A clinical study indicated that SLBZP (1 dose per day, decocted in water, twice daily) could improve the symptoms of UC patients, and the mechanism may involve a decrease in the expression of MMP-2 and MMP-9 (Wang, 2016).

Repair and reconstruction of the damaged colonic mucosa are central to UC treatment. The repair and reconstruction of colonic mucosa rely primarily on colonic mucosa stem cells that can differentiate into mature colonic mucosa cells (He et al., 2012b). Bone mesenchymal stem cells (BMSCs) have good immune regulatory effects and homing feature that promotes migration to the injury site, adhesion, and colonization, in turn repairing and reconstructing the colonic mucosal tissue of UC (Zheng and Wang, 2022). The differentiation, growth, migration, and homing of BMSCs are regulated by a combination of various factors, including several chemokines and adhesion molecules (such as ICAM-1, VCAM-1, and VLA-4) (He et al., 2012a). The study revealed that inflammatory damage to UC could promote homing of BMSCs to colon tissue; however, it did not play a role in the repair and regeneration of the tissue injured due to UC. Research indicated that SLBZP (22.6 g/kg, concentrated water decoction) could not only promote BMSCs homing to colon tissue but also help repair and regenerate tissue injured due to UC, which may involve the enhancement of the SDF-1/CXCR4 signaling pathway (Cui et al., 2020). Meanwhile, studies have shown that SLBZP (22.6 g/kg, concentrated water decoction) could promote the proliferation and migration of BMSCs and increase the adhesion properties by regulating the expression of VCAM-1 and VLA-4 (Liu et al., 2018b; Shi et al., 2018a).

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are produced during oxygen metabolism, and low-to medium-concentration ROS and RNS are molecular signals of mitogenic response or defense responses against invasion by pathogens; excessive expression of these factors can induce oxidative stress (Li et al., 2020a). Oxidative stress altering the inflammatory response causes damage to lipids, proteins, and DNA, and also results in cell apoptosis and cancer cell transformation, which is potentially dangerous. Research showed that oxidative stress is a key factor involved in the progression of many diseases such as UC (Piechota-Polanczyk and Fichna, 2014). Antioxidants inhibit the process of cell oxidation or scavenge ROS, such as free radicals. When antioxidants are inadequate or exhibit lower activity, oxidant molecules can prevail, disrupting the cell functions and leading to cell death. The endogenous cellular antioxidant defense system consists of enzymatic antioxidants (SOD, CAT, GSH-Px, and GR) and non-enzymatic antioxidants (antioxidant vitamins, trace elements, coenzymes, and cofactors) (Wang et al., 2019). Abnormal free radical metabolism is generally observed in UC patients, and the ROS can induce excess lipid oxidation in UC, exacerbating the damage to intestinal mucosa (Pavlick et al., 2002). Therefore, maintaining the oxidant/antioxidant status balance is critical to treating UC and SOD, and MDA plays a significant role in balancing the system. SOD represents the ability to scavenge free radicals and can inhibit the response of excess lipid peroxidation. MDA levels reflect the degree of lipid peroxidation in the body and indirectly reflect the degree of cellular damage (Deng et al., 2016). In a study UC model rats were induced by environment and diet intervention combined with composite TNBS and ethanol, and oral administration with sulfasalazine (0.5 g/kg), SLBZP (12 g/kg, concentrated water decoction), and vehicle (0.9% sodium chloride injection) once a day for 14 days results showed that SLBZP could increase the SOD levels and decrease MDA levels, subsequently leading to clinical benefits in UC rats (Li et al., 2012). In another study, UC model rats were treated with SLBZP (0.472, 0.945, 1.89 g/kg, granule of SLBZP was dissolved in water). Compared with the control group, the levels of PCT, CRP, EPO, and HIF-1α were significantly upregulated, and levels of iNOS, MPO, SOD, and MDA were significantly downregulated in the model group. Compared with the model group, the levels of PCT, CRP, EPO, and HIF-1α were significantly downregulated, and levels of iNOS, MPO, SOD, and MDA were significantly upregulated in the SLBZP group, in particular, high dosage SLBZP group (Xiong et al., 2021).

The expression of aquaporins (AQPs) in the intestinal tissue is closely related to UC pathogenesis. Studies indicated that the low expression of AQPs was observed in the early stage of UC before the appearance of intestinal epithelial injury. AQPs are distributed extensively in the intestinal tract and play an important in regulating water transport, permeability, secretion, and absorption of fluid in the intestinal tract (Cohly et al., 2008). Evidence showed that inhibiting the expression of AQP3 and AQP4 could cause diarrhea, leading to an inflammatory response, ultimately resulting in UC(Hardin et al., 2004; Planell et al., 2013). Additionally, the MAPK pathway consists of p38MAPK, ERK, and JUK, which can regulate cell growth, differentiation, and apoptosis, and take part in the regulation of AQP3 and AQP4 (Li et al., 2015c). Animal experiments indicated that SLBZP (12 g/kg, concentrated water decoction) could increase the expression of AQP3 and AQP4 in UC, and this effect was partially inhibited by U0126 (ERK1/2 inhibitor) or SB203580 (p38MAPK inhibitor). This suggests that SLBZP can ameliorate UC by increasing the expression of AQP3 and AQP4 through ERK/P38MAPK pathway (Li et al., 2015a).

Gut microbiota has important immune, metabolic, and intestinal protective functions. Moreover, gut microbiota can inhibit the growth of potentially pathogenic bacteria by producing antibacterial factors and colonization resistance. Gut microbiota in healthy individuals is in a dynamic equilibrium state. In contrast, UC patients or mice showed imbalance, manifested as the abundance of enteropathogenic bacteria and lack of beneficial bacteria in the intestinal tract (Yu, 2018). Studies have shown that Escherichia/Shigella and especially Escherichia coli, which belongs to the family Enterobacteriaceae, are enriched in patients or mice with UC. At the same time, firmicutes are in reduced quantity, particularly Blautia, Clostridium, Coproccocus, and Roseburia (Bian et al., 2020). In recent years, regulation of gut microbiota for UC treatment has added a new therapeutic strategy and has increased the possibility of curing UC patients (Chen et al., 2014). Animal experiments have shown that high dosage of SLBZP (24 g/kg, concentrated water decoction) could increase Prevotella and Oscillospira that produce SCFAs and decrease the opportunistic pathogens, including Desulfovibrio and Bilophila, which reduce the diversity of gut microbiota and increase abundance (Gu et al., 2021). Another clinical experiment showed that SLBZP combined mesalamine with (6 g of SLBZP particles three times a day; 6 g of mesalamine a day for 8 weeks) could improve the clinical syndrome of UC by regulating the gut microbiota and increasing the microbial levels of tryptophan metabolites, including indole-3-propionic acid and indole-3-acetic acid (Jiao et al., 2022). Only a few studies have assessed the effect of SLBZP on gut microbiota, and more in-depth and comprehensive research on gut microbiota and SLBZP in UC is needed in the future.

Atractylodes macrocephala Koidz., a common drug in TCM, possesses the effects of tonifying qi and strengthening the spleen. It is used to cure patients with splenic asthenia, anorexia, edema, excessive perspiration, and abnormal fetal movement. Modern research showed that the major constituents of Atractylodes macrocephala Koidz. were sesquiterpenes, polyacetylenes, polysaccharides, and organic acids, exhibiting pleiotropic biological activities, including anti-inflammatory, anti-tumor, regulation of gastrointestinal function and immune function (Yao et al., 2019). In recent studies, Atractylodes macrocephala Koidz. and its constituents have demonstrated potential efficacy in different experimental models of UC. A study reported that the water extract of Atractylodes macrocephala Koidz. (10 g/kg, concentrated water decoction) could protect against the acetic acid and dinitrochlorobenzene-induced colitis in a rat model by regulating the levels of IL-2, IL-10, and IL-17 cytokines in serum (Zhu et al., 2014). Meanwhile, another study showed that Atractylodes macrocephala Koidz. (10 g/kg, concentrated water decoction) could reduce the expression of TNF-α, IL-6, and IL-1β and regulate the balance of gut microbiota to treat the DSS-induced UC rats (Ye et al., 2014a). Similarly, the active ingredients of Atractylodes macrocephala Koidz., including polysaccharides, atractylenolide III, and atractylenolide I, exhibited potential efficacy in treating UC mice induced with DSS. Feng et al. reported that polysaccharides from Atractylodes macrocephala Koidz. (10, 20, 40 mg/kg) could regulate the balance of gut microbiota and its metabolism to achieve the therapeutic effects of UC(Feng et al., 2020). Additionally, polysaccharides from Atractylodes macrocephala Koidz. (540 mg/kg) could not only promote BMSC homing to the injured tissue and regulate cytokines such as IL-6, IL-10, IL-17 A, and TGF-β for preventing TNBS-induced rats colitis but also promote the migration of IEC in vitro and influence multiple genes (Zheng and Wang, 2022). Han and colleagues reported that atractylenolide III (5, 10 mg/kg) could ameliorate DSS-induced colitis inflammatory and oxidative stress by regulating the MDA and GSH contents, SOD activity, and the expression of TNF-α, IL-6, COX-2, and iNOS mRNA. Additionally, the intestinal epithelial barrier destruction and mitochondrial dysfunction were decreased. LPS-treated IEC-6 cells and DSS-induced colitis mouse model revealed that the expression of p-AMPK, SIRT1, and PGC-1α, along with acetylated PGC-1α, was facilitated by atractylenolide III (40 and 80 μM) (Han et al., 2022). Linghang Qu et al. demonstrated that atractylenolide I (50 mg/kg) could improve the induction of mucoprotein MUC2, tight junction proteins (ZO-1, Occludin), and inflammatory factors TNF-α, IL-6, IL-1β in DSS-induced colitis mice. Meanwhile, atractylenolide I could regulate the diversity and abundance of gut microbiota and its metabolism. Furthermore, they found that two genes, SPHK1 and B4GALT2, relating to the metabolism of fructose and galactose, and the activation of the PI3K-AKT pathway, were inhibited in UC mice treated using atractylenolide I (Qu et al., 2022a).

Poria cocos (SchW.) Wolf. can promote diuresis, eliminate dampness, invigorate the spleen, and calm the heart. The polysaccharides of Poria cocos (SchW.) Wolf. are its major bioactivity component and account for approximately 70–90% of dry sclerotium, which has proven therapeutic activities such as anti-tumor, anti-inflammatory, and immunomodulation (Deng et al., 2020). A study reported that a carboxymethyl polysaccharide CMP33 from Poria cocos (SchW.) Wolf. (100, 300 mg/kg) could improve the syndrome of TNBS-induced colitis mice by regulating the MPO and MDA contents and the levels of pro-inflammatory (TNF-α, IL-6, L-1β, IL-12, IFN-γ, IL-2, IL-17) cytokines and anti-inflammatory cytokines (IL-4, IL-10). The results of proteomic and metabolomic studies showed that 2-hydroxybutyric acid-(GPT, GGH)-glutathione-ALB-testosterone-TTR-dihydrotestosterone and (PYY, FABP2, HMGCS2)-oleic acid-TTR-dihydrotestosterone were the key protein–metabolite pathways (Liu et al., 2018d). Tonger Liang et al. reported that polysaccharides from Poria cocos (SchW.) Wolf. (50, 100, 200 mg/kg) could protect against the TNBS-caused colitis in a rat model by decreasing the levels of IL-33, IL-5, IL-13, IL-6 cytokines and expression of IL-33 and ST2 proteins to inhibit the IL-33/ST2 signaling pathway (Liang et al., 2020).

Glycyrrhiza uralensis Fisch. primarily contains triterpenoids, polysaccharides, flavonoids, and coumarins. Modern research has showed that Glycyrrhiza uralensis Fisch. has various pharmacological activities, including anti-tumor, anti-inflammatory, antibacterial, and anti-viral properties (Deng et al., 2021). An animal experiment suggested that Glycyrrhiza uralensis Fisch. extract (50, 100 mg/kg) is effective against DSS-induced colitis in mice. It functions by decreasing the levels of inflammatory factors, including IL-6 and TNF-α, and suppressing the expression of COX-2, NF-κB, and PGE2 proteins (Jeon et al., 2016a). Qin Lu and colleagues found that Glycyrrhiza uralensis Fisch. extract could inhibit apoptosis by regulating the expression of apoptotic or anti-apoptotic proteins, including muc3, BAX, muc1, bcl-2, FGF-15, P-gp, SHP, and regulating the immune function through FXR/P-gp pathway (Lu et al., 2021). In addition, triterpenoids, polysaccharides, and flavonoids from Glycyrrhiza uralensis Fisch. are considered to have a potential therapeutic role in UC. A study reported that glycyrrhetic acid (10, 50 mg/kg) could decrease the levels of IL-6, IL-1β, and TNF-α, and suppress the expression of COX-2, NF-κB, and PGE2 protein for treating the DSS-induced colitis mice (Jeon et al., 2016b). Nahla E. El-Ashmawy et al. reported that glabridin (50 mg/kg) exhibits anti-inflammatory and antioxidant effects in DSS-induced colitis mice by regulating the levels of TNF-a and cAMP, the activity of MPO, and gene expression of iNOS in the colon (El-Ashmawy et al., 2018). A report suggested that licochalcone A (20, 40, 80 mg/kg) could reverse the increases in relative levels of inflammatory factors, including TNF-α, IL-1β and IL-6, MPO activity, and NO level and decrease GSH and SOD levels via the NF-κB signaling pathway and Nrf2 signaling pathway in DSS-induced colitis mice (Liu et al., 2018e). A report by Juan Zhang et al. suggested that licoflavone B (120 mg/kg) could repair the damage to the colonic barrier by inhibiting colonic cell apoptosis, protecting the expression of occludin, claudin-1, and ZO-1, and suppressing harmful bacteria (such as Enterococcus) and boosting beneficial microorganisms (such as Bacteroides). Furthermore, licoflavone B could suppress the expression of MAPK pathway-related proteins, including perk, p-p38, and pJNK(Zhang et al., 2022b). In vitro experiments have revealed that a flavonoid-rich extract of Glycyrrhiza uralensis Fisch. (6.25, 12.5, 25 mg/kg) could prevent and restore the intestinal barrier dysfunction induced by TNF-α in Caco-2 cell monolayers. Moreover, a flavonoid-rich extract of glycyrrhiza glabra could repair intestinal barrier damage by increasing the expression of occluding and ZO-1 protein in TNBS-induced colitis rats (Murugan et al., 2022). Chunying Huang et al. reported that polysaccharides from Glycyrrhiza uralensis Fisch. (100, 200, and 400 mg/kg) or the positive control drug sulfasalazine (200 mg/kg) could reduce intestinal permeability and inhibit the inflammatory response (IL-1, IL-6, TNF-α, IL-10 levels) in DSS-induced UC mice (Huang et al., 2022).

Platycodon grandiflorum (Jacq.) A. DC is commonly used to relieve cough and asthma in clinical practice. The primary components of Platycodon grandiflorum (Jacq.) A. DC contain triterpenoid saponins, polysaccharides, and flavonoids, exhibiting antitussive, antiasthmatic, anti-inflammatory, antioxidant, and anti-tumor (Zuo et al., 2019). Platycodin D is a representative triterpenoid saponin component of Platycodon grandiflorum (Jacq.) A. DC. A study reported that platycodin D (10 mg/kg) was beneficial in DSS-induced colitis mice, which was related to macrophages. Further, platycodin D (2.5, 5 μM) could inhibit M1 macrophage polarization and promote M2 macrophage polarization in LPS-stimulated RAW 264.7 cells by PI3K/Akt, NF-κB, and AMPK-dependent signaling pathways (Guo et al., 2021). In a report by Yang liu et al., the MPO activity, contents of MDA, and expression of IL-1, IL-6, and TNF-α cytokines were inhibited significantly, and expression of IL-10 cytokine and levels of SOD were increased dramatically in UC mice treated with polysaccharides (100, 200, and 400 mg/kg) from Platycodon grandiflorum (Jacq.) A. DC (Liu et al., 2022b). In addition, Platycodon grandiflorum (Jacq) A. DC root fermentation broth (0.5, 1 ml per head per day) was suggested to improve UC prognosis by regulating the AMPK/NF-κB/NLRP3 signaling pathway (Wang et al., 2022).

Panax ginseng C.A.Mey. is a Chinese drug with a high medicinal value. It has the effects of invigorating vital energy, strengthening the spleen, tonifying the lung, engendering liquid, allaying thirst, AND tranquilizing the mind. Modern studies showed that Panax ginseng C.A.Mey. has various pharmacological effects such as anti-aging, antioxidant, anti-tumor, and immune enhancement (Yu et al., 2019a). Ginsenosides are the main activity components of Panax ginseng C.A.Mey., exhibiting immunomodulatory and anti-inflammatory activity against UC(Shi, 2011). A study reported that ginsenoside Rd (10, 20 and 40 mg/kg) could improve the syndrome of TNBS-induced colitis rats by enhancing the oxidation resistance of injured colons and inhibiting neutrophil infiltration (Yang et al., 2012). Meanwhile, ginsenoside Rd (10, 20 and 40 mg/kg) could inhibit the NLRP3 inflammasome through the AMPK/ULK1-autophagy signaling pathway in DSS-induced colitis mice (Liu et al., 2018f). In addition, ginsenoside Rd (20 mg/kg) could reduce the levels of TNF-α, IFN-γ, IL-6, IL-12/23p40, IL-17 A, and the expression of relative proteins including pJNK, p-p38, pIκBα, and p65 of NF-κB and p38 MAPK pathways, which eventually improve the condition of UC mice (Qu et al., 2022b). Weiwei hao et al. reported that ginsenoside Rg1 (50 and 200 mg/kg) could improve the hypercoagulability and microcirculation in DSS-induced colitis mice (Hao et al., 2013). Further, ginsenoside Rg1 (200 mg/kg) could ameliorate the symptoms in DSS-induced UC mice by regulating M1/M2 macrophage polarization associated with inhibition of the Nogo-B/RhoA signaling pathway, microbiota composition, and the balance of Treg/Th9 cells (Long et al., 2022a; Long et al., 2022b). Ginsenoside Rh2 (20 mg/kg) exhibited a potential therapeutic effect on UC, decreasing the mRNA expression of IL-6, TNFa, and INFc in the DSS-treated colon, and augmenting the TGFb signaling pathway (Ye et al., 2014b). Xuanqing Chen and colleagues suggested that ginsenoside Rh2 (50 mg/kg) is potentially valuable for treating UC, and its mechanism involves the downregulation of STAT3/miR-214 levels (Chen et al., 2021). Meanwhile, Yu Xu et al. successfully encapsulated ginsenoside Rh2 to form Rh2 nanoparticles that exhibit strong anti-inflammatory activity via significantly inhibiting the overproduction of nitric oxide (NO) and inflammatory cytokines (TNF-α, IL-1β and IL-6). Further, the Rh2 nanoparticles could regulate the oxidant stress levels and intestinal flora of UC mice (Xu et al., 2022). Zhiwei miu et al. reported that ginsenoside Rg3 (40 mg/kg) has significant therapeutic effects on DSS-induced colitis mice. It could regulate the imbalance of Th1/Th2 by decreasing TNF-α and IL-6 levels, increasing IL-10 levels, and suppressing the NF-κB signaling pathway by decreasing the expression of p-NF-κB p65 and NF-κB p65 (Miao et al., 2019). Evelyn Saba and colleagues found that ginsenoside Rg3 (20 mg/kg) could decrease the expression of pro-inflammatory mediators and cytokines including NO, IL-1β, IL-5, IL-13, and TNF-α, and levels of NLRP3 inflammasome in DSS-induced colitis mice (Saba et al., 2020). Mi Tian et al. reported that ginsenoside RK3 (20, 40 and 60 mg/kg) protected intestinal barrier function and inhibited NLRP3 inflammasome expression in DSS-induced colitis mice by regulating the MPO and iNOS activities and expression of TNF-α, IL-1β, IL-6, NLRP3, ASC, and Caspase-1 (Tian et al., 2020).

Amomum villosum Lour. mainly contains volatile oil, flavonoids, and phenolic acid, exhibiting various pharmacology activities, including gastrointestinal protection, antioxidant, antibacterial, and blood pressure-lowering effects (Qu et al., 2021). Among these, volatile oil and flavonoids from Amomum villosum Lour. are the potential drugs used to treat peptic colitis (Qu et al., 2021). Studies reported that volatile oil (0.84, 1.6 g/kg) from Amomum villosum Lour. could alleviate the oxidative damage caused by increasing SOD activity and levels of GSH-Px, decreasing the levels of NOS and expression of iNOS, decreasing colonic cell-to-cell adhesion by inhibiting the expression of ICAM, and suppressing inflammatory response by decreasing the expression of TNF-α and NF-κB p65 (Zhao, 2009; Zhu et al., 2009).

Dioscorea opposita Thunb. can help tonify spleen and stomach, benefit the lung and generating fluid, tonify the kidney and essence. Modern studies showed that the chemical composition of yam majorly included polysaccharides, amino acid, fatty acid, dioscin, and polyphenols (Chen et al., 2020). A study showed that polyphenols (240 mg/kg) from Dioscorea opposita Thunb. could protect against the DSS-induced colitis mice. Administering Dioscorea opposita Thunb. before modeling markedly mitigated colitis as well as intestinal mucosal damage and apoptosis of colonic epithelial cells by regulating the expression of occludin, caspase-8, and COX-2 (Li et al., 2021c).

Coix lacryma-jobi L. var. mayuen (Roman.) Stapf, as a TCM with a homology of medicine and food, has anti-inflammatory, anti-obesity, anti-tumor, and antiallergic activity. It primarily contains lipid acid, polysaccharides, lignans, and phenols (Li et al., 2020c). A study showed that the extract (1.5 g/kg) of Coix lacryma-jobi L. var. mayuen (Roman.) Stapf has a protective effect on DSS-induced UC rats, which may be related to the antioxidant potential (Hao et al., 2012). Further, Qilyu Zhou and colleagues found that the feed of Coix lacryma-jobi L. var. mayuen (Roman.) Stapf could not only relieve inflammatory cytokine secretion and alleviate oxidative stress but also change the innate immune cell proportion, which eventually ameliorated immune function disorders for treating UC mice (Zhou et al., 2021a).

Therapeutic effects of many constituents of herbs may depend on the transformative components after metabolism in vivo rather than prototype components (Yu et al., 2019b). In recent years, in addition to prototype components, metabolites of herbs can often be one of the substances that contribute to the efficacy of the herbs or prescriptions (Kang et al., 2020). Nowadays, lots metabolites of Chinese herbal medicines, such as ginsenoside compound K (CK), have shown various beneficial therapy effects on UC. Ginsenoside CK is the main metabolite of the protopanaxadiol type of ginsenoside (Liu et al., 2022c). Juan Li et al. and colleagues found that Ginsenoside CK (5, 10 and 20 mg/kg) could promote the recovery of the progression of UC and inhibit the inflammatory responses by suppressing NF-kB activation or regulating the activation of macrophages (Li et al., 2014b). Meanwhile, studies have found that the gut microbial metabolite CK had significant anti-inflammatory effects on UC even at low concentrations, compared to its parent ginsenoside Rb1 (Wang et al., 2018a). In addition, Hao Cai et al. found that the metabolites (Structures were shown in Figure 7) of Atractylodes macrocephala Koidz. including atractylenolide I-M1, atractylenolide I-M2, atractylenolide III-M1, atractylenolide III-M2, atractylenolide III-M3 and atractylenolide II-M1 were high degree correlated with the levels of TNF-α, IL-6, IL-10, and TGF-β1, demonstrating strong anti-UC effects (Cai et al., 2019). And further study is required to verify the effectiveness of Metabolites of Atractylodes macrocephala Koidz. for treating UC. Nevertheless, no data on the metabolites of SLBZP are currently available. Prototype components and metabolites of SLBZP that contribute to the therapeutic effects of UC and the mechanism need to be further investigated.