Chinese Journal of Natural Medicines  2019, Vol. 17Issue (2): 81-102  
0

Cite this article as: 

CAO Si-Yu, YE Sheng-Jie, WANG Wei-Wei, WANG Bing, ZHANG Tong, PU Yi-Qiong. Progress in active compounds effective on ulcerative colitis from Chinese medicines[J]. Chinese Journal of Natural Medicines, 2019, 17(2): 81-102.
[Copy]

Research funding

The work was supported by National Natural Science Foundation of China (No. 81303233), Shanghai Committee of Science and Technology (No. 18401931400), and Budget Program of Shanghai University of Traditional Chinese Medicine (No. 2016YSN22), and College Student Innovation Program Project of Shanghai University of Traditional Chinese Medicine (SHUTCM)

Corresponding author

PU Yi-Qiong, Tel: 86-21-51323068, E-mail: puyiq@163.com

Article history

Received on: 10-Sep-2018
Available online: 20 February, 2019
Progress in active compounds effective on ulcerative colitis from Chinese medicines
CAO Si-Yu1 , YE Sheng-Jie1 , WANG Wei-Wei1,2 , WANG Bing1,2 , ZHANG Tong1,2 , PU Yi-Qiong2     
1 School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China;
2 Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
[Abstract]: Ulcerative colitis (UC), a chronic inflammatory disease affecting the colon, has a rising incidence worldwide. The known pathogenesis is multifactorial and involves genetic predisposition, epithelial barrier defects, dysregulated immune responses, and environmental factors. Nowadays, the drugs for UC include 5-aminosalicylic acid, steroids, and immunosuppressants. Long-term use of these drugs, however, may cause several side effects, such as hepatic and renal toxicity, drug resistance and allergic reactions. Moreover, the use of traditional Chinese medicine (TCM) in the treatment of UC shows significantly positive effects, low recurrence rate, few side effects and other obvious advantages. This paper summarizes several kinds of active compounds used in the experimental research of anti-UC effects extracted from TCM, mainly including flavonoids, acids, terpenoids, phenols, alkaloids, quinones, and bile acids from some animal medicines. It is found that the anti-UC activities are mainly focused on targeting inflammation or oxidative stress, which is associated with increasing the levels of anti-inflammatory cytokine (IL-4, IL-10, SOD), suppressing the levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-8, IL-23, NF-κB, NO), reducing the activity of MPO, MDA, IFN-γ, and iNOS. This review may offer valuable reference for UC-related studies on the compounds from natural medicines.
[Key words]: Ulcerative colitis     Chinese medicine     Flavonoids     Terpenoids     Alkaloids    
Introduction

Ulcerative colitis (UC), a chronic non-specific inflammatory disease of the colon and rectum, is confined to the colorectal mucosa and submucosal layer. Lesions, mostly located in the sigmoid colon and rectum, can extend to the descending colon, and even the entire colon. Additionally, UC is a long-term recurrent disease, with clinical manifestations that include diarrhea, purulent stools, and stomachaches. Since the severity of UC is different, it has a chronic course of repeated episodes. Moreover, UC has a great probability of being carcinogenic.

From the updated studies, the current drugs commonly used to treat UC include aminosalicylates, immunomodulators, steroids and some biologics. However, all of them can easily lead to significant loss of patient compliance, and potential toxic or side effects [1-2]. Many researchers are now turning to natural Chinese medicine for seeking effective compounds that can be used against UC.

Traditional Chinese medicine (TCM) has a long history of treating UC. Treatment using TCM can help relieve abdominal pain and inflammation. Moreover, some active compounds extracted from TCM can potentially interact with other natural drugs or even Western medicines [3]. In recent years, the efficacy of TCM in treating inflam matory bowel disease (IBD) has been extensively chara cterized in preclinical and clinical studies and widely reported [4]. This review summarizes some types of active compounds for treating UC that are extracted from TCM, mainly including flavonoids, acids, terpenoids, phenols, alkaloids, quinones, and bile acids from some animal medicines, which have been reported to have potential in alleviating UC via direct or indirect action with bacteria, cytokines, channels, or migration of enterocytes. The current knowledge about the anti-UC activity of natural compounds extracted from TCM in this review has covered the studies published since 2009.

The chemical structures of the major compounds effective on UC extracted from Chinese medicines are shown in Fig. 1.

Fig. 1 Chemical structures of the major compounds effective on UC extracted from traditional Chinese medicines
Flavonoids Luteolin

Luteolin, an active compound in leaves, stems and bran ches of Reseda odorata L. flowers of Lonicera japonica Thunb., and other plants such as Capsicum annuum L., Ghry san themum indicum L. and Perilla frutescem (L.) Britt., has a variety of pharmacological activities, such as anti-inflam matory, anti-allergy, urate, anti-tumor, antibacterial, and antiviral. Luteolin acts as an anti-inflammatory agent against colon cancer by effectively suppressing inducible nitric oxide synthase (iNOS) and COX-2 expression levels in azoxymethane (AOM, a derivative of DSS)-colitis mice [5]. Moreover, luteolin inhibits DSS-induced NF-κB-dependent enterocyte COX-2 expression. In vitro studies have shown that luteolin blocked TNF-α induced COX-2 gene expression and Prostaglandins E2 (PGE2) enzyme secretion in HT29 cells, and sensitizes HT29 cells to TNF-α induced caspase-3 processing/activity and DNA frag mentation which is associated with the blockade of TNF-α induced NF-κB transcriptional activity and simultaneously decreases expression of downstream target genes C-IAP1 and C-IAP2. To sum up, the inhibitory effect of luteolin on NF-κB in the lamina propria mononuclear cells (LPMNC) by the strong impact of abundantly translocated luminal antigens by enhan cing injury, which leads to the enhancement of NF-κB activation (EGFP expression) in mononuclear cells from the colonic lamina propria, while cecal EGFP expression was attenuated [6].

Baicalin

Baicalin is abundant in roots and seeds of Scutellaria baicalensis Georgi. It displayed significant effects on reducing the severity of DSS-induced UC in mice and showed signi ficantly suppressed levels of IL-33 and NF-κB p65, while IκBα levels were increased. Baicalin treatment effectively alleviated DSS-induced chronic UC, and the protective mechanisms may involve the inhibition of IL-33 expression and subsequent NF-κB activation [7]. Moreover, baicalin regulates immune balance and relieves the UC-induced inflammation reaction by promoting the proliferation of CD4+ and CD29+ cells and modulates immunosuppressive pathways [8]. Additionally, baicalin simultaneously down-regulates the expression of migration inhibitory factor (Mφ), quantity of Mφs, and levels of Mφ-related cytokines, including macrophage chemotactic factor-1 (MCP-1, CCL2) and macrophage inflammatory protein-3α (MIP-3α) in UC rats [9].

Cardamonin

Cardamonin is a naturally occurring chalcone found in high concentration in conventional Chinese medicines, such as roots of Alpinia katsumadai Hayata [10]. It is reported to have protective effects such as anti-inflammation [11] and inhibition of NO release and iNOS expression [12]. In vivo, cardamonin reduced the levels of myeloperoxidase (MPO), iNOS, NF-κB, TNF-α, and MDA. Immunohistochemistry revealed the down-regulation of COX-2 and caspase-3 levels [13]. In vitro study has showed that the inhibitory effect of cardamonin on LPS-induced iNOS induction is due to a direct effect on transcription factor binding to DNA.

Myricetin

Among the known flavonoids, myricetin (3, 3', 4', 5, 5', 7-hexahydroxyflavone) is one of the major flavonoids found in several foods, including onions (Allium cepa L.), grapes (Vitis vinifera L.) and red wine. Myricetin has several beneficial effects, including anti-inflammatory [14], antioxidant [15], analgesic and anticarcinogenic effects [16-17]. Myricetin decreased the production of NO, MPO and MDA, while increasing the activity of SOD and GSH-Px. Furthermore, the levels of the cytokines IL-1β and IL-6 were significantly decreased. The anti-colitis effects of myricetin may be attributed to its anti-inflammatory and antioxidant actions [18].

Acids Chlorogenic acid

Chlorogenic acid (CGA) is a phenolic acid produced by caffeic acid and gallic acid. CGA is extracted from the dry buds or open flowers of Lonicera japora'ca Thunb., and is also commonly found in other Chinese herbs, such as Lonicera japonica Thunb., Crataegus pinnatifida Bge., and Eucommia almodies Oliv..

Some study showed that CGA reduced MPO, TNF-α levels and scavenge intracellular ROS by inhibiting H2O2-induced IL-8 production in Caco-2 cells in the colon tissue, and signi ficantly suppressed nuclear factor NF-κB transcriptional activity, nuclear translocation of the p65 subunit, and phosphorylation of IκB kinase (IKK), lead to the upstream of IKK, and the suppression of protein kinase D (PKD) [19-21]. CGA attenuated the weight loss, increased DAI, and suppressed the serious cellular injury and inflammatory intestinal diseases via suppressing the secretions of IFN-γ, TNF-α, and IL-6 and colonic infiltration of F4/80+ macrophages, CD177+ neutrophils, and CD3+ T-cells by inhibiting the active NF-κB signaling pathway. Moreover, CGA can relieve intestinal injury, inhibit the permeability of intestinal mucosa and alleviate the reduction in fecal microbiota, such as Firmicutes and Bacteroidetes in DSS-induced mice, while increase the proportion of themucin-degrading bacterium Akkermansia; however, CGA does not exert strong antimicrobial effects [19]. Furthermore, in vitro, CGA reduces the level of reactive oxygen species in IPEC-J2 cells. And simultaneous application of CGA and Lactobacillus plantarum 2142 supernatant leads to the protection against lipopolysaccharide (LPS)-induced inflammation and oxidative stress [22].

Gallic acid

Gallic acid (GA), which exists widely in plants, such as Rheum palmatum L., Eucalyptus robusta Smith, and Cornus officinalis Sieb. et Zucc., has biological activities, such as anti-oxidation, anti-bacteria, anti-viral, and anti-tumor.

GA relieves DSS-induced ulcerative colitis via reducting the neutrophilic infiltration in the colon accompanied by a decreased expression of CD68+ and inhibiting the activation of p-STAT, preventing the decrease of IκBα expression resulted in decreasing the expression levels of iNOS and COX-2, and in vitro inhibiting the nuclear translocation of p65-NF-κB in RAW264.7 macrophages in colonic mucosa [23]. A study showed that mango is rich in polyphenols especially high abundant in GA. The mango extract (only total polyphenolics) treatment resulted in decreasing the Ki-67 labeling index in the central and basal regions, and at the mRNA and protein level, it attenuated the expression of TNF-α, IL-1β, and iNOS. Moreover, the expression levels of PI3K, AKT, and mammalian target of rapamycin (mTOR) were reduced, while miR- 126 was upregulated in vivo. Moreover, mango extract suppressed the protein expression levels of p-NF-κB, NF-κB, 3-kinase (PI3K, p85β), HIF-1α, p70 ribosomal protein S6 kinase (p70S6K1), and RPS6 protein in LPS-treated CCD-18Co cells in vitro [24]. Another study showed that Mango extract suppressed the ratio of phosphorylated/total protein expression of the insulin-like growth factor-1 receptor (IGF)-1R-AKT/mTOR axis and down-regulates the mRNA expression of gene Insr, Igf1 and pik3cv [25].

3, 4-Oxo-isopropylidene-shikimic acid

3, 4-Oxo-isopropylidene-shikimic acid (ISA) is a derivative of shikimic acid extracted from Illicium verum Hook. Some study has illustrated that ISA exerts the anti-inflam matory effect on colitis induced by TNBS in rats. It is reported that the protective effect of ISA is probably associated with the reducing granulocyte infiltration, the depressing MDA, NO levels and iNOS activity, the enhancing GSH level as well as GSH-Px and SOD activities in the colon tissues of experimental colitis [26]. These protective effects were associated with a reduced level of NF-κB p65 subunit in the nucleus and changes in the expression of IκBα. The anti-inflam matory activity of ISA may be mediated, at least in part, by inhibition of the expressions of certain pro-inflammatory mediators which are regulated by the oxidative stress sensitive NF-κB signaling pathway [27].

Vanillic acid

As a benzoic acid derivative, vanillic acid (VA) is used as a flavoring agent. It is an oxidized form of vanillin produced during the conversion of vanillin to ferulic acid. Moreover, the highest quantity of VA in plants is found in the roots of Angelica sinensis (Oliv.) Diels.

VA has been proved that has the anti-colitis, anti-mutagenic, anti-angiogenetic, anti-sickling, and anti-analgesic effects. It exhibited the reduction of weight loss and colon shortening, and exerted anti-inflammatory effects via reducing IL-6 level and COX-2 levels, and significantly suppressing the activation of transcription NF-κB p65 in DSS-treated colon tissues [28].

Ursolic acid

Ursolic acid (UA), which was isolated from an ethanol extract of Cornus officinalis Sieb.et Zucc. seed, potently inhibited nuclear factor κ light-chain enhancer of activated B cells activation in LPS-stimulated peritoneal macrophages.

UA inhibited phosphorylation of IRAK1, TAK1, IKKβ, and IκBα as well as activation of NF-κB and MAPKs in LPS-stimulated macrophages. It suppressed LPS-stimulated IL-1β, IL-6, TNF-α, COX-2, and iNOS expression as well as PGE2 and NO levels. UA not only inhibited the Alexa Fluor 488conjugated LPS-mediated shift of macrophages but also reduced the intensity of fluorescent LPS bound to the macrophages transiently transfected with or without MyD88 siRNA. Oral administration of UA has significantly inhibited TNBS- induced colon shortening, MPO activity, COX-2 and iNOS expression as well as NF-κB activation in mice. It may ameliorate colitis by regulating NF-κB and MAPK signaling pathways via the inhibition of LPS binding to TLR4 on immune cells [29].

Terpenoids Menthol

Menthol is a monoterpene-based partial agonist of TRPV3 channel, and shows lower (−65%) activation of the TRPV3 channel compared with that by camphor. Menthol can be extra cted from some Chinese medicinal plants, such as Mentha haplocalyx Briq, Lysimachia christinae Hance, and Perilla frutescens (L.) Britt.

Menthol is an aromatic compound with high anti-inflam matory activity. It is reported to has potent anti-inflammatory and antioxidant activities in vitro and in vivo [30-31]. In a study to investigate the effectiveness of menthol on acetic acid-induced acute colitis in rats, menthol displayed similar effectiveness with dexamethasone; significantly reduced body weight loss, macroscopic damage score, ulcer area, colon weight, and colon length; and improved hematocrit in rats with colitis. Moreover, histopathological examination confirmed the anti-colitis effects of menthol. Menthol also significantly reduced the colonic levels of TNF-α, IL-1β, IL-6, and MPO in the inflamed colons [32].

Triptolide

Triptolide, an epoxy two terpene compound extracted from the root, leaf, flower, and fruit of Tripterygium wilfordii Hook. f, has anti-inflammatory and immunosuppressive effects [33]. Triptolide inhibits the migration, proliferation, and colony formation of colon cancer cells in vitro, decreases the incidence of colon cancer formation in mice by reducing the secretion of IL-6, IL-1β [34-35], the levels of JAK1, IL-6R, and phosphorylated STAT3; triptolide prohibited Rac1 protein (Rho GTP-bound) activity and blocked cyclin D1 and CDK4 expression, thereby leading to G1 arrest [36]. Furthermore, triptolide decreased extracellular matrix (ECM) deposition and collagen production in the colon, and inhibited the expression of collagen Iα1 transcripts and collagen I protein in the isolated subepithelial myofibroblasts of rats with colonic fibrosis. Besides, triptolide was indicated that can inhibit the expression of IL-8 and monocyte chemotactic protein (MCP)-1, and matrix metallo proteinases-3 (MMP-3) in period study [33].

Andrographolide

Andrographolide exists in the whole plant or leaf of the Andrographis paniculata (Burm.f.) Nees., which is a natural antibiotic drug that dispels heat, detoxifies, diminishes infla mmation, and relieves pain. The active compound has a special curative effect for bacterial and viral upper respiratory tract infections and dysentery.

Clinical trials show that andrographolide decreased the levels of proinflammatory factors IL-1β, TNF-α, IL-6 and IL-17A in patients' serum and in the colon tissues, and the percentages of Th17 cells in CD4+ cells, and suppressed the levels of IL-17A, IL-23, ROR-γt (key transcription factor of Th17 cells) and STAT3 in the colon tissues [37-38]. Moreover, an andrographolide derivative AL-1 (the andrographlide- lipoic acid conjugate), presented a significant reduction in DAI, which inhibits inflammatory response by decreasing the level of inflammatory cytokines and MPO activity. AL-1 attenuates the expression levels of p-IκBα, p-p65 proteins, cytochrome c oxidase subunit (COX)-2 and NF-κB, and increased the expression of peroxisome proliferator-activated receptor (PPAR)-γ, thereby alleviating colon injury [39]. Another andrographolide derivative CX-10 (a hemi chemical synthesized from andrographolide) reduced the expression of IL-6 and TNF-α and the activity of MPO in colonic tissues, and the expression of NF-κB, p65 and p-IκBα proteins, while increasing the expression of IκBα and regulated down the phosphorylation of p38 mitogen-activated protein kinase (MAPK), ERK and JNK [40].

Gentiopicroside (Gent)

Gentiopicroside (Gent), as a secoiridoid compound isolated from Gentiana lutea L., has been the subject of numerous reports on the choleretic, anti-hepatotoxic, adaptogenic, and anti-inflammatory properties.

MPO activity in the DSS-induced colitic colon was effectively suppressed by oral administration of Gent. Furthermore, Gent treatment significantly reduced the overproduction of pro-inflammatory cytokines and chemokines. The oral administration of Gent significantly reduced the mRNA expression of TNF-α, IL-1β, IL-6, and down-regulated the overexpression of COX-2 and iNOS proteins. Therefore, it was concluded that the protective effect of Gent in experimental colitis is related to the suppression of inflammatory factors activation [41].

Phenols Curcumin

Turmeric belongs to the family Zingiberaceae and has been used as medicine in India and China for thousands of years [42]. Curcumin, a natural hydrophobic polyphenol derived from the rhizomes of turmeric (Curcuma longa L.) [43], is known for its multiple pharmacologic activities [44] in NF-κB-mediated inflammation, oxidative stress-mediated inflammation, and ER stress-mediated apoptosis and inflammation [45]. Curcumin has recently received increasing attention for UC therapy because it efficiently down-regulates inflammatory cytokines, scavenges free radicals, and promotes mucosal healing [46-48]. In vivo, curcumin can be a therapeutic agent for blocking NF-κB activation [49], and alleviate visceral hyperalgesia and reverse increasing expression of TRPV1 and p-TRPV1 in rats modeled by DSS. In vitro, in the HEK293 cell line stably expressing TRPV1, curcumin inhibited phorbol myristate acetate-induced upregulation of membrane TRPV1. By downregulating the colonic expression and phosphorylation of TRPV1 on the afferent fibers projected from the peptidergic and non-peptidergic nociceptive neurons of the dorsal root ganglion, oral administration of curcumin alleviated visceral hyperalgesia in DSS-induced colitis rats [50]. Moreover, for the therapeutic effect of curcumin on DSS- induced ulcerative colitis, the expression levels of TNF-α and MPO in the colon tissue was determined with ELISA, and colon p-p38MAPK and p38MAPK mRNA expression levels were evaluated by immunohistochemistry and RT-PCR. Curcumin displayed a therapeutic effect, which was probably enacted by inhibiting the p38MAPK signaling pathway, thereby reducing the release of TNF-α [51]. Furthermore, curcumin plus soy oligosaccharide was reported to decrease TNF-α and IL-8 expression and reduce colonic mucosa inflammation and tissue damage [52].

Gingerols

Ginger (Zingiber officinale Rosc.) has been used for centuries for the treatment of various illnesses that involve inflammation and which are caused by oxidative stress. It is well acknowledged that gingerols consist of 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol, which share analogous structural features. It has reported that the three gingerols (6-gingerol, 8-gingerol, and 10-gingerol) have a strong and relatively equal efficacy in the treatment of colitis [53].

6-gingerol, a component of gingerols extracted from ginger, has been reported to improve ulcerative colitis. It has been reported that 6-gingerol can suppress the induction of UC in mice, via antioxidant and anti-inflammatory activities [54]. In vitro, 6-gingerol can attenuate colitic symptoms evoked by dextran sulfate sodium, significantly elevated superoxide dis mutase activity, decrease malondialdehyde levels and myelopero xidase activity in the colon tissue, and markedly reduce the content of TNF-α and IL-1β in the serum [53].

6-shogaol, which can be extracted from Zingiber officinale Rose., has proved to have antioxidative, anti-inflam matory, and anticarcinogenic properties [55-57]. It is recently demonstrated that a specific population of ginger-derived nanoparticles (NPs) may effectively reduce colitis [58-60]. In another study, the NPs exhibited very good biocompatibility both in vitro and in vivo. They underwent efficient receptor- mediated uptake by colon-26 cells and activated Raw 264.7 macrophage cells in vitro, targeted colitis tissue, alleviated colitis symptoms, and accelerated colitis wound repair by regulating the expression levels of pro-inflammatory (TNF-α, IL-6, IL-1β, and iNOS) and anti- inflammatory (Nrf-2 and HO-1) factors in vivo [61].

Paeonol

Paeonol, 20-hydroxy-40methoxyacetophenone, is the main active component isolated from Cynanchum paniculatum and Aaeoina suffruticosa [62-63]. Paeonol has shown signi ficant anti-inflammation [64-66], anti-tumor [67-68], and anti-oxidant properties [69].

Paeonol was reported to reduce the activity of myelo peroxidase in the colon and inhibit the proliferation of iNOS, the expression of iNOS-mRNA induced by TNF-α+IFN-γ, and the activation of NF-κB and STAT1 signalling pathway in CW-2 and Jurkat cell lines, which was possibly contributed to its anti-inflammation and anti-UC properties. In addition, in the DSS-induced UC model of mice treated with paeonol, the anti-inflammatory and anti-oxidative activities of paeonol and its metabolite were related to the blocking of the MAPK/ERK/p38 signaling pathway [70]. Moreover, paeonol can reduce the levels of IL-17 and IL-6 in rat serum and increased the levels of TGF-β1 and inhibit colitis inflammation by regulating the balance of Treg/Th17 via downregulating Th17 cells and upregulating Treg cells [71].

Epicatechin

Epicatechin can be extracted from Acacia catechu (L. f.) Willd. and Hippophae rhamnoides L. Ficus carica fruit, a source of bioactive functional ingredients, have been traditionally used for its medicinal benefits as they improve the digestive system, treating constipation and used as a natural laxative. A recent study was investigated the ameliorative effect of Ficus carica L. aqueous extract (FCAE) on delayed gastric emptying and ulcerative colitis-improved motility disturbances in DSS-induced acute colitis in rats [72]. As a compound extracted from Ficus carica fruit, epicatechin can ameliorate ulcerative colitis as well. In C57BL/6J mice model with DSS-induced UC, epicatechin can decrease the disease activity index and colon macroscopic damage index scores, reduce body weight loss, and significantly relieve colon contracture and crypt damage. Besides, TNF-α, IL-6, NO, MPO, and MDA were reduced, whereas antioxidant enzymes showed increased activity. Furthermore, the effects of inhibited NF-κB activation have been demonstrated in vivo and in vitro. It is inferred that the inhibitory effect on DSS-induced acute UC of epicatechin is mainly related to its antioxidant effects and the inhibition of inflammatory molecules via the NF-κB pathway [73].

Proanthocyanidin

Proanthocyanidin, is a kind of naturally occurring oligomers and polymers of flavan-3-ol monomer units widely available in fruits, vegetables, nuts, seeds, flowers, and bark of Cynan chum paniculatum (Bge.) Kitag. and many other plants [74].

Grape seed extract proanthocyanidins (GSPs) are naturally occurring polyphenol that possesses antioxidant and anti-lipid peroxidation activities. It is reported that GSPs exerted a protective effect on TNBS-induced recurrent colitis in rats by modifying the inflammatory response, inhibiting inflammatory cell infiltration and antioxidation damage, promoting damaged tissue repair to improve colonic oxidative stress, and inhibiting the activity of iNOS to reduce the production of NO [75]. As for therapeutic effects in TNBS-induced UC rats, GSPs was effective on either acute or recurrent colitis.

Alkaloids Berberine

Berberine is an isoquinoline alkaloid and mainly originates from the roots and stems of Berberis julianae C. K. Schneid, which has the highest reported content of berberine at about 4.5%. As an antibacterial drug, the clinical effects of berberine are mainly for intestinal infections and dysentery. Moreover, berberine can attenuate pro-inflammatory cytokine-induced intestinal epithelial barrier dysfunction, preserve barrier function, and reduce and occlude the tight junction (TJ) protein zona occludens (ZO)-1, which prevents pro-inflam matory cytokine-disruption of barrier function in HT-29 cells and Caco-2 cells by modulating TJ proteins in vitro. Berberine increases the levels of superoxide dismutase and catalase in the colon and serum samples and reduces the levels of myeloperoxidase, reduces the macromolecule leak caused by cell layer exposure to cytomix and H2O2. In addition, berberine attenuates the T helper (Th)1/Th2/Th17 response and promotes Treg response in UC and leads to increased TNF-α, interleukin (IL)-23, and IL-6 mRNA expression levels. Furthermore, berberine may regulate transcription (STAT)3 to balance Th17 and Treg, reversed the up-regulation of IL-17 secretion from CD4+cells of spleens and mesenteric lymph node cells (MLNs) [76-78]. Besides, compared with 5-ASA treatment alone, the combination of berberine and 5-ASA therapy more pronouncedly reversed the up-regulation of the mRNA level in colonic TNF-α, as well as nuclear NF-κB and Janus kinase (JAK)2 phosphorylation by DSS; and more significantly inhibited lymphocyte TNF-α secretion [79]. Moreover, combination of berberine and 5-ASA therapy has less serious toxic effects on the spleen [80].

Matrine and oxymatrine

Matrine and oxymatrine are extracted from the dried roots, plants, and fruits of Sophora flavescens Ait. by using organic solvents, such as ethanol. Matrine can decrease the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in the colon mucosa cells, and has an inhibitory effect on lipopolysaccharide (LPS)-induced release of NO from macrophages. Matrine significantly decreases TNF-α, IL-1β, IL-4, and IL-10 levels. Additionally, matrine can heal ulcer cells and reduce the lesion areas in inflammatory cell infiltration, fibrosis, and edema [81]. Moreover, matrine can protect the colonic mucosa by reducing the overexpression of colonic mucosa proteins NOD2 and NF-κB p65 and decreasing IL-6 level [82]. Oxymatrine might attenuate UC by regulating the β2-adrenocepto (β2AR)-β-arrestin2-NF-κB and the delta opioid receptor (DOR)-β-arrestin1-Bcl-2 signal transduction pathway. The expression of NF-κB p65, DOR, β-arrestin1 and Bcl-2 protein and mRNA were significantly decreased while the expressions of β2AR and β-arrestin2 were significantly increased [83-84]. Oxymatrine ameliorated UC through pro-apo ptotic, down-regulating the Th1 and Th17 cells diffe ren tiation via phosphoinositide 3-kinase (PI3K)/AKT pathway [85].

Theophylline

Theophylline (1, 3-dimethyl-2, 6-dioxypurine), which can be extracted from Viridis tea and Camellia crassicolumna [86], is a non-specific phosphodiesterase inhibitor. Theophy lline showed anti-inflammatory activity both in vitro and in vivo [57, 87-88]. In vivo, studies showed that theophylline attenuated the response to allergen [89] and reduced bronchial mucosal eosinophils in patients with mild asthma [90]. Moreover, theophylline treatment also reduced myeloperoxidase (MPO) activity and tumor necrosis TNF-α, IL-1β and IL-6 concentrations in the inflamed colon [91].

Quinones Tanshinone IIa

Tanshinone IIa, is obtained from the dry roots and rhizomes of Salvia miltiorrhiza Bge. and the root of Salvia sclarea L.. Clinical study showed that tanshinone IIa presented a therapeutic role in UC by reducing DAI, enhancing the macrophage phagocyte system and the function of natural killer (NK) cell's suppression of non-specific immunity killing effects while improving humoral immunity, and activating interferon cytokine production to increase T cell and NK cell activity. Besides, tanshinone IIA sulfonate injection can significantly reduce the level of CRP protein [51]. Moreover, tanshinone IIa improved intestinal permeability, decreases the neutrophil (PMN) infiltration and activation of intestinal mucosa by the decreased production of MPO, reactive oxygen species (ROS), and inflammatory cytokines and suppress neutrophil migration to inhibit the adhesion of PMN and endothelial cells in DSS-treated mice [92]. In vitro, tanshinone IIa is an efficacious the pregnane X receptor (PXR, a known target of abrogating inflammation in IBD) agonist, as mediated by the transactivation of PXR. Tanshinone IIa induced CYP3A4 mRNA and protein expression in LS174T cells and HepG2 cells to inhibit the mRNA expression of inflammatory mediators such as TNF-α, IL-6, iNOS, and MCP [93].

Shikonin

Shikonin, obtained from the root of plants Lithosperraum erythrorhizon Sieb. et Zucc. and Arnebia euchroma (Royle) I.M. Johnst., has anti-cancer, anti-inflammatory, and anti-ba cterial functions. As a naphthoquinone, shikonin acts by blocking the activation of two major targets, NF-κB and STAT-3. Study showed that shikonin can reduce the activation of NF-κB, the expression of cyclooxygenase-2, inducible nitric oxide synthase, and myeloperoxidase activity, as well as pSTAT-3, TNF-α and IL-1β while promoting the production of IL-6 and present the cytotoxic in DSS-induced UC mice in vitro and in vivo [94-95]. Besides, in vitro, shikonin significantly enhanced intestinal epithelial cell (IEC)-18 restitution by enhancing the migration of intestinal epithelial cells via involves transforming growth factor (TGF)-β1 induction, without interfering with IEC-18 cell proliferation [96].

Rhubarb-type anthraquinones

Rhubarb-type anthraquinones are from Rheum palmatum L., Rheum tanguticum Maxim. ex Balf., or the dried roots and rhizomes of Rheum officinale Baill., including rhein, emodin, chrysophanol, and aloe emodin. The activities of β-glu cosidase and microbial β-glucosidase are significantly reduced which leads to the abrogation of enterohepatic recirculation due to under the action of aglycone of rhubarb-type anthrax quinones to improve microbial disturbance in the intestinal tract [97].

As an important component of the rhubarb-type anthrax quinones, rhein can significantly reduce the inflammation-associated migration of immune cells. In vitro, rhein decrease the levels of IL-6, IL-1β, and TNF-α. Rhein reduces NO production by suppressing the protein expressions of iNOS and COX-2, thereby showing that the anti-inflam matory action of rhein is partially associated with reducing the phosphorylation levels of NF-κB p65 and the suppression of NLRP3 expression in RAW264.7 macrophages [98].

Another important component of the rhubarb-type anthraquinone, emodin, decreased the DAI, intestinal damages and the count of white blood cells (WBC) in peripheral blood, and presented the prevention of the loss of body weight and colon shortening. It is reported that emodin decreased the level of anti-flagellin antibody in serum and significantly suppressed the expression of antibody toll like receptor 5 (TLR5) and NF-κB p65. In vitro, emodin showed that down-regulation of the expression of antibody TLR5 and MyD88, up-regulation of the expression of antibody IκB, and decreased the release of IL-8 in inflagellin-stimulated HT-29 cells [99].

Chrysophanol decreased DAI and attenuated the body weight loss by inhibiting the production of IL-6, PGE2 and the expression of COX-2 levels in DSS-induced colitis in vivo, and decreasing NF-κB (p65) and caspase-1 activation in LPS-stimulated mouse in vitro [100].

Bile acids Taurocholate

Taurocholate (TC) is a natural conjugated bile acid, which not only found in ox gall, but also in snakes bile, such as Zaocys dhumnades (Cantor) and Agkisrrodon acutus (Guen ther) [101]. It has been reported that TC has the anti-inflammatory effect against TNBS-induced colitis [102].

TC could decrease MPO activity, TNF-α, IFN-γ and IL-1β levels from colonic tissue. Oral TC significantly decreased MPO activity. These findings suggested that TC could inhibit neutrophils infiltrations in the inflamed colonic tissue and inhibit the development of inflammation and damage of epithelial cells. TC suppressed TNBS-induced colitis in mice and this supp ression effect at least associated with the expression of some cytokines, including TNF-α, IL-1β, IFN-γ and MPO [103].

Tauroursodeoxycholate

Tauroursodeoxycholate (TUDC), taurine-conjugated urso deo xycholic bile acid, is endogenous bile acid and found in biles of Selenarctos thibetanus (G. Cuvier) and Ursus arctos L. [101]. TUDC was proven to be potent anti-aggregation inhibitors via restraining the unfolded protein response and decreasing ER stress in intestinal epithelial cells to consider as a potential function for treatment of inflammatory bowel diseases in vitro [104-105].

It is reported that TUDC can reduce the number of MPO, and significantly suppress the secretion of TNF-α, IL-1β, and IFN-γ in TNBS-induced colitis, which was estimated that this effect might be associated with the expression of these cytokines, including TNF-α, IL-1β, IFN-γ and MPO [106].

Else Indirubin and isatin

Indirubin and isatin, the active compounds are isolated from Indigofera tinctoria L., is an indole antitumor drug and used for treating chronic myeloid leukemia.

Indirubin is an effective component of Chinese medicinal herb recipe Qingre Zaoshi Liangxue Fang (QRZSLXF) for the treatment of UC [107], wherein the role of indirubin during the mucosal healing process through the signaling pathway involved stimulating the mucosal type 3 innate lymphoid cells to produce IL-22, consequently inducing antimicrobial peptide and tight junction molecule production [108]. Indirubin and isatin reversed the elevation of DAI, thus ameliorating DSS-induced UC by reducing inflammatory cell infiltration in the colon mucosa, which in turn alleviated crypt distortion and mucosal injury. The levels of TNF-α, interferon (IFN)-γ, and IL-2, as well as MPO activity in colon tissues were significantly decreased, whereas the levels of IL-4 and IL-10 were distinctly increased. Moreover, indirubin remarkably suppressed CD4+ T cell infiltration in the colon of DSS-induced mice, and promoted the generation of Foxp3- expressing regulatory T cells, as well as inhibited DSS- induced activation of NF-κB signaling. The protective effect of indirubin/isatin combination therapy was superior to that of single-agent treatment [109-110]. Besides, isatin inhibited the increase of PGE2 levels, prevented the decrease of SOD activity and increase of glutathione reductase (GSH-Rd) activity, glutathione peroxidase (GSH-Px) as well as the depletion of glutathione (GSH) levels [111].

Brusatol

Brusatol (BR) is one of the main bioactive components derived from Brucea javanica (L.) Merr., a medicinal herb historically used in the treatment of dysenteric disorders (also known as ulcerative colitis). BR was found to exhibit diverse bioactivities including antimalarial, antineoplastic, anthelmintic and hypoglycemic activities [112-114]. In addition, BR was reported to be a potent anti-inflammatory agent by inhibition of protein synthesis [115].

BR treatment inhibited the levels of pro-inflammatory cytokines and PGE2, and promoted the production of the immunoregulatory mediators IL-4 and IL-10. The beneficial effect of BR might be intimately associated with the enhan cement of antioxidant enzymes including SOD and GSH-Px, as well as dose-dependent amelioration of MPO and MDA levels. In addition, treatment with BR aqueous solution caused significant attenuation of TLR4, MyD88 and NF-κB p65 expression in the colon tissue. Oral administration of BR could effectively attenuate colonic inflammation in mice, at least partially, via favorable regulation of anti-oxidative and anti-inflammatory status and inhibition of the TLR4-linked NF-κB signaling pathway [116].

Allicin

Allicin, a sulfur-containing natural compound which extract from Allium sativum L., with many different biolo gical properties, is responsible for the typical smell and taste of freshly cut or crushed garlic. Allicin has many beneficial effects, including antioxidant, anti-inflammatory, anti-proli ferative, and proapoptotic effects.

Allicin treatment significantly decreased CD68, MPO, MDA and pro-inflammatory cytokines, and increased the enzymic antioxidants significantly. In addition, allicin was capable of reducing the activation and nuclear accumulation of signal transducer, and activator of transcription 3 (STAT3), thereby it prevented the degradation of the inhibitory protein IκB and induced inhibition of the nuclear translocation of nuclear factor (NF)-κB-p65 in the colonic mucosa. These findings suggested that allicin exerted clinically useful anti- inflammatory effects through the suppression of the NF-κB and IL-6/p-STAT3Y705 pathways [117].

Resveratrol

Resveratrol is a naturally occurring and biologically active polyphenol ingredient that is present in grapes (Vitis vinifera L.), peanuts, and other plants. Resveratrol presents a variety of biologic activities, including immune regulation, anti-inflammation, anti-oxidation, anti-angiogenesis, and reduction of tissue damage [118-119].

Previous studies demonstrated that resveratrol exhibited anti-inflammatory effects on colitis in mice via antioxidant activities [118]. Recently, two reports shown that resveratrol has excellent therapeutic efficacy on UC by reducing neutrophilic exudate, inhibiting adhesion molecules, and regulating cytokine levels [120-121]. It was found that resveratrol can regulate the rebalancing of Treg/Th17, increase TGF-β1 and IL-10 levels, decrease IL-6 and IL-17 levels, and inhibit hypoxia- mTOR-HIF-1α-Th17 and IL-6-STAT3-HIF-1α-Th17 path ways. The therapeutic efficacy of resveratrol in UC was dose-depen dent and closely associated with the regulation of Treg/Th17 balance and the HIF-1α/ mTOR signaling pathway [122].

Discussion and Future Prospects

The detailed information on the above-mentioned com pounds from TCM effective on UC, both in vivo and in vitro/ex vivo studies, are shown in Tables 1 and 2. The anti-UC activities are mainly focus on targeting inflammation or oxidative stress, which is associated with increasing the levels of anti-inflammatory cytokine (IL-4, IL-10, SOD), suppressing the levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-8, IL-23, NF-κB, NO), reducing the activity of MPO, MDA, IFN-γ, and iNOS. In additional to regular anti-inflam matory mechanism, some compounds may lower the ulce ration of the intestinal mucosa and extent of neutrophil infiltration, or inhibit the downregulation of TJ protein ZO-1 and E-cadherin, which also present their anti-inflam mation activities in inflammatory colons of ulcerative colitis.

Table 1 Compounds from Chinese medicines effective on ulcerative colitis (in vivo studies)
Table 2 Compounds from Chinese medicines effective on ulcerative colitis (in vitro/ex vivo studies)

In conclusion, these natural active compounds in various Chinese medicines present favorable effects on experimental UC models, most of which are found to be active in anti- inflammation or anti-oxidation with oral administration to avoid severe toxic or side effects. TCM, with their unique, mild, and long-term effectiveness on UC, might benefit this inflammatory bowel disease, with further efforts on the investigations on their drugability. However, the majority of the compounds are used in the acute experimental colitis (from 3 to 15 days), except triptolide (20 weeks). Since the clinical UC has been found to be a long-term recurrent disease, the applicability of these compounds still needs further investigation and evaluation, before they are practically employed with medication purpose.

References
[1]
Wan P, Chen H, Guo Y, et al. Advances in treatment of ulcerative colitis with herbs: from bench to bedside[J]. World J Gastroenterol, 2014, 20(39): 14099-14104. DOI:10.3748/wjg.v20.i39.14099
[2]
Pastorelli L, Pizarro TT, Cominelli F, et al. Emerging drugs for the treatment of ulcerative colitis[J]. Expert Opin Emerg Drugs, 2009, 14(3): 505-521. DOI:10.1517/14728210903146882
[3]
Zhang C, Jiang M, Lu A. Considerations of traditional Chinese medicine as adjunct therapy in the management of ulcerative colitis[J]. Clin Rev Allergy Immunol, 2013, 44(3): 274-283. DOI:10.1007/s12016-012-8328-9
[4]
Salaga M, Zatorski H, Sobczak M, et al. Chinese herbal medi cines in the treatment of IBD and colorectal cancer: a review[J]. Curr Treat Options Oncol, 2014, 15(3): 405-420. DOI:10.1007/s11864-014-0288-2
[5]
Pandurangan AK, Kumar SA, Dharmalingam P, et al. Luteolin, a bioflavonoid inhibits azoxymethane-induced colon carcino genesis: involvement of iNOS and COX-2[J]. Pharmacogn Mag, 2014, 10(Suppl 2): S306-310.
[6]
Karrasch T, Kim JS, Jang BI, et al. The flavonoid luteolin worsens chemical-induced colitis in NF-kappaB (EGFP) trans genic mice through blockade of NF-kappaB-dependent protective molecules[J]. PLos One, 2007, 2(7): e596. DOI:10.1371/journal.pone.0000596
[7]
Zhang CL, Zhang S, He WX, et al. Baicalin may alleviate inflammatory infiltration in dextran sodium sulfate-induced chronic ulcerative colitis via inhibiting IL-33 expression[J]. Life Sci, 2017, 186: 125-132. DOI:10.1016/j.lfs.2017.08.010
[8]
Yu FY, Huang SG, Zhang HY, et al. Effects of baicalin in CD4 + CD29 + T cell subsets of ulcerative colitis patients[J]. World J Gastroenterol, 2014, 20(41): 15299-15309. DOI:10.3748/wjg.v20.i41.15299
[9]
Dai SX, Zou Y, Feng YL, et al. Baicalin down-regulates the expression of macrophage migration inhibitory factor (MIF) effectively for rats with ulcerative colitis[J]. Phytother Res, 2012, 26(4): 498-504.
[10]
Goncalves LM, Valente IM, Rodrigues JA. An overview on cardamonin[J]. J Med Food, 2014, 17(6): 633-640. DOI:10.1089/jmf.2013.0061
[11]
Kim YJ, Ko H, Park JS, et al. Dimethyl cardamonin inhibits lipopolysaccharide-induced inflammatory factors through blocking NF-kappaB p65 activation[J]. Int Immunopharmacol, 2010, 10(9): 1127-1134. DOI:10.1016/j.intimp.2010.06.017
[12]
Hatziieremia S, Gray AI, Ferro VA, et al. The effects of cardamonin on lipopolysaccharide-induced inflammatory protein production and MAP kinase and NF-kappaB signalling path ways in monocytes/macrophages[J]. Br J Pharmacol, 2006, 149(2): 188-198.
[13]
Ali AA, Abd Al Haleem EN, Khaleel SA, et al. Protective effect of cardamonin against acetic acid-induced ulcerative colitis in rats[J]. Pharmacol Rep, 2017, 69(2): 268-275.
[14]
Lee YS, Choi EM. Myricetin inhibits IL-1beta-induced inflam matory mediators in SW982 human synovial sarcoma cells[J]. Int Immunopharmacol, 2010, 10(7): 812-814. DOI:10.1016/j.intimp.2010.04.010
[15]
Chen W, Li Y, Li J, et al. Myricetin affords protection against peroxynitrite-mediated DNA damage and hydroxyl radical formation[J]. Food Chem Toxicol, 2011, 49(9): 2439-2444. DOI:10.1016/j.fct.2011.06.066
[16]
Nirmala P, Ramanathan M. Effect of myricetin on 1, 2 dimethylhydrazine induced rat colon carcinogenesis[J]. J Exp Ther Oncol, 2011, 9(2): 101-108.
[17]
Kang NJ, Jung SK, Lee KW, et al. Myricetin is a potent chemopreventive phytochemical in skin carcinogenesis[J]. Ann N Y Acad Sci, 2011, 1229: 124-132. DOI:10.1111/j.1749-6632.2011.06122.x
[18]
Zhao J, Hong T, Dong M, et al. Protective effect of myricetin in dextran sulphate sodium-induced murine ulcerative colitis[J]. Mol Med Rep, 2013, 7(2): 565-570.
[19]
Zhang Z, Wu X, Cao S, et al. Chlorogenic acid ameliorates experimental colitis by promoting growth of akkermansia in mice[J]. Nutrients, 2017, 9(7): 677. DOI:10.3390/nu9070677
[20]
Zatorski H, Salaga M, Zielinska M, et al. Experimental colitis in mice is attenuated by topical administration of chlorogenic acid[J]. Naunyn Schmiedebergs Arch Pharmacol, 2015, 388(6): 643-651. DOI:10.1007/s00210-015-1110-9
[21]
Shin HS, Satsu H, Bae MJ, et al. Catechol groups enable reactive oxygen species scavenging-mediated suppression of PKD-NFkappaB-IL-8 signaling pathway by chlorogenic and caffeic acids in human intestinal cells[J]. Nutrients, 2017, 9(2): 165. DOI:10.3390/nu9020165
[22]
Palócz O, Pászti-Gere E, Gálfi P, et al. Chlorogenic acid combined with lactobacillus plantarum 2142 reduced LPS- induced intestinal inflammation and oxidative stress in IPEC-J2 Cells[J]. PLoS One, 2016, 11(11): e0166642. DOI:10.1371/journal.pone.0166642
[23]
Pandurangan AK, Mohebali N, Esa NM, et al. Gallic acid suppresses inflammation in dextran sodium sulfate-induced colitis in mice: possible mechanisms[J]. Int Immuno phar macol, 2015, 28(2): 1034-1043. DOI:10.1016/j.intimp.2015.08.019
[24]
Kim H, Banerjee N, Barnes RC, et al. Mango polyphenolics reduce inflammation in intestinal colitis-involvement of the miR-126/PI3K/AKT/mTOR axis in vitro and in vivo[J]. Mol Carcinog, 2017, 56(1): 197-207.
[25]
Kim H, Banerjee N, Ivanov I, et al. Comparison of anti-in flammatory mechanisms of mango (Mangifera Indica L.) and pomegranate (Punica Granatum L.) in a preclinical model of colitis[J]. Mol Nutr Food Res, 2016, 60(9): 1912-1923. DOI:10.1002/mnfr.v60.9
[26]
Xing JF, Sun JN, Sun JY, et al. Protective effects of 3, 4-oxo- isopropylidene-shikimic acid on experimental colitis induced by trinitrobenzenesulfonic acid in rats[J]. Dig Dis Sci, 2012, 57(8): 2045-2054. DOI:10.1007/s10620-012-2155-y
[27]
Xing J, You C, Dong K, et al. Ameliorative effects of 3, 4-oxo- isopropylidene-shikimic acid on experimental colitis and their mechanisms in rats[J]. Int Immunopharmacol, 2013, 15(3): 524-531. DOI:10.1016/j.intimp.2013.02.008
[28]
Kim SJ, Kim MC, Um JY, et al. The beneficial effect of vanillic acid on ulcerative colitis[J]. Molecules, 2010, 15(10): 7208-7217. DOI:10.3390/molecules15107208
[29]
Jang SE, Jeong JJ, Hyam SR, et al. Ursolic acid isolated from the seed of Cornus officinalis ameliorates colitis in mice by inhibiting the binding of lipopolysaccharide to Toll-like receptor 4 on macrophages[J]. J Agric Food Chem, 2014, 62(40): 9711-9721. DOI:10.1021/jf501487v
[30]
Li Q, Wang X, Yang Z, et al. Menthol induces cell death via the TRPM8 channel in the human bladder cancer cell line T24[J]. Oncology, 2009, 77(6): 335-341. DOI:10.1159/000264627
[31]
Wang Y, Wang X, Yang Z, et al. Menthol inhibits the prolife ration and motility of prostate cancer DU145 cells[J]. Pathol Oncol Res, 2012, 18(4): 903-910. DOI:10.1007/s12253-012-9520-1
[32]
Ghasemi-Pirbaluti M, Motaghi E, Bozorgi H. The effect of menthol on acute experimental colitis in rats[J]. Eur J Pharmacol, 2017, 805: 101-107. DOI:10.1016/j.ejphar.2017.03.003
[33]
Tao Q, Wang B, Zheng Y, et al. Triptolide ameliorates colonic fibrosis in an experimental rat model[J]. Mol Med Rep, 2015, 12(2): 1891-1897. DOI:10.3892/mmr.2015.3582
[34]
Zhang H, Gong C, Qu L, et al. Therapeutic effects of triptolide via the inhibition of IL-1beta expression in a mouse model of ulcerative colitis[J]. Exp Ther Med, 2016, 12(3): 1279-1286. DOI:10.3892/etm.2016.3490
[35]
Zhang H, Chen W. Interleukin 6 inhibition by triptolide prevents inflammation in a mouse model of ulcerative colitis[J]. Exp Ther Med, 2017, 14(3): 2271-2276. DOI:10.3892/etm.2017.4778
[36]
Wang Z, Jin H, Xu R, et al. Triptolide downregulates Rac1 and the JAK/STAT3 pathway and inhibits colitis-related colon cancer progression[J]. Exp Mol Med, 2009, 41(10): 717-727. DOI:10.3858/emm.2009.41.10.078
[37]
Zhu Q, Zheng P, Chen X, et al. Andrographolide presents thera peutic effect on ulcerative colitis through the inhibition of IL-23/IL-17 axis[J]. Am J Transl Res, 2018, 10(2): 465-473.
[38]
Zhu Q, Zheng P, Zhou J, et al. Andrographolide affects Th1/ Th2/Th17 responses of peripheral blood mononuclear cells from ulcerative colitis patients[J]. Mol Med Rep, 2018, 18(1): 622-626.
[39]
Yang Y, Yan H, Jing M, et al. Andrographolide derivative AL-1 ameliorates TNBS-induced colitis in mice: involvement of NF-small ka, CyrillicB and PPAR-gamma signaling pathways[J]. Sci Rep, 2016, 6: 29716. DOI:10.1038/srep29716
[40]
Gao Z, Yu C, Liang H, et al. Andrographolide derivative CX-10 ameliorates dextran sulphate sodium-induced ulcerative colitis in mice: Involvement of NF-kappaB and MAPK signalling pathways[J]. Int Immunopharmacol, 2018, 57: 82-90. DOI:10.1016/j.intimp.2018.02.012
[41]
Niu YT, Zhao YP, Jiao YF, et al. Protective effect of gentio picroside against dextran sodium sulfate induced colitis in mice[J]. Int Immunopharmacol, 2016, 39: 16-22. DOI:10.1016/j.intimp.2016.07.003
[42]
Asher GN, Spelman K. Clinical utility of curcumin extract[J]. Altern Ther Health Med, 2013, 19(2): 20-22.
[43]
Salomon N, Lang A, Gamus D. Curcumin add-on therapy for ulcerative colitis[J]. Harefuah, 2015, 154(1): 56-58, 66.
[44]
Vecchi Brumatti L, Marcuzzi A, Tricarico PM, et al. Curcumin and inflammatory bowel disease: potential and limits of innovative treatments[J]. Molecules, 2014, 19(12): 21127-21153. DOI:10.3390/molecules191221127
[45]
Sreedhar R, Arumugam S, Thandavarayan RA, et al. Curcumin as a therapeutic agent in the chemoprevention of inflammatory bowel disease[J]. Drug Discov Today, 2016, 21(5): 843-849. DOI:10.1016/j.drudis.2016.03.007
[46]
Baliga MS, Joseph N, Venkataranganna MV, et al. Curcumin, an active component of turmeric in the prevention and treat ment of ulcerative colitis: preclinical and clinical observations[J]. Food Funct, 2012, 3(11): 1109-1117. DOI:10.1039/c2fo30097d
[47]
Viljakainen HT, Pekkinen M, Saarnio E, et al. Dual effect of adipose tissue on bone health during growth[J]. Bone, 2011, 48(2): 212-217. DOI:10.1016/j.bone.2010.09.022
[48]
Deguchi Y, Andoh A, Inatomi O, et al. Curcumin prevents the development of dextran sulfate Sodium (DSS)-induced experi mental colitis[J]. Dig Dis Sci, 2007, 52(11): 2993-2998. DOI:10.1007/s10620-006-9138-9
[49]
Wang Y, Tang Q, Duan P, et al. Curcumin as a therapeutic agent for blocking NF-kappaB activation in ulcerative colitis[J]. Immunopharmacol Immunotoxicol, 2018. DOI:10.1080/08923973.2018.1469145
[50]
Yang M, Wang J, Yang C, et al. Oral administration of curcu min attenuates visceral hyperalgesia through inhibiting pho spho rylation of TRPV1 in rat model of ulcerative colitis[J]. Mol Pain, 2017, 13: 1744806917726416.
[51]
Xin KB, Zhang JL, Yang J, et al. A Study on the effect of Tanshinone IIA sulfonate injection on the clinical efficacy of ulcerative colitis[J]. Prog Modern Biomed, 2015, 15(34): 6701-6703, 6623.
[52]
Huang G, Ye L, Du G, et al. Effects of curcumin plus Soy oligosaccharides on intestinal flora of rats with ulcerative colitis[J]. Cell Mol Biol (Noisy-le-grand), 2017, 63(7): 20-25. DOI:10.14715/cmb/2017.63.7.3
[53]
Zhang F, Ma N, Gao YF, et al. Therapeutic effects of 6-gingerol, 8-gingerol, and 10-gingerol on dextran sulfate sodium-nduced acute ulcerative colitis in rats[J]. Phytother Res, 2017, 31(9): 1427-1432. DOI:10.1002/ptr.v31.9
[54]
Ajayi BO, Adedara IA, Farombi EO. Pharmacological activity of 6-gingerol in dextran sulphate sodium-induced ulcerative colitis in BALB/c mice[J]. Phytother Res, 2015, 29(4): 566-572. DOI:10.1002/ptr.v29.4
[55]
Dugasani S, Pichika MR, Nadarajah VD, et al. Comparative antioxidant and anti-inflammatory effects of 6-gingerol, 8-gingerol, 10-gingerol and 6-shogaol[J]. J Ethnopharmacol, 2010, 127(2): 515-520. DOI:10.1016/j.jep.2009.10.004
[56]
Shim S, Kim S, Choi DS, et al. Anti-inflammatory effects of 6-shogaol: potential roles of HDAC inhibition and HSP70 induction[J]. Food Chem Toxicol, 2011, 49(11): 2734-2740. DOI:10.1016/j.fct.2011.08.012
[57]
Sun X, Li Q, Gong Y, et al. Low-dose theophylline restores corticosteroid responsiveness in rats with smoke-induced airway inflammation[J]. Can J Physiol Pharmacol, 2012, 90(7): 895-902. DOI:10.1139/y2012-079
[58]
Zhang M, Viennois E, Prasad M, et al. Edible ginger-derived nanoparticles: a novel therapeutic approach for the prevention and treatment of inflammatory bowel disease and colitis- associated cancer[J]. Biomaterials, 2016, 101: 321-340. DOI:10.1016/j.biomaterials.2016.06.018
[59]
Zhang M, Xiao B, Wang H, et al. Edible ginger-derived nano- lipids loaded with doxorubicin as a novel drug-delivery approach for colon cancer therapy[J]. Mol Ther, 2016, 24(10): 1783-1796. DOI:10.1038/mt.2016.159
[60]
Zhang M, Collins JF, Merlin D. Do ginger-derived nanopar ticles represent an attractive treatment strategy for inflam matory bowel diseases?[J]. Nanomedicine (Lond), 2016, 11(23): 3035-3037. DOI:10.2217/nnm-2016-0353
[61]
Zhang M, Xu C, Liu D, et al. Oral delivery of nanoparticles loaded with ginger active compound, 6-shogaol, attenuates Ulcerative Colitis and Promotes Wound Healing in a Murine Model of Ulcerative Colitis[J]. J Crohns Colitis, 2018, 12(2): 217-229. DOI:10.1093/ecco-jcc/jjx115
[62]
Yun CS, Choi YG, Jeong MY, et al. Moutan cortex radicis inhibits inflammatory changes of gene expression in lipopoly saccharide-stimulated gingival fibroblasts[J]. J Nat Med, 2013, 67(3): 576-589. DOI:10.1007/s11418-012-0714-3
[63]
Jamal J, Mustafa MR, Wong PF. Paeonol protects against premature senescence in endothelial cells by modulating Sirtuin 1 pathway[J]. J Ethnopharmacol, 2014, 154(2): 428-436. DOI:10.1016/j.jep.2014.04.025
[64]
Gong X, Yang Y, Huang L, et al. Antioxidation, anti-inflam mation and anti-apoptosis by paeonol in LPS/d-GalN-induced acute liver failure in mice[J]. Int Immunopharmacol, 2017, 46: 124-132. DOI:10.1016/j.intimp.2017.03.003
[65]
Fu PK, Yang CY, Huang SC, et al. Evaluation of LPS-induced acute lung injury attenuation in rats by aminothiazole-paeonol derivatives[J]. Molecules, 2017, 22(10): 1605. DOI:10.3390/molecules22101605
[66]
Meng Y, Wang M, Xie X, et al. Paeonol ameliorates imiqui mod-induced psoriasis-like skin lesions in BALB/c mice by inhibiting the maturation and activation of dendritic cells[J]. Int J Mol Med, 2017, 39(5): 1101-1110. DOI:10.3892/ijmm.2017.2930
[67]
Zhang L, Tao L, Shi T, et al. Paeonol inhibits B16F10 melanoma metastasis in vitro and in vivo via disrupting proinflammatory cytokines-mediated NF-kappaB and STAT3 pathways[J]. IUBMB Life, 2015, 67(10): 778-788. DOI:10.1002/iub.1435
[68]
Li M, Tan SY, Wang XF. Paeonol exerts an anticancer effect on human colorectal cancer cells through inhibition of PGE(2) synthesis and COX-2 expression[J]. Oncol Rep, 2014, 32(6): 2845-2853. DOI:10.3892/or.2014.3543
[69]
Liu J, Wang S, Feng L, et al. Hypoglycemic and antioxidant activities of paeonol and its beneficial effect on diabetic encephalopathy in streptozotocin-induced diabetic rats[J]. J Med Food, 2013, 16(7): 577-586. DOI:10.1089/jmf.2012.2654
[70]
Jin X, Wang J, Xia ZM, et al. Anti-inflammatory and anti- oxidative activities of paeonol and its metabolites through blocking MAPK/ERK/p38 signaling pathway[J]. Inflam mation, 2016, 39(1): 434-446. DOI:10.1007/s10753-015-0265-3
[71]
Zong S, Pu Y, Li S, et al. Beneficial anti-inflammatory effect of paeonol self-microemulsion-loaded colon-specific capsules on experimental ulcerative colitis rats[J]. Artif Cells Nanomed Biotechnol, 2018. DOI:10.1080/21691401.2017.1423497
[72]
Rtibi K, Grami D, Wannes D, et al. Ficus carica aqueous extract alleviates delayed gastric emptying and recovers ulcerative colitis-enhanced acute functional gastrointestinal disorders in rats[J]. J Ethnopharmacol, 2018, 224: 242-249. DOI:10.1016/j.jep.2018.06.001
[73]
Zhang H, Deng A, Zhang Z, et al. The protective effect of epicatechin on experimental ulcerative colitis in mice is mediated by increasing antioxidation and by the inhibition of NF-kappaB pathway[J]. Pharmacol Rep, 2016, 68(3): 514-520. DOI:10.1016/j.pharep.2015.12.011
[74]
De Rezende AA, Graf U, Guterres Zda R, et al. Protective effects of proanthocyanidins of grape (Vitis vinifera L.) seeds on DNA damage induced by doxorubicin in somatic cells of drosophila melanogaster[J]. Food Chem Toxicol, 2009, 47(7): 1466-1472. DOI:10.1016/j.fct.2009.03.031
[75]
Wang YH, Yang XL, Wang L, et al. Effects of proanthocya nidins from grape seed on treatment of recurrent ulcerative colitis in rats[J]. Can J Physiol Pharmacol, 2010, 88(9): 888-898. DOI:10.1139/Y10-071
[76]
Li YH, Xiao HT, Hu DD, et al. Berberine ameliorates chronic relapsing dextran sulfate sodium-induced colitis in C57BL/6 mice by suppressing Th17 responses[J]. Pharmacol Res, 2016, 110: 227-239. DOI:10.1016/j.phrs.2016.02.010
[77]
Zhang LC, Wang Y, Tong LC, et al. Berberine alleviates dextran sodium sulfate-induced colitis by improving intestinal barrier function and reducing inflammation and oxidative stress[J]. Exp Ther Med, 2017, 13(6): 3374-3382. DOI:10.3892/etm.2017.4402
[78]
DiGuilio KM, Mercogliano CM, Born J, et al. Sieving characteristics of cytokine- and peroxide-induced epithelial barrier leak: inhibition by berberine[J]. World J Gastrointest Pathophysiol, 2016, 7(2): 223-234. DOI:10.4291/wjgp.v7.i2.223
[79]
Li YH, Zhang M, Xiao HT, et al. Addition of berberine to 5-aminosalicylic acid for treatment of dextran sulfate sodium-induced chronic colitis in C57BL/6 mice[J]. PLoS One, 2015, 10(12): e0144101. DOI:10.1371/journal.pone.0144101
[80]
Li YH, Zhang M, Fu HB, et al. Pre-clinical toxicity of a combination of berberine and 5-aminosalicylic acid in mice[J]. Food Chem Toxicol, 2016, 97: 150-158. DOI:10.1016/j.fct.2016.08.031
[81]
Zhong Z, Xiong Y, Yang L. Effect of matrine on the expression of cytokines and free radicals of intestinal mucosa in rats with TNBS-induced ulcerative colitis[J]. Chin Med Biotechnol, 2011, 6(4): 251-254.
[82]
Tang Q, Fan H, Shou Z, et al. Study on protective mechanism of kushenin injection on colonic mucosa of experimental colitis rats[J]. China J Chin Mater Med, 2012, 37(12): 1814-1817.
[83]
Fan H, Liao Y, Tang Q, et al. Role of beta2-adrenoceptor- beta-arrestin2-nuclear factor-kappaB signal transduction pathway and intervention effects of oxymatrine in ulcerative colitis[J]. Chin J Integr Med, 2012, 18(7): 514-521. DOI:10.1007/s11655-012-1146-3
[84]
Zhou PQ, Fan H, Hu H, et al. Role of DOR-beta-arrestin1-Bcl2 signal transduction pathway and intervention effects of oxymatrine in ulcerative colitis[J]. J Huazhong Univ Sci Technolog Med Sci, 2014, 34(6): 815-820. DOI:10.1007/s11596-014-1358-1
[85]
Chen Q, Duan X, Fan H, et al. Oxymatrine protects against DSS-induced colitis via inhibiting the PI3K/AKT signaling pathway[J]. Int Immunopharmacol, 2017, 53: 149-157. DOI:10.1016/j.intimp.2017.10.025
[86]
Liu Q, Zhang YJ, Yang CR, et al. Phenolic antioxidants from green tea produced from Camellia crassicolumna Var. multiplex[J]. J Agric Food Chem, 2009, 57(2): 586-590. DOI:10.1021/jf802974m
[87]
Pal R, Chaudhary MJ, Tiwari PC, et al. Protective role of theophylline and their interaction with nitric oxide (NO) in adjuvant-induced rheumatoid arthritis in rats[J]. Int Immuno pharmacol, 2015, 29(2): 854-862. DOI:10.1016/j.intimp.2015.08.031
[88]
Lal D, Manocha S, Ray A, et al. Comparative study of the efficacy and safety of theophylline and doxofylline in patients with bronchial asthma and chronic obstructive pulmonary disease[J]. J Basic Clin Physiol Pharmacol, 2015, 26(5): 443-451.
[89]
Urbanova A, Kertys M, Simekova M, et al. Bronchodilator and anti-inflammatory action of theophylline in a model of ovalbumin-induced allergic inflammation[J]. Adv Exp Med Biol, 2016, 935: 53-62. DOI:10.1007/978-3-319-44485-7
[90]
Barnes PJ. Theophylline: new perspectives for an old drug[J]. Am J Respir Crit Care Med, 2003, 167(6): 813-818. DOI:10.1164/rccm.200210-1142PP
[91]
Ghasemi-Pirbaluti M, Motaghi E, Najafi A, et al. The effect of theophylline on acetic acid induced ulcerative colitis in rats[J]. Biomed Pharmacother, 2017, 90: 153-159. DOI:10.1016/j.biopha.2017.03.038
[92]
Liu X, He H, Huang T, et al. Tanshinone IIA protects against dextran sulfate sodium- (DSS-) induced colitis in mice by modulation of neutrophil infiltration and activation[J]. Oxid Med Cell Longev, 2016, 2016: 7916763.
[93]
Zhang X, Wang Y, Ma Z, et al. Tanshinone IIA ameliorates dextran sulfate sodium-induced inflammatory bowel disease via the pregnane X receptor[J]. Drug Des Devel Ther, 2015, 9: 6343-6362.
[94]
Andujar I, Rios JL, Giner RM, et al. Beneficial effect of shikonin on experimental colitis induced by dextran sulfate sodium in BALB/c mice[J]. Evid Based Complement Alternat Med, 2012, 2012: 271606.
[95]
Andujar I, Marti-Rodrigo A, Giner RM, et al. Shikonin prevents early phase inflammation associated with azoxyme thane/dextran sulfate sodium-induced colon cancer and induces apoptosis in human colon cancer cells[J]. Planta Med, 2018, 84(9-10): 674-683.
[96]
Andujar I, Rios JL, Giner RM, et al. Shikonin promotes intestinal wound healing in vitro via induction of TGF-beta release in IEC-18 cells[J]. Eur J Pharm Sci, 2013, 49(4): 637-641. DOI:10.1016/j.ejps.2013.05.018
[97]
Wu WJ, Yan R, Li T, et al. Pharmacokinetic alterations of rhubarb anthraquinones in experimental colitis induced by dextran sulfate sodium in the rat[J]. J Ethnopharmacol, 2017, 198: 600-607. DOI:10.1016/j.jep.2017.01.049
[98]
Ge H, Tang H, Liang Y, et al. Rhein attenuates inflammation through inhibition of NF-kappaB and NALP3 inflammasome in vivo and in vitro[J]. Drug Des Devel Ther, 2017, 11: 1663-1671. DOI:10.2147/DDDT
[99]
Luo S, Deng X, Liu Q, et al. Emodin ameliorates ulcerative colitis by the flagellin-TLR5 dependent pathway in mice[J]. Int Immunopharmacol, 2018, 59: 269-275. DOI:10.1016/j.intimp.2018.04.010
[100]
Kim SJ, Kim MC, Lee BJ, et al. Anti-inflammatory activity of chrysophanol through the suppression of NF-kappaB/caspase-1 activation in vitro and in vivo[J]. Molecules, 2010, 15(9): 6436-6451. DOI:10.3390/molecules15096436
[101]
Qiao X, Ye M, Pan DL, et al. Differentiation of various traditional Chinese medicines derived from animal bile and gallstone: simultaneous determination of bile acids by liquid chromatography coupled with triple quadrupole mass spec trometry[J]. J Chromatogr A, 2011, 1218(1): 107-117. DOI:10.1016/j.chroma.2010.10.116
[102]
Arumugam S, Sreedhar R, Thandavarayan RA, et al. Telmi sartan treatment targets inflammatory cytokines to suppress the pathogenesis of acute colitis induced by dextran sulphate sodium[J]. Cytokine, 2015, 74(2): 305-312. DOI:10.1016/j.cyto.2015.03.017
[103]
Yang Y, He J, Suo Y, et al. Anti-inflammatory effect of taurocholate on TNBS-induced ulcerative colitis in mice[J]. Biomed Pharmacother, 2016, 81: 424-430. DOI:10.1016/j.biopha.2016.04.037
[104]
Cao SS, Zimmermann EM, Chuang BM, et al. The unfolded protein response and chemical chaperones reduce protein misfolding and colitis in mice[J]. Gastroenterology, 2013, 144(5): 989-1000. DOI:10.1053/j.gastro.2013.01.023
[105]
Berger E, Haller D. Structure-function analysis of the tertiary bile acid TUDCA for the resolution of endoplasmic reticulum stress in intestinal epithelial cells[J]. Biochem Biophys Res Commun, 2011, 409(4): 610-615. DOI:10.1016/j.bbrc.2011.05.043
[106]
Yang Y, He J, Suo Y, et al. Tauroursodeoxycholate improves 2, 4, 6-trinitrobenzenesulfonic acid-induced experimental acute ulcerative colitis in mice[J]. Int Immunopharmacol, 2016, 36: 271-276. DOI:10.1016/j.intimp.2016.04.037
[107]
Fan H, Liu XX, Zhang LJ, et al. Intervention effects of QRZSLXF, a Chinese medicinal herb recipe, on the DOR- beta-arrestin1-Bcl2 signal transduction pathway in a rat model of ulcerative colitis[J]. J Ethnopharmacol, 2014, 154(1): 88-97. DOI:10.1016/j.jep.2014.03.021
[108]
Sugimoto S, Naganuma M, Kanai T. Indole compounds may be promising medicines for ulcerative colitis[J]. J Gastroenterol, 2016, 51(9): 853-861. DOI:10.1007/s00535-016-1220-2
[109]
Gao W, Guo Y, Wang C, et al. Indirubin ameliorates dextran sulfate sodium-induced ulcerative colitis in mice through the inhibition of inflammation and the induction of Foxp3- expressing regulatory T cells[J]. Acta Histochem, 2016, 118(6): 606-614. DOI:10.1016/j.acthis.2016.06.004
[110]
Gao W, Zhang L, Wang X, et al. The combination of indirubin and isatin attenuates dextran sodium sulfate-induced ulcerative colitis in mice[J]. Biochem Cell Biol, 2018, 96(5): 636-645. DOI:10.1139/bcb-2018-0041
[111]
Socca EA, Luiz-Ferreira A, de Faria FM, et al. Inhibition of tumor necrosis factor-alpha and cyclooxigenase-2 by Isatin: a molecular mechanism of protection against TNBS-induced colitis in rats[J]. Chem Biol Interact, 2014, 209: 48-55. DOI:10.1016/j.cbi.2013.11.019
[112]
NoorShahida A, Wong TW, Choo CY. Hypoglycemic effect of quassinoids from Brucea javanica (L.) Merr (Simaroubaceae) seeds[J]. J Ethnopharmacol, 2009, 124(3): 586-591. DOI:10.1016/j.jep.2009.04.058
[113]
Zhang L, Feng X, Ma D, et al. Brusatol isolated from Brucea javanica (L.) Merr. induces apoptotic death of insect cell lines[J]. Pestic Biochem Physiol, 2013, 107(1): 18-24. DOI:10.1016/j.pestbp.2013.04.007
[114]
Turpaev K, Welsh N. Brusatol inhibits the response of cultured beta-cells to pro-inflammatory cytokines in vitro[J]. Biochem Biophys Res Commun, 2015, 460(3): 868-872. DOI:10.1016/j.bbrc.2015.03.124
[115]
Tang W, Xie J, Xu S, et al. Novel nitric oxide-releasing derivatives of brusatol as anti-inflammatory agents: design, synthesis, biological evaluation, and nitric oxide release studies[J]. J Med Chem, 2014, 57(18): 7600-7612. DOI:10.1021/jm5007534
[116]
Zhou J, Tan L, Xie J, et al. Characterization of brusatol self-microemulsifying drug delivery system and its therapeutic effect against dextran sodium sulfate-induced ulcerative colitis in mice[J]. Drug Deliv, 2017, 24(1): 1667-1679. DOI:10.1080/10717544.2017.1384521
[117]
Pandurangan AK, Ismail S, Saadatdoust Z, et al. Allicin alleviates dextran sodium sulfate- (DSS-) induced ulcerative colitis in BALB/c mice[J]. Oxid Med Cell Longev, 2015, 2015: 605208.
[118]
Yao J, Wang JY, Liu L, et al. Anti-oxidant effects of resveratrol on mice with DSS-induced ulcerative colitis[J]. Arch Med Res, 2010, 41(4): 288-294. DOI:10.1016/j.arcmed.2010.05.002
[119]
Trapp V, Parmakhtiar B, Papazian V, et al. Anti-angiogenic effects of resveratrol mediated by decreased VEGF and increased TSP1 expression in melanoma-endothelial cell co-culture[J]. Angiogenesis, 2010, 13(4): 305-315. DOI:10.1007/s10456-010-9187-8
[120]
Singh UP, Singh NP, Singh B, et al. Role of resveratrol- induced CD11b+ Gr-1+ myeloid derived suppressor cells (MDSCs) in the reduction of CXCR3+ T cells and amelioration of chronic colitis in IL-10-/- mice[J]. Brain Behav Immun, 2012, 26(1): 72-82. DOI:10.1016/j.bbi.2011.07.236
[121]
Abdallah DM, Ismael NR. Resveratrol abrogates adhesion molecules and protects against TNBS-induced ulcerative colitis in rats[J]. Can J Physiol Pharmacol, 2011, 89(11): 811-818.
[122]
Yao J, Wei C, Wang JY, et al. Effect of resveratrol on Treg/ Th17 signaling and ulcerative colitis treatment in mice[J]. World J Gastroenterol, 2015, 21(21): 6572-6581. DOI:10.3748/wjg.v21.i21.6572
[123]
Wang Z, Jin H, Xu R, et al. Triptolide downregulates Rac1 and the JAK/STAT3 pathway and inhibits colitis-related colon cancer progression[J]. Exp Mol Med, 2009, 41(10): 717-727. DOI:10.3858/emm.2009.41.10.078
[124]
Li CP, Li JH, He SY, et al. Effect of curcumin on p38MAPK expression in DSS-induced murine ulcerative colitis[J]. Genet Mol Res, 2015, 14(2): 3450-3458. DOI:10.4238/2015.April.15.8
[125]
Ghasemi-Pirbaluti M, Motaghi E, Najafi A, et al. The effect of theophylline on acetic acid induced ulcerative colitis in rats[J]. Biomed Pharmacother, 2017, 90: 153-159. DOI:10.1016/j.biopha.2017.03.038
[126]
Zhu SM, Hao WW, Tang ZP, et al. Effect of indirubin on cytokinesin colonic mucosa of DSS-induced colitisin mice[J]. Chin J Integr West Med Dig, 2011, 19(6): 370-372.
[127]
Yu FY, Huang SG, Zhang HY, et al. Effect of baicalin on signal transduction and activating transcription factor expression in ulcerative colitis patients[J]. Chin J Integr Tradit Chin West, 2015, 35(4): 419-424.
[128]
Shin HS, Satsu H, Bae MJ, et al. Catechol groups enable reactive oxygen species scavenging-mediated suppression of PKD-NFkappaB-IL-8 signaling pathway by chlorogenic and caffeic acids in human intestinal cells[J]. Nutrients, 2017, 9(2): 165. DOI:10.3390/nu9020165
[129]
Palócz O, Pászti-Gere E, Gálfi P, et al. Chlorogenic acid combined with Lactobacillus plantarum 2142 reduced LPS- induced intestinal inflammation and oxidative stress in IPEC-J2 Cells[J]. PLoS ONE, 2016, 11(11): e0166642. DOI:10.1371/journal.pone.0166642
[130]
Bai A, Lu N, Guo Y, et al. Tanshinone IIA ameliorates trinitro benzene sulfonic acid (TNBS)-induced murine colitis[J]. Dig Dis Sci, 2008, 53(2): 421-428. DOI:10.1007/s10620-007-9863-8