Anti-inflammatory/anti-apoptotic impact of betulin attenuates experimentally induced ulcerative colitis: An insight into TLR4/NF-kB/caspase signalling modulation

El‐Sherbiny, Mohamed; Eisa, Nada H.; El-Magd, Nada F. Abo; Elsherbiny, Nehal M.; Said, Eman; Khodir, Ahmed E.

doi:10.1016/j.etap.2021.103750

Cited by 15 publications

(15 citation statements)

References 49 publications

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“…P2 arginine [ 54 – 56 ], P5 trigonelline [ 57 ], P59 ginsenoside Rg1 [ 58 ], P69 isoliquiritigenin [ 59 ], P82 ginsenoside Rd [ 60 , 61 ], and P84 glycyrrhizic acid [ 62 – 64 ] would alleviate the symptom of UC based on anti-inflammation or antioxidant activities. Besides, P15 isoleucine [ 65 ], P17 uridine [ 12 , 66 ], P21 guanosine [ 67 ], P23 gallic acid [ 68 , 69 ], P43 rutin [ 70 , 71 ], P51 vanillic acid [ 72 ], P70 quercetin [ 73 , 74 ], P72 ginsenoside Rb1 [ 75 ], and P81 betulin [ 76 ]were confirmed to treat UC through NF- κ B pathway. P8 stachyose increased beneficial microbiota and bacterial diversity to alleviate colitis mice [ 77 ].…”

Section: Resultsmentioning

confidence: 99%

Chemical Characterization and Metabolic Profiling of the Compounds in the Chinese Herbal Formula Li Chang Decoction by UPLC-QTOF/MS

Lin

Guo

Hong

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. Li Chang decoction (LCD), a Chinese medicine formula, is commonly used to treat ulcerative colitis (UC) in clinics. Purpose. This study aimed to identify the major components in LCD and its prototype and metabolic components in rat biological samples. Methods. The chemical constituents in LCD were identified by establishing a reliable ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF/MS) method. Afterwards, the rats were orally administered with LCD, and the biological samples (plasma, urine, and feces) were collected for further analyzing the effective compounds in the treatment of UC. Result. A total of 104 compounds were discriminated in LCD, including 26 flavonoids, 20 organic acids, 20 saponins, 8 amino acids, 5 oligosaccharides, 5 tannins, 3 lignans, 2 alkaloids, and 15 others (nucleosides, glycosides, esters, etc.). About 50 prototype and 94 metabolic components of LCD were identified in biological samples. In total, 29 prototype components and 22 metabolic types were detected in plasma. About 27 prototypes and 96 metabolites were discriminated in urine, and 34 prototypes and 18 metabolites were identified in feces. Conclusion. The flavonoids, organic acids, and saponins were the major compounds of LCD, and this study promotes the further pharmacokinetic and pharmacological evaluation of LCD.

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Section: Resultsmentioning

confidence: 99%

Chemical Characterization and Metabolic Profiling of the Compounds in the Chinese Herbal Formula Li Chang Decoction by UPLC-QTOF/MS

Lin

Guo

Hong

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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“…El-Sherbiny et al [ 44 ] evaluated the effects of betulin, a bioactive compound richly found in the birch tree bark, in an acetic acid-induced Sprague Dawley model of colitis. They observed decreased lactate dehydrogenase (LDH) activity, TLR4 content, CD68 cell infiltration, IL-6, TNF-α and IL-1β content, NF-kB expression, and caspase-3 and caspase-8 activation.…”

Section: Discussionmentioning

confidence: 99%

Phytochemicals and Regulation of NF-kB in Inflammatory Bowel Diseases: An Overview of In Vitro and In Vivo Effects

et al. 2023

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Inflammatory bowel diseases (IBD) are chronic relapsing idiopathic inflammatory conditions affecting the gastrointestinal tract. They are mainly represented by two forms, ulcerative colitis (UC) and Crohn’s disease (CD). IBD can be associated with the activation of nuclear factors, such as nuclear factor-kB (NF-kB), leading to increased transcription of pro-inflammatory mediators that result in diarrhea, abdominal pain, bleeding, and many extra-intestinal manifestations. Phytochemicals can interfere with many inflammation targets, including NF-κB pathways. Thus, this review aimed to investigate the effects of different phytochemicals in the NF-KB pathways in vitro and in vivo models of IBD. Fifty-six phytochemicals were included in this study, such as curcumin, resveratrol, kaempferol, sesamol, pinocembrin, astragalin, oxyberberine, berberine hydrochloride, botulin, taxifolin, naringin, thymol, isobavachalcone, lancemaside A, aesculin, tetrandrine, Ginsenoside Rk3, mangiferin, diosgenin, theanine, tryptanthrin, lycopene, gyngerol, alantolactone, mangostin, ophiopogonin D, fisetin, sinomenine, piperine, oxymatrine, euphol, artesunate, galangin, and nobiletin. The main observed effects related to NF-kB pathways were reductions in tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, interferon-gamma (IFN-γ), and cyclooxygenase-2 (COX-2), and augmented occludin, claudin-1, zonula occludens-1, and IL-10 expression levels. Moreover, phytochemicals can improve weight loss, stool consistency, and rectal bleeding in IBD. Therefore, phytochemicals can constitute a powerful treatment option for IBD in humans.

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“…Betulin reduced inflammation via modulation of TLR4/NF-κB signaling pathway in experimental ulcerative colitis (UC) and kidney injury in septic rats [ 134 , 186 ]. Moreover, betulin showed immune modulating activities by inhibiting activated T cells in autoimmune hepatitis in mice [ 133 ].…”

Section: Natural Products In Animal Research For Autoimmune Diseasesmentioning

confidence: 99%

“…In addition, inflammatory cell infiltration, mucosal necrosis, and hemorrhage were reduced in betulin-treated UC rats. Moreover, the production of inflammatory cytokines TNF-α, IL-1β, and IL-6 was reduced in the colon of these rats [ 134 ]. Betulin (10 or 20 mg/kg) also decreased serum levels of TNF-α, IFN-γ, and IL-6 in AIH in mice, ameliorated liver injury, and inhibited natural killer T cells, as well as conventional T-cell activation.…”

Section: Natural Products In Animal Research For Autoimmune Diseasesmentioning

confidence: 99%

“…Interesting is the low dosage of 1 mg/kg needed for this effect; for comparison, 5 mg/kg DEX was necessary in this study [ 138 ] to obtain a similar effect. It should be noted that the other natural products used in the above-mentioned inflammatory animal models were applied in concentrations of 8–20 mg/kg for betulin [ 133 , 134 ], 50–75 mg/kg for DHA [ 122 , 123 ], or 20–160 mg/kg for HES [ 40 , 41 ].…”

Section: Natural Products In Animal Research For Autoimmune Diseasesmentioning

confidence: 99%

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Drug Candidates for Autoimmune Diseases

et al. 2022

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Most of the immunosuppressive drugs used in the clinic to prevent organ rejection or to treat autoimmune disorders were originally isolated from fungi or bacteria. Therefore, in addition to plants, these are valuable sources for identification of new potent drugs. Many side effects of established drugs limit their usage and make the identification of new immunosuppressants necessary. In this review, we present a comprehensive overview of natural products with potent anti-inflammatory activities that have been tested successfully in different models of chronic inflammatory autoimmune diseases. Some of these candidates already have passed first clinical trials. The anti-inflammatory potency of these natural products was often comparable to those of established drugs, and they could be used at least in addition to standard therapy to reduce their dose to minimize unwanted side effects. A frequent mode of action is the inhibition of classical inflammatory signaling pathways, such as NF-κB, in combination with downregulation of oxidative stress. A drawback for the therapeutic use of those natural products is their moderate bioavailability, which can be optimized by chemical modifications and, in addition, further safety studies are necessary. Altogether, very interesting candidate compounds exist which have the potential to serve as starting points for the development of new immunosuppressive drugs.

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Anti-inflammatory/anti-apoptotic impact of betulin attenuates experimentally induced ulcerative colitis: An insight into TLR4/NF-kB/caspase signalling modulation

Cited by 15 publications

References 49 publications

Chemical Characterization and Metabolic Profiling of the Compounds in the Chinese Herbal Formula Li Chang Decoction by UPLC-QTOF/MS

Chemical Characterization and Metabolic Profiling of the Compounds in the Chinese Herbal Formula Li Chang Decoction by UPLC-QTOF/MS

Phytochemicals and Regulation of NF-kB in Inflammatory Bowel Diseases: An Overview of In Vitro and In Vivo Effects

Drug Candidates for Autoimmune Diseases

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