|
1
|
He L, Gao Y, Ju C, Wang X, Zhang Y, Yu Q, Zhang L, Chen C, Duan Y. Collagen peptides alleviate hyperglycemia in mice by modulating insulin resistance, glucose metabolism and gut microbiota. Int J Biol Macromol 2025; 301:140498. [PMID: 39889980 DOI: 10.1016/j.ijbiomac.2025.140498] [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: 07/05/2024] [Revised: 01/02/2025] [Accepted: 01/28/2025] [Indexed: 02/03/2025]
Abstract
In vitro studies have demonstrated that collagen peptides (CP) inhibit the activity of dipeptidyl peptidase-IV. However, the relationship between the AMPK-mediated insulin signaling pathway and gut microbiota modulation in Type 2 Diabetes Mellitus (T2DM) remains underexplored. Current research investigated the hypoglycemic mechanisms associated with CP intervention in a T2DM mouse model induced by a high-fat diet and streptozotocin (STZ). The findings revealed that administering CP (400 mg/kg/day) for 4 weeks significantly eased symptoms such as polydipsia, polyphagia, weight loss, and organ damage in diabetic mice. Following CP intervention, diabetic mice exhibited notable reductions in blood glucose and lipid levels, as well as decreased abundance ratios of Firmicutes and Bacteroides, whereas increased short-chain fatty acid concentration in the gut microbiota and the serum GLP-1 level, accompanied by a substantial decrease in the serum insulin resistance index. Furthermore, in the livers of mice post-CP intervention, there was an upregulation of IRS1, the increase of p-AMPK/AMPK and p-GSK3β/GSK3β (P < 0.01), coupled with downregulation of PEPCK and FoxO1 expression (P < 0.05), thereby facilitating glycogen synthesis, regulation of insulin sensitivity, and inhibition of glucose production. These results provide foundational insights into the potential of collagen peptide intervention in managing and preventing T2DM.
Collapse
Affiliation(s)
- Long He
- College of Food Science and Engineering, Gansu Agricultural University, Lanzhou 730070, China.
| | - Yongfang Gao
- College of Life Science and Engineering, Lanzhou University of Technology, Lanzhou 730050, China
| | - Chaoqiang Ju
- College of Life Science and Engineering, Lanzhou University of Technology, Lanzhou 730050, China
| | - Xinyue Wang
- College of Food Science and Engineering, Gansu Agricultural University, Lanzhou 730070, China
| | - Yueyue Zhang
- College of Food Science and Engineering, Gansu Agricultural University, Lanzhou 730070, China
| | - Qunli Yu
- College of Food Science and Engineering, Gansu Agricultural University, Lanzhou 730070, China
| | - Li Zhang
- College of Food Science and Engineering, Gansu Agricultural University, Lanzhou 730070, China
| | - Cheng Chen
- College of Food Science and Engineering, Gansu Agricultural University, Lanzhou 730070, China
| | - Yufeng Duan
- College of Food Science and Engineering, Gansu Agricultural University, Lanzhou 730070, China
| |
Collapse
|
|
2
|
Staśkiewicz-Bartecka W, Masłoń K, Kołodziejczyk A, Białek-Dratwa A, Kiciak A, Jaruga-Sękowska S, Dobkowska-Szefer D, Grajek M, Kowalski O, Kardas M. Nutritional knowledge, insulin resistance, and the risk of orthorexia nervosa: a comparative cross-sectional study among polish women. Front Public Health 2025; 13:1562866. [PMID: 40177090 PMCID: PMC11962019 DOI: 10.3389/fpubh.2025.1562866] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2025] [Accepted: 03/07/2025] [Indexed: 04/05/2025] Open
Abstract
Background The global rise in insulin resistance has led to an increased emphasis on dietary modifications as a primary strategy for its management. While such interventions are essential for improving metabolic health, they can also contribute to heightened nutritional knowledge. However, this increased focus on diet may inadvertently lead to the development of disordered eating patterns, including orthorexia nervosa. This study aimed to determine the level of nutritional knowledge regarding proper eating habits among women with insulin resistance and to assess the relationship between this knowledge and the risk of developing orthorexia nervosa. Methods The study was using the Computer-Assisted Web Interview method, involving 133 female participants from a primary care clinic in Katowice, Poland. Of these, 101 women had a medically confirmed diagnosis of insulin resistance, and 32 were healthy controls. Data were collected using an online survey, which included a demographic section, a 15-item questionnaire to assess nutritional knowledge, and the ORTO-15 tool to evaluate orthorexia nervosa risk. Results Women with insulin resistance had significantly higher Body Mass Index values and demonstrated greater nutritional knowledge than their healthy counterparts. However, 56.44% of women with insulin resistance were at risk of orthorexia nervosa, compared to 15.63% of the control group. Increased dietary knowledge in women with insulin resistance was also associated with a higher risk of developing orthorexic behavior. Conclusion The findings indicate that while women with insulin resistance benefit from improved nutritional knowledge in managing their condition, this knowledge may simultaneously increase their risk of developing orthorexia nervosa. Balancing the promotion of healthy eating habits with strategies that prevent the emergence of distorted eating behaviors is crucial. Future interventions should emphasize flexibility, psychological support, and individualized guidance to ensure both metabolic and mental well-being.
Collapse
Affiliation(s)
- Wiktoria Staśkiewicz-Bartecka
- Department of Food Technology and Quality Evaluation, Department of Dietetics, Faculty of Public Health in Bytom, Medical University of Silesia in Katowice, Zabrze, Poland
| | - Karolina Masłoń
- Department of Food Technology and Quality Evaluation, Department of Dietetics, Faculty of Public Health in Bytom, Medical University of Silesia in Katowice, Zabrze, Poland
| | - Aleksandra Kołodziejczyk
- Department of Food Technology and Quality Evaluation, Department of Dietetics, Faculty of Public Health in Bytom, Medical University of Silesia in Katowice, Zabrze, Poland
| | - Agnieszka Białek-Dratwa
- Department of Human Nutrition, Department of Dietetics, School of Public Health in Bytom, Medical University of Silesia in Katowice, Zabrze, Poland
| | - Agata Kiciak
- Department of Food Technology and Quality Evaluation, Department of Dietetics, Faculty of Public Health in Bytom, Medical University of Silesia in Katowice, Zabrze, Poland
| | - Sylwia Jaruga-Sękowska
- Department of Health Promotion, Faculty of Public Health in Bytom, Medical University of Silesia in Katowice, Bytom, Poland
| | - Daria Dobkowska-Szefer
- Department of Food Technology and Quality Evaluation, Department of Dietetics, Faculty of Public Health in Bytom, Medical University of Silesia in Katowice, Zabrze, Poland
| | - Mateusz Grajek
- Department of Public Health, Department of Public Health Policy, Faculty of Public Health in Bytom, Medical University of Silesia in Katowice, Bytom, Poland
| | - Oskar Kowalski
- Department of Human Nutrition, Department of Dietetics, School of Public Health in Bytom, Medical University of Silesia in Katowice, Zabrze, Poland
| | - Marek Kardas
- Department of Food Technology and Quality Evaluation, Department of Dietetics, Faculty of Public Health in Bytom, Medical University of Silesia in Katowice, Zabrze, Poland
| |
Collapse
|
|
3
|
Bandala C, Carro-Rodríguez J, Cárdenas-Rodríguez N, Peña-Montero I, Gómez-López M, Hernández-Roldán AP, Huerta-Cruz JC, Muñoz-González F, Ignacio-Mejía I, Domínguez B, Lara-Padilla E. Comparative Effects of Gymnema sylvestre and Berberine on Adipokines, Body Composition, and Metabolic Parameters in Obese Patients: A Randomized Study. Nutrients 2024; 16:2284. [PMID: 39064727 PMCID: PMC11280467 DOI: 10.3390/nu16142284] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2024] [Revised: 07/09/2024] [Accepted: 07/12/2024] [Indexed: 07/28/2024] Open
Abstract
Gymnema sylvestre (GS) and berberine (BBR) are natural products that have demonstrated therapeutic potential for the management of obesity and its comorbidities, as effective and safe alternatives to synthetic drugs. Although their anti-obesogenic and antidiabetic properties have been widely studied, comparative research on their impact on the gene expression of adipokines, such as resistin (Res), omentin (Ome), visfatin (Vis) and apelin (Ap), has not been reported. METHODOLOGY We performed a comparative study in 50 adult Mexican patients with obesity treated with GS or BBR for 3 months. The baseline and final biochemical parameters, body composition, blood pressure, gene expression of Res, Ome, Vis, and Ap, and safety parameters were evaluated. RESULTS BBR significantly decreased (p < 0.05) body weight, blood pressure and Vis and Ap gene expression and increased Ome, while GS decreased fasting glucose and Res gene expression (p < 0.05). A comparative analysis of the final measurements revealed a lower gene expression of Ap and Vis (p < 0.05) in patients treated with BBR than in those treated with GS. The most frequent adverse effects in both groups were gastrointestinal symptoms, which attenuated during the first month of treatment. CONCLUSION In patients with obesity, BBR has a better effect on body composition, blood pressure, and the gene expression of adipokines related to metabolic risk, while GS has a better effect on fasting glucose and adipokines related to insulin resistance, with minimal side effects.
Collapse
Affiliation(s)
- Cindy Bandala
- Laboratorio de Neurociencia Traslacional Aplicada a Enfermedades Crónicas y Emergentes, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City 11340, Mexico; (C.B.); (J.C.-R.); (A.P.H.-R.); (F.M.-G.); (B.D.)
| | - Jazmín Carro-Rodríguez
- Laboratorio de Neurociencia Traslacional Aplicada a Enfermedades Crónicas y Emergentes, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City 11340, Mexico; (C.B.); (J.C.-R.); (A.P.H.-R.); (F.M.-G.); (B.D.)
| | | | - Itzel Peña-Montero
- Laboratorio de Obesidad, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City 11340, Mexico; (I.P.-M.); (M.G.-L.)
| | - Modesto Gómez-López
- Laboratorio de Obesidad, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City 11340, Mexico; (I.P.-M.); (M.G.-L.)
| | - Ana Paola Hernández-Roldán
- Laboratorio de Neurociencia Traslacional Aplicada a Enfermedades Crónicas y Emergentes, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City 11340, Mexico; (C.B.); (J.C.-R.); (A.P.H.-R.); (F.M.-G.); (B.D.)
| | - Juan Carlos Huerta-Cruz
- Unidad de Investigación en Farmacología, Instituto Nacional de Enfermedades Respiratorias, Ismael Cosio Villegas, Secretaria de Salud, Mexico City 14080, Mexico;
| | - Felipe Muñoz-González
- Laboratorio de Neurociencia Traslacional Aplicada a Enfermedades Crónicas y Emergentes, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City 11340, Mexico; (C.B.); (J.C.-R.); (A.P.H.-R.); (F.M.-G.); (B.D.)
- Laboratorio de Diseño y Desarrollo de Nuevos Fármacos e Innovación Biotecnológica, Mexico City 11340, Mexico
| | - Iván Ignacio-Mejía
- Laboratorio de Medicina Traslacional, Escuela Militar de Graduados en Sanidad, Universidad del Ejército y Fuerza Aérea, Mexico City 11200, Mexico;
| | - Brayan Domínguez
- Laboratorio de Neurociencia Traslacional Aplicada a Enfermedades Crónicas y Emergentes, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City 11340, Mexico; (C.B.); (J.C.-R.); (A.P.H.-R.); (F.M.-G.); (B.D.)
| | - Eleazar Lara-Padilla
- Laboratorio de Obesidad, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City 11340, Mexico; (I.P.-M.); (M.G.-L.)
| |
Collapse
|
|
4
|
Alkanad M, Hani U, V AH, Ghazwani M, Haider N, Osmani RAM, M D P, Hamsalakshmi, Bhat R. Bitter yet beneficial: The dual role of dietary alkaloids in managing diabetes and enhancing cognitive function. Biofactors 2024; 50:634-673. [PMID: 38169069 DOI: 10.1002/biof.2034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2023] [Accepted: 12/11/2023] [Indexed: 01/05/2024]
Abstract
With the rising prevalence of diabetes and its association with cognitive impairment, interest in the use of dietary alkaloids and other natural products has grown significantly. Understanding how these compounds manage diabetic cognitive dysfunction (DCD) is crucial. This comprehensive review explores the etiology of DCD and the effects of alkaloids in foods and dietary supplements that have been investigated as DCD therapies. Data on how dietary alkaloids like berberine, trigonelline, caffeine, capsaicin, 1-deoxynojirimycin, nuciferine, neferine, aegeline, tetramethylpyrazine, piperine, and others regulate cognition in diabetic disorders were collected from PubMed, Research Gate, Web of Science, Science Direct, and other relevant databases. Dietary alkaloids could improve memory in behavioral models and modulate the mechanisms underlying the cognitive benefits of these compounds, including their effects on glucose metabolism, gut microbiota, vasculopathy, neuroinflammation, and oxidative stress. Evidence suggests that dietary alkaloids hold promise for improving cognition in diabetic patients and could open exciting avenues for future research in diabetes management.
Collapse
Affiliation(s)
- Maged Alkanad
- Department of Pharmacognosy, Sri Adichunchanagiri College of Pharmacy, Adichunchanagiri University, Mandya, India
| | - Umme Hani
- Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha, Saudi Arabia
| | - Annegowda H V
- Department of Pharmacognosy, Sri Adichunchanagiri College of Pharmacy, Adichunchanagiri University, Mandya, India
| | - Mohammed Ghazwani
- Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha, Saudi Arabia
| | - Nazima Haider
- Department of Pathology, College of Medicine, King Khalid University, Abha, Saudi Arabia
| | - Riyaz Ali M Osmani
- Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysuru, India
| | - Pandareesh M D
- Center for Research and Innovations, Adichunchanagiri University, BGSIT, Mandya, India
| | - Hamsalakshmi
- Department of Pharmacognosy, Cauvery College of Pharmacy, Cauvery Group of Institutions, Mysuru, India
| | - Rajeev Bhat
- ERA-Chair in Food By-Products Valorisation Technologies (VALORTECH), Estonian University of Life Sciences, Tartu, Estonia
| |
Collapse
|
|
5
|
Tian W, Liu L, Wang R, Quan Y, Tang B, Yu D, Zhang L, Hua H, Zhao J. Gut microbiota in insulin resistance: a bibliometric analysis. J Diabetes Metab Disord 2024; 23:173-188. [PMID: 38932838 PMCID: PMC11196565 DOI: 10.1007/s40200-023-01342-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2023] [Accepted: 11/06/2023] [Indexed: 06/28/2024]
Abstract
Background Insulin resistance (IR) is considered the pathogenic driver of diabetes, and can lead to obesity, hypertension, coronary artery disease, metabolic syndrome, and other metabolic disorders. Accumulating evidence indicates that the connection between gut microbiota and IR. This bibliometric analysis aimed to summarize the knowledge structure of gut microbiota in IR. Methods Articles and reviews related to gut microbiota in IR from 2013 to 2022 were retrieved from the Web of Science Core Collection (WoSCC), and the bibliometric analysis and visualization were performed by Microsoft Excel, Origin, R package (bibliometrix), Citespace, and VOSviewer. Results A total of 4 749 publications from WoSCC were retrieved, including 3 050 articles and 1 699 reviews. The majority of publications were from China and USA. The University Copenhagen and Shanghai Jiao Tong University were the most active institutions. The journal of Nutrients published the most papers, while Nature was the top 1 co-cited journal, and the major area of these publications was molecular, biology, and immunology. Nieuwdorp M published the highest number of papers, and Cani PD had the highest co-citations. Keyword analysis showed that the most frequently occurring keywords were "gut microbiota", "insulin-resistance", "obesity", and "inflammation". Trend topics and thematic maps showed that serum metabolome and natural products, such as resveratrol, flavonoids were the research hotspots in this field. Conclusion This bibliometric analysis summarised the hotspots, frontiers, pathogenesis, and treatment strategies, providing a clear and comprehensive profile of gut microbiota in IR. Supplementary Information The online version contains supplementary material available at 10.1007/s40200-023-01342-x.
Collapse
Affiliation(s)
- Weiwei Tian
- Key Lab.: Biological Evaluation of TCM Quality of the State Administration of Traditional Chinese Medicine, Translational Chinese Medicine Key Laboratory of Sichuan Province, Sichuan Engineering Technology Research Center of Genuine Regional Drug, Sichuan Provincial Engineering Research Center of Formation Principle and Quality Evaluation of Genuine Medicinal Materials, Sichuan Academy of Chinese Medical Sciences, Sichuan Institute for Translational Chinese Medicine, 610041 Chengdu, China
| | - Li Liu
- Key Lab.: Biological Evaluation of TCM Quality of the State Administration of Traditional Chinese Medicine, Translational Chinese Medicine Key Laboratory of Sichuan Province, Sichuan Engineering Technology Research Center of Genuine Regional Drug, Sichuan Provincial Engineering Research Center of Formation Principle and Quality Evaluation of Genuine Medicinal Materials, Sichuan Academy of Chinese Medical Sciences, Sichuan Institute for Translational Chinese Medicine, 610041 Chengdu, China
| | - Ruirui Wang
- Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, 201203 Shanghai, China
| | - Yunyun Quan
- Key Lab.: Biological Evaluation of TCM Quality of the State Administration of Traditional Chinese Medicine, Translational Chinese Medicine Key Laboratory of Sichuan Province, Sichuan Engineering Technology Research Center of Genuine Regional Drug, Sichuan Provincial Engineering Research Center of Formation Principle and Quality Evaluation of Genuine Medicinal Materials, Sichuan Academy of Chinese Medical Sciences, Sichuan Institute for Translational Chinese Medicine, 610041 Chengdu, China
| | - Bihua Tang
- Key Lab.: Biological Evaluation of TCM Quality of the State Administration of Traditional Chinese Medicine, Translational Chinese Medicine Key Laboratory of Sichuan Province, Sichuan Engineering Technology Research Center of Genuine Regional Drug, Sichuan Provincial Engineering Research Center of Formation Principle and Quality Evaluation of Genuine Medicinal Materials, Sichuan Academy of Chinese Medical Sciences, Sichuan Institute for Translational Chinese Medicine, 610041 Chengdu, China
| | - Dongmei Yu
- Key Lab.: Biological Evaluation of TCM Quality of the State Administration of Traditional Chinese Medicine, Translational Chinese Medicine Key Laboratory of Sichuan Province, Sichuan Engineering Technology Research Center of Genuine Regional Drug, Sichuan Provincial Engineering Research Center of Formation Principle and Quality Evaluation of Genuine Medicinal Materials, Sichuan Academy of Chinese Medical Sciences, Sichuan Institute for Translational Chinese Medicine, 610041 Chengdu, China
| | - Lei Zhang
- Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, 201203 Shanghai, China
| | - Hua Hua
- Key Lab.: Biological Evaluation of TCM Quality of the State Administration of Traditional Chinese Medicine, Translational Chinese Medicine Key Laboratory of Sichuan Province, Sichuan Engineering Technology Research Center of Genuine Regional Drug, Sichuan Provincial Engineering Research Center of Formation Principle and Quality Evaluation of Genuine Medicinal Materials, Sichuan Academy of Chinese Medical Sciences, Sichuan Institute for Translational Chinese Medicine, 610041 Chengdu, China
| | - Junning Zhao
- Key Lab.: Biological Evaluation of TCM Quality of the State Administration of Traditional Chinese Medicine, Translational Chinese Medicine Key Laboratory of Sichuan Province, Sichuan Engineering Technology Research Center of Genuine Regional Drug, Sichuan Provincial Engineering Research Center of Formation Principle and Quality Evaluation of Genuine Medicinal Materials, Sichuan Academy of Chinese Medical Sciences, Sichuan Institute for Translational Chinese Medicine, 610041 Chengdu, China
| |
Collapse
|
|
6
|
Wang S, Cui Z, Yang H. Interactions between host and gut microbiota in gestational diabetes mellitus and their impacts on offspring. BMC Microbiol 2024; 24:161. [PMID: 38730357 PMCID: PMC11083820 DOI: 10.1186/s12866-024-03255-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Accepted: 03/08/2024] [Indexed: 05/12/2024] Open
Abstract
Gestational diabetes mellitus (GDM) is characterized by insulin resistance and low-grade inflammation, and most studies have demonstrated gut dysbiosis in GDM pregnancies. Overall, they were manifested as a reduction in microbiome diversity and richness, depleted short chain fatty acid (SCFA)-producing genera and a dominant of Gram-negative pathogens releasing lipopolysaccharide (LPS). The SCFAs functioned as energy substance or signaling molecules to interact with host locally and beyond the gut. LPS contributed to pathophysiology of diseases through activating Toll-like receptor 4 (TLR4) and involved in inflammatory responses. The gut microbiome dysbiosis was not only closely related with GDM, it was also vital to fetal health through vertical transmission. In this review, we summarized gut microbiota signature in GDM pregnancies of each trimester, and presented a brief introduction of microbiome derived SCFAs. We then discussed mechanisms of microbiome-host interactions in the physiopathology of GDM and associated metabolic disorders. Finally, we compared offspring microbiota composition from GDM with that from normal pregnancies, and described the possible mechanism.
Collapse
Affiliation(s)
- Shuxian Wang
- Department of Obstetrics and Gynaecology, Peking University First Hospital, Beijing, China
- Beijing Key Laboratory of Maternal Fetal Medicine of Gestational Diabetes Mellitus, Beijing, China
| | - Zifeng Cui
- Department of Obstetrics and Gynaecology, Peking University First Hospital, Beijing, China
- Beijing Key Laboratory of Maternal Fetal Medicine of Gestational Diabetes Mellitus, Beijing, China
| | - Huixia Yang
- Department of Obstetrics and Gynaecology, Peking University First Hospital, Beijing, China.
- Beijing Key Laboratory of Maternal Fetal Medicine of Gestational Diabetes Mellitus, Beijing, China.
| |
Collapse
|
|
7
|
Niu ZX, Wang YT, Wang JF. Recent advances in total synthesis of protoberberine and chiral tetrahydroberberine alkaloids. Nat Prod Rep 2024. [PMID: 38712365 DOI: 10.1039/d4np00016a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/08/2024]
Abstract
Covering: Up to 2024Due to the widespread distribution of protoberberine alkaloids (PBs) and tetrahydroberberine alkaloids (THPBs) in nature, coupled with their myriad unique physiological activities, they have garnered considerable attention from medical practitioners. Over the past few decades, synthetic chemists have devised various total synthesis methods to attain these structures, continually expanding reaction pathways to achieve more efficient synthetic strategies. Simultaneously, the chiral construction of THPBs has become a focal point. In this comprehensive review, we categorically summarized the developmental trajectory of the total synthesis of these alkaloids based on the core closure strategies of protoberberine and tetrahydroberberine.
Collapse
Affiliation(s)
- Zhen-Xi Niu
- Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 450018, China.
| | - Ya-Tao Wang
- First People's Hospital of Shangqiu, Shangqiu 476000, Henan Province, China.
- Department of Orthopedics, China-Japan Union Hospital, Jilin University, Changchun 130033, China
| | - Jun-Feng Wang
- Gordon Center for Medical Imaging, Massachusetts General Hospital, Harvard Medical School, 125 Nashua Street, Suite 660, Boston, Massachusetts 02114, USA.
| |
Collapse
|
|
8
|
Huang J, Huang T, Li J. Regulation Mechanism and Potential Value of Active Substances in Spices in Alcohol-Liver-Intestine Axis Health. Int J Mol Sci 2024; 25:3728. [PMID: 38612538 PMCID: PMC11011869 DOI: 10.3390/ijms25073728] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 03/22/2024] [Accepted: 03/25/2024] [Indexed: 04/14/2024] Open
Abstract
Excessive alcohol intake will aggravate the health risk between the liver and intestine and affect the multi-directional information exchange of metabolites between host cells and microbial communities. Because of the side effects of clinical drugs, people tend to explore the intervention value of natural drugs on diseases. As a flavor substance, spices have been proven to have medicinal value, but they are still rare in treating hepatointestinal diseases caused by alcohol. This paper summarized the metabolic transformation of alcohol in the liver and intestine and summarized the potential value of various perfume active substances in improving liver and intestine diseases caused by alcohol. It is also found that bioactive substances in spices can exert antioxidant activity in the liver and intestine environment and reduce the oxidative stress caused by diseases. These substances can interfere with fatty acid synthesis, promote sugar and lipid metabolism, and reduce liver injury caused by steatosis. They can effectively regulate the balance of intestinal flora, promote the production of SCFAs, and restore the intestinal microenvironment.
Collapse
Affiliation(s)
- Jianyu Huang
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Institute of Food Science, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China;
- College of Food and Pharmaceutical Science, Ningbo University, Ningbo 315211, China
| | - Tao Huang
- College of Food and Pharmaceutical Science, Ningbo University, Ningbo 315211, China
| | - Jinjun Li
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Institute of Food Science, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China;
| |
Collapse
|
|
9
|
Xu H, Guo NN, Zhu CY, Ye LY, Yan XY, Liu YQ, Zhang ZY, Zhang G, Hussain L. Diterpenoid Tanshinones Can Inhibit Lung Cancer Progression by Improving the Tumor Microenvironment and Downregulation of NF-κB Expression. ACS OMEGA 2024; 9:7230-7238. [PMID: 38371808 PMCID: PMC10870295 DOI: 10.1021/acsomega.3c09667] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Revised: 01/10/2024] [Accepted: 01/23/2024] [Indexed: 02/20/2024]
Abstract
Diterpenoid tanshinones (DTs) are a bioactive fraction extracted from Salvia miltiorrhiza. High-performance liquid chromatography analysis revealed the presence of four compounds, namely, tanshinone IIA, tanshinone I, cryptotanshinone, and dihydrotanshinone. In this study, we aimed to propose a possible mechanism for the anti-lung cancer effect of DT. To do so, we utilized a lung cancer nude mice model and a lung cancer cell line (PC9) to investigate the effect of DT on lung cancer. We employed immunohistochemistry, enzyme-linked immunosorbent assay, hematoxylin and eosin staining, and immunofluorescence to analyze the pharmacological role of DT in the inhibition of lung cancer growth. The results showed that DT inhibited tumor growth, induced apoptosis in the nude mice model, and reduced inflammatory cell infiltration. Additionally, DT inhibited PC9 lung cancer cells, growth, proliferation, and migration. The mechanism of action of DT involves not only directly inhibiting cell proliferation and migration but also improving the tumor microenvironment. DT significantly increased the expression of important intestinal gap junction proteins, such as zonula occludens 1 (ZO-1) and occludin I. This upregulation contributes to the reinforcement of the intestinal mucosal barrier, thereby reducing the paracellular transport of lipopolysaccharides (LPS) through the intestine. Consequently, the decreased LPS levels lead to the inhibition of NF-κB expression and downregulation of macrophage polarization, as indicated by the decreased expression of CD68. In conclusion, this study has confirmed that DT has anti-lung cancer properties by improving the inflammatory tumor microenvironment via regulating macrophage polarization and inhibiting LPS-associated immune response. These results provide new insights into the mechanism of DT action against lung cancer.
Collapse
Affiliation(s)
- Hao Xu
- College
of Basic Medical Sciences, Zhejiang Chinese
Medical University, Hangzhou 310053, P. R. China
| | - Ning Ning Guo
- Inner
Mongolia Medical University, Inner Mongolia, Hohhot 010110, P. R. China
| | - Chen Ying Zhu
- Department
of Public Health, Zhejiang University School
of Medicine, Hangzhou 310058, P. R. China
| | - Lin Yan Ye
- Department
of Public Health, Zhejiang University School
of Medicine, Hangzhou 310058, P. R. China
| | - Xing Yi Yan
- Department
of Public Health, Zhejiang University School
of Medicine, Hangzhou 310058, P. R. China
| | - Yong Qin Liu
- Department
of Public Health, Zhejiang University School
of Medicine, Hangzhou 310058, P. R. China
| | - Ze Yan Zhang
- Department
of Public Health, Zhejiang University School
of Medicine, Hangzhou 310058, P. R. China
| | - Guangji Zhang
- College
of Basic Medical Sciences, Zhejiang Chinese
Medical University, Hangzhou 310053, P. R. China
| | - Liaqat Hussain
- Department
of Pharmacology, Faculty of Pharmaceutical Science, Government College University, Faisalabad 38000, Pakistan
| |
Collapse
|
|
10
|
Lin X, Zhang J, Chu Y, Nie Q, Zhang J. Berberine prevents NAFLD and HCC by modulating metabolic disorders. Pharmacol Ther 2024; 254:108593. [PMID: 38301771 DOI: 10.1016/j.pharmthera.2024.108593] [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: 10/25/2023] [Revised: 12/28/2023] [Accepted: 12/29/2023] [Indexed: 02/03/2024]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a global metabolic disease with high prevalence in both adults and children. Importantly, NAFLD is becoming the main cause of hepatocellular carcinoma (HCC). Berberine (BBR), a naturally occurring plant component, has been demonstrated to have advantageous effects on a number of metabolic pathways as well as the ability to kill liver tumor cells by causing cell death and other routes. This permits us to speculate and make assumptions about the value of BBR in the prevention and defense against NAFLD and HCC by a global modulation of metabolic disorders. Herein, we briefly describe the etiology of NAFLD and NAFLD-related HCC, with a particular emphasis on analyzing the potential mechanisms of BBR in the treatment of NAFLD from aspects including increasing insulin sensitivity, controlling the intestinal milieu, and controlling lipid metabolism. We also elucidate the mechanism of BBR in the treatment of HCC. More significantly, we provided a list of clinical studies for BBR in NAFLD. Taking into account our conclusions and perspectives, we can make further progress in the treatment of BBR in NAFLD and NAFLD-related HCC.
Collapse
Affiliation(s)
- Xinyue Lin
- School of Pharmacy, State Key Laboratory of Applied Organic Chemistry, and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China
| | - Juanhong Zhang
- School of Pharmacy, State Key Laboratory of Applied Organic Chemistry, and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China; College of Life Science, Northwest Normal University, Lanzhou 730070, China
| | - Yajun Chu
- School of Pharmacy, State Key Laboratory of Applied Organic Chemistry, and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China
| | - Qiuying Nie
- School of Pharmacy, State Key Laboratory of Applied Organic Chemistry, and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China
| | - Junmin Zhang
- School of Pharmacy, State Key Laboratory of Applied Organic Chemistry, and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China.
| |
Collapse
|
|
11
|
Coppinger C, Pomales B, Movahed MR, Marefat M, Hashemzadeh M. Berberine: A Multi-Target Natural PCSK9 Inhibitor with the Potential to Treat Diabetes, Alzheimer's, Cancer and Cardiovascular Disease. Curr Rev Clin Exp Pharmacol 2024; 19:312-326. [PMID: 38361373 DOI: 10.2174/0127724328250471231222094648] [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: 08/25/2023] [Revised: 11/22/2023] [Accepted: 11/24/2023] [Indexed: 02/17/2024]
Abstract
Berberine is a natural product with a wide range of pharmacological effects. It has antimicrobial, anti-cancer, anti-inflammatory, anti-hyperlipidemic, neuroprotective, and cholesterollowering properties, among others. It has been used in traditional Chinese and Ayurvedic medicine for 3000 years and is generally well-tolerated with few side effects. Its main drawback is low oral bioavailability, which has hindered widespread clinical use. However, recent interest has surged with the emergence of evidence that berberine is effective in treating cancer, diabetes, Alzheimer's disease, and cardiovascular disease via multiple mechanisms. It enhances insulin sensitivity and secretion by pancreatic β-cells in Type 2 Diabetes Mellitus in addition to reducing pro-inflammatory cytokines such as IL-6, IL-1β, TLR4 and TNF-α. These cytokines are elevated in Alzheimer's disease, cardiovascular disease, and diabetes. Reductions in pro-inflammatory cytokine levels are associated with positive outcomes such as improved cognition, reduced cardiovascular events, and improved glucose metabolism and insulin sensitivity. Berberine is a natural PCSK9 inhibitor, which contributes to its hypolipidemic effects. It also increases low-density lipoprotein receptor expression, reduces intestinal cholesterol absorption, and promotes cholesterol excretion from the liver to the bile. This translates into a notable decrease in LDL cholesterol levels. High LDL cholesterol levels are associated with increased cardiovascular disease risk. Novel synthetic berberine derivatives are currently being developed that optimize LDL reduction, bioavailability, and other pharmacokinetic properties.
Collapse
Affiliation(s)
- Caroline Coppinger
- Department of Chemistry, Pima College, Tucson, AZ, USA
- Department of Medicine, University of Arizona, Tucson, AZ, USA
| | - Briana Pomales
- Department of Chemistry, Pima College, Tucson, AZ, USA
- Department of Medicine, University of Arizona, Tucson, AZ, USA
| | - Mohammad Reza Movahed
- Department of Medicine, University of Arizona, Tucson, AZ, USA
- Department of Medicine, University of Arizona College of Medicine, Phoenix, USA
| | | | - Mehrnoosh Hashemzadeh
- Department of Chemistry, Pima College, Tucson, AZ, USA
- Department of Medicine, University of Arizona College of Medicine, Phoenix, USA
| |
Collapse
|
|
12
|
Wang S, Ma L, Ji J, Huo R, Dong S, Bai Y, Hua L, Lei J, Tian S, Wang M, Yu Y. Protective effect of soy isolate protein against streptozotocin induced gestational diabetes mellitus via TLR4/MyD88/NF-κB signaling pathway. Biomed Pharmacother 2023; 168:115688. [PMID: 37890205 DOI: 10.1016/j.biopha.2023.115688] [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: 07/23/2023] [Revised: 10/04/2023] [Accepted: 10/09/2023] [Indexed: 10/29/2023] Open
Abstract
BACKGROUND Gestational diabetes mellitus (GDM) is a serious complication of pregnancy that is characterized by high blood sugar levels that occur due to insulin resistance and dysfunction in glucose metabolism during pregnancy. It usually develops in the second or third trimester of pregnancy and affects about 7 % of all pregnancies worldwide. In this experimental study, we scrutinized the GDM protective effect of soy isolate protein against streptozotocin (STZ) induced GDM in rats and explore the underlying mechanism. MATERIAL AND METHODS Sprague-Dawley (SD) rats were used in this experimental study. A 55 mg/kg intraperitoneal injection of streptozotocin (STZ) was administered to induce diabetes in female rats, followed by oral administration of soy isolate protein for 18 days. Body weight, glucose levels, and insulin were measured at different time intervals (0, 9, and 18 days). Lipid profiles, antioxidant levels, inflammatory cytokines, apoptosis parameters, and mRNA expression were also assessed. Pancreatic and liver tissues were collected for histopathological examination during the experimental study. RESULTS Soy isolate protein significantly (P < 0.001) reduced the glucose level and enhanced the insulin level and body weight. Soy isolate protein remarkably decreased the placental weight and increased the fetal weight. Soy isolate protein significantly (P < 0.001) decreased the HbA1c, hepatic glycogen, serum C-peptide and increased the level of free fatty acid. Soy isolate protein significantly (P < 0.001) altered the level of lipid, antioxidant and inflammatory cytokines. Soy isolate protein significantly (P < 0.001) improved the level of adiponectin, visfatin and suppressed the level of leptin and ICAM-1. Soy isolate protein significantly (P < 0.001) altered the mRNA expression and also restored the alteration of histopathology. CONCLUSION Based on the result, soy isolate protein exhibited the GDM protective effect against the STZ induced GDM in rats via alteration of TLR4/MyD88/NF-κB signaling pathway.
Collapse
Affiliation(s)
- Shuijing Wang
- School of Public Health, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Shaanxi SANZ Pharmaceutical Co., Ltd, Xi'an, Shaanxi 710086, China
| | - Liangkun Ma
- Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, PUMC Hospital, CAMS and PUMC, Beijing100730, China
| | - Jing Ji
- Northwest Women's and Children's Hospital, Xi'an, Shaanxi 710061, China
| | - Ruichao Huo
- Pingyao Agriculture and Rural Bureau, Pingyao, Shanxi 031100, China
| | - Shan Dong
- Nutritional Department, Maternal and Child Health Care Hospital of HaiDian District, Beijing 100000, China
| | - Yunfeng Bai
- School of Public Health, Shaanxi University of Chinese Medicine, Xianyang 712046, China
| | - Linlin Hua
- Department of Advanced Medical Research, The Second Affiliated Hospital of Zhengzhou University, Jingba road, Jinshui district, Zhengzhou 450014, China
| | - Jiao Lei
- Shaanxi SANZ Pharmaceutical Co., Ltd, Xi'an, Shaanxi 710086, China
| | - Sasa Tian
- Shaanxi SANZ Pharmaceutical Co., Ltd, Xi'an, Shaanxi 710086, China
| | - Manning Wang
- Shaanxi SANZ Pharmaceutical Co., Ltd, Xi'an, Shaanxi 710086, China
| | - Yan Yu
- School of Public Health, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
| |
Collapse
|
|
13
|
Wu YJ, Wang L, Wang KX, Du JR, Long FY. Modulation of Xiongdanjiuxin pills on the gut-liver axis in high-fat diet rats. Life Sci 2023; 333:122134. [PMID: 37778415 DOI: 10.1016/j.lfs.2023.122134] [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: 07/29/2023] [Revised: 09/23/2023] [Accepted: 09/28/2023] [Indexed: 10/03/2023]
Abstract
AIM Xiongdanjiuxin pill (XP) is a traditional Chinese medicine formula for the prevention and treatment of hyperlipidemia (HLP) and related complications. In this study, the gut-liver axis was used as the breakthrough point to analyze the therapeutic effect and potential mechanism of XP on HLP model rats and related complications. MAIN METHODS We used high-fat diet (HFD) to establish the HLP model of rats and treated them with XP. The 16S rRNA sequencing method was used to explore the effect of XP on the gut microbiota of HFD rats, and the effects of XP on ileum pathology, intestinal barrier and circulatory inflammation in HFD rats were also investigated. We further explored the molecular mechanism of XP treating liver inflammation in rats with HFD by regulating toll-like receptor 4 (TLR4) signaling. KEY FINDINGS We found that XP could regulate the imbalance of gut microbiota in HFD rats, and up-regulate the expression of tight junction protein in intestinal epithelium of HFD rats, thereby improving the intestinal barrier damage and intestinal inflammatory response. In addition, XP could significantly reduce the levels of inflammatory cytokines in HFD rats, and inhibit TLR4 signaling pathway, thereby reducing liver inflammation in HFD rats. SIGNIFICANCE XP can effectively improve the imbalance of gut-liver axis in hyperlipidemic rats and alleviate the inflammatory damage of liver. Its mechanism may be related to regulating the disorder of gut microbiota and inhibiting TLR4 signal pathway, so as to achieve the therapeutic effect on hyperlipidemic fatty liver in rats.
Collapse
Affiliation(s)
- Yi-Jin Wu
- Department of Pharmacology, West China School of Pharmacy, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan University, Chengdu, Sichuan, China
| | - Liu Wang
- Department of Pharmacology, West China School of Pharmacy, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan University, Chengdu, Sichuan, China
| | - Ke-Xin Wang
- Department of Pharmacology, West China School of Pharmacy, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan University, Chengdu, Sichuan, China
| | - Jun-Rong Du
- Department of Pharmacology, West China School of Pharmacy, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan University, Chengdu, Sichuan, China.
| | - Fang-Yi Long
- Department of Pharmacology, West China School of Pharmacy, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan University, Chengdu, Sichuan, China; Laboratory Medicine Center, Sichuan Provincial Maternity and Child Health Care Hospital, Affiliated Women's and Children's Hospital of Chengdu Medical College, Chengdu, Sichuan, China.
| |
Collapse
|
|
14
|
Shrivastava S, Sharma A, Saxena N, Bhamra R, Kumar S. Addressing the preventive and therapeutic perspective of berberine against diabetes. Heliyon 2023; 9:e21233. [PMID: 38027723 PMCID: PMC10663750 DOI: 10.1016/j.heliyon.2023.e21233] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 09/20/2023] [Accepted: 10/18/2023] [Indexed: 12/01/2023] Open
Abstract
Diabetes has emerged as one the leading detrimental factors for human life expectancy worldwide. The disease is mainly considered as outcome of dysregulation in glucose metabolism, resulting in consistent high glucose concentration in blood. At initial stages, the diabetes particularly type 2 diabetes, is manageable by lifestyle interventions such as regular physical activity and diet with less carbohydrates. However, in advance stage, regular intake of external insulin dose and medicines like metformin are recommended. The long-term consumption of metformin is associated with several side effects such as nausea, vomiting, diarrhoea, lectic acidosis etc., In this scenario, several plant-based medicines have shown promising potential for the prevention and treatment of diabetes. Berberine is the bioactive compound present in the different plant parts of berberis family. Biochemical studies have shown that berberine improve insulin sensitivity and insulin secretion. Additionally, berberine induces glucose metabolism by activating AMPK signaling and inhibition of inflammation. A series of studies have demonstrated the antidiabetic potential of berberine at in vitro, pre-clinical and clinical trials. This review provides comprehensive details of preventive and therapeutic potential of berberine against diabetes.
Collapse
Affiliation(s)
- Suyesh Shrivastava
- ICMR-National Institute of Research in Tribal Health, Nagpur Road, Jabalpur-482003, India
| | - Anamika Sharma
- National Institute of Pharmaceutical and Education and Research 500037, Hyderabad, India
| | - Nishant Saxena
- ICMR-National Institute of Research in Tribal Health, Nagpur Road, Jabalpur-482003, India
| | - Rashmi Bhamra
- Global Research Institute of Pharmacy, Radour-135133, Haryana, India
| | - Sandeep Kumar
- ICMR-National Institute of Research in Tribal Health, Nagpur Road, Jabalpur-482003, India
| |
Collapse
|
|
15
|
Sun Y, Zhou Q, Chen F, Gao X, Yang L, Jin X, Wink M, Sharopov FS, Sethi G. Berberine inhibits breast carcinoma proliferation and metastasis under hypoxic microenvironment involving gut microbiota and endogenous metabolites. Pharmacol Res 2023:106817. [PMID: 37315824 DOI: 10.1016/j.phrs.2023.106817] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Revised: 06/04/2023] [Accepted: 06/08/2023] [Indexed: 06/16/2023]
Abstract
A potential role of berberine, a benzyl isoquinoline alkaloid, in cancer therapy is apparent. Its underlying mechanisms of berberine against breast carcinoma under hypoxia have not been elucidated. We focused on the doubt how berberine restrains breast carcinoma under hypoxia in vitro and in vivo. A molecular analysis of the microbiome via 16S rDNA gene sequencing of DNA from mouse faeces confirmed that the abundances and diversity of gut microbiota were significantly altered in 4T1/Luc mice with higher survival rate following berberine treatment. A metabolome analysis liquid chromatography-mass spectrometer/mass spectrometer (LC-MS/MS) revealed that berberine regulated various endogenous metabolites, especially L-palmitoylcarnitine. Furthermore, the cytotoxicity of berberine was investigated in MDA-MB-231, MCF-7, and 4T1 cells. In vitro to simulate under hypoxic environment, MTT assay showed that berberine inhibited the proliferation of MDA-MB-231, MCF-7, and 4T1 cells with IC50 values of 4.14 ± 0.35μM, 26.53 ± 3.12μM and 11.62 ± 1.44μM, respectively. Wound healing and trans-well invasion studies revealed that berberine inhibited the invasion and migration of breast cancer cells. RT-qPCR analysis shed light that berberine reduced the expression of hypoxia-inducible factor-1α (HIF-1α) gene. Immunofluorescence and western blot demonstrated that berberine decreased the expression of E-cadherin and HIF-1α protein. Taken together, these results provide evidence that berberine efficiently suppresses breast carcinoma growth and metastasis in a hypoxic microenvironment, highlighting the potential of berberine as a promising anti-neoplastic agent to combat breast carcinoma.
Collapse
Affiliation(s)
- Yanfang Sun
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China.
| | - QianQian Zhou
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China
| | - Fangming Chen
- Animal Research Center, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Xiaoyan Gao
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China
| | - Linjun Yang
- Municipal Hospital Affiliated to Medical School of Taizhou University, Taizhou 318000, China
| | - Xiaoyan Jin
- Municipal Hospital Affiliated to Medical School of Taizhou University, Taizhou 318000, China
| | - Michael Wink
- Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Im Neuenheimer Feld 329, 69120 Heidelberg, Germany
| | - Farukh S Sharopov
- Research Institution "Chinese-Tajik Innovation Center for Natural Products", National Academy of Sciences of Tajikistan, Rudaki Avenue 33, 734025 Dushanbe, Tajikistan
| | - Gautam Sethi
- Department of Pharmacology, National University of Singapore, Building MD3, 117600 Medical Drive, Singapore.
| |
Collapse
|
|
16
|
Bellavite P, Fazio S, Affuso F. A Descriptive Review of the Action Mechanisms of Berberine, Quercetin and Silymarin on Insulin Resistance/Hyperinsulinemia and Cardiovascular Prevention. Molecules 2023; 28:4491. [PMID: 37298967 PMCID: PMC10254920 DOI: 10.3390/molecules28114491] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 05/26/2023] [Accepted: 05/30/2023] [Indexed: 06/12/2023] Open
Abstract
Insulin resistance (IR) and the associated hyperinsulinemia are early pathophysiological changes which, if not well treated, can lead to type 2 diabetes, endothelial dysfunction and cardiovascular disease. While diabetes care is fairly well standardized, the prevention and treatment of IR lacks a single pharmaceutical approach and many lifestyle and dietary interventions have been proposed, including a wide range of food supplements. Among the most interesting and well-known natural remedies, alkaloid berberine and the flavonol quercetin have particular relevance in the literature, while silymarin-the active principle of the Silybum marianum thistle-was traditionally used for lipid metabolism disorders and to sustain liver function. This review describes the major defects of insulin signaling leading to IR and the main properties of the three mentioned natural substances, their molecular targets and synergistic action mechanisms. The actions of berberine, quercetin and silymarin are partially superimposable as remedies against reactive oxygen intermediates generated by a high-lipid diet and by NADPH oxidase, which is triggered by phagocyte activation. Furthermore, these compounds inhibit the secretion of a battery of pro-inflammatory cytokines, modulate intestinal microbiota and are especially able to control the various disorders of the insulin receptor and post-receptor signaling systems. Although most of the evidence on the effects of berberine, quercetin and silymarin in modulating insulin resistance and preventing cardiovascular disease derive from experimental studies on animals, the amount of pre-clinical knowledge strongly suggests the need to investigate the therapeutic potential of these substances in human pathology.
Collapse
Affiliation(s)
- Paolo Bellavite
- Pathophysiology Chair, Homeopathic Medical School of Verona, 37121 Verona, Italy
| | - Serafino Fazio
- Department of Internal Medicine, University of Naples Federico II, 80138 Naples, Italy;
| | | |
Collapse
|
|
17
|
Liu D, Zhang S, Li S, Zhang Q, Cai Y, Li P, Li H, Shen B, Liao Q, Hong Y, Xie Z. Indoleacrylic acid produced by Parabacteroides distasonis alleviates type 2 diabetes via activation of AhR to repair intestinal barrier. BMC Biol 2023; 21:90. [PMID: 37072819 PMCID: PMC10114473 DOI: 10.1186/s12915-023-01578-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Accepted: 03/27/2023] [Indexed: 04/20/2023] Open
Abstract
BACKGROUND Anti-inflammatory therapy is an effective strategy in the treatment of type 2 diabetes (T2D). Studies found that inflammatory responses in vivo were strongly associated with defects in the mucosal barrier function of the gut epithelium. While some microbial strains could help repair the intestinal mucosa and maintain the integrity of the intestinal barrier, the specific mechanisms remain to be fully elucidated. The present study investigated the effects of Parabacteroides distasonis (P. distasonis) on the intestinal barrier and the inflammation level in T2D rats and explored the specific mechanisms. RESULTS By analyzing the intestinal barrier function, the inflammatory conditions, and the gut microbiome, we found that P. distasonis could attenuate insulin resistance by repairing the intestinal barrier and reducing inflammation caused by the disturbed gut microbiota. We quantitatively profiled the level of tryptophan and indole derivatives (IDs) in rats and fermentation broth of the strain, demonstrating that indoleacrylic acid (IA) was the most significant factor correlated with the microbial alterations among all types of endogenous metabolites. Finally, we used molecular and cell biological techniques to determine that the metabolic benefits of P. distasonis were mainly attributed to its ability to promote IA generation, active the aryl hydrocarbon receptor (AhR) signaling pathway, and increase the expression level of interleukin-22 (IL-22), thus enhancing the expression of intestinal barrier-related proteins. CONCLUSIONS Our study revealed the effects of P. distasonis in the treatment of T2D via intestinal barrier repairment and inflammation reduction and highlighted a host-microbial co-metabolite indoleacrylic acid that could active AhR to perform its physiological effects. Our study provided new therapeutic strategies for metabolic diseases by targeting the gut microbiota and tryptophan metabolism.
Collapse
Affiliation(s)
- Deliang Liu
- School of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sen University, Guangzhou, 510006, People's Republic of China
| | - Shaobao Zhang
- School of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sen University, Guangzhou, 510006, People's Republic of China
| | - Siju Li
- School of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sen University, Guangzhou, 510006, People's Republic of China
| | - Qian Zhang
- School of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sen University, Guangzhou, 510006, People's Republic of China
| | - Ying Cai
- School of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sen University, Guangzhou, 510006, People's Republic of China
| | - Pei Li
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, People's Republic of China
| | - Hao Li
- School of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sen University, Guangzhou, 510006, People's Republic of China
| | - Baochun Shen
- School of Pharmacy, Kunming Medical University, Kunming, 650500, People's Republic of China
| | - Qiongfeng Liao
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, People's Republic of China.
| | - Yanjun Hong
- School of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sen University, Guangzhou, 510006, People's Republic of China.
| | - Zhiyong Xie
- School of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sen University, Guangzhou, 510006, People's Republic of China.
| |
Collapse
|
|
18
|
Liu M, Zhou J, Li Y, Ding Y, Lian J, Dong Q, Qu Q, Lv W, Guo S. Effects of dietary polyherbal mixtures on growth performance, antioxidant capacity, immune function and jejunal health of yellow-feathered broilers. Poult Sci 2023; 102:102714. [PMID: 37172360 DOI: 10.1016/j.psj.2023.102714] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Revised: 04/06/2023] [Accepted: 04/09/2023] [Indexed: 05/14/2023] Open
Abstract
This study aimed to investigate the effects of polyherbal mixtures (PHM) on growth performance, antioxidant capacities, immune function, and intestinal health in yellow-feathered broilers. PHM is composed of five traditional Chinese medicine herbs (Portulaca oleracea L., Radix Sophora flavescens, Thalictrum glandulosissimum, Terra flava usta, and Pogostemon cablin). A total of 270 one-day-old yellow-feathered broilers were randomly allotted into 3 treatments for a 42-d feeding trial, each with 6 replicates of 15 birds. The dietary treatments consisted of a basal diet (CON), a basal diet supplemented with 50 mg/kg chlortetracycline (CTC), and a basal diet supplemented with 1000 mg/kg PHM. The results showed that dietary PHM supplementation increased body weight, ADG, and decreased F/G compared to the CON. PHM also increased spleen index and mRNA expression of IL-4 (d 21), and thymus index, serum IgA (d 42) and IgG, IL-4 and sIgA in jejunal mucosa (d 21 and 42), but decreased serum IFN-γ and mRNA expression of IFN-γ (d 21 and 42). In addition, PHM increased serum SOD, GSH-Px (d 21 and 42) and T-AOC (d 42), but decreased the content of serum MDA (d 21), the up-regulated mRNA expression of GSH-Px, CAT (d 21), SOD and CAT (d 42). Furthermore, PHM also improved the intestinal epithelial barrier indicators by the up-regulated mRNA expression of CLDN-1, OCLN (d 21 and 42) and ZO-1 (d 21), and the increased of villus height and villus height to crypt depth in jejunum (d 42). The high-throughput sequencing results showed that dietary PHM supplementation increased the alpha diversity and relative abundance of Oscillospira and Ruminococcus (d 21) and Lactobacillus (d 42), whereas decreasing that of Enterococcus (d 21) compared with CON. PICRUSt analysis revealed that metabolic pathways of carbohydrate, energy, lipid, cofactors, and vitamins were significantly enriched in the PHM group. Spearman's correlation analysis revealed that the genera Lactobacillus, Enterococcus, Ruminococcus, Oscillospira, and Faecalibacterium were related to growth performance, intestinal integrity, immune-related factors, antioxidant indices, and tight junction proteins. In conclusion, the results indicated that dietary PHM supplementation improved growth performance and immune status of yellow-feathered broilers by enhancing antioxidant capacities, barrier function, and modulated jejunal microbial communities. PHM used in our study has the potential to replace prophylactic antibiotic use in poultry production systems.
Collapse
Affiliation(s)
- Mengjie Liu
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, People's Republic of China
| | - Jing Zhou
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, People's Republic of China
| | - Yue Li
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, People's Republic of China
| | - Yiqing Ding
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, People's Republic of China
| | - Jiale Lian
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, People's Republic of China
| | - Qi Dong
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, People's Republic of China
| | - Qian Qu
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, People's Republic of China
| | - Weijie Lv
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, People's Republic of China
| | - Shining Guo
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, People's Republic of China; Guangdong Technology Research center for Traditional Chinese Veterinary Medicine and Natural Medicine, Guangzhou, People's Republic of China.
| |
Collapse
|
|
19
|
Zhang Q, Bai Y, Wang W, Li J, Zhang L, Tang Y, Yue S. Role of herbal medicine and gut microbiota in the prevention and treatment of obesity. JOURNAL OF ETHNOPHARMACOLOGY 2023; 305:116127. [PMID: 36603782 DOI: 10.1016/j.jep.2022.116127] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/23/2022] [Revised: 12/16/2022] [Accepted: 12/30/2022] [Indexed: 06/17/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Obesity is a common metabolic dysfunction disease, which is highly correlated with the homeostasis of gut microbiota (GM). The dysregulation of GM on energy metabolism, immune response, insulin resistance and endogenous metabolites (e.g., short chain fatty acids and secondary bile acids) can affect the occurrence and development of obesity. Herbal medicine (HM) has particular advantages and definite therapeutic effects in the prevention and treatment of obesity, but its underlying mechanism is not fully clear. AIM OF THE STUDY In this review, the representative basic and clinical anti-obesity studies associated with the homeostasis of GM regulated by HM including active components, single herb and herbal formulae were summarized and discussed. We aim to provide a state of art reference for the mechanism research of HM in treating obesity and the further development of new anti-obesity drugs. MATERIALS AND METHODS The relevant information was collected by searching keywords (obesity, herbal medicine, prescriptions, mechanism, GM, short chain fatty acids, etc.) from scientific databases (CNKI, PubMed, SpringerLink, Web of Science, SciFinder, etc.). RESULTS GM dysbiosis did occur in obese patients and mice, whiles the intervention of GM could ameliorate the condition of obesity. HM (e.g., berberine, Ephedra sinica, Rehjnannia glutinosa, and Buzhong Yiqi prescription) has been proved to possess a certain regulation on GM and an explicit effect on obesity, but the exact mechanism of HM in improving obesity by regulating GM remains superficial. CONCLUSION GM is involved in HM against obesity, and GM can be a novel therapeutic target for treating obesity.
Collapse
Affiliation(s)
- Qiao Zhang
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi Traditional Chinese Medicine Processing Technology Heritage Base, Shaanxi University of Chinese Medicine, Xi'an, 712046, China.
| | - Yaya Bai
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi Traditional Chinese Medicine Processing Technology Heritage Base, Shaanxi University of Chinese Medicine, Xi'an, 712046, China.
| | - Wenxiao Wang
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi Traditional Chinese Medicine Processing Technology Heritage Base, Shaanxi University of Chinese Medicine, Xi'an, 712046, China.
| | - Jiajia Li
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi Traditional Chinese Medicine Processing Technology Heritage Base, Shaanxi University of Chinese Medicine, Xi'an, 712046, China.
| | - Li Zhang
- Hanlin College, Nanjing University of Chinese Medicine, Taizhou, 225300, Jiangsu Province, China.
| | - Yuping Tang
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi Traditional Chinese Medicine Processing Technology Heritage Base, Shaanxi University of Chinese Medicine, Xi'an, 712046, China.
| | - Shijun Yue
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi Traditional Chinese Medicine Processing Technology Heritage Base, Shaanxi University of Chinese Medicine, Xi'an, 712046, China.
| |
Collapse
|
|
20
|
Liu YF, Wang HH, Geng YH, Han L, Tu SH, Wang H. Advances of berberine against metabolic syndrome-associated kidney disease: Regarding effect and mechanism. Front Pharmacol 2023; 14:1112088. [PMID: 36814494 PMCID: PMC9939707 DOI: 10.3389/fphar.2023.1112088] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 01/17/2023] [Indexed: 02/09/2023] Open
Abstract
The prevalence of metabolic syndrome (MetS) is drastically growing worldwide, resulting in MetS-associated kidney disease. According to traditional theories, preventing blood pressure, lipid, glycose, and obesity and improving insulin resistance (IR), a couple of medications are required for MetS. It not only lowers patients' compliance but also elevates adverse reactions. Accordingly, we attempted to seek answers from complementary and alternative medicine. Ultimately, berberine (BBR) was chosen due to its efficacy and safety on MetS through multi-pathways and multi-targets. The effects and mechanisms of BBR on obesity, IR, diabetic nephropathy, hypertension, hyperlipidemia, and hyperuricemia were elaborated. In addition, the overall properties of BBR and interventions for various kidney diseases were also collected. However, more clinical trials are expected to further identify the beneficial effects of BBR.
Collapse
Affiliation(s)
- Ya-Fei Liu
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Huan-Huan Wang
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yin-Hong Geng
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Liang Han
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Sheng-Hao Tu
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Hui Wang
- Nephrology Department of Integrated Traditional Chinese and Western Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| |
Collapse
|
|
21
|
Winiarska-Mieczan A, Kwiecień M, Jachimowicz-Rogowska K, Donaldson J, Tomaszewska E, Baranowska-Wójcik E. Anti-Inflammatory, Antioxidant, and Neuroprotective Effects of Polyphenols-Polyphenols as an Element of Diet Therapy in Depressive Disorders. Int J Mol Sci 2023; 24:ijms24032258. [PMID: 36768580 PMCID: PMC9916817 DOI: 10.3390/ijms24032258] [Citation(s) in RCA: 37] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Revised: 01/15/2023] [Accepted: 01/20/2023] [Indexed: 01/26/2023] Open
Abstract
Depressive disorders can affect up to 350 million people worldwide, and in developed countries, the percentage of patients with depressive disorders may be as high as 10%. During depression, activation of pro-inflammatory pathways, mitochondrial dysfunction, increased markers of oxidative stress, and a reduction in the antioxidant effectiveness of the body are observed. It is estimated that approximately 30% of depressed patients do not respond to traditional pharmacological treatments. However, more and more attention is being paid to the influence of active ingredients in food on the course and risk of neurological disorders, including depression. The possibility of using foods containing polyphenols as an element of diet therapy in depression was analyzed in the review. The possibility of whether the consumption of products such as polyphenols could alleviate the course of depression or prevent the progression of it was also considered. Results from preclinical studies demonstrate the potential of phenolic compounds have the potential to reduce depressive behaviors by regulating factors related to oxidative stress, neuroinflammation, and modulation of the intestinal microbiota.
Collapse
Affiliation(s)
- Anna Winiarska-Mieczan
- Institute of Animal Nutrition and Bromatology, University of Life Sciences in Lublin, Akademicka St. 13, 20-950 Lublin, Poland
- Correspondence: ; Tel.: +48-81-445-67-44
| | - Małgorzata Kwiecień
- Institute of Animal Nutrition and Bromatology, University of Life Sciences in Lublin, Akademicka St. 13, 20-950 Lublin, Poland
| | - Karolina Jachimowicz-Rogowska
- Institute of Animal Nutrition and Bromatology, University of Life Sciences in Lublin, Akademicka St. 13, 20-950 Lublin, Poland
| | - Janine Donaldson
- School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, South Africa
| | - Ewa Tomaszewska
- Department of Animal Physiology, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, Akademicka St. 12, 20-950 Lublin, Poland
| | - Ewa Baranowska-Wójcik
- Department of Biotechnology, Microbiology and Human Nutrition, University of Life Sciences in Lublin, Skromna St. 8, 20-704 Lublin, Poland
| |
Collapse
|
|
22
|
Ionescu OM, Frincu F, Mehedintu A, Plotogea M, Cirstoiu M, Petca A, Varlas V, Mehedintu C. Berberine-A Promising Therapeutic Approach to Polycystic Ovary Syndrome in Infertile/Pregnant Women. LIFE (BASEL, SWITZERLAND) 2023; 13:life13010125. [PMID: 36676074 PMCID: PMC9864590 DOI: 10.3390/life13010125] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 12/25/2022] [Accepted: 12/29/2022] [Indexed: 01/03/2023]
Abstract
Polycystic ovary syndrome (PCOS) is a disorder with an unknown etiology that features a wide range of endocrine and metabolic abnormalities that hamper fertility. PCOS women experience difficulties getting pregnant, and if pregnant, they are prone to miscarriage, gestational diabetes, pregnancy-induced hypertension and preeclampsia, high fetal morbidity, and perinatal mortality. Insulin, the pancreatic hormone best known for its important role in glucose metabolism, has an underrated position in reproduction. PCOS women who have associated insulin resistance (with consequent hyperinsulinemia) have fertility issues and adverse pregnancy outcomes. Lowering the endogen insulin levels and insulin resistance appears to be a target to improve fertility and pregnancy outcomes in those women. Berberine is an alkaloid with a high concentration in various medicinal herbs that exhibits a hypoglycaemic effect alongside a broad range of other therapeutic activities. Its medical benefits may stand up for treating different conditions, including diabetes mellitus. So far, a small number of pharmacological/clinical trials available in the English language draw attention towards the good results of berberine's use in PCOS women with insulin resistance for improving fertility and pregnancy outcomes. Our study aims to uncover how berberine can counteract the negative effect of insulin resistance in PCOS women and improve fertility and pregnancy outcomes.
Collapse
Affiliation(s)
- Oana-Maria Ionescu
- Faculty of Medicine “Carol Davila”, University of Medicine and Pharmacy Bucharest, 050474 Bucharest, Romania
| | - Francesca Frincu
- Faculty of Medicine “Carol Davila”, University of Medicine and Pharmacy Bucharest, 050474 Bucharest, Romania
- Correspondence:
| | - Andra Mehedintu
- Faculty of Medicine “Carol Davila”, University of Medicine and Pharmacy Bucharest, 050474 Bucharest, Romania
| | - Mihaela Plotogea
- Department of Obstetrics and Gynecology, “Nicolae Malaxa” Clinical Hospital, 022441 Bucharest, Romania
| | - Monica Cirstoiu
- Faculty of Medicine “Carol Davila”, University of Medicine and Pharmacy Bucharest, 050474 Bucharest, Romania
| | - Aida Petca
- Faculty of Medicine “Carol Davila”, University of Medicine and Pharmacy Bucharest, 050474 Bucharest, Romania
| | - Valentin Varlas
- Faculty of Medicine “Carol Davila”, University of Medicine and Pharmacy Bucharest, 050474 Bucharest, Romania
| | - Claudia Mehedintu
- Faculty of Medicine “Carol Davila”, University of Medicine and Pharmacy Bucharest, 050474 Bucharest, Romania
| |
Collapse
|
|
23
|
Amssayef A, Eddouks M. Alkaloids as Promising Agents for the Management of Insulin Resistance: A Review. Curr Pharm Des 2023; 29:3123-3136. [PMID: 38038009 DOI: 10.2174/0113816128270340231121043038] [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: 07/27/2023] [Revised: 09/10/2023] [Accepted: 09/21/2023] [Indexed: 12/02/2023]
Abstract
BACKGROUND Insulin resistance is one of the main factors that lead to the development of type 2 diabetes mellitus (T2DM). The effect of alkaloids on insulin resistance has been extensively examined according to multiple scientific researches. OBJECTIVE In this work, we aimed to summarize the interesting results from preclinical and clinical studies that assessed the effects of natural alkaloids (berberine, nigelladine A, piperine, trigonelline, capsaicin, nuciferine, evodiamine, mahanine, and magnoflorine) on impaired insulin sensitivity and worsened insulin resistance, which play a pivotal role in the pathogenesis of type 2 diabetes. METHODS In the current review, PubMed, ScienceDirect, Springer, and Google Scholar databases were used. The inclusion criteria were based on the following keywords and phrases: insulin sensitivity, insulin resistance, alkaloids and insulin resistance, alkaloids and type 2 diabetes, mechanisms of action, and alkaloids. RESULTS The outcomes reported in this review demonstrated that the selected alkaloids increased insulin sensitivity and reduced insulin resistance in vitro and in vivo evidence, as well as in clinical trials, through improving insulin-signaling transduction mainly in hepatocytes, myocytes, and adipocytes, both at cellular and molecular levels. Insulin signaling components (InsR, IRS-1, PI3K, Akt, etc.), protein kinases and phosphatases, receptors, ion channels, cytokines, adipokines, and microRNAs, are influenced by alkaloids at transcriptional and translational levels, also in terms of function (activity and/or phosphorylation). Multiple perturbations associated with insulin resistance, such as ectopic lipid accumulation, inflammation, ER stress, oxidative stress, mitochondrial dysfunction, gut microbiota dysbiosis, and β-cell failure, are reversed after treatment with alkaloids. Furthermore, various indices and tests are employed to assess insulin resistance, including the Matsuda index, insulin sensitivity index (ISI), oral glucose tolerance test (OGTT), and insulin tolerance test (ITT), which are all enhanced by alkaloids. These improvements extend to fasting blood glucose, fasting insulin, and HbA1c levels as well. Additionally, the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and the Homeostasis Model Assessment of β-cell function (HOMA-β) are recognized as robust markers of insulin sensitivity and β-cell function, and it is noteworthy that alkaloids also lead to improvements in these two markers. CONCLUSION Based on the findings of the current review, alkaloids may serve as both preventive and curative agents for metabolic disorders, specifically type 2 diabetes. Nonetheless, there is an urgent need for additional clinical trials to explore the potential benefits of alkaloids in both healthy individuals and those with type 2 diabetes. Additionally, it is crucial to assess any possible side effects and interactions with antidiabetic drugs.
Collapse
Affiliation(s)
- Ayoub Amssayef
- Department of Biology, Faculty of Sciences and Techniques Errachidia, Moulay Ismail University of Meknes, BP 509, Boutalamine, Errachidia, Morocco
| | - Mohamed Eddouks
- Department of Biology, Faculty of Sciences and Techniques Errachidia, Moulay Ismail University of Meknes, BP 509, Boutalamine, Errachidia, Morocco
| |
Collapse
|
|
24
|
Gao L, Xia X, Shuai Y, Zhang H, Jin W, Zhang X, Zhang Y. Gut microbiota, a hidden protagonist of traditional Chinese medicine for acute ischemic stroke. Front Pharmacol 2023; 14:1164150. [PMID: 37124192 PMCID: PMC10133705 DOI: 10.3389/fphar.2023.1164150] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2023] [Accepted: 04/04/2023] [Indexed: 05/02/2023] Open
Abstract
Acute ischemic stroke (AIS) is one of the leading diseases causing death and disability worldwide, and treatment options remain very limited. Traditional Chinese Medicine (TCM) has been used for thousands of years to treat ischemic stroke and has been proven to have significant efficacy, but its mechanism of action is still unclear. As research related to the brain-gut-microbe axis progresses, there is increasing evidence that the gut microbiota plays an important role during AIS. The interaction between TCM and the gut microbiota has been suggested as a possible key link to the therapeutic effects of TCM. We have compiled and reviewed recent studies on the relationship between AIS, TCM, and gut microbiota, with the expectation of providing more ideas to elucidate the mechanism of action of TCM in the treatment of AIS.
Collapse
Affiliation(s)
- Lin Gao
- Emergency Department, Chengdu University of Traditional Chinese Medicine Affiliated Hospital, Chengdu, Sichuan, China
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Xiuwen Xia
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Yinqi Shuai
- Emergency Department, Chengdu University of Traditional Chinese Medicine Affiliated Hospital, Chengdu, Sichuan, China
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Hong Zhang
- Emergency Department, Chengdu University of Traditional Chinese Medicine Affiliated Hospital, Chengdu, Sichuan, China
| | - Wei Jin
- Emergency Department, Chengdu University of Traditional Chinese Medicine Affiliated Hospital, Chengdu, Sichuan, China
| | - Xiaoyun Zhang
- Emergency Department, Chengdu University of Traditional Chinese Medicine Affiliated Hospital, Chengdu, Sichuan, China
- *Correspondence: Yi Zhang, ; Xiaoyun Zhang,
| | - Yi Zhang
- Geriatric Department, Chengdu University of Traditional Chinese Medicine Affiliated Hospital, Chengdu, Sichuan, China
- *Correspondence: Yi Zhang, ; Xiaoyun Zhang,
| |
Collapse
|
|
25
|
Bertoncini-Silva C, Zingg JM, Fassini PG, Suen VMM. Bioactive dietary components-Anti-obesity effects related to energy metabolism and inflammation. Biofactors 2022; 49:297-321. [PMID: 36468445 DOI: 10.1002/biof.1921] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Accepted: 11/18/2022] [Indexed: 12/10/2022]
Abstract
Obesity is the result of the long-term energy imbalance between the excess calories consumed and the few calories expended. Reducing the intake of energy dense foods (fats, sugars), and strategies such as fasting and caloric restriction can promote body weight loss. Not only energy in terms of calories, but also the specific composition of the diet can affect the way the food is absorbed and how its energy is stored, used or dissipated. Recent research has shown that bioactive components of food, such as polyphenols and vitamins, can influence obesity and its pathologic complications such as insulin resistance, inflammation and metabolic syndrome. Individual micronutrients can influence lipid turnover but for long-term effects on weight stability, dietary patterns containing several micronutrients may be required. At the molecular level, these molecules modulate signaling and the expression of genes that are involved in the regulation of energy intake, lipid metabolism, adipogenesis into white, beige and brown adipose tissue, thermogenesis, lipotoxicity, adipo/cytokine synthesis, and inflammation. Higher concentrations of these molecules can be reached in the intestine, where they can modulate the composition and action of the microbiome. In this review, the molecular mechanisms by which bioactive compounds and vitamins modulate energy metabolism, inflammation and obesity are discussed.
Collapse
Affiliation(s)
- Caroline Bertoncini-Silva
- Department of Internal Medicine, Division of Nutrology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
| | - Jean-Marc Zingg
- Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, Florida, USA
| | - Priscila Giacomo Fassini
- Department of Internal Medicine, Division of Nutrology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
| | - Vivian Marques Miguel Suen
- Department of Internal Medicine, Division of Nutrology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
| |
Collapse
|
|
26
|
Izadparast F, Riahi-Zajani B, Yarmohammadi F, Hayes AW, Karimi G. Protective effect of berberine against LPS-induced injury in the intestine: a review. Cell Cycle 2022; 21:2365-2378. [PMID: 35852392 PMCID: PMC9645259 DOI: 10.1080/15384101.2022.2100682] [Citation(s) in RCA: 50] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2022] [Revised: 07/03/2022] [Accepted: 07/08/2022] [Indexed: 12/11/2022] Open
Abstract
Sepsis is a systemic inflammatory condition caused by an unbalanced immunological response to infection, which affects numerous organs, including the intestines. Lipopolysaccharide (LPS; also known as endotoxin), a substance found in Gram-negative bacteria, plays a major role in sepsis and is mostly responsible for the disease's morbidity and mortality. Berberine is an isoquinoline alkaloid found in a variety of plant species that has anti-inflammatory properties. For many years, berberine has been used to treat intestinal inflammation and infection. Berberine has been reported to reduce LPS-induced intestinal damage. The potential pathways through which berberine protects against LPS-induced intestinal damage by inhibiting NF-κB, suppressing MAPK, modulating ApoM/S1P pathway, inhibiting COX-2, modulating Wnt/Beta-Catenin signaling pathway, and/or increasing ZIP14 expression are reviewed.Abbreviations: LPS, lipopolysaccharide; TLR, Toll-like receptor; MD-2, myeloid differentiation factor 2; CD14, cluster of differentiation 14; LBP, lipopolysaccharide-binding protein; MYD88, myeloid differentiation primary response 88; NF-κB, nuclear factor kappa light-chain enhancer of activated B cells; MAPK, mitogen-activated protein kinase; IL, interleukin; TNFα, tumor necrosis factor-alpha; Caco-2, cyanocobalamin uptake by human colon adenocarcinoma cell line; MLCK, myosin light-chain kinase; TJ, tight junction; IκBα, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha; IBS, irritable bowel syndrome; ERK, extracellular signal-regulated kinase; JNK, c-Jun N-terminal kinase (JNK; GVB, gut-vascular barrier; ApoM, apolipoprotein M; S1P, sphingosine-1-phosphate; VE-cadherin, vascular endothelial cadherin; AJ, adherens junction; PV1, plasmalemma vesicle-associated protein-1; HDL, high-density lipoprotein; Wnt, wingless-related integration site; Fzd, 7-span transmembrane protein Frizzled; LRP, low-density lipoprotein receptor-related protein; TEER, transendothelial/transepithelial electrical resistance; COX-2, cyclooxygenase-2; iNOS, inducible nitric oxide synthase; IGF, insulin-like growth factor; IGFBP, insulin-like growth factor-binding protein; ZIP, Zrt-Irt-like protein; PPAR, peroxisome proliferator-activated receptors; p-PPAR, phosphorylated-peroxisome proliferator-activated receptors; ATF, activating transcription factors; SOD, superoxide dismutase; GSH-Px, glutathione peroxidase; SARA, subacute ruminal acidosis; IPEC-J2, porcine intestinal epithelial cells; ALI, acute lung injury; ARDS, acute respiratory distress syndrome.
Collapse
Affiliation(s)
- Faezeh Izadparast
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Bamdad Riahi-Zajani
- Medical Toxicology Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Fatemeh Yarmohammadi
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - A. Wallace Hayes
- Center for Environmental Occupational Risk Analysis and Management, College of Public Health, University of South Florida, Tampa, FL, USA
| | - Gholamreza Karimi
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| |
Collapse
|
|
27
|
Yang S, Hao S, Wang Q, Lou Y, Jia L, Chen D. The interactions between traditional Chinese medicine and gut microbiota: Global research status and trends. Front Cell Infect Microbiol 2022; 12:1005730. [PMID: 36171760 PMCID: PMC9510645 DOI: 10.3389/fcimb.2022.1005730] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Accepted: 08/22/2022] [Indexed: 11/15/2022] Open
Abstract
Background There is a crosstalk between traditional Chinese medicine (TCM) and gut microbiota (GM), many articles have studied and discussed the relationship between the two. The purpose of this study is to use bibliometric analysis to explore the research status and development trends of the TCM/GM research, identify and analyze the highly cited papers relating to the TCM/GM. Methods A literature search regarding TCM/GM publications from 2004 to 2021 was undertaken on August 13, 2022. The main information (full record and cited references) of publications was extracted from the Science Citation Index Expanded (SCI-E) of Web of Science Core Collection (WoSCC). The Bibliometrix of R package, CiteSpace and VOSviewer were used for bibliometric analysis. Results A total of 830 papers were included. The publication years of papers were from 2004 to 2021. The number of papers had increased rapidly since 2018. China had the most publications and made most contributions to this field. Nanjing University of Chinese Medicine and Beijing University of Chinese Medicine were in the leading productive position in TCM/GM research, Chinese Academy of Chinese Medical Sciences had the highest total citations (TC). Duan Jin-ao from Nanjing University of Chinese Medicine had the largest number of publications, and Tong Xiao-lin from China Academy of Chinese Medical Sciences had the most TC. The Journal of Ethnopharmacology had the most published papers and the most TC. The main themes in TCM/GM included the role of GM in TCM treatment of glucolipid metabolism diseases and lower gastrointestinal diseases; the mechanism of interactions between GM and TCM to treat diseases; the links between TCM/GM and metabolism; and the relationship between GM and oral bioavailability of TCM. Conclusion This study gained insight into the research status, hotspots and trends of global TCM/GM research, identified the most cited articles in TCM/GM and analyzed their characteristics, which may inform clinical researchers and practitioners’ future directions.
Collapse
Affiliation(s)
- Shanshan Yang
- Oncology Department of Integrated Traditional Chinese and Western Medicine, China-Japan Friendship Hospital, Beijing, China
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Shaodong Hao
- Sixth Clinical School of Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Qin Wang
- Oncology Department of Integrated Traditional Chinese and Western Medicine, China-Japan Friendship Hospital, Beijing, China
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Yanni Lou
- Oncology Department of Integrated Traditional Chinese and Western Medicine, China-Japan Friendship Hospital, Beijing, China
| | - Liqun Jia
- Oncology Department of Integrated Traditional Chinese and Western Medicine, China-Japan Friendship Hospital, Beijing, China
- *Correspondence: Liqun Jia, ; Dongmei Chen,
| | - Dongmei Chen
- Oncology Department of Integrated Traditional Chinese and Western Medicine, China-Japan Friendship Hospital, Beijing, China
- *Correspondence: Liqun Jia, ; Dongmei Chen,
| |
Collapse
|
|
28
|
Wang H, Zhang H, Gao Z, Zhang Q, Gu C. The mechanism of berberine alleviating metabolic disorder based on gut microbiome. Front Cell Infect Microbiol 2022; 12:854885. [PMID: 36093200 PMCID: PMC9452888 DOI: 10.3389/fcimb.2022.854885] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Accepted: 08/01/2022] [Indexed: 11/13/2022] Open
Abstract
With socioeconomic advances and improved living standards, metabolic syndrome has increasingly come into the attention. In recent decades, a growing number of studies have shown that the gut microbiome and its metabolites are closely related to the occurrence and development of many metabolic diseases, and play an important role that cannot be ignored, for instance, obesity, type 2 diabetes (T2DM), non-alcoholic fatty liver disease (NAFLD), cardiovascular disease and others. The correlation between gut microbiota and metabolic disorder has been widely recognized. Metabolic disorder could cause imbalance in gut microbiota, and disturbance of gut microbiota could aggravate metabolic disorder as well. Berberine (BBR), as a natural ingredient, plays an important role in the treatment of metabolic disorder. Studies have shown that BBR can alleviate the pathological conditions of metabolic disorders, and the mechanism is related to the regulation of gut microbiota: gut microbiota could regulate the absorption and utilization of berberine in the body; meanwhile, the structure and function of gut microbiota also changed after intervention by berberine. Therefore, we summarize relevant mechanism research, including the expressions of nitroreductases-producing bacteria to promote the absorption and utilization of berberine, strengthening intestinal barrier function, ameliorating inflammation regulating bile acid signal pathway and axis of bacteria-gut-brain. The aim of our study is to clarify the therapeutic characteristics of berberine further and provide the theoretical basis for the regulation of metabolic disorder from the perspective of gut microbiota.
Collapse
Affiliation(s)
- Han Wang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Haiyu Zhang
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Zezheng Gao
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Qiqi Zhang
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Chengjuan Gu
- Shenzhen Hospital (Futian), Guangzhou University of Chinese Medicine, Shenzhen, China
- *Correspondence: Chengjuan Gu,
| |
Collapse
|
|
29
|
Cheng H, Liu J, Tan Y, Feng W, Peng C. Interactions between gut microbiota and berberine, a necessary procedure to understand the mechanisms of berberine. J Pharm Anal 2022; 12:541-555. [PMID: 36105164 PMCID: PMC9463479 DOI: 10.1016/j.jpha.2021.10.003] [Citation(s) in RCA: 72] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2021] [Revised: 09/23/2021] [Accepted: 10/19/2021] [Indexed: 02/06/2023] Open
Abstract
Berberine (BBR), an isoquinoline alkaloid, has been found in many plants, such as Coptis chinensis Franch and Phellodendron chinense Schneid. Although BBR has a wide spectrum of pharmacological effects, its oral bioavailability is extremely low. In recent years, gut microbiota has emerged as a cynosure to understand the mechanisms of action of herbal compounds. Numerous studies have demonstrated that due to its low bioavailability, BBR can interact with the gut microbiota, thereby exhibiting altered pharmacological effects. However, no systematic and comprehensive review has summarized these interactions and their corresponding influences on pharmacological effects. Here, we describe the direct interactive relationships between BBR and gut microbiota, including regulation of gut microbiota composition and metabolism by BBR and metabolization of BBR by gut microbiota. In addition, the complex interactions between gut microbiota and BBR as well as the side effects and personalized use of BBR are discussed. Furthermore, we provide our viewpoint on future research directions regarding BBR and gut microbiota. This review not only helps to explain the mechanisms underlying BBR activity but also provides support for the rational use of BBR in clinical practice.
Collapse
Affiliation(s)
| | | | - Yuzhu Tan
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Wuwen Feng
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Cheng Peng
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| |
Collapse
|
|
30
|
Winiarska-Mieczan A, Tomaszewska E, Donaldson J, Jachimowicz K. The Role of Nutritional Factors in the Modulation of the Composition of the Gut Microbiota in People with Autoimmune Diabetes. Nutrients 2022; 14:2498. [PMID: 35745227 PMCID: PMC9227140 DOI: 10.3390/nu14122498] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Revised: 06/13/2022] [Accepted: 06/15/2022] [Indexed: 12/14/2022] Open
Abstract
Type 1 diabetes mellitus (T1DM) is a disease marked by oxidative stress, chronic inflammation, and the presence of autoantibodies. The gut microbiota has been shown to be involved in the alleviation of oxidative stress and inflammation as well as strengthening immunity, thus its' possible involvement in the pathogenesis of T1DM has been highlighted. The goal of the present study is to analyze information on the relationship between the structure of the intestinal microbiome and the occurrence of T1DM. The modification of the intestinal microbiota can increase the proportion of SCFA-producing bacteria, which could in turn be effective in the prevention and/or treatment of T1DM. The increased daily intake of soluble and non-soluble fibers, as well as the inclusion of pro-biotics, prebiotics, herbs, spices, and teas that are sources of phytobiotics, in the diet, could be important in improving the composition and activity of the microbiota and thus in the prevention of metabolic disorders. Understanding how the microbiota interacts with immune cells to create immune tolerance could enable the development of new therapeutic strategies for T1DM and improve the quality of life of people with T1DM.
Collapse
Affiliation(s)
- Anna Winiarska-Mieczan
- Department of Bromatology and Nutrition Physiology, Institute of Animal Nutrition and Bromatology, University of Life Sciences in Lublin, Akademicka St. 13, 20-950 Lublin, Poland;
| | - Ewa Tomaszewska
- Department of Animal Physiology, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, Akademicka St. 12, 20-950 Lublin, Poland
| | - Janine Donaldson
- School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, South Africa;
| | - Karolina Jachimowicz
- Department of Bromatology and Nutrition Physiology, Institute of Animal Nutrition and Bromatology, University of Life Sciences in Lublin, Akademicka St. 13, 20-950 Lublin, Poland;
| |
Collapse
|
|
31
|
Liu Y, Xu Z, Huang H, Xue Y, Zhang D, Zhang Y, Li W, Li X. Fucoidan ameliorates glucose metabolism by the improvement of intestinal barrier and inflammatory damage in type 2 diabetic rats. Int J Biol Macromol 2022; 201:616-629. [PMID: 35077745 DOI: 10.1016/j.ijbiomac.2022.01.102] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Revised: 12/26/2021] [Accepted: 01/15/2022] [Indexed: 12/19/2022]
Abstract
It has been reported that fucoidan possesses anti-diabetic activities by inhibiting α-glucosidase activity, improving β-cell dysfunction, and enhancing insulin sensitivity. However, as a macromolecular carbohydrate, fucoidan is rarely absorbed and indigestible in gastrointestinal tract. The study aimed to explore whether the fucoidan can regulate glucose metabolism by improving intestinal barrier and inflammation in type 2 diabetes mellitus (T2DM) rats. A high-fat diet combined with streptozotocin was used to induce T2DM rats. Different doses of fucoidan (50, 100 and 200 mg/kg) were administered respectively by lavage to T2DM rats for 8 weeks and saline was given to controls. The results showed that in addition to hyperglycemia and hyperlipidemia, T2DM rats were also characterized by increased intestinal permeability and proinflammatory cytokines. Notably, fucoidan reduced fasting blood glucose and insulin resistance index along with alleviated the accumulation of proinflammatory cytokines in T2DM rats. Furthermore, fucoidan repaired the intestinal barrier function, which was accompanied by the up-regulation of tight junction proteins and the improvement of intestinal inflammation via inhibiting TLR4/NF-κB signaling. Meanwhile, fucoidan also mitigated the liver damage, and alleviated insulin resistance by activating PI3K/AKT signaling. Collectively, these findings supported the potential of fucoidan to be used as a functional ingredient to prevent T2DM.
Collapse
Affiliation(s)
- Yaping Liu
- Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, China
| | - Ze Xu
- Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, China
| | - Haoyue Huang
- Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, China
| | - Yuan Xue
- Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, China
| | - Dongdong Zhang
- Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, China
| | - Yujing Zhang
- Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, China
| | - Wenjie Li
- Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, China.
| | - Xing Li
- Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, China.
| |
Collapse
|
|
32
|
Li H, Liu NN, Li JR, Dong B, Wang MX, Tan JL, Wang XK, Jiang J, Lei L, Li HY, Sun H, Jiang JD, Peng ZG. Combined Use of Bicyclol and Berberine Alleviates Mouse Nonalcoholic Fatty Liver Disease. Front Pharmacol 2022; 13:843872. [PMID: 35250593 PMCID: PMC8889073 DOI: 10.3389/fphar.2022.843872] [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] [Received: 12/27/2021] [Accepted: 01/12/2022] [Indexed: 11/20/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD), ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), is a liver disease worldwide without approved therapeutic drugs. Anti-inflammatory and hepatoprotective drug bicyclol and multi-pharmacological active drug berberine, respectively, have shown beneficial effects on NAFLD in murine nutritional models and patients, though the therapeutic mechanisms remain to be illustrated. Here, we investigated the combined effects of bicyclol and berberine on mouse steatosis induced by Western diet (WD), and NASH induced by WD/CCl4. The combined use of these was rather safe and better reduced the levels of transaminase in serum and triglycerides and cholesterol in the liver than their respective monotherapy, accompanied with more significantly attenuating hepatic inflammation, steatosis, and ballooning in mice with steatosis and NASH. The combined therapy also significantly inhibited fibrogenesis, characterized by the decreased hepatic collagen deposition and fibrotic surface. As per mechanism, bicyclol enhanced lipolysis and β-oxidation through restoring the p62-Nrf2-CES2 signaling axis and p62-Nrf2-PPARα signaling axis, respectively, while berberine suppressed de novo lipogenesis through downregulating the expression of acetyl-CoA carboxylase and fatty acid synthetase, along with enrichment of lipid metabolism-related Bacteroidaceae (family) and Bacteroides (genus). Of note, the combined use of bicyclol and berberine did not influence each other but enhanced the overall therapeutic role in the amelioration of NAFLD. Conclusion: Combined use of bicyclol and berberine might be a new available strategy to treat NAFLD.
Collapse
Affiliation(s)
- Hu Li
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Nan-Nan Liu
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jian-Rui Li
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Biao Dong
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Mei-Xi Wang
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jia-Li Tan
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xue-Kai Wang
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jing Jiang
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lei Lei
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hong-Ying Li
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Han Sun
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jian-Dong Jiang
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zong-Gen Peng
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Key Laboratory of Biotechnology of Antibiotics, The National Health and Family Planning Commission (NHFPC), Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| |
Collapse
|
|
33
|
Pu Z, Sun Y, Jiang H, Hou Q, Yan H, Wen H, Li G. Effects of Berberine on Gut Microbiota in Patients with Mild Metabolic Disorders Induced by Olanzapine. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2022; 49:1949-1963. [PMID: 34961418 DOI: 10.1142/s0192415x21500920] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Secondary metabolic disturbances in patients with schizophrenia or bipolar disorder may be attributed to olanzapine. It is important to prevent mild metabolic disorders progressing to metabolic syndrome. This study aims to investigate the effects of berberine on intestinal flora in patients with mild metabolic disorders induced by olanzapine. A total of 132 patients with schizophrenia, bipolar disorder, or schizoaffective psychosis that had been treated with olanzapine for at least 9 months were randomly assigned ([Formula: see text] = 66 each) to receive berberine or placebo tablets for 12 weeks. Metabolic assessments and intestinal flora were quantified at baseline and after 4, 8, and 12 weeks of treatment. Incidence rates of adverse reactions were recorded. FPG, FPI, HOMA-IR, HbA1, TG, BMI, and WC were significantly lower in patients who received berberine compared to placebo after 12 weeks of treatment ([Formula: see text]< 0.05). The abundance of firmicutes and coliform were significantly lower and the abundance of bacteroides significantly higher in patients who received berberine compared to placebo after 12 weeks of treatment ([Formula: see text]< 0.05). In patients who received berberine, the abundance of firmicutes was significantly decreased, and the abundance of bacteroides was significantly increased, and in patients who received placebo, the abundance of firmicutes was significantly increased post-treatment, compared to baseline (both [Formula: see text]< 0.05). In conclusions, berberine may regulate intestinal flora and metabolism in patients with schizophrenia or bipolar disorder and mild metabolic disturbances induced by olanzapine.
Collapse
Affiliation(s)
- Zhengping Pu
- Shanghai Mental Health Center, Shanghai Jiao Tong, University School of Medicine, Xuhui 200030, Shanghai, P. R. China.,Department of Psychiatry, Kangci Hospital of Jiaxing, Tongxiang 314500, Zhejiang, P. R. China
| | - Yunying Sun
- Endocrinology Department, First People's Hospital of Haining, Haining 314400, Zhejiang, P. R. China
| | - Hongxia Jiang
- Department of Psychiatry, Kangci Hospital of Jiaxing, Tongxiang 314500, Zhejiang, P. R. China
| | - Qingmei Hou
- Department of Clinical Psychology, The Second Specialized Hospital of Hegang, Hegang 154102, Heilongjiang, P. R. China
| | - Hui Yan
- Department of Psychiatry, Second People's Hospital of Taizhou, Tiantai 317200, Zhejiang, P. R. China
| | - Hui Wen
- Department of Traditional Chinese Medicine, Second People's Hospital of Tongxiang, Tongxiang 314500, Zhejiang, P. R. China
| | - Guorong Li
- Department of Psychiatry, Kangci Hospital of Jiaxing, Tongxiang 314500, Zhejiang, P. R. China
| |
Collapse
|
|
34
|
Anti-obesity natural products and gut microbiota. Food Res Int 2022; 151:110819. [PMID: 34980371 DOI: 10.1016/j.foodres.2021.110819] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 10/15/2021] [Accepted: 11/21/2021] [Indexed: 12/18/2022]
Abstract
The link between gut microbiota and obesity or other metabolic syndromes is growing increasingly clear. Natural products are appreciated for their beneficial health effects in humans. Increasing investigations demonstrated that the anti-obesity bioactivities of many natural products are gut microbiota dependent. In this review, we summarized the current knowledge on anti-obesity natural products acting through gut microbiota according to their chemical structures and signaling metabolites. Manipulation of the gut microbiota by natural products may serve as a potential therapeutic strategy to prevent obesity.
Collapse
|
|
35
|
Microbiome-based therapeutics: Opportunity and challenges. PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE 2022; 191:229-262. [DOI: 10.1016/bs.pmbts.2022.07.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
|
|
36
|
Khvostov MV, Gladkova ED, Borisov SA, Zhukova NA, Marenina MK, Meshkova YV, Luzina OA, Tolstikova TG, Salakhutdinov NF. Discovery of the First in Class 9-N-Berberine Derivative as Hypoglycemic Agent with Extra-Strong Action. Pharmaceutics 2021; 13:pharmaceutics13122138. [PMID: 34959419 PMCID: PMC8708145 DOI: 10.3390/pharmaceutics13122138] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Revised: 12/06/2021] [Accepted: 12/10/2021] [Indexed: 12/13/2022] Open
Abstract
Berberine is well known for its ability to reduce the blood glucose level, but its high effective dose and poor bioavailability limits its use. In this work we synthesized a new derivative of berberine, 9-(hexylamino)-2,3-methylenedioxy-10-methoxyprotoberberine chloride (SHE-196), and analyzed the profile of its hypoglycemic effects. Biological tests have shown that the substance has a very pronounced hypoglycemic activity due to increased insulin sensitivity after single and multiple dosing. In obese type 2 diabetes mellitus (T2DM) mice, it was characterized by improved glucose tolerance, decreased fasting insulin levels and sensitivity, decreased total body weight and interscapular fat mass, and increased interscapular brown fat activity. All these effects were also confirmed histologically, where a decrease in fatty degeneration of the liver, an improvement in the condition of the islets of Langerhans and a decrease in the size of fat droplets in brown adipose tissue were found. Our results indicate that 9-(hexylamino)-2,3-methylenedioxy-10-methoxyprotoberberine chloride could be the first in a new series of therapeutic agents for the treatment of diabetes mellitus.
Collapse
|
|
37
|
Chen Y, Wang M. New Insights of Anti-Hyperglycemic Agents and Traditional Chinese Medicine on Gut Microbiota in Type 2 Diabetes. Drug Des Devel Ther 2021; 15:4849-4863. [PMID: 34876807 PMCID: PMC8643148 DOI: 10.2147/dddt.s334325] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2021] [Accepted: 11/19/2021] [Indexed: 12/11/2022] Open
Abstract
Type 2 diabetes mellitus (T2DM) is a widespread metabolic disease characterized by chronic hyperglycemia. Human microbiota, which is regarded as a “hidden organ”, plays an important role in the initiation and development of T2DM. In addition, anti-hyperglycemic agents and traditional Chinese medicine may affect the composition of gut microbiota and consequently improve glucose metabolism. However, the relationship between gut microbiota, T2DM and anti-hyperglycemic agents or traditional Chinese medicine is poorly understood. In this review, we summarized pre-clinical and clinical studies to elucidate the possible underlying mechanism. Some anti-hyperglycemic agents and traditional Chinese medicine may partly exert hypoglycemic effects by altering the gut microbiota composition in ways that reduce metabolic endotoxemia, maintain the integrity of intestinal mucosal barrier, promote the production of short-chain fatty acids (SCFAs), decrease trimethylamine-N-oxide (TMAO) and regulate bile acid metabolism. In conclusion, gut microbiota may provide some new therapeutic targets for treatment of patients with diabetes mellitus.
Collapse
Affiliation(s)
- Yanxia Chen
- Department of Endocrinology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050051, People's Republic of China
| | - Mian Wang
- Department of Endocrinology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050051, People's Republic of China
| |
Collapse
|
|
38
|
Potencjalne możliwości wykorzystania berberyny w przeciwdziałaniu insulinooporności i w cukrzycy typu 2. POSTEP HIG MED DOSW 2021. [DOI: 10.2478/ahem-2021-0038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Abstrakt
Insulinooporność to stan zmniejszonej wrażliwości tkanek docelowych na działanie insuliny, mimo jej prawidłowego lub podwyższonego stężenia w surowicy krwi. Jest ważnym czynnikiem w patogenezie zespołu metabolicznego, w tym stanu przedcukrzycowego i cukrzycy typu 2, a także chorób sercowo-naczyniowych oraz zespołu policystycznych jajników. Wzrasta zainteresowanie wykorzystaniem środków pochodzenia roślinnego w leczeniu pacjentów z chorobami metabolicznymi. Jednymi z nich są rośliny z rodziny berberysowatych zawierające alkaloidy izochinolinowe, takie jak berberyna. Sugeruje się, iż berberyna może wpływać na zmniejszenie insulinooporności, gospodarkę węglowodanową oraz metabolizm lipidów. Naukowcy wykazali, że ten roślinny alkaloid może tłumić różnicowanie adipocytów i wspomagać redukcję masy ciała. Inne właściwości berberyny obejmują działanie hipotensyjne oraz ochronne wobec śródbłonka naczyniowego. W artykule skoncentrowano się przede wszystkim na przedstawieniu potencjalnych możliwości wykorzystania berberyny w przeciwdziałaniu insulinooporności w cukrzycy typu 2.
Collapse
|
|
39
|
Natural Ingredients from Medicine Food Homology as Chemopreventive Reagents against Type 2 Diabetes Mellitus by Modulating Gut Microbiota Homoeostasis. Molecules 2021; 26:molecules26226934. [PMID: 34834027 PMCID: PMC8625827 DOI: 10.3390/molecules26226934] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Revised: 11/10/2021] [Accepted: 11/11/2021] [Indexed: 01/30/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM) is a noteworthy worldwide public health problem. It represents a complex metabolic disorder, mainly characterized as hyperglycemia and lipid dysfunction. The gut microbiota dysbiosis has been proposed to play a role in the development of diabetes. Recently, there has been considerable interest in the use of medicine food homology (MFH) and functional food herbs (FF) to ameliorate diabetes and lead to a natural and healthy life. Hence, this review compiles some reports and findings to demonstrate that the practical use of the MFH/FF can modulate the homoeostasis of gut microbiota, thereby ameliorating the development of T2DM. The results provided useful data to support further investigation of the functional basis and application of MFH/FF to treat T2DM through maintaining intestinal homeostasis.
Collapse
|
|
40
|
Yan LS, Cheng BCY, Zhang SF, Luo G, Zhang C, Wang QG, Fu XQ, Wang YW, Zhang Y. Tibetan Medicine for Diabetes Mellitus: Overview of Pharmacological Perspectives. Front Pharmacol 2021; 12:748500. [PMID: 34744728 PMCID: PMC8566911 DOI: 10.3389/fphar.2021.748500] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Accepted: 10/04/2021] [Indexed: 11/13/2022] Open
Abstract
Diabetes mellitus (DM) and its complications pose a major public health threat which is approaching epidemic proportions globally. Current drug options may not provide good efficacy and even cause serious adverse effects. Seeking safe and effective agents for DM treatment has been an area of intensive interest. As a healing system originating in Tibet, Traditional Tibetan Medicine (TTM) has been widely used by Tibetan people for the prevention and treatment of DM and its complications for hundreds of years. Tibetan Materia Medica (TMM) including the flower of Edgeworthia gardneri (Wall.) Meisn., Phyllanthi Fructus, Chebulae Fructus, Huidouba, and Berberidis Cortex are most frequently used and studied. These TMMs possess hypoglycemic, anti-insulin resistant, anti-glycation, lipid lowering, anti-inflammatory, and anti-oxidative effects. The underlying mechanisms of these actions may be related to their α-glucosidase inhibitory, insulin signaling promoting, PPARs-activating, gut microbiota modulation, islet β cell-preserving, and TNF-α signaling suppressive properties. This review presents a comprehensive overview of the mode and mechanisms of action of various active constituents, extracts, preparations, and formulas from TMM. The dynamic beneficial effects of the products prepared from TMM for the management of DM and its complications are summarized. These TMMs are valuable materia medica which have the potential to be developed as safe and effective anti-DM agents.
Collapse
Affiliation(s)
- Li-Shan Yan
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Brian Chi-Yan Cheng
- College of Professional and Continuing Education, Hong Kong Polytechnic University, Hong Kong, China
| | - Shuo-Feng Zhang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Gan Luo
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Chao Zhang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Qing-Gao Wang
- First Affiliated Hospital, Guangxi University of Chinese Medicine, Guangxi, China
| | - Xiu-Qiong Fu
- Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China
| | - Yi-Wei Wang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Yi Zhang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| |
Collapse
|
|
41
|
Shaping the gut microbiota by bioactive phytochemicals: An emerging approach for the prevention and treatment of human diseases. Biochimie 2021; 193:38-63. [PMID: 34688789 DOI: 10.1016/j.biochi.2021.10.010] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 09/30/2021] [Accepted: 10/16/2021] [Indexed: 12/11/2022]
Abstract
The human digestive tract is the cottage to trillions of live microorganisms, which regulate health and illness. A healthy Gut Microbiota (GM) is necessary for preventing microbial growth, body growth, obesity, cancer, diabetes, and enhancing immunity. The equilibrium in GM's composition and the presence/absence of critical species enable specific responses to be essential for the host's better health condition. Research evidences revealed that the dietary plants and their bioactive phytochemicals (BPs) play an extensive and critical role in shaping the GM to get beneficial health effects. BPs are also known to improve gastrointestinal health and reduce the risk of several diseases by modulating GM-mediated cellular and molecular processes. Regular intake of BPs-rich vegetables, fruits, and herbal preparations promotes probiotic bacteria, including Bifidobacteria and Lactobacillus species, while inhibiting unwanted gut residents' development Escherichia coli, and Salmonella typhimurium etc. Upon consumption, BPs contact the GM that gets transformed before being absorbed from the gastrointestinal tract. Biotransformation of BPs by GM is linked with the enhancement of bioactivity/toxicity diminishment of the BPs compared to parental phytochemicals. Therefore, the current review focuses on the role of BPs in shaping GM for the prevention and treatment of human diseases.
Collapse
|
|
42
|
Rondanelli M, Riva A, Petrangolini G, Allegrini P, Giacosa A, Fazia T, Bernardinelli L, Gasparri C, Peroni G, Perna S. Berberine Phospholipid Is an Effective Insulin Sensitizer and Improves Metabolic and Hormonal Disorders in Women with Polycystic Ovary Syndrome: A One-Group Pretest-Post-Test Explanatory Study. Nutrients 2021; 13:3665. [PMID: 34684666 PMCID: PMC8538182 DOI: 10.3390/nu13103665] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 10/15/2021] [Accepted: 10/15/2021] [Indexed: 12/22/2022] Open
Abstract
Polycystic Ovary Syndrome (PCOS) is the most frequent endocrine disease in females of reproductive age and is characterized by multifactorial unhealthy conditions related to hormonal unbalance and also to dysmetabolism and inflammation. Recently, increasing evidence has shown that natural plant-based products may play a role in PCOS management. The aim of this one-group pretest-post-test explanatory study was to evaluate, in normal-overweight PCOS women with normal menses, the effectiveness of berberine on: Insulin resistance (IR) by Homeostasis Model Assessment (HOMA); Inflammation by C-Reactive Protein (CRP), Tumor Necrosis Factor α (TNF-α); Lipid metabolism; Sex hormone profile and symptoms correlated to hyperandrogenism, such as acne, by Global Acne Grading System (GAGS) and Cardiff Acne Disability Index (CADI); Body composition by DXA. Finally, adverse effects were assessed by liver and kidney functions and creatine phosphokinase (CPK). All these parameters were collected at baseline and 60 days after supplementation with a new bioavailable and safe berberine formulation. Twelve females (aged 26.6 ± 4.9, BMI 25.3 ± 3.6) were supplied for 60 days with two tablets/day (550 mg/table) of the bioavailable berberine. Results showed a statistically significant decrease in HOMA, CRP, TNF-α, Triglycerides, testosterone, Body Mass Index (BMI), Visceral Adipose Tissue (VAT), fat mass, GAGS and CADI scores, and a statistically significant increase in sex hormone-binding globulin (SHBG). Liver and kidney functions and CPK are not statistically significantly different. Therefore, berberine can represent a safe novel dietary supplement, helpful in treatment strategy for PCOS.
Collapse
Affiliation(s)
- Mariangela Rondanelli
- IRCCS Mondino Foundation, 27100 Pavia, Italy;
- Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy
| | - Antonella Riva
- Research and Development Department, Indena SpA, 20139 Milan, Italy; (A.R.); (G.P.); (P.A.)
| | - Giovanna Petrangolini
- Research and Development Department, Indena SpA, 20139 Milan, Italy; (A.R.); (G.P.); (P.A.)
| | - Pietro Allegrini
- Research and Development Department, Indena SpA, 20139 Milan, Italy; (A.R.); (G.P.); (P.A.)
| | - Attilio Giacosa
- Department of Gastroenterology and Clinical Nutrition, Policlinico di Monza, Via Amati 111, 20900 Monza, Italy;
| | - Teresa Fazia
- Department of Brain and Behavioral Science, University of Pavia, 27100 Pavia, Italy; (T.F.); (L.B.)
| | - Luisa Bernardinelli
- Department of Brain and Behavioral Science, University of Pavia, 27100 Pavia, Italy; (T.F.); (L.B.)
| | - Clara Gasparri
- Endocrinology and Nutrition Unit, Azienda di Servizi Alla Persona ‘‘Istituto Santa Margherita’’, University of Pavia, 27100 Pavia, Italy;
| | - Gabriella Peroni
- Endocrinology and Nutrition Unit, Azienda di Servizi Alla Persona ‘‘Istituto Santa Margherita’’, University of Pavia, 27100 Pavia, Italy;
| | - Simone Perna
- Department of Biology, College of Science, Sakhir Campus, University of Bahrain, Zallaq 32038, Bahrain;
| |
Collapse
|
|
43
|
Xi Y, Xu PF. Diabetes and gut microbiota. World J Diabetes 2021; 12:1693-1703. [PMID: 34754371 PMCID: PMC8554376 DOI: 10.4239/wjd.v12.i10.1693] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Revised: 04/20/2021] [Accepted: 08/05/2021] [Indexed: 02/06/2023] Open
Abstract
The prevalence of diabetes has increased rapidly throughout the world in recent years. Currently, approximately 463 million people are living with diabetes, and the number has tripled over the last two decades. Here, we describe the global epidemiology of diabetes in 2019 and forecast the trends to 2030 and 2045 in China, India, USA, and the globally. The gut microbiota plays a major role in metabolic diseases, especially diabetes. In this review, we describe the interaction between diabetes and gut microbiota in three aspects: probiotics, antidiabetic medication, and diet. Recent findings indicate that probiotics, antidiabetic medications, or dietary interventions treat diabetes by shifting the gut microbiome, particularly by raising beneficial bacteria and reducing harmful bacteria. We conclude that targeting the gut microbiota is becoming a novel therapeutic strategy for diabetes.
Collapse
Affiliation(s)
- Yue Xi
- Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA 15261, USA
| | - Peng-Fei Xu
- Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA 15261, USA
- Key Laboratory for Cell Proliferation and Regulation Biology of State Education Ministry, College of Life Sciences, Beijing Normal University, Beijing 100875, China
| |
Collapse
|
|
44
|
Xu G, Wan H, Yi L, Chen W, Luo Y, Huang Y, Liu X. Berberine administrated with different routes attenuates inhaled LPS-induced acute respiratory distress syndrome through TLR4/NF-κB and JAK2/STAT3 inhibition. Eur J Pharmacol 2021; 908:174349. [PMID: 34284014 PMCID: PMC8285933 DOI: 10.1016/j.ejphar.2021.174349] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 07/07/2021] [Accepted: 07/12/2021] [Indexed: 12/17/2022]
Abstract
Accumulating evidence showed that berberine possessed the anti-inflammatory action in various diseases caused by inflammation. However, it was still unclear whether both inhalation and injection with berberine produced pulmonary protective role in acute respiratory distress syndrome (ARDS). This study was aimed to evaluate the effects of both administration routes including inhalation and injection with berberine in ARDS induced by lipopolysaccharide (LPS) inhalation. Histopathological examination and weight of lung were evaluated. Phosphorylation of NF-κB, JAK2 and STAT3 were measured to assess the activity of inflammation related signaling pathways. Proinflammatory cytokines including interleukin (IL)-1β and tumor necrosis factor (TNF)-α in the bronchoalveolar lavage fluid (BALF) and serum were also detected. The results showed that LPS caused the lung injury, while both administration routes with berberine attenuated the injury and improved the pulmonary morphology. In addition, the primary TLR4/NF-κB and secondary JAK2/STAT3 signaling pathways which were activated by LPS in lung were totally inhibited by berberine administration. Moreover, proinflammatory cytokines in both BALF and serum were decreased by berberine. Considering that molecular docking simulation indicated that berberine could bind with TLR4, the present suggested that the inhibition of the inflammation related TLR4/NF-κB and JAK2/STAT3 signaling pathways might be involved in the pulmonary protective effect of berberine in LPS-induced ARDS.
Collapse
Affiliation(s)
- Guanghui Xu
- Pharmaceutical Research Center, Xiamen Medicine Research Institute, Xiamen, 361008, Fujian province, PR China.
| | - Huiqi Wan
- Pharmaceutical Research Center, Xiamen Medicine Research Institute, Xiamen, 361008, Fujian province, PR China
| | - Litao Yi
- Department of Chemical and Pharmaceutical Engineering, College of Chemical Engineering, Huaqiao University, Xiamen, 361021, Fujian province, PR China.
| | - Wei Chen
- Pharmaceutical Research Center, Xiamen Medicine Research Institute, Xiamen, 361008, Fujian province, PR China
| | - Youhua Luo
- Pharmaceutical Research Center, Xiamen Medicine Research Institute, Xiamen, 361008, Fujian province, PR China
| | - Yiqi Huang
- Pharmaceutical Research Center, Xiamen Medicine Research Institute, Xiamen, 361008, Fujian province, PR China
| | - Xiaojuan Liu
- Pharmaceutical Research Center, Xiamen Medicine Research Institute, Xiamen, 361008, Fujian province, PR China
| |
Collapse
|
|
45
|
Pharmacokinetics and Pharmacological Activities of Berberine in Diabetes Mellitus Treatment. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:9987097. [PMID: 34471420 PMCID: PMC8405293 DOI: 10.1155/2021/9987097] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Revised: 08/09/2021] [Accepted: 08/16/2021] [Indexed: 02/07/2023]
Abstract
Traditional Chinese medicine (TCM) has good clinical application prospects in diabetes treatment. In addition, TCM is less toxic and/or has fewer side effects and provides various therapeutic effects. Berberine (BBR) is isolated as the main component in many TCM kinds (e.g., Rhizoma Coptidis and Berberidis Cortex). Furthermore, BBR can reduce blood sugar and blood fat, alleviate inflammation, and improve the state of patients. Based on the recent study results of BBR in diabetes treatment, the BBR pharmacokinetics and mechanism on diabetes are mainly studied, and the specific molecular mechanism of related experimental BBR is systematically summarized and analyzed. Clinical studies have proved that BBR has a good therapeutic effect on diabetes, suggesting that BBR may be a promising drug candidate for diabetes. More detailed BBR mechanisms and pathways of BBR need to be studied further in depth, which will help understand the BBR pharmacology in diabetes treatment.
Collapse
|
|
46
|
Xia F, Wen LP, Ge BC, Li YX, Li FP, Zhou BJ. Gut microbiota as a target for prevention and treatment of type 2 diabetes: Mechanisms and dietary natural products. World J Diabetes 2021; 12:1146-1163. [PMID: 34512884 PMCID: PMC8394227 DOI: 10.4239/wjd.v12.i8.1146] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 05/10/2021] [Accepted: 07/05/2021] [Indexed: 02/06/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM) is among the most remarkable public health concerns globally. Accumulating research evidence documents that alteration of gut microbiota has an indispensable role in the onset and progression of obesity and T2DM. A reduced microbial diversity is linked to insulin resistance and energy metabolism, especially for the rise of the Firmicutes/Bacteroidetes ratio. Changes in metabolites followed by the gut dysbacteriosis are linked to the presence of T2DM. Moreover, endotoxin leakage and gut permeability caused by gut dysbacteriosis is more of a trigger for the onset and progression of T2DM. Research documents that natural products are remarkable arsenals of bioactive agents for the discovery of anti-T2DM drugs. Many studies have elucidated that the possible mechanisms of the anti-T2DM effects of natural products are remarkably linked to its regulation on the composition of gut microflora and the successive changes in metabolites directly or indirectly. This review presents a brief overview of the gut microbiota in T2DM and several relevant mechanisms, including short-chain fatty acids, biosynthesis and metabolism of branched-chain fatty acids, trimethylamine N-oxide, bile acid signaling, endotoxin leakage, and gut permeability, and describes how dietary natural products can improve T2DM via the gut microbiota.
Collapse
Affiliation(s)
- Fan Xia
- Department of Pharmacy, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen 518107, Guangdong Province, China
| | - Lu-Ping Wen
- Department of Pharmacy, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen 518107, Guangdong Province, China
| | - Bing-Chen Ge
- Department of Pharmacy, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen 518107, Guangdong Province, China
| | - Yu-Xin Li
- Department of Pharmacology, Guangdong Medical University, Zhanjiang 524023, Guangdong Province, China
| | - Fang-Ping Li
- Department of Endocrinology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen 518107, Guangdong Province, China
| | - Ben-Jie Zhou
- Department of Pharmacy, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen 518107, Guangdong Province, China
| |
Collapse
|
|
47
|
Ming J, Yu X, Xu X, Wang L, Ding C, Wang Z, Xie X, Li S, Yang W, Luo S, He Q, Du Y, Tian Z, Gao X, Ma K, Fang Y, Li C, Zhao J, Wang X, Ji Q. Effectiveness and safety of Bifidobacterium and berberine in human hyperglycemia and their regulatory effect on the gut microbiota: a multi-center, double-blind, randomized, parallel-controlled study. Genome Med 2021; 13:125. [PMID: 34365978 PMCID: PMC8351344 DOI: 10.1186/s13073-021-00942-7] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Accepted: 07/21/2021] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND Berberine and Bifidobacterium have been reported to improve glucose tolerance in people with hyperglycemia or other metabolic disorders. This study aimed to assess the hypoglycemic effect and the regulation of the gut microbiota caused by berberine and Bifidobacterium and the possible additive benefits of their combination. METHODS This was an 18-week, multi-center, randomized, double-blind, parallel-controlled study of patients newly diagnosed with hyperglycemia. After a 2-week run-in period, 300 participants were randomly assigned to the following four groups for 16 weeks of treatment: berberine (Be), Bifidobacterium (Bi), berberine and Bifidobacterium (BB), and placebo group. The primary efficacy endpoint was the absolute value of fasting plasma glucose (FPG) compared with baseline after 16 weeks of treatment. RESULTS Between October 2015 and April 2018, a total of 297 participants were included in the primary analysis. Significant reductions of FPG were observed in the Be and BB groups compared with the placebo group, with a least square (LS) mean difference of - 0.50, 95% CI [- 0.85, - 0.15] mmol/L, and - 0.55, 95% CI [- 0.91, - 0.20] mmol/L, respectively. The Be and BB groups also showed significant reductions in 2-h postprandial plasma glucose. A pronounced decrease in HbA1c occurred in the BB group compared to the placebo group. Moreover, compared with the Bi and placebo groups, the Be and BB groups had more changes in the gut microbiota from the baseline. CONCLUSIONS Berberine could regulate the structure and function of the human gut microbiota, and Bifidobacterium has the potential to enhance the hypoglycemic effect of berberine. These findings provide new insights into the hypoglycemic potential of berberine and Bifidobacterium. TRIAL REGISTRATION ClinicalTrials.gov , NCT03330184. Retrospectively registered on 18 October 2017.
Collapse
Affiliation(s)
- Jie Ming
- Endocrinology Research Center, Department of Endocrinology and Metabolism, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China
| | - Xinwen Yu
- Endocrinology Research Center, Department of Endocrinology and Metabolism, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China
| | | | - Li Wang
- Endocrinology Research Center, Department of Endocrinology and Metabolism, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China
| | - Chao Ding
- Department of General Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
| | | | - Xuan Xie
- Department of Endocrinology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Sheli Li
- Department of Endocrinology, Affiliated Hospital of Yan'an University, Yan'an, China
| | - Wenjuan Yang
- The Fifth Department of Internal Medicine, Shaanxi Aerospace Hospital, Xi'an, China
- Department of Endocrinology, Xi'an Daxing Hospital, Xi'an, China
| | - Shu Luo
- Genertec Universal Xi'an Aero-Engine Hospital, Xi'an, China
| | - Qingzhen He
- Department of Endocrinology, Xi'an High-Tech Hospital, Xi'an, China
| | - Yafang Du
- Department of Endocrinology, Chang'an Hospital, Xi'an, China
| | - Zhufang Tian
- Department of Endocrinology, Xi'an Central Hospital, Xi'an, China
| | - Xiling Gao
- Department of Endocrinology, Yan'an People's Hospital, Yan'an, China
| | - Kaiyan Ma
- Department of Endocrinology, Shangluo Central Hospital, Shangluo, China
| | - Yujie Fang
- Endocrinology Research Center, Department of Endocrinology and Metabolism, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China
| | - Chen Li
- Department of Health Statistics, Fourth Military Medical University, Xi'an, China
| | - Jiajun Zhao
- Department of Endocrinology and Metabolism, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China.
| | | | - Qiuhe Ji
- Endocrinology Research Center, Department of Endocrinology and Metabolism, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
| |
Collapse
|
|
48
|
Diabetes Mellitus and Cardiovascular Diseases: Nutraceutical Interventions Related to Caloric Restriction. Int J Mol Sci 2021; 22:ijms22157772. [PMID: 34360538 PMCID: PMC8345941 DOI: 10.3390/ijms22157772] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 07/15/2021] [Accepted: 07/18/2021] [Indexed: 12/17/2022] Open
Abstract
Type 2 diabetes (T2DM) and cardiovascular disease (CVD) are closely associated and represent a key public health problem worldwide. An excess of adipose tissue, NAFLD, and gut dysbiosis establish a vicious circle that leads to chronic inflammation and oxidative stress. Caloric restriction (CR) is the most promising nutritional approach capable of improving cardiometabolic health. However, adherence to CR represents a barrier to patients and is the primary cause of therapeutic failure. To overcome this problem, many different nutraceutical strategies have been designed. Based on several data that have shown that CR action is mediated by AMPK/SIRT1 activation, several nutraceutical compounds capable of activating AMPK/SIRT1 signaling have been identified. In this review, we summarize recent data on the possible role of berberine, resveratrol, quercetin, and L-carnitine as CR-related nutrients. Additionally, we discuss the limitations related to the use of these nutrients in the management of T2DM and CVD.
Collapse
|
|
49
|
Plants Secondary Metabolites as Blood Glucose-Lowering Molecules. Molecules 2021; 26:molecules26144333. [PMID: 34299610 PMCID: PMC8307461 DOI: 10.3390/molecules26144333] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 07/06/2021] [Accepted: 07/07/2021] [Indexed: 02/06/2023] Open
Abstract
Recently, significant advances in modern medicine and therapeutic agents have been achieved. However, the search for effective antidiabetic drugs is continuous and challenging. Over the past decades, there has been an increasing body of literature related to the effects of secondary metabolites from botanical sources on diabetes. Plants-derived metabolites including alkaloids, phenols, anthocyanins, flavonoids, stilbenoids, saponins, tannins, polysaccharides, coumarins, and terpenes can target cellular and molecular mechanisms involved in carbohydrate metabolism. In addition, they can grant protection to pancreatic beta cells from damage, repairing abnormal insulin signaling, minimizing oxidative stress and inflammation, activating AMP-activated protein kinase (AMPK), and inhibiting carbohydrate digestion and absorption. Studies have highlighted many bioactive naturally occurring plants' secondary metabolites as candidates against diabetes. This review summarizes the current knowledge compiled from the latest studies published during the past decade on the mechanism-based action of plants-derived secondary metabolites that can target various metabolic pathways in humans against diabetes. It is worth mentioning that the compiled data in this review will provide a guide for researchers in the field, to develop candidates into environment-friendly effective, yet safe antidiabetics.
Collapse
|
|
50
|
Yang S, Li D, Yu Z, Li Y, Wu M. Multi-Pharmacology of Berberine in Atherosclerosis and Metabolic Diseases: Potential Contribution of Gut Microbiota. Front Pharmacol 2021; 12:709629. [PMID: 34305616 PMCID: PMC8299362 DOI: 10.3389/fphar.2021.709629] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 06/29/2021] [Indexed: 12/13/2022] Open
Abstract
Atherosclerosis (AS), especially atherosclerotic cardiovascular diseases (ASCVDs), and metabolic diseases (such as diabetes, obesity, dyslipidemia, and nonalcoholic fatty liver disease) are major public health issues worldwide that seriously threaten human health. Exploring effective natural product-based drugs is a promising strategy for the treatment of AS and metabolic diseases. Berberine (BBR), an important isoquinoline alkaloid found in various medicinal plants, has been shown to have multiple pharmacological effects and therapeutic applications. In view of its low bioavailability, increasing evidence indicates that the gut microbiota may serve as a target for the multifunctional effects of BBR. Under the pathological conditions of AS and metabolic diseases, BBR improves intestinal barrier function and reduces inflammation induced by gut microbiota-derived lipopolysaccharide (LPS). Moreover, BBR reverses or induces structural and compositional alterations in the gut microbiota and regulates gut microbe-dependent metabolites as well as related downstream pathways; this improves glucose and lipid metabolism and energy homeostasis. These findings at least partly explain the effect of BBR on AS and metabolic diseases. In this review, we elaborate on the research progress of BBR and its mechanisms of action in the treatment of AS and metabolic diseases from the perspective of gut microbiota, to reveal the potential contribution of gut microbiota to the multifunctional biological effects of BBR.
Collapse
Affiliation(s)
- Shengjie Yang
- Guang’an men Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Dan Li
- Guang’an men Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Zongliang Yu
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yujuan Li
- Guang’an men Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Min Wu
- Guang’an men Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| |
Collapse
|