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Zhao X, He MJ, Zhao M, Li HR, Zhuang ZM, Xing Y, Zhang XL, Zhao P. Crude Polygalae Radix after boiling with licorice decoction alleviates intestinal mucosal barrier injury of rats by regulating TLR4/NF-κB signaling pathway. JOURNAL OF ETHNOPHARMACOLOGY 2025; 346:119661. [PMID: 40120702 DOI: 10.1016/j.jep.2025.119661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/23/2025] [Revised: 03/11/2025] [Accepted: 03/19/2025] [Indexed: 03/25/2025]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Polygala tenuifolia Willd. (pharmacologically termed Polygalae Radix, PR), a nootropic botanical in traditional Chinese medicine, demonstrates anxiolytic and cognitive-enhancing properties with two millennia of documented therapeutic applications. Long-term or large-dose use of crude Polygalae Radix (CPR) causes intestinal injury, which could be reduced by use of Glycyrrhiza uralensis Fisch. (licorice) decoction-boiled Polygalae Radix. However, the effects of boiling CPR with licorice decoction on reducing intestinal mucosal barrier injury have not been studied. AIM OF THE STUDY Our research mainly focused on the alleviating effects and underlying mechanism of CPR after boiling with licorice decoction on intestinal mucosal barrier injury in rats. METHODS AND MATERIALS SD rats were orally administered CPR and licorice decoction-boiled PR (LPR) extracts respectively for 15 consecutive days. Subsequently, levels of pro-inflammatory cytokines and immunoglobulins were measured, and histopathological changes in intestinal tissues were examined. The mRNA expression levels of pro-inflammatory cytokines were evaluated by qRT-PCR. The expression difference of TLR4/NF-κB signaling pathway key protein and tight junction (TJ) protein were evaluated using Western blotting and immunohistochemistry. RESULTS Processing PR with licorice decoction significantly ameliorated the downregulation of intestinal TJ proteins (occludin, claudin-1, and ZO-1) and elevated serum lipopolysaccharide levels induced by CPR. It alleviated the suppression of intestinal immunoglobulin A, serum immunoglobulin A and immunoglobulin G levels caused by CPR while mitigating intestinal mucosal injury and inflammatory responses. Additionally, processing PR with licorice decoction inhibited CPR-triggered upregulation of TLR4, NF-κB p65, p-NF-κB p65, and p-κBα proteins expression, while preventing IκBα downregulation in intestinal tissues. Furthermore, it significantly suppressed the upregulation of interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF-α) mRNA expression while concurrently inhibiting the secretion levels of these pro-inflammatory cytokines in small intestine. CONCLUSION Our experimental data suggest that licorice decoction boiling effectively prevents CPR-induced reductions in TJ proteins and immunoglobulins expression, alleviates intestinal mucosal barrier injuries, and mediates these effects through suppression of TLR4/NF-κB signaling pathway activation and subsequent production of IL-6, IL-8, and TNF-α.
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Affiliation(s)
- Xin Zhao
- Medical School, Shandong Xiehe University, Jinan, 250109, PR China; Department of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, PR China
| | - Meng-Jiao He
- Department of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, PR China
| | - Meng Zhao
- Medical School, Shandong Xiehe University, Jinan, 250109, PR China
| | - Hao-Ran Li
- Department of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, PR China
| | - Zi-Ming Zhuang
- Department of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, PR China
| | - Yue Xing
- Department of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, PR China
| | - Xue-Lan Zhang
- Medical School, Shandong Xiehe University, Jinan, 250109, PR China; Department of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, PR China.
| | - Pan Zhao
- Department of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, PR China.
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Qiu YT, Luo XY, Deng YF, Zheng X, Qiu JG, Zhang LS, Huang XQ, Zheng XB, Huang HY. Modified Pulsatilla decoction alleviates 5-fluorouracil-induced intestinal mucositis by modulating the TLR4/MyD88/NF-κB pathway and gut microbiota. World J Gastroenterol 2025; 31:98806. [PMID: 39991674 PMCID: PMC11755253 DOI: 10.3748/wjg.v31.i7.98806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Revised: 11/19/2024] [Accepted: 12/25/2024] [Indexed: 01/20/2025] Open
Abstract
BACKGROUND Modified Pulsatilla decoction (PD), a PD with licorice and ejiao, is a classic Traditional Chinese Medicine formula with significant efficacy in treating intestinal mucositis (IM) induced by tumor therapy. However, its specific molecular and biological mechanisms remain unclear. AIM To investigate the therapeutic effect and mechanism of modified PD in IM. METHODS This study used an IM mouse model established using 5-fluorouracil injections to investigate the effects of the modified PD (3, 6, and 12 g/kg) in IM. The primary chemical components of the modified PD were identified using liquid chromatography-mass spectrometry. Body weight loss, diarrhea scores, intestinal length, histopathological scores, and inflammatory cytokine levels were measured to evaluate the effects of the modified PD in IM. Effects on the TLR4/MyD88/NF-κB pathway were evaluated using western blot analysis. The intestinal microbiota was characterized using Illumina NovaSeq sequencing. RESULTS The results showed that modified PD significantly improved weight loss and diarrhea and shortened the intestines in IM mice. Mechanistically, modified PD suppressed the TLR4/MyD88/NF-κB pathway and downregulated the expression of reactive oxygen species, lipopolysaccharides, and pro-inflammatory cytokines (IL-1β, TNF-α, IFN-γ, IL-6, IL-8, and IL-17), while increasing the expression of the anti-inflammatory cytokine IL-10. Furthermore, modified PD protected the intestinal mucosal barrier by increasing the expression of tight junction proteins (occludin-1, claudin-1, and ZO-1) and mucin-2. Finally, 16S rDNA sequencing revealed that modified PD improved intestinal dysbiosis. CONCLUSION Our research offers new insights into the potential mechanism of modified PD in alleviating IM and provides experimental evidence supporting its pharmaceutical application in clinical IM treatment.
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Affiliation(s)
- Yi-Tong Qiu
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 525000, Guangdong Province, China
| | - Xin-Yi Luo
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 525000, Guangdong Province, China
- Druggability Research Team, Dongguan Institute of Guangzhou University of Chinese Medicine, Dongguan 523808, Guangdong Province, China
| | - Ya-Feng Deng
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 525000, Guangdong Province, China
| | - Xue Zheng
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 525000, Guangdong Province, China
- Druggability Research Team, Dongguan Institute of Guangzhou University of Chinese Medicine, Dongguan 523808, Guangdong Province, China
| | - Jian-Guo Qiu
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 525000, Guangdong Province, China
- Institute of Traditional Chinese Medicine, Dongguan Hospital of Traditional Chinese Medicine, Dongguan 523000, Guangdong Province, China
| | - Lin-Sheng Zhang
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 525000, Guangdong Province, China
| | - Xiao-Qi Huang
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 525000, Guangdong Province, China
- Druggability Research Team, Dongguan Institute of Guangzhou University of Chinese Medicine, Dongguan 523808, Guangdong Province, China
| | - Xue-Bao Zheng
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 525000, Guangdong Province, China
- Druggability Research Team, Dongguan Institute of Guangzhou University of Chinese Medicine, Dongguan 523808, Guangdong Province, China
| | - Hai-Yang Huang
- Institute of Traditional Chinese Medicine, Dongguan Hospital of Traditional Chinese Medicine, Dongguan 523000, Guangdong Province, China
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Yang Z, Man J, Liu H, Wu D, Gu Q, Zhang H, Liu Y, Shao D, Hao B, Wang S. Study on the In Vitro and In Vivo Antioxidant Activity and Potential Mechanism of Polygonum viviparum L. Antioxidants (Basel) 2025; 14:41. [PMID: 39857375 PMCID: PMC11762547 DOI: 10.3390/antiox14010041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2024] [Revised: 12/25/2024] [Accepted: 12/30/2024] [Indexed: 01/27/2025] Open
Abstract
Oxidative stress refers to the phenomenon in which the redox balance of the body is disrupted in response to stimuli, leading to an excessive accumulation of reactive oxygen species in vivo, which can lead to a variety of diseases. In contrast to artificial antioxidants, whose safety is controversial, natural antioxidants, which are widely available, pharmacologically active, and have little toxic side effects, are expected to be candidates for the treatment of oxidative stress-related diseases. Polygonum viviparum L. (PV) is a natural herbal medicine with antioxidant properties and is used as a traditional medicine in the Tibetan Plateau region. However, there are few studies that have focused on its antioxidant activity and mechanism of action in vitro and in vivo. Therefore, the present study firstly demonstrated that PV could exert good in vitro antioxidant effects by scavenging DPPH radicals and inhibiting the production of hydroxyl radicals through in vitro experiments. Secondly, PV was proven to attenuate the effects of oxidative stress on body weight gain and thymus development by establishing the Senna leaf-induced diarrhea model in rats, as well as to increase the activity of antioxidant enzymes and the content of non-enzymatic antioxidants in the intestinal tract and to enhance the rats' own antioxidant defenses, to mitigate the oxidative damage caused by diarrhea. Subsequently, the application of the cellular oxidative stress model evidenced that PV could play a protective role against cellular oxidative stress by inhibiting the overaccumulation of ROS in macrophages. Furthermore, the candidate antioxidant targets of PV were analyzed and screened using a comprehensive network pharmacology method, and their expression were then examined at the mRNA level and protein level. Our results suggest that PV may protect against H2O2-induced oxidative damage in macrophages by activating BCL2L1 and inhibiting ESR1, JAK2/STAT3, and MMP2. These findings open new perspectives on the antioxidant mechanism of PV and the prospect of developing it as a novel natural antioxidant drug.
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Affiliation(s)
- Zhen Yang
- Key Laboratory of New Animal Drug Project, Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agriculture Sciences, Lanzhou 730050, China; (Z.Y.); (J.M.); (H.L.); (D.W.); (H.Z.); (Y.L.); (D.S.)
| | - Jingyuan Man
- Key Laboratory of New Animal Drug Project, Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agriculture Sciences, Lanzhou 730050, China; (Z.Y.); (J.M.); (H.L.); (D.W.); (H.Z.); (Y.L.); (D.S.)
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China
| | - Haoyu Liu
- Key Laboratory of New Animal Drug Project, Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agriculture Sciences, Lanzhou 730050, China; (Z.Y.); (J.M.); (H.L.); (D.W.); (H.Z.); (Y.L.); (D.S.)
| | - Di Wu
- Key Laboratory of New Animal Drug Project, Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agriculture Sciences, Lanzhou 730050, China; (Z.Y.); (J.M.); (H.L.); (D.W.); (H.Z.); (Y.L.); (D.S.)
| | - Qiangwen Gu
- Animal Husbandry and Veterinary Workstation, Heli Town, Gaotai County, Zhangye 734000, China;
| | - Hongjuan Zhang
- Key Laboratory of New Animal Drug Project, Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agriculture Sciences, Lanzhou 730050, China; (Z.Y.); (J.M.); (H.L.); (D.W.); (H.Z.); (Y.L.); (D.S.)
| | - Yu Liu
- Key Laboratory of New Animal Drug Project, Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agriculture Sciences, Lanzhou 730050, China; (Z.Y.); (J.M.); (H.L.); (D.W.); (H.Z.); (Y.L.); (D.S.)
| | - Dan Shao
- Key Laboratory of New Animal Drug Project, Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agriculture Sciences, Lanzhou 730050, China; (Z.Y.); (J.M.); (H.L.); (D.W.); (H.Z.); (Y.L.); (D.S.)
| | - Baocheng Hao
- Key Laboratory of New Animal Drug Project, Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agriculture Sciences, Lanzhou 730050, China; (Z.Y.); (J.M.); (H.L.); (D.W.); (H.Z.); (Y.L.); (D.S.)
| | - Shengyi Wang
- Key Laboratory of New Animal Drug Project, Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agriculture Sciences, Lanzhou 730050, China; (Z.Y.); (J.M.); (H.L.); (D.W.); (H.Z.); (Y.L.); (D.S.)
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Haghighat ZA, Safekordi A, Ardjmand M, Akbarzadeh A. Exploring the Antitumor Efficacy of PEGylated Liposomes Loaded with Licorice Extract for Cancer Therapy. Curr Cancer Drug Targets 2025; 25:357-369. [PMID: 38685810 DOI: 10.2174/0115680096292153240416115744] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2023] [Revised: 03/04/2024] [Accepted: 03/08/2024] [Indexed: 05/02/2024]
Abstract
BACKGROUND Glycyrrhizic Acid (GA), a compound derived from licorice, has exhibited promising anticancer properties against several cancer types, including Prostate Cancer (PCa) and Gastric Cancer (GCa). OBJECTIVE This study has introduced a novel approach involving the encapsulation of GA and Licorice extract (Lic) into Polyethylene Glycol Liposomes (PEG-Lip) and assessed their efficacy against AGS (human gastric cancer) and PC-3 (human prostate cancer) cells, marking the first report of this endeavor. METHODS We synthesized GA-loaded PEG-Lip (GA PEG-Lip) and Lic-loaded PEG-Lip (Lic PEG-Lip) through the reverse-phase evaporation method. RESULTS Characterization of these liposomal formulations revealed their size, drug encapsulation, and loading efficiencies to be 110 ± 2.05 nm, 117 ± 1.24 nm; 61 ± 0.81%, 34 ± 0.47%; and 8 ± 0.41% and 4.6 ± 0.21%, respectively. Importantly, the process has retained the chemical structure of both GA and Lic. Furthermore, GA and Lic have been released from the PEG-Lip formulations in a controlled manner. In our experiments, both nanoformulations exhibited enhanced cytotoxic effects against AGS and PC-3 cells. Notably, GA PEG-Lip outperformed Lic PEG-Lip, reducing the viability of PC-3 and AGS cells by 12.5% and 15.9%, respectively. CONCLUSION These results have been corroborated by apoptosis assays, which have demonstrated GA PEG-Lip and Lic PEG-Lip to induce stronger apoptotic effects compared to free GA and Lic on both PC-3 and AGS cells. This study has underscored the potential of encapsulating GA and Lic in PEG-Lip as a promising strategy to augment their anticancer efficacy against prostate and gastric cancers.
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Affiliation(s)
- Zeinab Azizi Haghighat
- Department of Chemical Engineering, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Aliakbar Safekordi
- Chemical Engineering Department, Sharif University of Technology, Tehran, Iran
| | - Mehdi Ardjmand
- Department of Chemical Engineering, South Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Azim Akbarzadeh
- Department of Pilot Nanobiotechnology, Pasteur Institute of Iran, Tehran, Iran
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Huang L, Luo S, Tong S, Lv Z, Wu J. The development of nanocarriers for natural products. WILEY INTERDISCIPLINARY REVIEWS. NANOMEDICINE AND NANOBIOTECHNOLOGY 2024; 16:e1967. [PMID: 38757428 DOI: 10.1002/wnan.1967] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 04/01/2024] [Accepted: 04/24/2024] [Indexed: 05/18/2024]
Abstract
Natural bioactive compounds from plants exhibit substantial pharmacological potency and therapeutic value. However, the development of most plant bioactive compounds is hindered by low solubility and instability. Conventional pharmaceutical forms, such as tablets and capsules, only partially overcome these limitations, restricting their efficacy. With the recent development of nanotechnology, nanocarriers can enhance the bioavailability, stability, and precise intracellular transport of plant bioactive compounds. Researchers are increasingly integrating nanocarrier-based drug delivery systems (NDDS) into the development of natural plant compounds with significant success. Moreover, natural products benefit from nanotechnological enhancement and contribute to the innovation and optimization of nanocarriers via self-assembly, grafting modifications, and biomimetic designs. This review aims to elucidate the collaborative and reciprocal advancement achieved by integrating nanocarriers with botanical products, such as bioactive compounds, polysaccharides, proteins, and extracellular vesicles. This review underscores the salient challenges in nanomedicine, encompassing long-term safety evaluations of nanomedicine formulations, precise targeting mechanisms, biodistribution complexities, and hurdles in clinical translation. Further, this study provides new perspectives to leverage nanotechnology in promoting the development and optimization of natural plant products for nanomedical applications and guiding the progression of NDDS toward enhanced efficiency, precision, and safety. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.
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Affiliation(s)
- Liying Huang
- The Key Laboratory of Microcosmic Syndrome Differentiation, Yunnan University of Chinese Medicine, Kunming, Yunnan, China
- Yunnan Key Laboratory of Integrated Traditional Chinese and Western Medicine for Chronic Disease in Prevention and Treatment, Yunnan University of Chinese Medicine, Kunming, Yunnan, China
| | - Shicui Luo
- The Key Laboratory of Microcosmic Syndrome Differentiation, Yunnan University of Chinese Medicine, Kunming, Yunnan, China
- Yunnan Key Laboratory of Integrated Traditional Chinese and Western Medicine for Chronic Disease in Prevention and Treatment, Yunnan University of Chinese Medicine, Kunming, Yunnan, China
| | - Sen Tong
- The Key Laboratory of Microcosmic Syndrome Differentiation, Yunnan University of Chinese Medicine, Kunming, Yunnan, China
- Yunnan Key Laboratory of Integrated Traditional Chinese and Western Medicine for Chronic Disease in Prevention and Treatment, Yunnan University of Chinese Medicine, Kunming, Yunnan, China
| | - Zhuo Lv
- The Key Laboratory of Microcosmic Syndrome Differentiation, Yunnan University of Chinese Medicine, Kunming, Yunnan, China
- Yunnan Key Laboratory of Integrated Traditional Chinese and Western Medicine for Chronic Disease in Prevention and Treatment, Yunnan University of Chinese Medicine, Kunming, Yunnan, China
| | - Junzi Wu
- The Key Laboratory of Microcosmic Syndrome Differentiation, Yunnan University of Chinese Medicine, Kunming, Yunnan, China
- Yunnan Key Laboratory of Integrated Traditional Chinese and Western Medicine for Chronic Disease in Prevention and Treatment, Yunnan University of Chinese Medicine, Kunming, Yunnan, China
- Yunnan Clinical Medical Research Center for Geriatric Diseases, Yunnan First People's Hospital, Kunming, Yunnan, China
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Garbati P, Picco C, Magrassi R, Signorello P, Cacopardo L, Dalla Serra M, Faticato MG, De Luca M, Balestra F, Scavo MP, Viti F. Targeting the Gut: A Systematic Review of Specific Drug Nanocarriers. Pharmaceutics 2024; 16:431. [PMID: 38543324 PMCID: PMC10974668 DOI: 10.3390/pharmaceutics16030431] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Revised: 03/16/2024] [Accepted: 03/19/2024] [Indexed: 01/05/2025] Open
Abstract
The intestine is essential for the modulation of nutrient absorption and the removal of waste. Gut pathologies, such as cancer, inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS), and celiac disease, which extensively impact gut functions, are thus critical for human health. Targeted drug delivery is essential to tackle these diseases, improve therapy efficacy, and minimize side effects. Recent strategies have taken advantage of both active and passive nanocarriers, which are designed to protect the drug until it reaches the correct delivery site and to modulate drug release via the use of different physical-chemical strategies. In this systematic review, we present a literature overview of the different nanocarriers used for drug delivery in a set of chronic intestinal pathologies, highlighting the rationale behind the controlled release of intestinal therapies. The overall aim is to provide the reader with useful information on the current approaches for gut targeting in novel therapeutic strategies.
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Affiliation(s)
- Patrizia Garbati
- Institute of Biophysics, National Research Council, Via De Marini 16, 16149 Genova, Italy; (P.G.); (C.P.); (R.M.); (M.D.S.)
| | - Cristiana Picco
- Institute of Biophysics, National Research Council, Via De Marini 16, 16149 Genova, Italy; (P.G.); (C.P.); (R.M.); (M.D.S.)
| | - Raffaella Magrassi
- Institute of Biophysics, National Research Council, Via De Marini 16, 16149 Genova, Italy; (P.G.); (C.P.); (R.M.); (M.D.S.)
| | - Paolo Signorello
- Department of Information Engineering, University of Pisa, Via Girolamo Caruso 16, 56122 Pisa, Italy; (P.S.); (L.C.)
- Research Center ‘E. Piaggio’, University of Pisa, Largo Lucio Lazzarino 1, 56122 Pisa, Italy
- Centro 3R: Interuniversity Center for the Promotion of the 3Rs Principles in Teaching and Research, 56122 Pisa, Italy
| | - Ludovica Cacopardo
- Department of Information Engineering, University of Pisa, Via Girolamo Caruso 16, 56122 Pisa, Italy; (P.S.); (L.C.)
- Research Center ‘E. Piaggio’, University of Pisa, Largo Lucio Lazzarino 1, 56122 Pisa, Italy
- Centro 3R: Interuniversity Center for the Promotion of the 3Rs Principles in Teaching and Research, 56122 Pisa, Italy
| | - Mauro Dalla Serra
- Institute of Biophysics, National Research Council, Via De Marini 16, 16149 Genova, Italy; (P.G.); (C.P.); (R.M.); (M.D.S.)
| | - Maria Grazia Faticato
- Pediatric Surgery, IRCCS Istituto Giannina Gaslini, Via Gerolamo Gaslini 5, 16147 Genova, Italy;
| | - Maria De Luca
- National Institute of Gastroenterology, IRCCS de Bellis, Via Turi 27, 70013 Castellana Grotte, Bari, Italy; (M.D.L.); (F.B.); (M.P.S.)
| | - Francesco Balestra
- National Institute of Gastroenterology, IRCCS de Bellis, Via Turi 27, 70013 Castellana Grotte, Bari, Italy; (M.D.L.); (F.B.); (M.P.S.)
| | - Maria Principia Scavo
- National Institute of Gastroenterology, IRCCS de Bellis, Via Turi 27, 70013 Castellana Grotte, Bari, Italy; (M.D.L.); (F.B.); (M.P.S.)
| | - Federica Viti
- Institute of Biophysics, National Research Council, Via De Marini 16, 16149 Genova, Italy; (P.G.); (C.P.); (R.M.); (M.D.S.)
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Chauhan S, Harwansh RK. Recent advances in nanocarrier systems for ulcerative colitis: A new era of targeted therapy and biomarker integration. J Drug Deliv Sci Technol 2024; 93:105466. [DOI: 10.1016/j.jddst.2024.105466] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Fu ZL, Yang Y, Ma L, Malmuthuge N, Guan LL, Bu DP. Dynamics of oxidative stress and immune responses in neonatal calves during diarrhea. J Dairy Sci 2024; 107:1286-1298. [PMID: 37776998 DOI: 10.3168/jds.2023-23630] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Accepted: 09/08/2023] [Indexed: 10/02/2023]
Abstract
Oxidative stress is the imbalanced redox status between oxidant production and their scavengers leading to intestinal physiological dysfunction. However, the role of systemic and local oxidative status during neonatal calf diarrhea is not known. This study assessed systemic (serum) and local (fecal) oxidative status when calves either naturally developed diarrhea or naturally recovered. Healthy calves were enrolled in the study at d 18 of age, and their health status was monitored from the enrollment. Based on their enteric health status on d 21 and 28, calves were grouped as continuous diarrhea from d 21 to 28 (n = 14), diarrhea at d 21 but recovered at d 28 (DH group, n = 19), healthy at d 21 but developed diarrhea at d 28 (HD group, n = 15), and healthy throughout the study (HH group, n = 16). Serum and fecal samples were collected at d 21 and 28 from all calves in the morning 2 h after feeding. Dynamics of oxidative stress indicators including reactive oxygen species (ROS), malondialdehyde (MDA), H2O2, 8-hydroxy-2'-deoxyguanosine (8-OHDG), glutathione peroxidase, superoxide dismutase, catalase (CAT), and total antioxidant capacity and inflammatory indicators TNF-α, IL-1β, IL-4, IL-6, IL-10, and IFN-γ were evaluated using serum samples. In addition, fecal oxidative stress indicators ROS and MDA were measured. Serum ROS, MDA, 8-OHDG, as well as fecal ROS and MDA, were higher, whereas serum CAT and H2O2 were lower in diarrheic calves than those of healthy calves. Serum ROS, MDA, and 8OHDG and fecal ROS and MDA increased in the HD group from d 21 to 28 as they developed diarrhea. In contrast, all these oxidative stress markers decreased in the DH group from d 21 to 28 as they recovered. However, serum H2O2 had an opposite changing trend, which became lower in the HD group and higher in the DH group at d 28. In conclusion, both systemic and local oxidative stress markers and cytokine profiles altered as calves moved from being healthy to having diarrhea or vice versa. Serum ROS, MDA, and 8-OHDG can be used to develop biomarkers to screen calves prone to enteric infections during the preweaning period.
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Affiliation(s)
- Z L Fu
- State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, China; Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, T6G 2P5, Canada
| | - Y Yang
- State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, China; School of Agriculture and Food Science, University College Dublin, Belfield, Dublin 4, A94 R704, Ireland
| | - L Ma
- State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
| | - N Malmuthuge
- Lethbridge Research and Development Centre, Agriculture and Agri-Food Canada, Lethbridge, AB, T1J 4B1, Canada
| | - L L Guan
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, T6G 2P5, Canada; Faculty of Land and Food Systems, the University of British Columbia, Vancouver, BC, V6T 1Z4 Canada.
| | - D P Bu
- State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.
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Fu W, Xu L, Chen Z, Kan L, Ma Y, Qian H, Wang W. Recent advances on emerging nanomaterials for diagnosis and treatment of inflammatory bowel disease. J Control Release 2023; 363:149-179. [PMID: 37741461 DOI: 10.1016/j.jconrel.2023.09.033] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2023] [Revised: 09/16/2023] [Accepted: 09/18/2023] [Indexed: 09/25/2023]
Abstract
Inflammatory bowel disease (IBD) is a chronic idiopathic inflammatory disorder that affects the entire gastrointestinal tract and is associated with an increased risk of colorectal cancer. Mainstream clinical testing methods are time-consuming, painful for patients, and insufficiently sensitive to detect early symptoms. Currently, there is no definitive cure for IBD, and frequent doses of medications with potentially severe side effects may affect patient response. In recent years, nanomaterials have demonstrated considerable potential for IBD management due to their diverse structures, composition, and physical and chemical properties. In this review, we provide an overview of the advances in nanomaterial-based diagnosis and treatment of IBD in recent five years. Multi-functional bio-nano platforms, including contrast agents, near-infrared (NIR) fluorescent probes, and bioactive substance detection agents have been developed for IBD diagnosis. Based on a series of pathogenic characteristics of IBD, the therapeutic strategies of antioxidant, anti-inflammatory, and intestinal microbiome regulation of IBD based on nanomaterials are systematically introduced. Finally, the future challenges and prospects in this field are presented to facilitate the development of diagnosis and treatment of IBD.
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Affiliation(s)
- Wanyue Fu
- School of Biomedical Engineering, Anhui Provincial Institute of Translational Medicine, Anhui Medical University, Hefei 230032, PR China; Anhui Engineering Research Center for Medical Micro-Nano Devices, Hefei, Anhui 230012, China
| | - Lingling Xu
- School of Biomedical Engineering, Anhui Provincial Institute of Translational Medicine, Anhui Medical University, Hefei 230032, PR China; Anhui Engineering Research Center for Medical Micro-Nano Devices, Hefei, Anhui 230012, China
| | - Zetong Chen
- School of Stomatology, Anhui Medical University, Hefei, Anhui 230032, PR China
| | - Lingling Kan
- School of Biomedical Engineering, Anhui Provincial Institute of Translational Medicine, Anhui Medical University, Hefei 230032, PR China; Anhui Engineering Research Center for Medical Micro-Nano Devices, Hefei, Anhui 230012, China
| | - Yan Ma
- School of Biomedical Engineering, Anhui Provincial Institute of Translational Medicine, Anhui Medical University, Hefei 230032, PR China; Anhui Engineering Research Center for Medical Micro-Nano Devices, Hefei, Anhui 230012, China.
| | - Haisheng Qian
- School of Biomedical Engineering, Anhui Provincial Institute of Translational Medicine, Anhui Medical University, Hefei 230032, PR China; Anhui Engineering Research Center for Medical Micro-Nano Devices, Hefei, Anhui 230012, China.
| | - Wanni Wang
- School of Biomedical Engineering, Anhui Provincial Institute of Translational Medicine, Anhui Medical University, Hefei 230032, PR China; Anhui Engineering Research Center for Medical Micro-Nano Devices, Hefei, Anhui 230012, China.
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10
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Madani F, Kazemi S, Shirafkan F, Lotfi M, Hosseini SM, Moghadamnia AA. Thymoquinone protects against 5-Fluorouracil-induced mucositis by NF-κβ and HIF-1 mechanisms in mice. J Biochem Mol Toxicol 2023; 37:e23405. [PMID: 37338137 DOI: 10.1002/jbt.23405] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 03/07/2023] [Accepted: 06/08/2023] [Indexed: 06/21/2023]
Abstract
Mucositis is among the most common side effects of 5-Fluorouracil (5-FU) and other cancer therapeutic drugs. Thymoquinone (TQ), a bioactive constituent extracted from Nigella sativa, has antioxidant and anti-inflammatory properties and can modify acute gastrointestinal injury. To investigate the effects of TQ on mucositis induced by 5-FU, studied animals were divided into four groups: control, 5-FU unit dose (300 mg/kg) to cause oral and intestinal mucositis (OM and IM), TQ (2.5 mg/kg) and TQ (2.5 mg/kg) plus 5-FU. Due to The molecular mechanisms, it was confirmed that the expression of NF-κβ and HIF-1 increases in OM. The serum levels of malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD), as well as pathological parameters, were assessed. Based on our results, the nuclear factor-kappa β gene expression in the tongue was downregulated significantly in the 5-FU + TQ compared to the 5-FU. TQ treatment can diminish MDA, and a reduction in oxidative stress was shown. TQ could also reduce the severity of tissue destruction and damaging effects induced by 5-FU on the tongue and intestine. We also observed lower villus length and width in the intestine of the 5-FU group compared to the control group. According to our research's pathological, biochemical, and molecular results, treatment with TQ as an anti-inflammatory and antioxidant compound may be the potential to improve and treat 5-FU-induced OM and IM, and TQ could be used against cancer treatment drugs and exhibit fewer adverse effects.
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Affiliation(s)
- Fatemeh Madani
- Student Research Committee, Health Research Center, Babol University of Medical Sciences, Babol, Iran
| | - Sohrab Kazemi
- Cellular and Molecular Biology Research Center, Health Research Center, Babol University of Medical, Babol University of Medical Sciences, Babol, Iran
| | - Fatemeh Shirafkan
- Department of Pharmacology and Toxicology, Babol University of Medical Sciences, Babol, Iran
| | - Mandana Lotfi
- Department of Pharmacology and Toxicology, Babol University of Medical Sciences, Babol, Iran
| | - Seyed M Hosseini
- Department of Veterinary Parasitology, Babol-Branch, Islamic Azad University, Babol, Iran
| | - Ali A Moghadamnia
- Department of Pharmacology and Toxicology, Babol University of Medical Sciences, Babol, Iran
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11
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Zeeshan M, Ain QU, Weigmann B, Story D, Smith BR, Ali H. Dual pH and microbial-sensitive galactosylated polymeric nanocargoes for multi-level targeting to combat ulcerative colitis. Asian J Pharm Sci 2023; 18:100831. [PMID: 37588990 PMCID: PMC10425895 DOI: 10.1016/j.ajps.2023.100831] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 05/15/2023] [Accepted: 06/06/2023] [Indexed: 08/18/2023] Open
Abstract
Ulcerative colitis (UC) is a type of inflammatory bowel disease characterized by inflammation, ulcers and irritation of the mucosal lining. Oral drug delivery in UC encounters challenges because of multifaceted barriers. Dexamethasone-loaded galactosylated-PLGA/Eudragit S100/pullulan nanocargoes (Dexa-GP/ES/Pu NCs) have been developed with a dual stimuli-sensitive coating responsive to both colonic pH and microbiota, and an underneath galactosylated-PLGA core (GP). The galactose ligand of the GP preferentially binds to the macrophage galactose type-lectin-C (MGL-2) surface receptor. Therefore, both stimuli and ligand-mediated targeting facilitate nanocargoes to deliver Dexa specifically to the colon with enhanced macrophage uptake. Modified emulsion method coupled with a solvent evaporation coating technique was employed to prepare Dexa-GP/ES/Pu NCs. The nanocargoes were tested using in vitro, ex vivo techniques and dextran sodium sulfate (DSS) induced UC model. Prepared nanocargoes had desired physicochemical properties, drug release, cell uptake and cellular viability. Investigations using a DSS-colitis model showed high localization and mitigation of colitis with downregulation of NF-ĸB and COX-2, and restoration of clinical, histopathological, biochemical indices, antioxidant balance, microbial alterations, FTIR spectra, and epithelial junctions' integrity. Thus, Dexa-GP/ES/Pu NCs found to be biocompatible nanocargoes capable of delivering drugs to the inflamed colon with unique targeting properties for prolonged duration.
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Affiliation(s)
- Mahira Zeeshan
- Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan
- Department of Medicine 1, University of Erlangen-Nuremberg, Kussmaul Campus for Medical Research, Erlangen 91052, Germany
- Faculty of Pharmacy, Capital University of Science and Technology, Islamabad 44000, Pakistan
| | - Qurat Ul Ain
- Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan
| | - Benno Weigmann
- Department of Medicine 1, University of Erlangen-Nuremberg, Kussmaul Campus for Medical Research, Erlangen 91052, Germany
| | - Darren Story
- Biomedical Engineering Department, Michigan State University, East Lansing 48824, USA
- Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing 48824, USA
| | - Bryan R. Smith
- Biomedical Engineering Department, Michigan State University, East Lansing 48824, USA
- Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing 48824, USA
| | - Hussain Ali
- Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan
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12
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Zhang Y, Xi Y, Yang C, Gong W, Wang C, Wu L, Wang D. Short-Chain Fatty Acids Attenuate 5-Fluorouracil-Induced THP-1 Cell Inflammation through Inhibiting NF-κB/NLRP3 Signaling via Glycerolphospholipid and Sphingolipid Metabolism. Molecules 2023; 28:molecules28020494. [PMID: 36677551 PMCID: PMC9864921 DOI: 10.3390/molecules28020494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 12/26/2022] [Accepted: 12/30/2022] [Indexed: 01/06/2023] Open
Abstract
5-Fluorouracil (5-FU) is a common anti-tumor drug, but there is no effective treatment for its side effect, intestinal mucositis. The inflammatory reaction of macrophages in intestinal mucosa induced by 5-FU is an important cause of intestinal mucositis. In this study, we investigated the anti-inflammatory effects of the three important short-chain fatty acids (SCFAs), including sodium acetate (NaAc), sodium propionate (NaPc), and sodium butyrate (NaB), on human mononuclear macrophage-derived THP-1 cells induced by 5-FU. The expressions of intracellular ROS, pro-inflammatory/anti-inflammatory cytokines, as well as the nuclear factor-κB/NLR family and pyrin domain-containing protein 3 (NF-κB/NLRP3) signaling pathway proteins were determined. Furthermore, the cell metabolites were analyzed by untargeted metabolomics techniques. Our results revealed that the three SCFAs inhibited pro-inflammatory factor expressions, including IL-1β and IL-6, when treated with 5-FU (p < 0.05). The ROS expression and NF-κB activity of 5-FU-treated THP-1 cells were inhibited by the three SCFAs pre-incubated (p < 0.05). Moreover, NLRP3 knockdown abolished 5-FU-induced IL-1β expression (p < 0.05). Further experiments showed that the three SCFAs affected 20 kinds of metabolites that belong to amino acid and phosphatidylcholine metabolism in THP-1 cells. These significantly altered metabolites were involved in amino acid metabolism and glycerolphospholipid and sphingolipid metabolism. It is the first time that three important SCFAs (NaAc, NaPc, and NaB) were identified as inhibiting 5-FU-induced macrophage inflammation through inhibiting ROS/NF-κB/NLRP3 signaling pathways and regulating glycerolphospholipid and sphingolipid metabolism.
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Affiliation(s)
- Yanyan Zhang
- Testing Center, Yangzhou University, Yangzhou 225009, China
| | - Yue Xi
- Medical Laboratory Department, Huai’an Second People’s Hospital, Huai’an 223022, China
| | - Changshui Yang
- School of Medicine, Yangzhou University, Yangzhou 225009, China
| | - Weijuan Gong
- School of Medicine, Yangzhou University, Yangzhou 225009, China
- Correspondence: (W.G.); (D.W.)
| | - Chengyin Wang
- Testing Center, Yangzhou University, Yangzhou 225009, China
| | - Liang Wu
- Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, China
| | - Dongxu Wang
- School of Grain Science and Technology, Jiangsu University of Science and Technology, Zhenjiang 212100, China
- Correspondence: (W.G.); (D.W.)
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13
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Huang J, Hwang AYM, Jia Y, Kim B, Iskandar M, Mohammed AI, Cirillo N. Experimental Chemotherapy-Induced Mucositis: A Scoping Review Guiding the Design of Suitable Preclinical Models. Int J Mol Sci 2022; 23:15434. [PMID: 36499758 PMCID: PMC9737148 DOI: 10.3390/ijms232315434] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 12/01/2022] [Accepted: 12/04/2022] [Indexed: 12/12/2022] Open
Abstract
Mucositis is a common and most debilitating complication associated with the cytotoxicity of chemotherapy. The condition affects the entire alimentary canal from the mouth to the anus and has a significant clinical and economic impact. Although oral and intestinal mucositis can occur concurrently in the same individual, these conditions are often studied independently using organ-specific models that do not mimic human disease. Hence, the purpose of this scoping review was to provide a comprehensive yet systematic overview of the animal models that are utilised in the study of chemotherapy-induced mucositis. A search of PubMed/MEDLINE and Scopus databases was conducted to identify all relevant studies. Multiple phases of filtering were conducted, including deduplication, title/abstract screening, full-text screening, and data extraction. Studies were reported according to the updated Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. An inter-rater reliability test was conducted using Cohen's Kappa score. After title, abstract, and full-text screening, 251 articles met the inclusion criteria. Seven articles investigated both chemotherapy-induced intestinal and oral mucositis, 198 articles investigated chemotherapy-induced intestinal mucositis, and 46 studies investigated chemotherapy-induced oral mucositis. Among a total of 205 articles on chemotherapy-induced intestinal mucositis, 103 utilised 5-fluorouracil, 34 irinotecan, 16 platinum-based drugs, 33 methotrexate, and 32 other chemotherapeutic agents. Thirteen articles reported the use of a combination of 5-fluorouracil, irinotecan, platinum-based drugs, or methotrexate to induce intestinal mucositis. Among a total of 53 articles on chemotherapy-induced oral mucositis, 50 utilised 5-fluorouracil, 2 irinotecan, 2 methotrexate, 1 topotecan and 1 with other chemotherapeutic drugs. Three articles used a combination of these drugs to induce oral mucositis. Various animal models such as mice, rats, hamsters, piglets, rabbits, and zebrafish were used. The chemotherapeutic agents were introduced at various dosages via three routes of administration. Animals were mainly mice and rats. Unlike intestinal mucositis, most oral mucositis models combined mechanical or chemical irritation with chemotherapy. In conclusion, this extensive assessment of the literature revealed that there was a large variation among studies that reproduce oral and intestinal mucositis in animals. To assist with the design of a suitable preclinical model of chemotherapy-induced alimentary tract mucositis, animal types, routes of administration, dosages, and types of drugs were reported in this study. Further research is required to define an optimal protocol that improves the translatability of findings to humans.
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Affiliation(s)
| | | | | | | | | | | | - Nicola Cirillo
- Melbourne Dental School, The University of Melbourne, Carlton, VIC 3053, Australia
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14
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Xia J, Chen J, Vashisth MK, Ge Y, Dai Q, He S, Shi YL, Wang XB. Metformin ameliorates 5-fluorouracil-induced intestinal injury by inhibiting cellular senescence, inflammation, and oxidative stress. Int Immunopharmacol 2022; 113:109342. [DOI: 10.1016/j.intimp.2022.109342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Revised: 09/30/2022] [Accepted: 10/09/2022] [Indexed: 11/05/2022]
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15
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Cetin Aluc C, Gok B, Kecel-Gunduz S, Budama-Kilinc Y. Glycyrrhizic acid Poly(D,L-lactide-co-glycolide) nanoparticles: anti-aging cosmeceutical formulation for topical applications. PeerJ 2022. [DOI: 10.7717/peerj.14139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Glycyrrhizic acid (GA) is one of the components of licorice roots (Glycyrrhiza glabra L.). GA is a triterpenoid saponin can be used as a medicinal plant with its antiallergic, antiviral, anti-inflammatory, anti-ulcer, hepatoprotective, anticancer, anti-oxidation activities and several other therapeutic properties. The aim of this study is to develop an anti-aging formulation for topical application containing GA. In this context, GA-loaded Poly (D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) were prepared using the double emulsion method, and were characterized by various spectroscopic methods. The efficacy of GA-PLGA NPs was evaluated with in vitro and in silico methods. The encapsulation efficiency and loading capacity were calculated. The in vitro release study was conducted, and the GA release profile was determined. The genotoxic activity of GA and GA-PLGA NPs was evaluated by the Ames test using TA98 and TA100 mutant strains of Salmonella typhimurium. The cytotoxic potential of GA-PLGA NPs was evaluated on the HaCaT cell line using the MTT assay. According to the genotoxicity and cytotoxicity results, it was found that the GA-PLGA NP formulation did not exhibit genotoxic and cytotoxic effects. Moreover, the efficacy of GA in preventing UVB-induced photo-aging in HaCaT cells and the clarification of the molecular mechanism of GA binding to MMPs were revealed by molecular docking analysis. In addition, through molecular dynamics (MD) analysis, the binding interaction of GA with MMPs in a dynamic system, and protein-ligand stability were predicted as a result of 50 ns MD simulation studies considering various analysis parameters. Finally, it was evaluated that GA-PLGA nanoformulation might be used as an alternative anti-aging skin care product candidate via topical application.
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Affiliation(s)
- Cigdem Cetin Aluc
- Graduate School of Natural and Applied Science, Yildiz Technical University, Istanbul, Türkiye
- Abdi Ibrahim Pharmaceuticals, Abdi Ibrahim Production Facilities, Istanbul, Türkiye
| | - Bahar Gok
- Graduate School of Natural and Applied Science, Yildiz Technical University, Istanbul, Türkiye
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16
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Li C, Xie J, Wang J, Cao Y, Pu M, Gong Q, Lu Q. Therapeutic effects and mechanisms of plant-derived natural compounds against intestinal mucositis. Front Pharmacol 2022; 13:969550. [PMID: 36210837 PMCID: PMC9533105 DOI: 10.3389/fphar.2022.969550] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Accepted: 09/05/2022] [Indexed: 01/26/2023] Open
Abstract
Intestinal mucositis is a clinically related adverse reaction of antitumor treatment. Majority of patients receiving high-dose chemical therapy, radiotherapy, and bone-marrow transplant suffer from intestinal mucositis. Clinical manifestations of intestinal mucositis mainly include pain, body-weight reduction, inflammatory symptom, diarrhea, hemoproctia, and infection, which all affect regular nutritional input and enteric function. Intestinal mucositis often influences adherence to antitumor treatment because it frequently restricts the sufferer’s capacity to tolerate treatment, thus resulting in schedule delay, interruption, or premature suspension. In certain circumstances, partial and general secondary infections are found, increasing the expenditures on medical care and hospitalization. Current methods of treating intestinal mucositis are provided, which do not always counteract this disorder. Against this background, novel therapeutical measures are extremely required to prevent and treat intestinal mucositis. Plant-derived natural compounds have lately become potential candidates against enteric injury ascribed to the capacity to facilitate mucosal healing and anti-inflammatory effects. These roles are associated with the improvement of intestinal mucosal barrier, suppression of inflammatory response and oxidant stress, and modulation of gut microflora and immune system. The present article aims at systematically discussing the recent progress of plant-derived natural compounds as promising treatments for intestinal mucositis.
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Affiliation(s)
- Cailan Li
- Department of Pharmacology, Zunyi Medical University, Zhuhai Campus, Zhuhai, China
- Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, China
- Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi Medical University, Zunyi, China
| | - Jianhui Xie
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jiahao Wang
- Department of Pharmacology, Zunyi Medical University, Zhuhai Campus, Zhuhai, China
- Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, China
- Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi Medical University, Zunyi, China
| | - Ying Cao
- Department of Pharmaceutical Sciences, Zunyi Medical University, Zhuhai Campus, Zhuhai, China
| | - Min Pu
- Department of Pharmaceutical Sciences, Zunyi Medical University, Zhuhai Campus, Zhuhai, China
| | - Qihai Gong
- Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, China
- Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi Medical University, Zunyi, China
- *Correspondence: Qihai Gong, ; Qiang Lu,
| | - Qiang Lu
- Department of Pharmaceutical Sciences, Zunyi Medical University, Zhuhai Campus, Zhuhai, China
- *Correspondence: Qihai Gong, ; Qiang Lu,
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17
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Ibrahim IAA, Hussein AI, Muter MS, Mohammed AT, Al-Medhtiy MH, Shareef SH, Aziz PY, Agha NFS, Abdulla MA. Effect of nano silver on gastroprotective activity against ethanol-induced stomach ulcer in rats. Biomed Pharmacother 2022; 154:113550. [PMID: 35994814 DOI: 10.1016/j.biopha.2022.113550] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 08/03/2022] [Accepted: 08/11/2022] [Indexed: 11/02/2022] Open
Abstract
Silver nanoparticles (Ag NPs) have unique properties and display an important role in bioactivities such as antimicrobial, antiviral, antifungal, and anticancer. Stable Ag NPs were prepared by reaction of silver nitrate solution with extract of Melissa and characterized by UV-Vis spectroscopy, AFM, SEM, XRD, and Zeta potential. The resulted Ag NPs have a size range between 20 and 35 nm. The current study aims to evaluate the gastroprotective effect of Ag NPs against ethanol-induced gastric ulcers in rats. Thirty rats were randomly divided into five groups. The experimental groups were fed 175 and 350 ppm/p.o of Ag NPs orally. Ag NPs improved the adversative influence of ethanol-induced stomach damage as confirmed by declining ulcer index and raised the percentage of ulcer prevention. Significantly reduced ethanol-induced gastric lesions were evidenced by increased mucus secretion and pH of stomach content, decreased ulcer area, nonappearance of edema, and leucocyte penetration of the subcutaneous layer. In gastric homogenate, Ag NPs displayed a substantial upsurge in superoxide dismutase (SOD), catalase (CAT) activities, and significantly reduced malondialdehyde (MDA) levels., Ag NPs increased the intensity of periodic acid Schiff stained (PAS) and produced over-regulation of HSP-70 and down-regulation of Bax proteins. Ag NPs confirmed gastro-protection which might be attributed to its antioxidant effect, increased mucus secretion, increased SOD, and CAT, reduced MDA level, over-regulation of HSP-70 protein, and down-regulation of Bax protein.
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Affiliation(s)
- Ibrahim Abdel Aziz Ibrahim
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Abbas I Hussein
- Department of Dentistry, College of Medicine, University of Anbar, Al Anbar, Iraq
| | - Mahmoud S Muter
- Department of Dentistry, College of Medicine, University of Anbar, Al Anbar, Iraq
| | - Abdulalah T Mohammed
- Department of Medical Laboratory Techniques, Al-Huda University College, Al Anbar, Iraq
| | - Morteta H Al-Medhtiy
- Department of Anatomy and Histology, Faculty of Veterinary Medicine, University of Kufa, Iraq
| | - Suhayla Hamad Shareef
- Department of Biology, College of Education, Salahaddin University-Erbil, Erbil, Kurdistan Region, Iraq.
| | - Peshawa Yunis Aziz
- Department of Medical Laboratory Science, Technical College of Applied Science, Sulaimani Polytechnic University, Sulaymaniyah, Kurdistan Region, Iraq
| | - Nabaz Fisal Shakir Agha
- Department of Anesthesia, Medical Technical Institute, Erbil Polytechnic University, Erbil, Kurdistan Region, Iraq
| | - Mahmood Ameen Abdulla
- Department of Medical Microbiology, College of Science, Cihan University-Erbil, Erbil, Kurdistan Region, Iraq
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Li DF, Yang MF, Xu HM, Zhu MZ, Zhang Y, Tian CM, Nie YQ, Wang JY, Liang YJ, Yao J, Wang LS. Nanoparticles for oral delivery: targeted therapy for inflammatory bowel disease. J Mater Chem B 2022; 10:5853-5872. [PMID: 35876136 DOI: 10.1039/d2tb01190e] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
As a group of chronic and idiopathic gastrointestinal (GI) disorders, inflammatory bowel disease (IBD) is characterized by recurrent intestinal mucosal inflammation. Oral administration is critical for the treatment of IBD. Unfortunately, it is difficult to target the bowel located in the GI tract due to multiple physical barriers. The unique physicochemical properties of nanoparticle-based drug delivery systems (DDSs) and their enhanced permeability and retention effects in the inflamed bowel, render nanomedicines to be used to implement precise drug delivery at diseased sites in IBD therapy. In this review, we described the pathophysiological features of IBD, and designed strategies to exploit these features for intestinal targeting. In addition, we introduced the types of currently developed nano-targeted carriers, including synthetic nanoparticle-based and emerging naturally derived nanoparticles (e.g., extracellular vesicles and plant-derived nanoparticles). Moreover, recent developments in targeted oral nanoparticles for IBD therapy were also highlighted. Finally, we presented challenges associated with nanotechnology and potential directions for future IBD treatment.
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Affiliation(s)
- De-Feng Li
- Department of Gastroenterology, Shenzhen People's Hospital (the Second Clinical Medical College, Jinan University, the First Affiliated Hospital, Southern University of Science and Technology), No. 1017, Dongmen North Road, Luohu District, Shenzhen 518020, Guangdong, China.
| | - Mei-Feng Yang
- Department of Hematology, Yantian District People's Hospital, Shenzhen 518020, Guangdong, China
| | - Hao-Ming Xu
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510030, China
| | - Min-Zheng Zhu
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510030, China
| | - Yuan Zhang
- Department of Medical Administration, Huizhou Institute of Occupational Diseases Control and Prevention, Huizhou 516000, Guangdong, China
| | - Cheng-Mei Tian
- Department of Emergency, Shenzhen People's Hospital (the Second Clinical Medical College, Jinan University, the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China
| | - Yu-Qiang Nie
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510030, China
| | - Jian-Yao Wang
- Department of General Surgery, Shenzhen Children's Hospital, No. 7019, Yitian Road, Futian District, Shenzhen 518026, Guangdong, China.
| | - Yu-Jie Liang
- Shenzhen Kangning Hospital, No. 1080, Cuizu Road, Luohu District, Shenzhen 518020, Guangdong, China.
| | - Jun Yao
- Department of Gastroenterology, Shenzhen People's Hospital (the Second Clinical Medical College, Jinan University, the First Affiliated Hospital, Southern University of Science and Technology), No. 1017, Dongmen North Road, Luohu District, Shenzhen 518020, Guangdong, China.
| | - Li-Sheng Wang
- Department of Gastroenterology, Shenzhen People's Hospital (the Second Clinical Medical College, Jinan University, the First Affiliated Hospital, Southern University of Science and Technology), No. 1017, Dongmen North Road, Luohu District, Shenzhen 518020, Guangdong, China.
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19
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Wang KL, Yu YC, Chen HY, Chiang YF, Ali M, Shieh TM, Hsia SM. Recent Advances in Glycyrrhiza glabra (Licorice)-Containing Herbs Alleviating Radiotherapy- and Chemotherapy-Induced Adverse Reactions in Cancer Treatment. Metabolites 2022; 12:metabo12060535. [PMID: 35736467 PMCID: PMC9227067 DOI: 10.3390/metabo12060535] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 05/31/2022] [Accepted: 06/02/2022] [Indexed: 11/16/2022] Open
Abstract
Cancers represent a significant cause of morbidity and mortality worldwide. They also impose a large economic burden on patients, their families, and health insurance systems. Notably, cancers and the adverse reactions to their therapeutic options, chemotherapy and radiotherapy, dramatically affect the quality of life of afflicted patients. Therefore, developing approaches to manage chemotherapy- and radiotherapy-induced adverse reactions gained greater attention in recent years. Glycyrrhiza glabra (licorice), a perennial plant that is one of the most frequently used herbs in traditional Chinese medicine, has been heavily investigated in relation to cancer therapy. Licorice/licorice-related regimes, used in combination with chemotherapy, may improve the adverse effects of chemotherapy. However, there is little awareness of licorice-containing herbs alleviating reactions to radiotherapy and chemotherapy, or to other induced adverse reactions in cancer treatment. We aimed to provide a descriptive review, and to emphasize the possibility that licorice-related medicines could be used as an adjuvant regimen with chemotherapy to improve quality of life (QoL) and to reduce side effects, thus, improving compliance with chemotherapy. The experimental method involved searching different databases, including PubMed, the Cochrane Library, and Wang Fang database, as of May 2022, to identify any relevant studies. Despite a lack of high-quality and large-scale randomized controlled trials, we still discovered the potential benefits of licorice-containing herbs from published clinical studies. These studies find that licorice-containing herbs, and their active ingredients, reduce the adverse reactions caused by chemotherapy and radiotherapy, and improve the QoL of patients. This comprehensive review will serve as a cornerstone to encourage more scientists to evaluate and develop effective Traditional Chinese medicine prescriptions to improve the side effects of chemotherapy and radiation therapy.
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Affiliation(s)
- Kai-Lee Wang
- Department of Nursing, Ching Kuo Institute of Management and Health, Keelung 20301, Taiwan;
- School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan; (H.-Y.C.); (Y.-F.C.)
| | - Ying-Chun Yu
- Sex Hormonal Research Center, Department of Obstetrics and Gynecology, China Medical University Hospital, Taichung 40403, Taiwan;
- Graduate Institute of Biomedical Sciences, Center for Tumor Biology, School of Medicine, China Medical University, Taichung 40403, Taiwan
| | - Hsin-Yuan Chen
- School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan; (H.-Y.C.); (Y.-F.C.)
| | - Yi-Fen Chiang
- School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan; (H.-Y.C.); (Y.-F.C.)
| | - Mohamed Ali
- Clinical Pharmacy Department, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt;
| | - Tzong-Ming Shieh
- School of Dentistry, China Medical University, Taichung 40403, Taiwan;
| | - Shih-Min Hsia
- School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan; (H.-Y.C.); (Y.-F.C.)
- Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan
- School of Food and Safety, Taipei Medical University, Taipei 11031, Taiwan
- Nutrition Research Center, Taipei Medical University Hospital, Taipei 11031, Taiwan
- Correspondence:
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Synergistic Effects of Licorice Root and Walnut Leaf Extracts on Gastrointestinal Candidiasis, Inflammation and Gut Microbiota Composition in Mice. Microbiol Spectr 2022; 10:e0235521. [PMID: 35262409 PMCID: PMC9045305 DOI: 10.1128/spectrum.02355-21] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Candida albicans is an opportunistic pathogen that causes gastrointestinal (GI) candidiasis closely associated with intestinal inflammation and dysbiosis. Drug resistance, side effects of available antifungal agents, and the high recurrence of candidiasis highlight the need for new treatments. We investigated the effects of hydroethanolic extracts of licorice root (LRE) and walnut leaf (WLE) on GI colonization by C. albicans, colon inflammation, and gut microbiota composition in C57BL/6 female mice. Oral administration of LRE and WLE alone or in combination once daily for 12 days before C. albicans infection and then for 5 days after infection significantly reduced the level of C. albicans in the feces of gastrointestinal infected mice as well as colonization of the GI tract, both extracts showing robust antifungal activity. Although total bacterial content was unaffected by the extracts (individually or combined), the abundance of protective bacteria, such as Bifidobacterium spp. and Faecalibacterium prausnitzii, increased with the combination, in contrast to that of certain pathobiont bacteria, which decreased. Interestingly, the combination induced a more robust decrease in the expression of proinflammatory genes than either extract alone. The anti-inflammatory activity of the combination was further supported by the reciprocal increase in the expression of anti-inflammatory cytokines and the significant decrease in enzymes involved in the synthesis of proinflammatory eicosanoids and oxidative stress. These findings suggest that LRE and WLE have synergistic effects and that the LRE/WLE combination could be a good candidate for limiting GI candidiasis and associated inflammation, likely by modulating the composition of the gut microbiota. IMPORTANCE The adverse effects and emergence of resistance of currently available antifungals and the high recurrence of candidiasis prompt the need for alternative and complementary strategies. We demonstrated that oral administration of hydroethanolic extracts of licorice root (LRE) and walnut leaf (WLE) separately or in combination significantly reduced the colonization of the gastrointestinal (GI) tract by C. albicans, highlighting a robust antifungal activity of these plant extracts. Interestingly, our data indicate a correlation between LRE and WLE consumption, in particular the combination, and a shift within the gut microbiome toward a protective profile, a decrease in colonic inflammation and prooxidant enzymes, suggesting a synergistic effect. This study highlights the significant prebiotic potential of the LRE/WLE combination and suggests that the health benefits are due, at least in part, to their ability to modulate the gut microbiota, reduce inflammation and oxidative stress, and protect against opportunistic infection.
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