Research Advances in Protective Effects of Ursolic Acid and Oleanolic Acid Against Gastrointestinal Diseases

Shi, Yajing; Leng, Yufang; Liu, Disheng; Liu, Xin; Ren, Yixing; Zhang, Jianmin; Chen, Feng

doi:10.1142/s0192415x21500191

“…Also, UA concentration-dependently blocked clonality of SW620 cells (Figure D). In addition, the impact of UA on normal colonic cells was evaluated, showing that treatment with UA at 7.5, 15, and 30 μM for 24 h did not influence the growth of NCM460 cells (Figure E) nor the morphological feature (Figure F), consistent with some reports. ,, …”

Section: Resultssupporting

confidence: 90%

Ursolic Acid Suppresses Colorectal Cancer by Down-Regulation of Wnt/β-Catenin Signaling Pathway Activity

Zhao

¹

,

Tang

²

,

Qiu

³

et al. 2023

J. Agric. Food Chem.

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Overwhelming evidence points to an abnormally active Wnt/β-catenin signaling as a key player in colorectal cancer (CRC) pathogenesis. Ursolic acid (UA) is a pentacyclic triterpenoid that has been found in a broad variety of fruits, spices, and medicinal plants. UA has been shown to have potent bioactivity against a variety of cancers, including CRC, with the action mechanism obscure. Our study tried to learn more about the efficacy of UA on CRC and its functional mechanism amid the Wnt/β-catenin signaling cascade. We determined the efficacy of UA on CRC SW620 cells with respect to the proliferation, migration, clonality, apoptosis, cell cycle, and Wnt/β-catenin signaling cascade, with assessment of the effect of UA on normal colonic NCM460 cells. Also, the effects of UA on the tumor development, apoptosis, cell cycle, and Wnt/β-catenin signaling axis were evaluated after a subcutaneous SW620 xenograft tumor model was established in mice. In this work, we showed that UA drastically suppressed proliferation, migration, and clonality; induced apoptosis; and arrested the cell cycle at the G0/G1 phase of SW620 cells, without the influence on NCM460 cells, accompanied by weakened activity of the Wnt/β-catenin signaling pathway. Besides, UA markedly deterred the growth of the xenograft tumor, ameliorated pathological features, triggered apoptosis, and arrested the cell cycle in xenograft CRC tissue, by lessening the Wnt/β-catenin signaling cascade. Overall, UA may inhibit the malignant phenotype, induce apoptosis, and arrest the cell cycle of CRC, potentially by attenuating the Wnt/β-catenin signaling axis, providing insights into the mechanism for the potency of UA on CRC.

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“…The body's vitamin D level was significantly deficient, and the risk of diffuse muscle pain in the waist, pelvis, and lower limbs was significantly increased [21]. It had been confirmed in foreign studies [22][23][24] that the level of 25 hydroxyvitamin D showed a significant correlation with the dosage of opioids in tumor patients. The low serum magnesium level was also an important reason for the decrease in opioid sensitivity [25].…”

Section: Discussionmentioning

confidence: 90%

Changes of Intestinal Flora and Its Relationship with Nutritional Status for Patients with Cancer Pain

Zhang

¹

,

Zhu

²

,

Wang

³

et al. 2022

Computational and Mathematical Methods in Medicine

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Objective. To study the changes in the intestinal flora and its relationship with nutritional status for patients with cancer pain. Methods. A prospective research method was adopted. One hundred twenty cancer patients with cancer pain were selected as the research objects, who were treated in our hospital from June 2019 to June 2020, and 120 cancer patients without cancer pain were selected as the control group, who were treated in the same period. The differences of the intestinal flora and nutritional status of patients with different severity between the observation group and the control group were compared to analyze the changes of intestinal flora in patients with cancer pain and its correlation with nutritional status. Results. Hemoglobin (HB) ( t = 17.141 , p ≤ 0.001 ), albumin (ALB) ( t = 27.654 , p ≤ 0.001 ), prealbumin (PAB) ( t = 96.192 , p ≤ 0.001 ), and total protein (TP) ( t = 18.781 , p ≤ 0.001 ) in the observation group were significantly lower than those in the control group. There were statistically significant differences in HB ( f = 13.569 , p ≤ 0.001 ), ALB ( f = 22.229 , p ≤ 0.001 ), PAB ( f = 19.521 , p ≤ 0.001 ), and TP ( f = 21.451 , p ≤ 0.001 ) among patients with cancer pain of different severity. Through these two comparisons, their nutritional indicators showed a significant downward trend with the increase in the severity for cancer pain patients; the levels of Lactobacillus ( t = 2.124 , p = 0.035 ), Bifidobacterium ( t = 4.823 , p ≤ 0.001 ), Enterococcus ( t = 3.578 , p ≤ 0.001 ), and Eubacterium ( t = 2.394 , p = 0.017 ) in the observation group were significantly lower than those in the control group. There were statistically significant differences in the levels of Lactobacillus ( f = 20.643 , p ≤ 0.001 ), Bifidobacterium ( f = 19.129 , p ≤ 0.001 ), Enterococcus ( f = 17.408 , p ≤ 0.001 ), and Eubacterium ( f = 22.343 , p ≤ 0.001 ) among patients with cancer pain of different severity. After pairwise comparison, their beneficial intestinal bacteria were significantly lower than those in the control group with the increase in pain in cancer pain patients. Nitric oxide (NO) ( t = 8.418 , p ≤ 0.001 ), galectin-3 ( t = 14.043 , p ≤ 0.001 ), occludin (OCLN) ( t = 47.308 , p ≤ 0.001 ), galectin-1 ( t = 15.298 , p ≤ 0.001 ), zonula occludens protein 1 (ZO-1) ( t = 23.093 , p ≤ 0.001 ), and cingulin ( t = 340.198 , p ≤ 0.001 ) in the observation group were significantly lower than those in the control group. There were statistically significant differences in NO, galectin-3, OCLN, galectin-1, ZO-1, and cingulin for patients with cancer pain of different severity. By comparison, the NO, galectin-3, OCLN, galectin-1, ZO-1, and cingulin of the patients showed a significant downward trend with the aggravation of cancer pain symptoms. Through correlation analysis, the nutritional indicators of patients were positively correlated with intestinal microorganisms and intestinal barrier function. Conclusion. There was a significant correlation between the changes in intestinal flora and nutritional status for patients with cancer pain, which could be used as an important basis for improving the treatment of cancer pain.

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“…Author details 1 The First Clinical Medical College, Lanzhou University, No. 199, Donggang Road West, Chengguan District, Lanzhou, Gansu, China.…”

Section: Abbreviationsmentioning

confidence: 99%

“…IRI occurs in various organs and tissues, such as the liver, kidney, brain, heart, lung, retina, and intestine. Intestinal IRI is a major complication of severe trauma, burns, infection, shock, and cardiopulmonary insufficiency [1]. Intestinal IRI damages intestinal epithelial cells (IECs) and causes intestinal Open Access *Correspondence: wanzhh19@lzu.edu.cn; lengyf@lzu.edu.cn barrier dysfunction, allowing bacterial translocation [2].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cells against intestinal ischemia–reperfusion injury: a systematic review and meta-analysis of preclinical studies

Shi

¹

,

Zhang

²

,

Wan

³

et al. 2022

Self Cite

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Background Intestinal ischemia–reperfusion injury (IRI) causes localized and distant tissue lesions. Multiple organ failure is a common complication of severe intestinal IRI, leading to its high rates of morbidity and mortality. Thus far, this is poorly treated, and there is an urgent need for new more efficacious treatments. This study evaluated the beneficial effects of mesenchymal stem cells (MSCs) therapy on intestinal IRI using many animal experiments. Methods We conducted a comprehensive literature search from 4 databases: Pubmed, Embase, Cochrane library, and Web of science. Primary outcomes included the survival rate, Chiu’s score, intestinal levels of IL-6, TNF-α and MDA, as well as serum levels of DAO, D-Lactate, and TNF-α. Statistical analysis was carried out using Review Manager 5.3. Results It included Eighteen eligible researches in the final analysis. We demonstrated that survival rates in animals following intestinal IRI were higher with MSCs treatment compared to vehicle treatment. Besides, MSCs treatment attenuated intestinal injury caused by IRI, characterized by lower Chiu’s score (− 1.96, 95% CI − 2.72 to − 1.19, P < 0.00001), less intestinal inflammation (IL-6 (− 2.73, 95% CI − 4.19 to − 1.27, P = 0.0002), TNF-α (− 3.00, 95% CI − 4.74 to − 1.26, P = 0.0007)) and oxidative stress (MDA (− 2.18, 95% CI − 3.17 to − 1.19, P < 0.0001)), and decreased serum levels of DAO (− 1.39, 95% CI − 2.07 to − 0.72, P < 0.0001), D-Lactate (− 1.54, 95% CI − 2.18 to − 0.90, P < 0.00001) and TNF-α (− 2.42, 95% CI − 3.45 to − 1.40, P < 0.00001). The possible mechanism for MSCs to treat intestinal IRI might be through reducing inflammation, alleviating oxidative stress, as well as inhibiting the apoptosis and pyroptosis of the intestinal epithelial cells. Conclusions Taken together, these studies revealed that MSCs as a promising new treatment for intestinal IRI, and the mechanism of which may be associated with inflammation, oxidative stress, apoptosis, and pyroptosis. However, further studies will be required to confirm these findings.

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Research Advances in Protective Effects of Ursolic Acid and Oleanolic Acid Against Gastrointestinal Diseases

Cited by 14 publications

References 95 publications

Ursolic Acid Suppresses Colorectal Cancer by Down-Regulation of Wnt/β-Catenin Signaling Pathway Activity

Ursolic Acid Suppresses Colorectal Cancer by Down-Regulation of Wnt/β-Catenin Signaling Pathway Activity

Changes of Intestinal Flora and Its Relationship with Nutritional Status for Patients with Cancer Pain

Mesenchymal stem cells against intestinal ischemia–reperfusion injury: a systematic review and meta-analysis of preclinical studies

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