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Research (Washington, D.C.) 2023Non-alcoholic fatty liver disease, especially nonalcoholic steatohepatitis (NASH), is a leading cause of cirrhosis and liver cancer worldwide; nevertheless, there are no...
Non-alcoholic fatty liver disease, especially nonalcoholic steatohepatitis (NASH), is a leading cause of cirrhosis and liver cancer worldwide; nevertheless, there are no Food and Drug Administration-approved drugs for treating NASH until now. Peroxisome proliferator-activated receptor alpha (PPARα) is an interesting therapeutic target for treating metabolic disorders in the clinic, including NASH. Herpetrione, a natural lignan compound isolated from Tibetan medicine , exerts various hepatoprotective effects, but its efficacy and molecular mechanism in treating NASH have not yet been elucidated. Here, we discovered that herpetrione lessened lipid accumulation and inflammation in hepatocytes stimulated with oleic acid and lipopolysaccharide, and effectively alleviated NASH caused by a high-fat diet or methionine-choline-deficient diet by regulating glucolipid metabolism, insulin resistance, and inflammation. Mechanistically, RNA-sequencing analyses further showed that herpetrione activated PPAR signaling, which was validated by protein expression. Furthermore, the analysis of molecular interactions illustrated that herpetrione bound directly to the PPARα protein, with binding sites extending to the Arm III domain. PPARα deficiency also abrogated the protective effects of herpetrione against NASH, suggesting that herpetrione protects against hepatic steatosis and inflammation by activation of PPARα signaling, thereby alleviating NASH. Our findings shed light on the efficacy of a natural product for treating NASH, as well as the broader prospects for NASH treatment by targeting PPARα.
PubMed: 38034083
DOI: 10.34133/research.0276 -
Acta Pharmaceutica Sinica. B Aug 2023Nonalcoholic steatohepatitis (NASH) is a spectrum of chronic liver disease characterized by hepatic lipid metabolism disorder. Recent reports emphasized the contribution...
Nonalcoholic steatohepatitis (NASH) is a spectrum of chronic liver disease characterized by hepatic lipid metabolism disorder. Recent reports emphasized the contribution of triglyceride and diglyceride accumulation to NASH, while the other lipids associated with the NASH pathogenesis remained unexplored. The specific purpose of our study was to explore a novel pathogenesis and treatment strategy of NASH profiling the metabolic characteristics of lipids. Herein, multi-omics techniques based on LC-Q-TOF/MS, LC-MS/MS and MS imaging were developed and used to screen the action targets related to NASH progress and treatment. A methionine and choline deficient (MCD) diet-induced mouse model of NASH was then constructed, and lignans extract (SLE) was applied to alleviate hepatic damage by regulating the lipid metabolism-related enzymes CES2A and CYP4A14. Hepatic lipidomics indicated that MCD-diet led to aberrant accumulation of phosphatidylethanolamines (PEs), and SLE could significantly reduce the accumulation of intrahepatic PEs. Notably, exogenous PE (18:0/18:1) was proved to significantly aggravate the mitochondrial damage and hepatocyte apoptosis. Supplementing PE (18:0/18:1) also deteriorated the NASH progress by up regulating intrahepatic proinflammatory and fibrotic factors, while PE synthase inhibitor exerted a prominent hepatoprotective role. The current work provides new insights into the relationship between PE metabolism and the pathogenesis of NASH.
PubMed: 37655337
DOI: 10.1016/j.apsb.2023.04.009 -
European Journal of Medical Research Jul 2023Flaxseed (Linum usitatissimum L) is an ancient perennial plant species regarded as a multipurpose plant owing to its richness in omega-3 polyunsaturated fatty acids... (Review)
Review
Flaxseed (Linum usitatissimum L) is an ancient perennial plant species regarded as a multipurpose plant owing to its richness in omega-3 polyunsaturated fatty acids (PUFA) including α-linolenic acid (ALA). The extensive biochemical analysis of flaxseed resulted in the identification of its bioactive, i.e., lignans with potential application in the improvement of human health. Flaxseed oil, fibers, and lignans exert potential health benefits including reduction of cardiovascular disease, atherosclerosis, diabetes, cancer, arthritis, osteoporosis, and autoimmune and neurological disorders that have led to the diversification of flaxseed plant applications. This comprehensive review focuses on flaxseed oil as the major product of flaxseed with emphasis on the interrelationship between its chemical composition and biological effects. Effects reviewed include antioxidant, anti-inflammatory, antimicrobial, anticancer, antiulcer, anti-osteoporotic, cardioprotective, metabolic, and neuroprotective. This study provides an overview of flaxseed oil effects with the reported action mechanisms related to its phytochemical composition and in comparison, to other PUFA-rich oils. This study presents the most updated and comprehensive review summarizing flaxseed oil's health benefits for the treatment of various diseases.
Topics: Humans; Linseed Oil; Flax; Cardiovascular Diseases; Antioxidants; Lignans
PubMed: 37464425
DOI: 10.1186/s40001-023-01203-6 -
Pharmaceuticals (Basel, Switzerland) Jul 2023Plants from the genus have been extensively used in folk medicines to treat diseases such as skin diseases and peptic ulcers and as an antiseptic and analgesic. Most... (Review)
Review
Plants from the genus have been extensively used in folk medicines to treat diseases such as skin diseases and peptic ulcers and as an antiseptic and analgesic. Most species, especially , which is used as an expectorant, antiseptic, and analgesic in Chinese traditional medicine, could screen resin after external injury. is also used in folk medicines in Korea to treat sore throat, bronchitis, cough, expectoration, paralysis, laryngitis, and inflammation. Different parts of various species can be widely employed for ethnopharmacological applications. Moreover, for ethnopharmacological use, these parts of species can be applied in combination with other folk medicines. species consist of versatile natural compounds, with some of them exhibiting particularly excellent pharmacological activities, such as cytotoxic, acetylcholinesterase inhibitory, antioxidant, and antifungal activities. Altogether, these exciting results indicate that a comprehensive review of plants belonging to this genus is essential for helping researchers to continuously conduct an in-depth investigation. In this review, the traditional uses, phytochemistry, corresponding pharmacological activities, and structure-activity relationships of different species are clarified and critically discussed. More insights into potential opportunities for future research are carefully assessed.
PubMed: 37513954
DOI: 10.3390/ph16071043 -
The American Journal of Clinical... Jul 2023Although increasing evidence suggests that polyphenol helps regulate blood pressure (BP), evidence from large-scale and long-term population-based studies is still...
BACKGROUND
Although increasing evidence suggests that polyphenol helps regulate blood pressure (BP), evidence from large-scale and long-term population-based studies is still lacking.
OBJECTIVES
This study aimed to investigate the association between dietary polyphenol and hypertension risk in the China Health and Nutrition Survey (N = 11,056).
METHODS
Food intake was assessed using 3-d, 24-h dietary recalls and household weighing method; polyphenol intake was calculated by multiplying consumption of each food and its polyphenol content. Hypertension was defined as BP ≥ 140/90 mmHg, physicians' diagnosis, or taking antihypertension medications. HR and 95% CI were estimated using mixed-effects Cox models.
RESULTS
During 91,561 person-years of follow-up, a total of 3866 participants developed hypertension (35%). The lowest multivariable-adjusted HR (95% CI) of hypertension risk occurred in the third quartile intake, which was 0.63 (0.57, 0.70) for total polyphenol, 0.61 (0.55, 0.68) for flavonoid, 0.62 (0.56, 0.69) for phenolic acid, 0.46 (0.42, 0.51) for lignan, and 0.58 (0.52, 0.64) for stilbene, compared with the lowest quartile. The polyphenol-hypertension associations were nonlinear (all P < 0.001), and different patterns were observed. U-shaped relations with hypertension were observed for total polyphenol, flavonoid, and phenolic acid, whereas L-shaped associations were observed for lignan and stilbene. Moreover, higher fiber intake strengthened the polyphenol-hypertension association, especially for lignan (P-interaction = 0.002) and stilbene (P-interaction = 0.004). Polyphenol-containing food, particularly vegetables and fruits rich in lignan and stilbene, were significantly associated with lower hypertension risk.
CONCLUSIONS
This study demonstrated an inverse and nonlinear association between dietary polyphenol, especially lignan and stilbene, and hypertension risk. The findings provide implications for hypertension prevention.
Topics: Humans; Polyphenols; Cohort Studies; Diet; Flavonoids; Hypertension; Eating; Lignans; China
PubMed: 37146758
DOI: 10.1016/j.ajcnut.2023.05.001 -
Foods (Basel, Switzerland) Apr 2024Sesame seeds ( L.) have been cultivated for thousands of years and have long been celebrated for their culinary versatility. Beyond their delightful nutty flavor and... (Review)
Review
Sesame seeds ( L.) have been cultivated for thousands of years and have long been celebrated for their culinary versatility. Beyond their delightful nutty flavor and crunchy texture, sesame seeds have also gained recognition for their remarkable health benefits. This article provides an in-depth exploration of the numerous ways in which sesame seeds contribute to overall well-being. Sesame seeds are a powerhouse of phytochemicals, including lignans derivatives, tocopherol isomers, phytosterols, and phytates, which have been associated with various health benefits, including the preservation of cardiovascular health and the prevention of cancer, neurodegenerative disorders, and brain dysfunction. These compounds have also been substantiated for their efficacy in cholesterol management. Their potential as a natural source of beneficial plant compounds is presented in detail. The article further explores the positive impact of sesame seeds on reducing the risk of chronic diseases thanks to their rich polyunsaturated fatty acids content. Nevertheless, it is crucial to remember the significance of maintaining a well-rounded diet to achieve the proper balance of n-3 and n-6 polyunsaturated fatty acids, a balance lacking in sesame seed oil. The significance of bioactive polypeptides derived from sesame seeds is also discussed, shedding light on their applications as nutritional supplements, nutraceuticals, and functional ingredients. Recognizing the pivotal role of processing methods on sesame seeds, this review discusses how these methods can influence bioactive compounds. While roasting the seeds enhances the antioxidant properties of the oil extract, certain processing techniques may reduce phenolic compounds.
PubMed: 38672826
DOI: 10.3390/foods13081153 -
Scientific Reports Sep 2023Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease that lacks effective treatment modalities. Once patients are diagnosed with IPF,...
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease that lacks effective treatment modalities. Once patients are diagnosed with IPF, their median survival is approximately 3-5 years. PPARγ is an important target for the prevention and treatment of pulmonary fibrosis. Asarinin is a lignan compound that can be extracted from food plant Asarum heterotropoides. In this study, we investigated the therapeutic effects of asarinin in a pulmonary fibrosis model constructed using bleomycin in mice and explored the underlying mechanisms. Intraperitoneal administration of asarinin to mice with pulmonary fibrosis showed that asarinin effectively attenuated pulmonary fibrosis, and this effect was significantly inhibited by the PPARγ inhibitor GW9662. Asarinin inhibited TGF-β1-induced fibroblast-to-myofibroblast transition in vitro, while GW9662 and PPARγ gene silencing significantly inhibited this effect. In addition, asarinin inhibited not only the canonical Smad pathway of TGF-β but also the non-canonical AKT and MAPK pathways by activating PPARγ. Our study demonstrates that asarinin can be used as a therapeutic agent for pulmonary fibrosis, and that PPARγ is its key target.
Topics: Animals; Mice; PPAR gamma; Lignans; Idiopathic Pulmonary Fibrosis; Bleomycin
PubMed: 37679587
DOI: 10.1038/s41598-023-41933-5 -
Biomedicine & Pharmacotherapy =... Nov 2023Sesamol is a lignan of sesame seeds and a natural phenolic molecule that has emerged as a useful medical agent. Sesamol is a non-toxic phytoconstituent, which exerts... (Review)
Review
Sesamol is a lignan of sesame seeds and a natural phenolic molecule that has emerged as a useful medical agent. Sesamol is a non-toxic phytoconstituent, which exerts certain valuable effects in the management of cancer, diabetes, cardiovascular diseases, neurodegenerative diseases (NDs), etc. Sesamol is known to depict its neuroprotective role by various mechanisms, such as metabolic regulators, action on oxidative stress, neuroinflammation, etc. However, its poor oral bioavailability, rapid excretion (as conjugates), and susceptibility to gastric irritation/toxicity (particularly in rats' forestomach) may restrict its effectiveness. To overcome the associated limitations, novel drug delivery system-based formulations of sesamol are emerging and being researched extensively. These can conjugate with sesamol and enhance the bioavailability and solubility of free sesamol, along with delivery at the target site. In this review, we have summarized various research works highlighting the role of sesamol on various NDs, including Alzheimer's disease, Huntington's disease, Amyotrophic lateral sclerosis, and Parkinson's disease. Moreover, the formulation strategies and neuroprotective role of sesamol-based nano-formulations have also been discussed.
PubMed: 37725878
DOI: 10.1016/j.biopha.2023.115512