|
1
|
Zhao Z, Deng Y, Li L, Zhu L, Wang X, Sun H, Li X, Han X, Li J. Enhancing Akkermansia growth via phytohormones: a strategy to modulate the gut-bone axis in postmenopausal osteoporosis therapy. J Transl Med 2025; 23:410. [PMID: 40205438 PMCID: PMC11984252 DOI: 10.1186/s12967-025-06426-1] [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: 09/09/2024] [Accepted: 03/25/2025] [Indexed: 04/11/2025] Open
Abstract
BACKGROUND Phytohormones have garnered considerable interest as potential modulators of the gut-bone axis. Denosumab (Deno), a widely utilized therapeutic agent for postmenopausal osteoporosis, has not been previously investigated for its effects on gut health. The objective of this study was to assess the efficacy of isoflavones (SI), naringin (Nar), and Deno in the management of postmenopausal osteoporosis by targeting the gut-bone axis. METHODS The postmenopausal osteoporosis model in mice was established via bilateral oophorectomy. Subsequently, mice in the Deno group received subcutaneous injections of Deno at a dosage of 10 mg/kg, administered twice weekly. In contrast, mice in the SI and Nar groups were subjected to oral gavage with 200 mg/kg/day of SI and Nar, respectively. The treatment period for all groups lasted for 8 weeks. Upon the conclusion of the experiment, a thorough evaluation of the effects of SI, Nar, and Deno on bone and gut health in mice was conducted through immunological, pathological, imaging, and multi-omics methodologies. RESULTS Deno, SI, and Nar significantly alleviated the physical symptoms in postmenopausal mice. However, only SI and Nar significantly modulated the gut microbiota. Akkermansia was significantly enriched after the gavage of SI and Nar. Akkermansia has the capacity to not only augment bone mass and alleviate strength deterioration via extracellular vesicles, but it also influences bone metabolism by diminishing inflammation and modulating lipid metabolism. Notably, no significant changes in the gut microbiota were observed in the Deno group, which may be attributed to the differences in the method of administration, as Deno was administered via subcutaneous injection rather than gavage. CONCLUSION SI and Nar may influence the gut-bone axis through Akkermansia and have the potential of alternative treatment options for postmenopausal osteoporosis. Although the gut microbiota is not significantly affected by the subcutaneous administration of Deno, the long-term management of postmenopausal osteoporosis and the exploration of various management models warrant additional scrutiny. Furthermore, this study has yet to establish a dose-response relationship, indicating that further research is essential to clarify the regulatory effects of varying doses of SI and Nar on postmenopausal osteoporosis especially the modulation of gut microbiota.
Collapse
Affiliation(s)
- Zhiqi Zhao
- State Key Laboratory for Quality and Safety of Agro-Products & Institute of Food Sciences, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China
- Department of Orthopedics, The First Hospital of Shanxi Medical University, Taiyuan, 030000, China
| | - Yixuan Deng
- School of Medicine, Wenzhou Medical University, Chashan University Town, Wenzhou, 325035, Zhejiang, People's Republic of China
| | - Li Li
- Clinical Medical College, Hangzhou Normal University, Hangzhou, 30021, China
| | - Liying Zhu
- State Key Laboratory for Quality and Safety of Agro-Products & Institute of Food Sciences, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China
| | - Xin Wang
- State Key Laboratory for Quality and Safety of Agro-Products & Institute of Food Sciences, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China
| | - Haibiao Sun
- Department of Orthopedics, The First Hospital of Shanxi Medical University, Taiyuan, 030000, China
| | - Xiaoqiong Li
- State Key Laboratory for Quality and Safety of Agro-Products & Institute of Food Sciences, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China.
| | - Xiaoqiang Han
- Department of Orthopedics, The First Hospital of Shanxi Medical University, Taiyuan, 030000, China.
| | - Jinjun Li
- State Key Laboratory for Quality and Safety of Agro-Products & Institute of Food Sciences, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China.
| |
Collapse
|
|
2
|
Jawad M, Talcott ST, Hillman AR, Brannan RG. A Comprehensive Polyphenolic Characterization of Five Montmorency Tart Cherry ( Prunus cerasus L.) Product Formulations. Foods 2025; 14:1154. [PMID: 40238295 PMCID: PMC11988622 DOI: 10.3390/foods14071154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2025] [Revised: 03/24/2025] [Accepted: 03/25/2025] [Indexed: 04/18/2025] Open
Abstract
The Montmorency tart cherry (Prunus cerasus L., MTC) polyphenols may contribute to reduced inflammation and oxidative stress biomarkers in the body. However, a comprehensive polyphenolic profile of MTC products is lacking. This study provides a comparative analysis of the polyphenolic distribution of individual anthocyanins, flavonols, flavanols, hydroxycinnamic acids, and hydroxybenzoic acids in five MTC products (frozen raw fruit, freeze-dried powder, sweet dried fruit, unsweetened dried fruit, juice concentrate). Twenty-three polyphenols were detected, and 21 were positively identified. Results from three replicates indicate that frozen raw MTC has the most total polyphenolics. Juice concentrate, unsweetened dried MTC, freeze-dried MTC powder, and sweet dried MTC contained 26%, 40%, 60%, and 77% fewer total polyphenolics than frozen raw MTC. Hydroxycinnamic acids, flavonols, and anthocyanins predominated, accounting for 87-99% of total polyphenols in MTC products. Chlorogenic acid, rutin, cyanidin-3-sophoroside, feruloquinic acid, ferulic acid, and coumaric acid isomers were noteworthy polyphenolics. Hydroxycinnamic acids predominated in sweet dried (82%), unsweetened dried (74%), juice concentrate (66%), and frozen-raw (54%) MTC. Flavonols predominated in freeze-dried MTC powder (52%). Anthocyanins, particularly cyanidin glycosides, were important polyphenolics in frozen-raw cherries (18%) but less so in other MTC products. These findings highlight the variability in polyphenols in MTC products and emphasize the importance of selecting appropriate MTC products for specific health benefits.
Collapse
Affiliation(s)
- Muhammad Jawad
- Department of Translational Biomedical Sciences, Ohio University, Athens, OH 45701, USA;
| | - Stephen T. Talcott
- Department of Food Science & Technology, Texas A&M University, College Station, TX 77845, USA;
| | - Angela R. Hillman
- Department of Exercise Physiology, Ohio University, Athens, OH 45701, USA;
| | - Robert G. Brannan
- Department of Food and Nutrition Sciences, Ohio University, Athens, OH 45701, USA
| |
Collapse
|
|
3
|
Kozłowska A. Clinical Insights into Non-Alcoholic Fatty Liver Disease and the Therapeutic Potential of Flavonoids: An Update. Nutrients 2025; 17:956. [PMID: 40289935 PMCID: PMC11944923 DOI: 10.3390/nu17060956] [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: 02/21/2025] [Revised: 03/04/2025] [Accepted: 03/06/2025] [Indexed: 04/30/2025] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is considered a significant global health issue related to serious metabolic disorders. However, effective pharmacological treatments are still limited. Flavonoids, a wide group of polyphenol substances, exert anti-inflammatory and lipid-lowering effects in preclinical data. Thus, implementing these research findings in clinical practice could significantly help manage NAFLD and its consequences. This narrative review assesses the therapeutic potential of flavonoids in managing NAFLD. The research collected randomized controlled trials (RCTs) and meta-analyses of RCTs from the past five years concerning the impact of flavonoids on NAFLD. A total of 20 studies were selected according to predetermined inclusion criteria, comprising thirteen randomized controlled trials (RCTs) and seven meta-analyses. The research underscores the beneficial effects of flavonoids in the management of NAFLD through the enhancement of lipid metabolism, the reduction in hepatic steatosis, and the provision of anti-inflammatory actions. Clinical trials demonstrate that interventions rich in flavonoids, including quercetin, epigallocatechin gallate, naringenin, and isoflavones, substantially reduce liver fat content and enhance liver enzyme profiles, with certain compounds exhibiting superior efficacy in particular subgroups, such as older adults and females. Nonetheless, whereas these therapies significantly diminish hepatic steatosis, their effect on fibrosis is constrained. To sum up, flavonoids exhibit significant potential as supplementary treatments for NAFLD by enhancing liver function, lipid metabolism, and inflammation. Additional extensive controlled clinical trials are necessary to create uniform treatment methods and ascertain their long-term therapeutic advantages.
Collapse
Affiliation(s)
- Aleksandra Kozłowska
- Department of Social Medicine and Public Health, Medical University of Warsaw, 02-106 Warsaw, Poland
| |
Collapse
|
|
4
|
Ziqubu K, Mazibuko-Mbeje SE, Dludla PV. Regulation of adipokine and batokine secretion by dietary flavonoids, as a prospective therapeutic approach for obesity and its metabolic complications. Biochimie 2025; 230:95-113. [PMID: 39551425 DOI: 10.1016/j.biochi.2024.11.007] [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: 08/17/2024] [Revised: 10/27/2024] [Accepted: 11/13/2024] [Indexed: 11/19/2024]
Abstract
Traditionally recognised as the energy reservoir and main site of adaptive thermogenesis, white and brown adipose tissues are complex endocrine organs regulating systemic energy metabolism via the secretion of bioactive molecules, termed "adipokines" and "batokines", respectively. Due to its significant role in regulating whole-body energy metabolism and other physiological processes, adipose tissue has been increasingly explored as a feasible therapeutic target for obesity. Flavonoids are one of the most significant plant polyphenolic compounds holding a great potential as therapeutic agents for combating obesity. However, understanding their mechanisms of action remains largely insufficient to formulate therapeutic theories. This review critically discusses scientific evidence highlighting the role of flavonoids in ameliorating obesity-related metabolic complications, including adipose tissue dysfunction, inflammation, insulin resistance, hepatic steatosis, and cardiovascular comorbidities in part by modulating the release of adipokines and batokines. Further discussion advocates for the use of therapeutics targeting these bioactive molecules as a potential avenue for developing effective treatment for obesity and its adverse metabolic diseases such as type 2 diabetes.
Collapse
Affiliation(s)
- Khanyisani Ziqubu
- Department of Biochemistry, North-West University, Mmabatho 2745, South Africa
| | | | - Phiwayinkosi V Dludla
- Cochrane South Africa, South African Medical Research Council, Tygerberg 7505, South Africa; Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa 3886, South Africa
| |
Collapse
|
|
5
|
Wu X, Wu H, Zhong M, Chen Y, Su W, Li P. Epigenetic regulation by naringenin and naringin: A literature review focused on the mechanisms underlying its pharmacological effects. Fitoterapia 2025; 181:106353. [PMID: 39706348 DOI: 10.1016/j.fitote.2024.106353] [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: 08/30/2024] [Revised: 12/06/2024] [Accepted: 12/15/2024] [Indexed: 12/23/2024]
Abstract
Epigenetics refers to heritable changes in gene expression or phenotypic changes that occur without changing the gene sequence. The main methods of epigenetics include non-coding RNA, histone modification, and DNA modification, which play an essential role in gene expression regulation and even the occurrence of diverse diseases. Naringenin, the aglycone form of naringin, is a natural flavonoid compound mainly found in fruits or plant derivatives such as citrus, tomatoes, and cherries. Naringenin and naringin exhibit a broad spectrum of biological activities and pharmacological effects, including anti-cancer, cardiovascular disease improving, anti-inflammatory, and anti-oxidant activities, all of which are advantageous for human health. Recent studies have uncovered that naringenin and naringin influence gene expression by modulating epigenetic pathways, including microRNA (miRNA) regulation. This mechanism plays a crucial role in the therapeutic potential for various diseases. This paper reviews the epigenetic researches on the physiological activities of naringenin and naringin. It highlights how these compounds can exert diverse effects through different signaling pathways, thereby ameliorating associated diseases. These findings provide valuable insights for the future applications of naringenin and naringin.
Collapse
Affiliation(s)
- Xiao Wu
- Guangdong Engineering and Technology Research Center for Quality and Efficacy Re-Evaluation of Post-Marketed TCM, Guangdong Provincial Key Laboratory of Plant Stress Biology, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, PR China
| | - Hao Wu
- Guangdong Engineering and Technology Research Center for Quality and Efficacy Re-Evaluation of Post-Marketed TCM, Guangdong Provincial Key Laboratory of Plant Stress Biology, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, PR China
| | - Mengli Zhong
- Guangdong Engineering and Technology Research Center for Quality and Efficacy Re-Evaluation of Post-Marketed TCM, Guangdong Provincial Key Laboratory of Plant Stress Biology, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, PR China
| | - Yixuan Chen
- Guangdong Engineering and Technology Research Center for Quality and Efficacy Re-Evaluation of Post-Marketed TCM, Guangdong Provincial Key Laboratory of Plant Stress Biology, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, PR China
| | - Weiwei Su
- Guangdong Engineering and Technology Research Center for Quality and Efficacy Re-Evaluation of Post-Marketed TCM, Guangdong Provincial Key Laboratory of Plant Stress Biology, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, PR China
| | - Peibo Li
- Guangdong Engineering and Technology Research Center for Quality and Efficacy Re-Evaluation of Post-Marketed TCM, Guangdong Provincial Key Laboratory of Plant Stress Biology, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, PR China.
| |
Collapse
|
|
6
|
Beaver LM, Jamieson PE, Wong CP, Hosseinikia M, Stevens JF, Ho E. Promotion of Healthy Aging Through the Nexus of Gut Microbiota and Dietary Phytochemicals. Adv Nutr 2025; 16:100376. [PMID: 39832641 PMCID: PMC11847308 DOI: 10.1016/j.advnut.2025.100376] [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: 10/25/2024] [Revised: 12/20/2024] [Accepted: 01/14/2025] [Indexed: 01/22/2025] Open
Abstract
Aging is associated with the decline of tissue and cellular functions, which can promote the development of age-related diseases like cancer, cardiovascular disease, neurodegeneration, and disorders of the musculoskeletal and immune systems. Healthspan is the length of time an individual is in good health and free from chronic diseases and disabilities associated with aging. Two modifiable factors that can influence healthspan, promote healthy aging, and prevent the development of age-related diseases, are diet and microbiota in the gastrointestinal tract (gut microbiota). This review will discuss how dietary phytochemicals and gut microbiota can work in concert to promote a healthy gut and healthy aging. First, an overview is provided of how the gut microbiota influences healthy aging through its impact on gut barrier integrity, immune function, mitochondria function, and oxidative stress. Next, the mechanisms by which phytochemicals effect gut health, inflammation, and nurture a diverse and healthy microbial composition are discussed. Lastly, we discuss how the gut microbiota can directly influence health by producing bioactive metabolites from phytochemicals in food like urolithin A, equol, hesperetin, and sulforaphane. These and other phytochemical-derived microbial metabolites that may promote healthspan are discussed. Importantly, an individual's capacity to produce health-promoting microbial metabolites from cruciferous vegetables, berries, nuts, citrus, and soy products will be dependent on the specific bacteria present in the individual's gut.
Collapse
Affiliation(s)
- Laura M Beaver
- Linus Pauling Institute, Oregon State University, Corvallis, OR, United States; School of Nutrition and Public Health, Oregon State University, Corvallis, OR, United States
| | - Paige E Jamieson
- Linus Pauling Institute, Oregon State University, Corvallis, OR, United States; School of Nutrition and Public Health, Oregon State University, Corvallis, OR, United States
| | - Carmen P Wong
- Linus Pauling Institute, Oregon State University, Corvallis, OR, United States; School of Nutrition and Public Health, Oregon State University, Corvallis, OR, United States
| | - Mahak Hosseinikia
- Linus Pauling Institute, Oregon State University, Corvallis, OR, United States; School of Nutrition and Public Health, Oregon State University, Corvallis, OR, United States
| | - Jan F Stevens
- Linus Pauling Institute, Oregon State University, Corvallis, OR, United States; Department of Pharmaceutical Sciences, Oregon State University, Corvallis, Oregon, United States
| | - Emily Ho
- Linus Pauling Institute, Oregon State University, Corvallis, OR, United States; School of Nutrition and Public Health, Oregon State University, Corvallis, OR, United States.
| |
Collapse
|
|
7
|
López-Almada G, Domínguez-Avila JA, Robles-Sánchez RM, Arauz-Cabrera J, Martínez-Coronilla G, González-Aguilar GA, Salazar-López NJ. Naringenin Decreases Retroperitoneal Adiposity and Improves Metabolic Parameters in a Rat Model of Western Diet-Induced Obesity. Metabolites 2025; 15:109. [PMID: 39997735 PMCID: PMC11857789 DOI: 10.3390/metabo15020109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2025] [Revised: 02/04/2025] [Accepted: 02/06/2025] [Indexed: 02/26/2025] Open
Abstract
Background: Obesity is a multifactorial disease with detrimental effects on health and quality of life; unregulated satiety plays a crucial role in food intake and obesity development. Naringenin (NAR) has shown beneficial effects on lipid and carbohydrate metabolism, although its impact on adiposity and satiety remains unclear. This study reports a Western diet (WD)-induced obesity model in rats, wherein 100 mg/kg of NAR was administered as an anti-obesity agent for 8 weeks; oxidative stress, lipid profile, and satiety biomarkers were then studied, as well as in silico interaction between NAR and cholecystokinin (CCK) and ghrelin receptors. Results: NAR supplementation resulted in a significant decrease in retroperitoneal adipose tissue and liver weight, as compared to the untreated WD group (p < 0.05), potentially associated with a decreased feed efficiency. NAR also inhibited the development of dyslipidemia, particularly by reducing serum triglycerides (p < 0.05). NAR supplementation increased CCK serum levels in the basal diet group, an effect that was abolished by the WD (p < 0.05); likewise, no changes were determined on ghrelin (p > 0.05). In silico data shows that NAR is capable of interacting with the CCK and ghrelin receptors, which suggests a potential for it to modulate hunger/satiety signaling by interacting with them. Conclusions: We conclude that NAR has anti-obesogenic effects and may regulate CCK serum levels, although further research is still needed.
Collapse
Affiliation(s)
- Gabriela López-Almada
- Facultad de Medicina de Mexicali, Universidad Autónoma de Baja California, Dr. Humberto Torres Sanginés, Centro Cívico, Mexicali 21000, BCN, Mexico; (G.L.-A.)
| | - J. Abraham Domínguez-Avila
- SECIHTI—Centro de Investigación en Alimentación y Desarrollo A.C., Carretera Gustavo Enrique Astiazarán Rosas No. 46, Col. La Victoria, Hermosillo 83304, SO, Mexico;
| | - Rosario Maribel Robles-Sánchez
- Departamento de Investigación y Posgrado en Alimentos, Universidad de Sonora, Blvd. Luis Encinas y Rosales, Col. Centro, Hermosillo 83000, SO, Mexico
| | - Jonathan Arauz-Cabrera
- Facultad de Medicina de Mexicali, Universidad Autónoma de Baja California, Dr. Humberto Torres Sanginés, Centro Cívico, Mexicali 21000, BCN, Mexico; (G.L.-A.)
| | - Gustavo Martínez-Coronilla
- Facultad de Medicina de Mexicali, Universidad Autónoma de Baja California, Dr. Humberto Torres Sanginés, Centro Cívico, Mexicali 21000, BCN, Mexico; (G.L.-A.)
| | - Gustavo A. González-Aguilar
- Centro de Investigación en Alimentación y Desarrollo A.C., Carretera Gustavo Enrique Astiazarán Rosas No. 46, Col. La Victoria, Hermosillo 83304, SO, Mexico
| | - Norma Julieta Salazar-López
- Facultad de Medicina de Mexicali, Universidad Autónoma de Baja California, Dr. Humberto Torres Sanginés, Centro Cívico, Mexicali 21000, BCN, Mexico; (G.L.-A.)
| |
Collapse
|
|
8
|
Handu D, Stote K, Piemonte T. Evaluating Bioactive-Substance-Based Interventions for Adults with MASLD: Results from a Systematic Scoping Review. Nutrients 2025; 17:453. [PMID: 39940310 PMCID: PMC11820841 DOI: 10.3390/nu17030453] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Revised: 01/17/2025] [Accepted: 01/20/2025] [Indexed: 02/14/2025] Open
Abstract
Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic condition affecting a broad population. This review aimed to identify and summarize the current evidence on bioactive-substance-based interventions for adults with MASLD, formerly known as nonalcoholic fatty liver disease (NAFLD), covering publications from 2000 to 2023. Methods: A search was conducted across six databases (MEDLINE, CINAHL, Cochrane CENTRAL, Cochrane Database of Systematic Reviews, Food Science Source, and SPORTDiscus) for randomized controlled trials and other study types (e.g., prospective cohort studies and systematic reviews), reflecting the scoping nature of this review. The search was limited to studies in adults (>18 years old), with an intervention of interest and at least one comparator group. Results: A total of 4572 articles were retrieved, with 201 full-text articles screened for eligibility. Of these, 131 primary studies and 49 systematic reviews were included in the scoping review. The most studied bioactive substances were Curcumin (Turmeric) (n = 25), Silymarin (Milk Thistle) (n = 17), Resveratrol (n = 10), Coffee (n = 7), Green Tea (n = 5), and Berberine (n = 5 each). Moreover, 46 studies reported on 36 other bioactive substances with 2 or fewer articles each. Among the included systematic reviews, 13 focused on Curcumin, 12 on Coffee or Tea, 10 on bioactive substance combinations, 6 on Resveratrol, and 2 each on Silymarin and Artichoke Leaf. The included studies showed substantial heterogeneity in reported outcomes, which primarily focused on hepatic health, body weight, adverse events, glycemic control, blood lipids, and body composition. Conclusions: This scoping review highlights a range of bioactive substances used in the treatment of MASLD. While evidence is abundant for bioactive substances like Curcumin and Silymarin, further research and synthesis of findings is necessary to establish the clinical efficacy of all bioactive substances.
Collapse
Affiliation(s)
- Deepa Handu
- Academy of Nutrition and Dietetics, Chicago, IL 60606, USA;
| | - Kim Stote
- Department of Allied Health Sciences, State University of New York, Empire State University, Saratoga Springs, NY 12866, USA;
| | - Tami Piemonte
- Academy of Nutrition and Dietetics, Chicago, IL 60606, USA;
| |
Collapse
|
|
9
|
Ranneh Y, Bedir AS, Abu-Elsaoud AM, Al Raish S. Polyphenol Intervention Ameliorates Non-Alcoholic Fatty Liver Disease: An Updated Comprehensive Systematic Review. Nutrients 2024; 16:4150. [PMID: 39683546 PMCID: PMC11644642 DOI: 10.3390/nu16234150] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 11/22/2024] [Accepted: 11/26/2024] [Indexed: 12/18/2024] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) has recently emerged as a challenging metabolic disorder with a strong emphasis on its prevention and management. Polyphenols, a group of naturally occurring plant compounds, have been associated with a decreased risk of various metabolic disorders related to NAFLD. The current systematic review aims to critically assess evidence about the ameliorative effect of polyphenol supplementation on NAFLD patients. A PRISMA systematic search appraisal was conducted in PubMed, Scopus, Web of Science Core Collection, and all relevant studies published prior to April 2024 and met the inclusion criteria were included. Twenty-nine randomized clinical trials (RCTs) comprised 1840 NAFLD patients. The studies primarily examined eleven phenolic compounds, including turmeric, curcumin, resveratrol, genistein, catechin, green tea extract, hesperidin, and silymarin. Turmeric and curcumin decreased liver enzymes, inflammatory cytokines, lipid profile, insulin resistance, and NAFLD score, while resveratrol did not present consistent results across all the studies. Most studies on silymarin showed a reduction in liver enzymes and lipid profile; however, no changes were observed in inflammatory cytokine levels. The dietary supplementation of hesperidin and naringenin or green tea extract caused improvements in liver enzyme, lipid profile, and inflammatory cytokine, while genistein supplementation did not modulate blood lipid profile. In conclusion, dietary supplementation of polyphenols could potentially prevent and ameliorate NAFLD. Still, the inconsistent results across the included RCTs require further clinical research to establish optimal dosage and duration.
Collapse
Affiliation(s)
- Yazan Ranneh
- Department of Nutrition and Dietetics, College of Pharmacy, Al-Ain University, Al-Ain P.O. Box 64141, United Arab Emirates;
| | - Alaa S. Bedir
- Department of Nutrition, College of Medicine and Health Science, United Arab Emirates University, Al Ain 15551, United Arab Emirates;
| | - Abdelghafar M. Abu-Elsaoud
- Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11623, Saudi Arabia;
| | - Seham Al Raish
- Department of Biology, College of Science, United Arab Emirates University, Al-Ain 15551, United Arab Emirates
| |
Collapse
|
|
10
|
Sethi N, Khokhar M, Mathur M, Batra Y, Mohandas A, Tomo S, Rao M, Banerjee M. Therapeutic Potential of Nutraceuticals against Drug-Induced Liver Injury. Semin Liver Dis 2024; 44:430-456. [PMID: 39393795 DOI: 10.1055/s-0044-1791559] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/13/2024]
Abstract
Drug-induced liver injury (DILI) continues to be a major concern in clinical practice, thus necessitating a need for novel therapeutic approaches to alleviate its impact on hepatic function. This review investigates the therapeutic potential of nutraceuticals against DILI, focusing on examining the underlying molecular mechanisms and cellular pathways. In preclinical and clinical studies, nutraceuticals, such as silymarin, curcumin, and N-acetylcysteine, have demonstrated remarkable efficacy in attenuating liver injury induced by diverse pharmaceutical agents. The molecular mechanisms underlying these hepatoprotective effects involve modulation of oxidative stress, inflammation, and apoptotic pathways. Furthermore, this review examines cellular routes affected by these nutritional components focusing on their influence on hepatocytes, Kupffer cells, and stellate cells. Key evidence highlights that autophagy modulation as well as unfolded protein response are essential cellular processes through which nutraceuticals exert their cytoprotective functions. In conclusion, nutraceuticals are emerging as promising therapeutic agents for mitigating DILI, by targeting different molecular pathways along with cell processes involved in it concurrently.
Collapse
Affiliation(s)
- Namya Sethi
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
| | - Manoj Khokhar
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
| | - Mitali Mathur
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
| | - Yashi Batra
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
| | - Amal Mohandas
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
| | - Sojit Tomo
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
| | - Mahadev Rao
- Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Karnataka, India
| | - Mithu Banerjee
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
| |
Collapse
|
|
11
|
Liao Y, Lv F, Quan T, Wang C, Li J. Flavonoids in natural products for the therapy of liver diseases: progress and future opportunities. Front Pharmacol 2024; 15:1485065. [PMID: 39512816 PMCID: PMC11540641 DOI: 10.3389/fphar.2024.1485065] [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: 08/23/2024] [Accepted: 10/17/2024] [Indexed: 11/15/2024] Open
Abstract
The liver is the largest, important organ and the site for essential biochemical reactions in the human body. It has the function to detoxify toxic substances and synthesize useful biomolecules. Liver diseases related complications represent a significant source of morbidity and mortality worldwide, creating a substantial economic burden. Oxidative stress, excessive inflammation, and dysregulated energy metabolism significantly contributed to liver diseases. Therefore, discovery of novel therapeutic drugs for the treatment of liver diseases are urgently required. For centuries, flavonoids and their preparations which have the beneficial health effects in chronic diseases have been used to treat various human illnesses. Flavonoids mainly include flavones, isoflavones, flavanols, dihydroflavones, dihydroflavonols, anthocyanins and chalcones. The primary objective of this review is to assess the efficacy and safety of flavonoids, mainly from a clinical point of view and considering clinically relevant end-points. We summarized the recent progress in the research of hepatoprotective and molecular mechanisms of different flavonoids bioactive ingredients and also outlined the networks of underlying molecular signaling pathways. Further pharmacology and toxicology research will contribute to the development of natural products in flavonoids and their derivatives as medicines with alluring prospect in the clinical application.
Collapse
Affiliation(s)
- Yanmei Liao
- Department of Pharmacy, Public Health Clinical Center of Chengdu, Chengdu, Sichuan, China
| | - Fei Lv
- Department of Pharmacy, Public Health Clinical Center of Chengdu, Chengdu, Sichuan, China
| | - Tianwen Quan
- Department of Pharmacy, Public Health Clinical Center of Chengdu, Chengdu, Sichuan, China
| | - Chuan Wang
- Scientific Research and Teaching Department, Public Health Clinical Center of Chengdu, Chengdu, Sichuan, China
| | - Jike Li
- Scientific Research and Teaching Department, Public Health Clinical Center of Chengdu, Chengdu, Sichuan, China
| |
Collapse
|
|
12
|
Sokal-Dembowska A, Jarmakiewicz-Czaja S, Filip R. Flavonoids and Their Role in Preventing the Development and Progression of MAFLD by Modifying the Microbiota. Int J Mol Sci 2024; 25:11187. [PMID: 39456969 PMCID: PMC11508831 DOI: 10.3390/ijms252011187] [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: 09/25/2024] [Revised: 10/15/2024] [Accepted: 10/16/2024] [Indexed: 10/28/2024] Open
Abstract
With the increasing prevalence and serious health consequences of metabolic-associated fatty liver disease (MAFLD), early diagnosis and intervention are key to effective treatment. Recent studies highlight the important role of dietary factors, including the use of flavonoids, in improving liver health. These compounds possess anti-inflammatory, antioxidant, and liver-protective properties. Flavonoids have been shown to affect the gut microbiota, which plays a key role in liver function and disease progression. Therefore, their role in preventing the development and progression of MAFLD through modulation of the microbiome seems to be of interest. This narrative review aims to consolidate the current evidence on the effects of selected flavonoids on MAFLD progression, their potential mechanisms of action, and the implications for the development of personalized dietary interventions for the management of liver disease.
Collapse
Affiliation(s)
- Aneta Sokal-Dembowska
- Institute of Health Sciences, Medical College of Rzeszow University, 35-959 Rzeszow, Poland.; (S.J.-C.)
| | - Sara Jarmakiewicz-Czaja
- Institute of Health Sciences, Medical College of Rzeszow University, 35-959 Rzeszow, Poland.; (S.J.-C.)
| | - Rafał Filip
- Institute of Medicine, Medical College of Rzeszow University, 35-959 Rzeszow, Poland
- Department of Gastroenterology with IBD Unit, Clinical Hospital No. 2, 35-301 Rzeszow, Poland
| |
Collapse
|
|
13
|
Cha M, Lee S, Han K. Dietary Nutritional Supplements Are Associated with the Deterioration of Hepatic Fibrosis in Women and Individuals without Underlying Disease. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2024; 21:1298. [PMID: 39457270 PMCID: PMC11506959 DOI: 10.3390/ijerph21101298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Revised: 09/19/2024] [Accepted: 09/27/2024] [Indexed: 10/28/2024]
Abstract
Despite the growing societal interest in the health benefits of dietary nutritional supplements, their safety and efficacy remain unclear. We aimed to investigate the correlation between hepatic fibrosis and the consumption of dietary nutritional supplements. This study utilized data from the Korea National Health and Nutrition Examination Survey spanning the period from 2014 to 2022. Significant fibrosis was defined as a fibrosis index based on four factors (FIB-4) ≥1.45 and an aspartate aminotransferase-to-platelet ratio index (APRI) ≥0.30. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were calculated. In a study involving 30,639 participants (supplement consumers [n = 17,772] and non-consumers [n = 12,867]), dietary nutritional supplement consumption was associated with alanine aminotransferase (ALT) elevation and increased hepatic fibrosis biomarkers (APRI and FIB-4). Dietary nutritional supplement consumption was independently linked to ALT elevation (AOR, 1.11; 95% CI, 1.04-1.18), FIB-4 (AOR, 1.07; 95% CI, 1.00-1.15), and APRI (AOR, 1.14; 95% CI, 1.07-1.21). This association was particularly significant in women and subgroups of people who were not diabetic or hypertriglyceridemic. In our comprehensive analysis, the consumption of dietary nutritional supplements was possibly associated with hepatic fibrosis, particularly in specific subgroups. Given the limitations of this study, these findings are not considered definitive conclusions; however, they serve as valuable preliminary data for future research.
Collapse
Affiliation(s)
- Minsu Cha
- Department of Emergency Medicine, International St. Mary’s Hospital, Catholic Kwandong University College of Medicine, Incheon 22711, Republic of Korea;
- Institute of Health and Medical Convergence Research, International St. Mary’s Hospital, Catholic Kwandong University College of Medicine, Incheon 22711, Republic of Korea
| | - Sangheun Lee
- Institute of Health and Medical Convergence Research, International St. Mary’s Hospital, Catholic Kwandong University College of Medicine, Incheon 22711, Republic of Korea
- Department of Internal Medicine, International St. Mary’s Hospital, Catholic Kwandong University College of Medicine, Incheon 22711, Republic of Korea;
- Division of Hepatology, International St. Mary’s Hospital, Catholic Kwandong University College of Medicine, Incheon 22711, Republic of Korea
| | - Kijun Han
- Department of Internal Medicine, International St. Mary’s Hospital, Catholic Kwandong University College of Medicine, Incheon 22711, Republic of Korea;
- Division of Hepatology, International St. Mary’s Hospital, Catholic Kwandong University College of Medicine, Incheon 22711, Republic of Korea
| |
Collapse
|
|
14
|
Aslan MN, Sukan-Karaçağıl B, Acar-Tek N. Roles of citrus fruits on energy expenditure, body weight management, and metabolic biomarkers: a comprehensive review. Nutr Rev 2024; 82:1292-1307. [PMID: 37702528 PMCID: PMC11317776 DOI: 10.1093/nutrit/nuad116] [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] [Indexed: 09/14/2023] Open
Abstract
Citrus fruits are widely consumed for their nutritional and health benefits. They belong to the Rutaceae and have many varieties, such as sweet orange (Citrus sinensis), which is the most popular. Citrus fruits are rich in water (>80%), dietary fiber, and vitamins. They also contain bioactive components, which may modulate energy metabolism and lipid oxidation through various mechanisms. These mechanisms include stimulating β3-adrenergic receptors, increasing mitochondrial biogenesis and thermogenesis, activating AMP kinase and peroxisome proliferator-activated receptor-gamma coactivator-1α pathways, inhibiting lipogenesis and lipid accumulation, and inducing browning of white adipose tissue. This review summarizes the mechanisms and outcomes of citrus fruits and their metabolites on energy metabolism and body weight in different experimental models. The literature was searched for in vitro and in vivo animal and human studies that investigated the effects of citrus consumption on energy expenditure, thermogenesis, adipogenesis, and lipid accumulation. Citrus fruits and their metabolites have shown promising effects on energy metabolism and lipid oxidation in in vitro and in vivo animal studies. However, the evidence from human studies is limited and inconsistent. Possible reasons for the discrepancy are briefly discussed, and knowledge gaps and research needs are identified for future studies. Citrus fruits may have beneficial effects on energy metabolism and body weight, but more rigorous and well-designed human trials are needed to confirm their efficacy and safety.
Collapse
Affiliation(s)
- Merve Nur Aslan
- Faculty of Health Sciences, Department of Nutrition and Dietetics, Bolu Abant Izzet Baysal University, Bolu, Turkey
- Department of Nutrition and Dietetics, Institute of Health Sciences, Gazi University, Ankara, Turkey
| | - Betül Sukan-Karaçağıl
- Department of Nutrition and Dietetics, Institute of Health Sciences, Gazi University, Ankara, Turkey
| | - Nilüfer Acar-Tek
- Faculty of Health Sciences, Department of Nutrition and Dietetics, Gazi University, Ankara, Turkey
| |
Collapse
|
|
15
|
Barbhuiya PA, Sen S, Pathak MP. Ameliorative role of bioactive phytoconstituents targeting obesity associated NAFLD by modulation of inflammation and lipogenesis pathways: a comprehensive review. PHYTOCHEMISTRY REVIEWS 2024; 23:969-996. [DOI: 10.1007/s11101-023-09912-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Accepted: 12/09/2023] [Indexed: 01/03/2025]
|
|
16
|
Liu H, Li Y, Jin Y, Li X, Wang D, Yu X, Jiang Z, Yin G, Chen S, Zhang X, Meng D, Yu W, Jiang W, Zhang F. Effects of different natural products in patients with non-alcoholic fatty liver disease-A network meta-analysis of randomized controlled trials. Phytother Res 2024; 38:3801-3824. [PMID: 38886838 DOI: 10.1002/ptr.8182] [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: 07/31/2023] [Revised: 02/06/2024] [Accepted: 02/23/2024] [Indexed: 06/20/2024]
Abstract
Due to a scarcity of appropriate therapeutic approaches capable of ameliorating or eliminating non-alcoholic fatty liver disease (NAFLD), many researchers have come to focus on natural products based on traditional medicine that can be utilized to successfully treat NAFLD. In this study, we aimed to evaluate the effects exerted by seven natural products (curcumin, silymarin, resveratrol, artichoke leaf extract, berberine, catechins, and naringenin) on patients with NAFLD. For this purpose, PubMed, Embase, Cochrane Library, and Web of Science, were searched for randomized controlled trials (RCTs) exclusively. The selected studies were evaluated for methodological quality via the Cochrane bias risk assessment tool, and data analysis software was used to analyze the data accordingly. The RCTs from the earliest available date until September 2022 were collected. This process resulted in 37 RCTs with a total sample size of 2509 patients being included. The results of the network meta-analysis showed that artichoke leaf extract confers a relative advantage in reducing the aspartate aminotransferase (AST) levels (SUCRA: 99.1%), alanine aminotransferase (ALT) levels (SUCRA: 88.2%) and low-density lipoprotein cholesterol (LDL-C) levels (SUCRA: 88.9%). Naringenin conferred an advantage in reducing triglyceride (TG) levels (SUCRA: 97.3%), total cholesterol (TC) levels (SUCRA: 73.9%), and improving high-density lipoprotein cholesterol (HDL-C) levels (SUCRA: 74.9%). High-density catechins significantly reduced body mass index (BMI) levels (SUCRA: 98.5%) compared with the placebo. The Ranking Plot of the Network indicated that artichoke leaf extract and naringenin performed better than the other natural products in facilitating patient recovery. Therefore, we propose that artichoke leaf extract and naringenin may exert a better therapeutic effect on NAFLD. This study may help guide clinicians and lead to further detailed studies.
Collapse
Affiliation(s)
- Hongshuai Liu
- Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China
| | - Yufei Li
- Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China
| | - Yan Jin
- Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China
| | - Xin Li
- Department of Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China
| | - Dongxian Wang
- Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China
| | - Xiaowen Yu
- Department of Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China
| | - Zhenyuan Jiang
- Department of Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China
| | - Guoliang Yin
- Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China
| | - Suwen Chen
- Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China
| | - Xin Zhang
- Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China
| | - Decheng Meng
- Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China
| | - Wenfei Yu
- Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China
| | - Wenyin Jiang
- Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China
| | - Fengxia Zhang
- Department of Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China
| |
Collapse
|
|
17
|
Ozkan G, Ceyhan T, Çatalkaya G, Rajan L, Ullah H, Daglia M, Capanoglu E. Encapsulated phenolic compounds: clinical efficacy of a novel delivery method. PHYTOCHEMISTRY REVIEWS 2024; 23:781-819. [DOI: 10.1007/s11101-023-09909-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Accepted: 12/05/2023] [Indexed: 01/15/2025]
Abstract
AbstractEncapsulation is a drug or food ingredient loaded-delivery system that entraps active components, protecting them from decomposition/degradation throughout the processing and storage stages and facilitates their delivery to the target tissue/organ, improving their bioactivities. The application of this technology is expanding gradually from pharmaceuticals to the food industry, since dietary bioactive ingredients, including polyphenols, are susceptible to environmental and/or gastrointestinal conditions. Polyphenols are the largest group of plants' secondary metabolites, with a wide range of biological effects. Literature data have indicated their potential in the prevention of several disorders and pathologies, ranging from simpler allergic conditions to more complex metabolic syndrome and cardiovascular and neurodegenerative diseases. Despite the promising health effects in preclinical studies, the clinical use of dietary polyphenols is still very limited due to their low bioaccessibility and/or bioavailability. Encapsulation can be successfully employed in the development of polyphenol-based functional foods, which may improve their bioaccessibility and/or bioavailability. Moreover, encapsulation can also aid in the targeted delivery of polyphenols and may prevent any possible adverse events. For the encapsulation of bioactive ingredients, several techniques are applied such as emulsion phase separation, emulsification/internal gelation, film formation, spray drying, spray-bed-drying, fluid-bed coating, spray-chilling, spray-cooling, and melt injection. The present review aims to throw light on the existing literature highlighting the possibility and clinical benefits of encapsulated polyphenols in health and disease. However, the clinical data is still very scarce and randomized clinical trials are needed before any conclusion is drawn.
Graphical abstract
Collapse
|
|
18
|
Yu T, Lu X, Liang Y, Yang L, Yin Y, Chen H. Naringenin alleviates liver fibrosis by triggering autophagy-dependent ferroptosis in hepatic stellate cells. Heliyon 2024; 10:e28865. [PMID: 38576562 PMCID: PMC10990976 DOI: 10.1016/j.heliyon.2024.e28865] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Revised: 03/26/2024] [Accepted: 03/26/2024] [Indexed: 04/06/2024] Open
Abstract
Inhibition of activated hepatic stellate cells (HSCs) is a promising approach for treating liver fibrosis, and the ferroptosis has emerged as a pivotal mechanism to achieve this inhibition. The effects of naringenin, a flavonoid with anti-inflammatory properties, have not been thoroughly examined in liver fibrosis. Therefore, we used cholestasis model to study the effect of naringenin on liver fibrosis. Our findings demonstrated a significant exacerbation of liver tissue damage and fibrosis in mice subjected to bile duct ligation (BDL), accompanied by a substantial upregulation of fibrogenesis-related gene expression. Notably, naringenin administration markedly alleviated liver injury and fibrosis in these mice. Furthermore, naringenin exhibited inhibitory effects on the activation of HSCs, concurrently inducing ferroptosis. Importantly, naringenin significantly increased autophagic activity in HSCs. This effect was counteracted by co-administration of the autophagy inhibitor 3-MA, leading to a notable reduction in naringenin-induced HSC ferroptosis. In BDL model mice, naringenin demonstrated a mitigating effect on liver fibrosis, suggesting a potential correlation with naringenin-induced ferroptosis of HSCs. These results provide novel insights into the molecular mechanisms of naringenin-induced ferroptosis and highlight autophagy-dependent ferroptosis as a promising therapeutic strategy for liver fibrosis.
Collapse
Affiliation(s)
- Ting Yu
- Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Dingjiaqiao, Nanjing, Jiangsu, 210009, People's Republic of China
| | - Xuejia Lu
- Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Dingjiaqiao, Nanjing, Jiangsu, 210009, People's Republic of China
| | - Yan Liang
- Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Dingjiaqiao, Nanjing, Jiangsu, 210009, People's Republic of China
| | - Lin Yang
- Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Dingjiaqiao, Nanjing, Jiangsu, 210009, People's Republic of China
| | - Yuehan Yin
- China HuaYou Group Corporation, Beijing, 100724, People's Republic of China
| | - Hong Chen
- Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Dingjiaqiao, Nanjing, Jiangsu, 210009, People's Republic of China
| |
Collapse
|
|
19
|
Merenda T, Juszczak F, Ferier E, Duez P, Patris S, Declèves AÉ, Nachtergael A. Natural compounds proposed for the management of non-alcoholic fatty liver disease. NATURAL PRODUCTS AND BIOPROSPECTING 2024; 14:24. [PMID: 38556609 PMCID: PMC10982245 DOI: 10.1007/s13659-024-00445-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Accepted: 03/20/2024] [Indexed: 04/02/2024]
Abstract
Although non-alcoholic fatty liver disease (NAFLD) presents as an intricate condition characterized by a growing prevalence, the often-recommended lifestyle interventions mostly lack high-level evidence of efficacy and there are currently no effective drugs proposed for this indication. The present review delves into NAFLD pathology, its diverse underlying physiopathological mechanisms and the available in vitro, in vivo, and clinical evidence regarding the use of natural compounds for its management, through three pivotal targets (oxidative stress, cellular inflammation, and insulin resistance). The promising perspectives that natural compounds offer for NAFLD management underscore the need for additional clinical and lifestyle intervention trials. Encouraging further research will contribute to establishing more robust evidence and practical recommendations tailored to patients with varying NAFLD grades.
Collapse
Affiliation(s)
- Théodora Merenda
- Unit of Clinical Pharmacy, Research Institute for Health Sciences and Technology, University of Mons (UMONS), Mons, Belgium
| | - Florian Juszczak
- Department of Metabolic and Molecular Biochemistry, Research Institute for Health Sciences and Technology, University of Mons (UMONS), Mons, Belgium
| | - Elisabeth Ferier
- Department of Metabolic and Molecular Biochemistry, Research Institute for Health Sciences and Technology, University of Mons (UMONS), Mons, Belgium
- Unit of Therapeutic Chemistry and Pharmacognosy, Research Institute for Health Sciences and Technology, University of Mons (UMONS), Mons, Belgium
| | - Pierre Duez
- Unit of Therapeutic Chemistry and Pharmacognosy, Research Institute for Health Sciences and Technology, University of Mons (UMONS), Mons, Belgium
| | - Stéphanie Patris
- Unit of Clinical Pharmacy, Research Institute for Health Sciences and Technology, University of Mons (UMONS), Mons, Belgium
| | - Anne-Émilie Declèves
- Department of Metabolic and Molecular Biochemistry, Research Institute for Health Sciences and Technology, University of Mons (UMONS), Mons, Belgium
| | - Amandine Nachtergael
- Unit of Therapeutic Chemistry and Pharmacognosy, Research Institute for Health Sciences and Technology, University of Mons (UMONS), Mons, Belgium.
| |
Collapse
|
|
20
|
Deepika, Dakal TC, Sharma NK, Ranga V, Maurya PK. Naringenin Orchestrates and Regulates the Reactive Oxygen Species-Mediated Pathways and Proinflammatory Signaling: Targeting Hallmarks of Aging-Associated Disorders. Rejuvenation Res 2024; 27:3-16. [PMID: 38308480 DOI: 10.1089/rej.2023.0065] [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] [Indexed: 02/04/2024] Open
Abstract
The therapeutic application of flavonoids in the management of infectious diseases, cancers, chronic wounds, aging, and neurodegenerative disorders has been well documented in scientific literature. The citric flavonoid naringenin comes under the category of flavanone and exhibits a plethora of health benefits. Very few flavonoids such as curcumin, resveratrol, catechin, quercetin, and kaempferol have been studied to exert their anti-aging properties in humans. The effect of naringenin in the context of age-associated disorders in detail has not been elucidated yet. The databases used for the literature search were Science Direct, Google Scholar, and PubMed. More emphasis has been put on the recent literature on "naringenin" and its effect on "age-associated disorders." Almost all chronic degenerative disorders are characterized by oxidative stress and inflammatory response. The study aims at highlighting the reactive oxygen species-mediated activity of naringenin and the underlying molecular mechanism leading to the prevention of various age-associated disorders. Altogether, the review presents a systematic comprehension of the pharmaceutical and clinicopathological benefits of naringenin in age-associated disorders.
Collapse
Affiliation(s)
- Deepika
- Department of Biochemistry, Central University of Haryana, Mahendergarh, INDIA
| | - Tikam Chand Dakal
- Genome and Computational Biology Laboratory, Department of Biotechnology, Mohanlal Sukhadia University, Udaipur, Rajasthan, India
| | - Narendra Kumar Sharma
- Department of Bioscience and Biotechnology, Banasthali Vidyapith, Tonk, Rajasthan, India
| | - Vipin Ranga
- DBT-NECAB, Assam Agricultural University, Jorhat, India
| | - Pawan Kumar Maurya
- Department of Biochemistry, Central University of Haryana, Mahendergarh, INDIA
| |
Collapse
|
|
21
|
Hu Q, Zhang W, Wei F, Huang M, Shu M, Song D, Wen J, Wang J, Nian Q, Ma X, Zeng J, Zhao Y. Human diet-derived polyphenolic compounds and hepatic diseases: From therapeutic mechanisms to clinical utilization. Phytother Res 2024; 38:280-304. [PMID: 37871899 DOI: 10.1002/ptr.8043] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Revised: 09/12/2023] [Accepted: 10/01/2023] [Indexed: 10/25/2023]
Abstract
This review focuses on the potential ameliorative effects of polyphenolic compounds derived from human diet on hepatic diseases. It discusses the molecular mechanisms and recent advancements in clinical applications. Edible polyphenols have been found to play a therapeutic role, particularly in liver injury, liver fibrosis, NAFLD/NASH, and HCC. In the regulation of liver injury, polyphenols exhibit anti-inflammatory and antioxidant effects, primarily targeting the TGF-β, NF-κB/TLR4, PI3K/AKT, and Nrf2/HO-1 signaling pathways. In the regulation of liver fibrosis, polyphenolic compounds effectively reverse the fibrotic process by inhibiting the activation of hepatic stellate cells (HSC). Furthermore, polyphenolic compounds show efficacy against NAFLD/NASH by inhibiting lipid oxidation and accumulation, mediated through the AMPK, SIRT, and PPARγ pathways. Moreover, several polyphenolic compounds exhibit anti-HCC activity by suppressing tumor cell proliferation and metastasis. This inhibition primarily involves blocking Akt and Wnt signaling, as well as inhibiting the epithelial-mesenchymal transition (EMT). Additionally, clinical trials and nutritional evidence support the notion that certain polyphenols can improve liver disease and associated metabolic disorders. However, further fundamental research and clinical trials are warranted to validate the efficacy of dietary polyphenols.
Collapse
Affiliation(s)
- Qichao Hu
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Department of Pharmacy, Chinese PLA General Hospital, Beijing, China
| | - Wenwen Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Feng Wei
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Meilan Huang
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Mengyao Shu
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Dan Song
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jianxia Wen
- School of Food and Bioengineering, Xihua University, Chengdu, China
| | - Jundong Wang
- Department of Gastroenterology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Qing Nian
- Department of Blood Transfusion, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Xiao Ma
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jinhao Zeng
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Department of Gastroenterology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yanling Zhao
- Department of Pharmacy, Chinese PLA General Hospital, Beijing, China
| |
Collapse
|
|
22
|
Ramos-Tovar E, Muriel P. NLRP3 inflammasome in hepatic diseases: A pharmacological target. Biochem Pharmacol 2023; 217:115861. [PMID: 37863329 DOI: 10.1016/j.bcp.2023.115861] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 10/13/2023] [Accepted: 10/16/2023] [Indexed: 10/22/2023]
Abstract
The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathway is mainly responsible for the activation and release of a cascade of proinflammatory mediators that contribute to the development of hepatic diseases. During alcoholic liver disease development, the NLRP3 inflammasome pathway contributes to the maturation of caspase-1, interleukin (IL)-1β, and IL-18, which induce a robust inflammatory response, leading to fibrosis by inducing profibrogenic hepatic stellate cell (HSC) activation. Substantial evidence demonstrates that nonalcoholic fatty liver disease (NAFLD) progresses to nonalcoholic steatohepatitis (NASH) via NLRP3 inflammasome activation, ultimately leading to fibrosis and hepatocellular carcinoma (HCC). Activation of the NLRP3 inflammasome in NASH can be attributed to several factors, such as reactive oxygen species (ROS), gut dysbiosis, leaky gut, which allow triggers such as cardiolipin, cholesterol crystals, endoplasmic reticulum stress, and uric acid to reach the liver. Because inflammation triggers HSC activation, the NLRP3 inflammasome pathway performs a central function in fibrogenesis regardless of the etiology. Chronic hepatic activation of the NLRP3 inflammasome can ultimately lead to HCC; however, inflammation also plays a role in decreasing tumor growth. Some data indicate that NLRP3 inflammasome activation plays an important role in autoimmune hepatitis, but the evidence is scarce. Most researchers have reported that NLRP3 inflammasome activation is essential in liver injury induced by a variety of drugs and hepatotropic virus infection; however, few reports indicate that this pathway can play a beneficial role by inducing liver regeneration. Modulation of the NLRP3 inflammasome appears to be a suitable strategy to treat liver diseases.
Collapse
Affiliation(s)
- Erika Ramos-Tovar
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina-IPN, Apartado Postal 11340, Plan de San Luis y Díaz Mirón s/n, Casco de Santo Tomás, Ciudad de México, México
| | - Pablo Muriel
- Laboratorio de Hepatología Experimental, Departamento de Farmacología, Cinvestav-IPN, Apartado Postal 14-740, Ciudad de México, México.
| |
Collapse
|
|
23
|
Luo Y, Zeng Y, Peng J, Zhang K, Wang L, Feng T, Nhamdriel T, Fan G. Phytochemicals for the treatment of metabolic diseases: Evidence from clinical studies. Biomed Pharmacother 2023; 165:115274. [PMID: 37542856 DOI: 10.1016/j.biopha.2023.115274] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Revised: 07/29/2023] [Accepted: 07/31/2023] [Indexed: 08/07/2023] Open
Abstract
With the continuous improvement of people's living standard, the incidence of metabolic diseases is gradually increasing in recent years. There is growing interest in finding drugs to treat metabolic diseases from natural compounds due to their good efficacy and limited side effects. Over the past few decades, many phytochemicals derived from natural plants, such as berberine, curcumin, quercetin, resveratrol, rutin, and hesperidin, have been shown to have good pharmacological activity against metabolic diseases in preclinical studies. More importantly, clinical trials using these phytochemicals to treat metabolic diseases have been increasing. This review comprehensively summarizes the clinical progress of phytochemicals derived from natural plants in the treatment of several metabolic diseases, including type 2 diabetes mellitus (T2DM), obesity and non-alcoholic fatty liver disease (NAFLD). Accumulating clinical evidence shows that a total of 18 phytochemicals have good therapeutic effects on the three metabolic diseases by lowering blood glucose and lipid levels, reducing insulin resistance, enhancing insulin sensitivity, increasing energy expenditure, improving liver function, and relieving inflammation and oxidative stress. The information will help us better understand the medicinal value of these phytochemicals and promote their clinical application in the treatment of metabolic diseases.
Collapse
Affiliation(s)
- Yuting Luo
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy and School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Yujiao Zeng
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy and School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Jiayan Peng
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy and School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Kun Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy and School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Lijie Wang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy and School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Tu Feng
- School of Ecological Engineering, Guizhou University of Engineering Science, Bijie 551700, China.
| | - Tsedien Nhamdriel
- Department of Tibetan medicine, University of Tibetan Medicine, Lhasa 850000, China.
| | - Gang Fan
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy and School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Meishan Hospital of Chengdu University of Traditional Chinese Medicine, Meishan 620010, China.
| |
Collapse
|
|
24
|
Zhou Y, Dai Z, Deng K, Wang Y, Ying J, Chu D, Zhou J, Tang C. Eight Zhes Decoction ameliorates the lipid dysfunction of nonalcoholic fatty liver disease using integrated lipidomics, network pharmacology and pharmacokinetics. J Pharm Anal 2023; 13:1058-1069. [PMID: 37842659 PMCID: PMC10568095 DOI: 10.1016/j.jpha.2023.05.012] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Revised: 04/19/2023] [Accepted: 05/21/2023] [Indexed: 10/17/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) has developed into the most common chronic liver disease and can lead to liver cancer. Our laboratory previously developed a novel prescription for NAFLD, "Eight Zhes Decoction" (EZD), which has shown good curative effects in clinical practice. However, the pharmacodynamic material basis and mechanism have not yet been revealed. A strategy integrating lipidomics, network pharmacology and pharmacokinetics was used to reveal the active components and mechanisms of EZD against NAFLD. The histopathological results showed that EZD attenuated the degrees of collagen deposition and steatosis in the livers of nonalcoholic steatofibrosis model mice. Furthermore, glycerophospholipid metabolism, arachidonic acid metabolism, glycerolipid metabolism and linoleic acid metabolism with phospholipase A2 group IVA (PLA2G4A) and cytochrome P450 as the core targets and 12,13-cis-epoxyoctadecenoic acid, 12(S)-hydroxyeicosatetraenoic acid, leukotriene B4, prostaglandin E2, phosphatidylcholines (PCs) and triacylglycerols (TGs) as the main lipids were found to be involved in the treatment of NAFLD by EZD. Importantly, naringenin, artemetin, canadine, and bicuculline were identified as the active ingredients of EZD against NAFLD; in particular, naringenin reduces PC consumption by inhibiting the expression of PLA2G4A and thus promotes sufficient synthesis of very-low-density lipoprotein to transport excess TGs in the liver. This research provides valuable data and theoretical support for the application of EZD against NAFLD.
Collapse
Affiliation(s)
- Yuping Zhou
- The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315020, China
- School of Public Health, Health Science Center, Ningbo University, Ningbo, Zhejiang, 315211, China
- Institute of Digestive Disease of Ningbo University, Ningbo, Zhejiang, 315020, China
| | - Ze Dai
- The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315020, China
- School of Public Health, Health Science Center, Ningbo University, Ningbo, Zhejiang, 315211, China
| | - Kaili Deng
- The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315020, China
- School of Public Health, Health Science Center, Ningbo University, Ningbo, Zhejiang, 315211, China
| | - Yubin Wang
- School of Public Health, Health Science Center, Ningbo University, Ningbo, Zhejiang, 315211, China
| | - Jiamin Ying
- School of Public Health, Health Science Center, Ningbo University, Ningbo, Zhejiang, 315211, China
| | - Donghui Chu
- School of Public Health, Health Science Center, Ningbo University, Ningbo, Zhejiang, 315211, China
| | - Jinyue Zhou
- School of Public Health, Health Science Center, Ningbo University, Ningbo, Zhejiang, 315211, China
| | - Chunlan Tang
- The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315020, China
- School of Public Health, Health Science Center, Ningbo University, Ningbo, Zhejiang, 315211, China
| |
Collapse
|
|
25
|
Naringenin inhibits lipid accumulation by activating the AMPK pathway in vivo and vitro. FOOD SCIENCE AND HUMAN WELLNESS 2023. [DOI: 10.1016/j.fshw.2022.10.043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
|
|
26
|
Kosmalski M, Frankowski R, Deska K, Różycka-Kosmalska M, Pietras T. Exploring the Impact of Nutrition on Non-Alcoholic Fatty Liver Disease Management: Unveiling the Roles of Various Foods, Food Components, and Compounds. Nutrients 2023; 15:2838. [PMID: 37447164 DOI: 10.3390/nu15132838] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 06/18/2023] [Accepted: 06/19/2023] [Indexed: 07/15/2023] Open
Abstract
There is a need to introduce standardized treatment options for non-alcoholic fatty liver disease (NAFLD) due to its global prevalence and the complications of this disease. Many studies have revealed that food-derived substances may be beneficial in dealing with this disease. Therefore, this review aims to evaluate the recently published studies on the food-derived treatment options for NAFLD. A comprehensive search of the PubMed database using keywords such as "NAFLD", "nutrition", "food", "derived", "therapy", and "guidelines" yielded 219 relevant papers for our analysis, published from 2004 to 2023. The results show the significant benefits of food-derived treatment in NAFLD therapy, including improvements in liver histology, hepatic fat amounts, anthropometric measures, lipid profile, and other metabolic measures. The availability of the substances discussed makes them a significant adjuvant in the treatment of this disease. The usefulness of Viusid as additional therapy to diet and physical activity should be emphasized due to improvements in liver histology; however, many other substances lead to a decrease in liver fat amounts including, e.g., berberine or omega-3 fatty acids. In addition, the synbiotic Protexin seems to be useful in terms of NAFLD treatment, especially because it is effective in both obese and lean subjects. Based on the latest research results, we suggest revising the therapeutic recommendations for patients suffering from NAFLD.
Collapse
Affiliation(s)
- Marcin Kosmalski
- Department of Clinical Pharmacology, Medical University of Lodz, 90-153 Lodz, Poland
| | - Rafał Frankowski
- Students' Research Club, Department of Clinical Pharmacology, Medical University of Lodz, 90-153 Lodz, Poland
| | - Kacper Deska
- Students' Research Club, Department of Clinical Pharmacology, Medical University of Lodz, 90-153 Lodz, Poland
| | | | - Tadeusz Pietras
- Department of Clinical Pharmacology, Medical University of Lodz, 90-153 Lodz, Poland
| |
Collapse
|
|
27
|
Kosmalski M, Frankowski R, Ziółkowska S, Różycka-Kosmalska M, Pietras T. What's New in the Treatment of Non-Alcoholic Fatty Liver Disease (NAFLD). J Clin Med 2023; 12:jcm12051852. [PMID: 36902639 PMCID: PMC10003344 DOI: 10.3390/jcm12051852] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 02/09/2023] [Accepted: 02/20/2023] [Indexed: 03/02/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a serious health problem due to its high incidence and consequences. In view of the existing controversies, new therapeutic options for NAFLD are still being sought. Therefore, the aim of our review was to evaluate the recently published studies on the treatment of NAFLD patients. We searched for articles in the PubMed database using appropriate terms, including "non-alcoholic fatty liver disease", "nonalcoholic fatty liver disease", "NAFLD", "diet", "treatment", "physical activity", "supplementation", "surgery", "overture" and "guidelines". One hundred forty-eight randomized clinical trials published from January 2020 to November 2022 were used for the final analysis. The results show significant benefits of NAFLD therapy associated with the use of not only the Mediterranean but also other types of diet (including low-calorie ketogenic, high-protein, anti-inflammatory and whole-grain diets), as well as enrichment with selected food products or supplements. Significant benefits in this group of patients are also associated with moderate aerobic physical training. The available therapeutic options indicate, above all, the usefulness of drugs related to weight reduction, as well as the reduction in insulin resistance or lipids level and drugs with anti-inflammatory or antioxidant properties. The usefulness of therapy with dulaglutide and the combination of tofogliflozin with pioglitazone should be emphasized. Based on the results of the latest research, the authors of this article suggest a revision of the therapeutic recommendations for NAFLD patients.
Collapse
Affiliation(s)
- Marcin Kosmalski
- Department of Clinical Pharmacology, Medical University of Lodz, 90-153 Lodz, Poland
- Correspondence: ; Tel.: +48-728-358-504
| | - Rafał Frankowski
- Students’ Research Club, Department of Clinical Pharmacology, Medical University of Lodz, 90-153 Lodz, Poland
| | - Sylwia Ziółkowska
- Department of Medical Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland
| | | | - Tadeusz Pietras
- Department of Clinical Pharmacology, Medical University of Lodz, 90-153 Lodz, Poland
| |
Collapse
|
|
28
|
Wang LL, Zhang PH, Yan HH. Functional foods and dietary supplements in the management of non-alcoholic fatty liver disease: A systematic review and meta-analysis. Front Nutr 2023; 10:1014010. [PMID: 36866059 PMCID: PMC9971819 DOI: 10.3389/fnut.2023.1014010] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Accepted: 01/30/2023] [Indexed: 02/16/2023] Open
Abstract
Objective In this systematic review and meta-analysis, we aimed to clarify the overall effects of functional foods and dietary supplements in non-alcoholic fatty liver disease (NAFLD) patients. Methods Randomized controlled trials (RCTs) published in PubMed, ISI Web of Science, Cochrane library, and Embase from January 1, 2000 to January 31, 2022 were systematically searched to assess the effects of functional foods and dietary supplements in patients with NAFLD. The primary outcomes were liver-related measures, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and hepatic fibrosis and steatosis, while the secondary outcomes included body mass index (BMI), waist circumference (WC), triacylglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). These indexes were all continuous variables, so the mean difference (MD) was used for calculating the effect size. Random-effects or fixed-effects models were used to estimate the mean difference (MD). The risk of bias in all studies was assessed with guidance provided in the Cochrane Handbook for Systematic Reviews of Interventions. Results Twenty-nine articles investigating functional foods and dietary supplements [antioxidants (phytonutrients and coenzyme Q10) = 18, probiotics/symbiotic/prebiotic = 6, fatty acids = 3, vitamin D = 1, and whole grain = 1] met the eligibility criteria. Our results showed that antioxidants could significantly reduce WC (MD: -1.28 cm; 95% CI: -1.58, -0.99, P < 0.05), ALT (MD: -7.65 IU/L; 95% CI: -11.14, -4.16, P < 0.001), AST (MD: -4.26 IU/L; 95% CI: -5.76, -2.76, P < 0.001), and LDL-C (MD: -0.24 mg/dL; 95% CI: -0.46, -0.02, P < 0.05) increased in patients with NAFLD but had no effect on BMI, TG, and TC. Probiotic/symbiotic/prebiotic supplementation could decrease BMI (MD: -0.57 kg/m2; 95% CI: -0.72, -0.42, P < 0.05), ALT (MD: -3.96 IU/L; 95% CI: -5.24, -2.69, P < 0.001), and AST (MD: -2.76; 95% CI: -3.97, -1.56, P < 0.0001) levels but did not have beneficial effects on serum lipid levels compared to the control group. Moreover, the efficacy of fatty acids for treating NAFLD was full of discrepancies. Additionally, vitamin D had no significant effect on BMI, liver transaminase, and serum lipids, while whole grain could reduce ALT and AST but did not affect serum lipid levels. Conclusion The current study suggests that antioxidant and probiotic/symbiotic/prebiotic supplements may be a promising regimen for NAFLD patients. However, the usage of fatty acids, vitamin D, and whole grain in clinical treatment is uncertain. Further exploration of the efficacy ranks of functional foods and dietary supplements is needed to provide a reliable basis for clinical application. Systematic review registration https://www.crd.york.ac.uk/prospero, identifier: CRD42022351763.
Collapse
Affiliation(s)
- Lei-lei Wang
- Department of Clinical Nutrition, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Pian-hong Zhang
- Department of Clinical Nutrition, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Hui-hui Yan
- Department of Gastroenterology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| |
Collapse
|
|
29
|
Could Naringenin Participate as a Regulator of Obesity and Satiety? Molecules 2023; 28:molecules28031450. [PMID: 36771113 PMCID: PMC9921626 DOI: 10.3390/molecules28031450] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Revised: 01/26/2023] [Accepted: 01/31/2023] [Indexed: 02/05/2023] Open
Abstract
Obesity is a serious health problem worldwide, since it is associated with multiple metabolic disorders and complications such as cardiovascular disease, type 2 diabetes, fatty liver disease and overall metabolic dysfunction. Dysregulation of the hunger-satiety pathway, which includes alterations of central and peripheral signaling, explains some forms of obesity by favoring hyperphagia and weight gain. The present work comprehensively summarizes the mechanisms by which naringenin (NAR), a predominant flavanone in citrus fruits, could modulate the main pathways associated with the development of obesity and some of its comorbidities, such as oxidative stress (OS), inflammation, insulin resistance (IR) and dyslipidemia, as well as the role of NAR in modulating the secretion of enterohormones of the satiety pathway and its possible antiobesogenic effect. The results of multiple in vitro and in vivo studies have shown that NAR has various potentially modulatory biological effects against obesity by countering IR, inflammation, OS, macrophage infiltration, dyslipidemia, hepatic steatosis, and adipose deposition. Likewise, NAR is capable of modulating peptides or peripheral hormones directly associated with the hunger-satiety pathway, such as ghrelin, cholecystokinin, insulin, adiponectin and leptin. The evidence supports the use of NAR as a promising alternative to prevent overweight and obesity.
Collapse
|
|
30
|
Abstract
Liver fibrosis has a high incidence worldwide and is the common pathological basis of many chronic liver diseases. Liver fibrosis is caused by the excessive deposition of extracellular matrix and concomitant collagen accumulation in livers and can lead to the development of liver cirrhosis and even liver cancer. A large number of studies have provided evidence that liver fibrosis can be blocked or even reversed by appropriate medical interventions. However, the antifibrosis drugs with ideal clinical efficacy are still insufficient. The edible plant-derived natural compounds have been reported to exert effective antifibrotic effects with few side-effects, representing a kind of promising source for the treatment of liver fibrosis. In this article, we reviewed the current progress of the natural compounds derived from dietary plants in the treatment of liver fibrosis, including phenolic compounds (capsaicin, chlorogenic acid, curcumin, ellagic acid, epigallocatechin-3-gallate, resveratrol, sinapic acid, syringic acid, vanillic acid and vitamin E), flavonoid compounds (genistein, hesperidin, hesperetin, naringenin, naringin and quercetin), sulfur-containing compounds (S-allylcysteine, ergothioneine, lipoic acid and sulforaphane) and other compounds (betaine, caffeine, cucurbitacin B, lycopene, α-mangostin, γ-mangostin, ursolic acid, vitamin C and yangonin). The pharmacological effects and related mechanisms of these compounds in in-vivo and in-vitro models of liver fibrosis are focused.
Collapse
|
|
31
|
Yan X, Lin T, Zhu Q, Zhang Y, Song Z, Pan X. Naringenin protects against acute pancreatitis-associated intestinal injury by inhibiting NLRP3 inflammasome activation via AhR signaling. Front Pharmacol 2023; 14:1090261. [PMID: 36713830 PMCID: PMC9881748 DOI: 10.3389/fphar.2023.1090261] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Accepted: 01/02/2023] [Indexed: 01/15/2023] Open
Abstract
Background: In this study, we examined the functions and mechanisms by which naringenin protects against SAP (severe acute pancreatitis)-related intestinal injury by modulating the AhR/NLRP3 signaling pathway. Material and methods: Fifteen healthy male C57BL/6 mice were randomly divided into SAP (n = 12) and normal (n = 3) groups. Mice in the SAP group received caerulein and lipopolysaccharide intraperitoneal injections and were then randomly assigned to the SAP, NAR, CH223191, and Dexamethasone (DEX) groups. Pathological changes in the pancreatic and intestinal mucosa were observed by Hematoxylin & Eosin (H&E) staining. In vitro, RAW264.7 cells were exposed to lipopolysaccharide and treated with naringenin. The levels of NLRP3, AhR, IL-1β, TNF, and IL-6 in the SAP model and RAW264.7 cells were evaluated by enzyme-linked immunosorbent assay (ELISA), quantitative real-time PCR (qRT-PCR), western blot, and immunohistochemistry. The nuclear translocation of AhR was shown by immunofluorescence. AutoDockTools was used to predict the conformations of naringenin-AhR binding, and PyMol 2.4 was used to visualize the conformations. Results: Mouse pancreatic and intestinal injury was alleviated by treatment with naringenin. Naringenin inhibited the activation of the NLRP3 inflammasome and inhibited damage to intestinal tight junctions. Moreover, naringenin increased AhR nuclear translocation and activated the AhR pathway. Conclusion: Naringenin can reduce SAP-associated intestinal injury by inhibiting the activation of the NLRP3 inflammasome via the AhR signaling pathway.
Collapse
Affiliation(s)
| | | | | | | | | | - Xinting Pan
- The Affiliated Hospital of Qingdao University, Qingdao, China
| |
Collapse
|
|
32
|
Sun M, Ye H. Natural Foods for the Treatment of Nonalcoholic Fatty Liver Disease. J Med Food 2023; 26:1-13. [PMID: 36579939 DOI: 10.1089/jmf.2022.k.0052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. The etiology of NAFLD is highly heterogeneous, which occurs and develops under the joint action of metabolism, inflammation, genetics, environment, and gut microbiota. At present, the principal therapeutic modalities targeting NAFLD are lifestyle interventions such as weight loss through diet and exercise. At present, there is no established therapy for the treatment of NAFLD, and many therapies are associated with a variety of side effects. A great number of in vitro and in vivo experiments have indicated that there are many natural foods that have therapeutic potential for NAFLD. This review summarizes the natural foods and their mechanisms that were found in recent years, furthermore, provides further information relevant to the treatment of NAFLD.
Collapse
Affiliation(s)
- Mengxia Sun
- The Affiliated Lihuili Hospital, Ningbo University, Ningbo, China
| | - Hua Ye
- The Affiliated Lihuili Hospital, Ningbo University, Ningbo, China
| |
Collapse
|
|
33
|
Yang K, Chen J, Zhang T, Yuan X, Ge A, Wang S, Xu H, Zeng L, Ge J. Efficacy and safety of dietary polyphenol supplementation in the treatment of non-alcoholic fatty liver disease: A systematic review and meta-analysis. Front Immunol 2022; 13:949746. [PMID: 36159792 PMCID: PMC9500378 DOI: 10.3389/fimmu.2022.949746] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2022] [Accepted: 07/21/2022] [Indexed: 11/23/2022] Open
Abstract
Background Dietary polyphenol treatment of non-alcoholic fatty liver disease (NAFLD) is a novel direction, and the existing clinical studies have little effective evidence for its therapeutic effect, and some studies have inconsistent results. The effectiveness of dietary polyphenols in the treatment of NAFLD is still controversial. The aim of this study was to evaluate the therapeutic efficacy of oral dietary polyphenols in patients with NAFLD. Methods The literature (both Chinese and English) published before 30 April 2022 in PubMed, Cochrane, Medline, CNKI, and other databases on the treatment of NAFLD with dietary polyphenols was searched. Manual screening, quality assessment, and data extraction of search results were conducted strictly according to the inclusion and exclusion criteria. RevMan 5.3 software was used to perform the meta-analysis. Results The RCTs included in this study involved dietary supplementation with eight polyphenols (curcumin, resveratrol, naringenin, anthocyanin, hesperidin, catechin, silymarin, and genistein) and 2,173 participants. This systematic review and meta-analysis found that 1) curcumin may decrease body mass index (BMI), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Triglycerides (TG) total cholesterol (TC), and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) compared to placebo; and curcumin does not increase the occurrence of adverse events. 2) Although the meta-analysis results of all randomized controlled trials (RCTs) did not reveal significant positive changes, individual RCTs showed meaningful results. 3) Naringenin significantly decreased the percentage of NAFLD grade, TG, TC, and low-density lipoprotein cholesterol (LDL-C) and increased high-density lipoprotein cholesterol (HDL-C) but had no significant effect on AST and ALT, and it is a safe supplementation. 4) Only one team presents a protocol about anthocyanin (from Cornus mas L. fruit extract) in the treatment of NAFLD. 5) Hesperidin may decrease BMI, AST, ALT, TG, TC, HOMA-IR, and so on. 6) Catechin may decrease BMI, HOMA-IR, and TG level, and it was well tolerated by the patients. 7) Silymarin was effective in improving ALT and AST and reducing hepatic fat accumulation and liver stiffness in NAFLD patients. Conclusion Based on current evidence, curcumin can reduce BMI, TG, TC, liver enzymes, and insulin resistance; catechin can reduce BMI, insulin resistance, and TG effectively; silymarin can reduce liver enzymes. For resveratrol, naringenin, anthocyanin, hesperidin, and catechin, more RCTs are needed to further evaluate their efficacy and safety.
Collapse
Affiliation(s)
- Kailin Yang
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, China
| | - Junpeng Chen
- School of Mechanical Engineering, Hunan University of Science and Technology, Xiangtan, China
| | - Tianqing Zhang
- The First Affiliated Hospital, Department of Cardiovascular Medicine, Hengyang Medical School, University of South China, Hengyang, China
| | - Xiao Yuan
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, China
| | - Anqi Ge
- The First Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Shanshan Wang
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, China
| | - Hao Xu
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, China
| | - Liuting Zeng
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Jinwen Ge
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, China
- Hunan Academy of Chinese Medicine, Changsha, China
- *Correspondence: Jinwen Ge,
| |
Collapse
|
|
34
|
Yousuf M, Shamsi A, Khan S, Khan P, Shahwan M, Elasbali AM, Haque QMR, Hassan MI. Naringenin as a potential inhibitor of human cyclin-dependent kinase 6: Molecular and structural insights into anti-cancer therapeutics. Int J Biol Macromol 2022; 213:944-954. [PMID: 35690164 DOI: 10.1016/j.ijbiomac.2022.06.013] [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: 04/29/2022] [Revised: 05/28/2022] [Accepted: 06/05/2022] [Indexed: 12/13/2022]
Abstract
Cancer is one of the major causes of global deaths and needs immediate therapeutic development. So far, several strategies have been undertaken to prevent cancer, including kinase targeting by small-molecule inhibitors. Cyclin dependent kinase 6 (CDK6) plays an essential role in cancer progression and development as its overexpression is associated with tumor development and progression. The present study demonstrated that Naringenin (NAG) binds strongly to CDK6 with a binding affinity of -7.51 kcal/mol. ATPase assay of CDK6 in the presence of NAG shows that it inhibits CDK6 with an IC50 = 3.13 μM. Fluorescence and isothermal titration calorimetry studies demonstrated that NAG binds to CDK6 with the binding constant (K) values of 3.55 × 106 M-1 and 7.06 ± 2.70 × 106 M-1, respectively. The cell-based functional studies showed that NAG decreases the cell viability of human cancer cell lines, induces apoptosis, and reduces their colonization ability. Outcomes of the present in silico and in vitro studies highlighted the significance of NAG for the development of anti-cancer leads in terms of CDK6 inhibitors and provided future implications for combinatorial anti-cancer therapies.
Collapse
Affiliation(s)
- Mohd Yousuf
- Department of Biosciences, Jamia Millia Islamia, Jamia Nagar, New Delhi, India
| | - Anas Shamsi
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India
| | - Shama Khan
- Vaccines and Infectious Disease Analytics (VIDA), University of the Witwatersrand, Johannesburg, South Africa
| | - Parvez Khan
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India
| | - Moyad Shahwan
- Centre of Medical and Bio-Allied Health Sciences Research, Ajman University, United Arab Emirates
| | - Abdelbaset Mohamed Elasbali
- Department of Clinical Laboratory Science, College of Applied Sciences-Qurayyat, Jouf University, Sakaka, Saudi Arabia; Department of Pathology, Faculty of Medicine, University of Benghazi, Benghazi-Libya.
| | | | - Md Imtaiyaz Hassan
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.
| |
Collapse
|