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Pandi A, Chakraborty B, Sen N, Kalappan VM. The hepatoprotective potential of ferulic acid against a spectrum of pharmaceuticals and toxic compounds. Arch Toxicol 2025; 99:2229-2234. [PMID: 40047862 DOI: 10.1007/s00204-025-03996-3] [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: 12/06/2024] [Accepted: 02/17/2025] [Indexed: 05/18/2025]
Abstract
Despite advancements in medicine, drug-induced liver injury continues to pose regulatory and clinical challenges. Ferulic acid, a naturally occurring polyphenol found in vegetables, fruits, and grains, has gained attention for its therapeutic properties. We report the hepatoprotective effects of ferulic acid against a range of pharmaceuticals and toxic compounds. Given the growing interest in natural hepatoprotective compounds, further research is essential to elucidate ferulic acid's role in liver protection.
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Affiliation(s)
- Anandakumar Pandi
- Department of Biochemistry, All India Institute of Medical Sciences, Deoghar, Jharkhand, India.
| | - Balarko Chakraborty
- Medical Research Unit, All India Institute of Medical Sciences, Deoghar, Jharkhand, India
| | - Nabendu Sen
- Department of Biochemistry, All India Institute of Medical Sciences, Deoghar, Jharkhand, India
| | - Vanitha Manickam Kalappan
- Department of Medical Biochemistry, University of Madras, Taramani Campus, Chennai, Tamilnadu, India
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Jin Y, Dang H, Li M. The Essential Role of Traditional Chinese Medicine Compounds in Regulating Recurrent Spontaneous Abortion by Inhibiting Oxidative Stress. Endocr Metab Immune Disord Drug Targets 2025; 25:353-363. [PMID: 39082177 DOI: 10.2174/0118715303302424240724070133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Revised: 05/24/2024] [Accepted: 06/04/2024] [Indexed: 04/09/2025]
Abstract
Due to the lack of accurate registration of RSA and miscarriages, many early miscarriages are overlooked and not diagnosed or treated promptly in hospitals. This uncertainty in pathogenesis prevents clinicians from taking targeted therapeutic measures, leading to unsatisfactory treatment outcomes and placing a heavy burden on the patient's family and the healthcare system. Oxidative stress is present in embryonic development and affects the regulation of oxidative stress in pregnancy and the reproductive endocrine system. Oxidative stress injury is a significant pathogenesis of RSA, so improving the body's ability to resist oxidative stress injury is crucial in treating RSA. For patients with RSA, there is an urgent need for safe, efficient, and cost-effective anti-oxidative stress drugs, and there is growing evidence that treatment with Traditional Chinese medicine (TCM) can improve pregnancy success with fewer adverse effects. Many active ingredients for treating RSA are mainly derived from certain components of TCM, including flavonoids, phenols, and other compounds, which have been shown to treat RSA directly or indirectly by targeting anti-oxidative stress-related pathways. This article summarizes the experimental and clinical evidence of several common TCM compounds for treating RSA. It provides ideas and perspectives for further exploring the pathogenesis of RSA and TCM compounds for treating RSA.
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Affiliation(s)
- Yi Jin
- Department of Renal Transplantation, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China
| | - Huimin Dang
- Department of Traditional Chinese Medicine, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China
| | - Meihe Li
- Department of Renal Transplantation, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China
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Elazab ST, Hsu WH. Ferulic acid ameliorates concanavalin A-induced hepatic fibrosis in mice via suppressing TGF-β/smad signaling. Toxicol Appl Pharmacol 2024; 492:117099. [PMID: 39260469 DOI: 10.1016/j.taap.2024.117099] [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: 06/08/2024] [Revised: 08/25/2024] [Accepted: 09/06/2024] [Indexed: 09/13/2024]
Abstract
BACKGROUND AND AIM Hepatic fibrosis, one of the main reasons for death globally, is a serious complication of chronic liver disorders. However, the available therapies for liver fibrosis are limited, ineffective, and often associated with adverse events. Hence, seeking for a novel, effective therapy is warranted. Our objective was to investigate the potential efficacy of ferulic acid (FA), a phenolic phytochemical, at different doses in hindering the progress of concanavalin A (Con A)-induced hepatic fibrosis and explore the involved mechanisms. METHODS Thirty-six mice were assorted into 6 groups (n = 6): Group I (control); group II received FA (20 mg/kg/day orally for 4 weeks); group III received Con A (6 mg/kg/week/i.v.) for 4 weeks; groups IV, V, and VI received Con A and were offered FA at 5, 10, and 20 mg/kg/day, respectively. RESULTS The data showed the palliative effect of FA against Con A-induced fibrosis in a dose-dependent manner. This was obvious from the recovery of liver markers and hepatic architecture with the regression of fibrosis in FA-treated mice. FA abolished Con A-mediated oxidative insults and promoted the antioxidant enzyme activities, which run through the Nrf2/HO-1 signaling. Additionally, FA suppressed Con A-induced increase in NF-kB and IL-β levels, and TNF-α immune-expression. The anti-fibrotic effect of FA was evident from the drop in TGF-β, smad3 levels, α-SMA expression, and hydroxyproline content. CONCLUSION FA attenuated Con A-induced liver fibrosis through stimulating Nrf2 signaling, suppressing NF-kB, and inhibiting the TGF-β/smad3 signaling pathway. Thus FA can be considered as a promising therapy for combating liver fibrosis.
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Affiliation(s)
- Sara T Elazab
- Department of Pharmacology, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt
| | - Walter H Hsu
- Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, Iowa 50011, USA.
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Rongala S, Kolusu AS, Jakkamsetti MS, Mohanty SK, Samudrala PK, Arakareddy BP. Ameliorative effect of ferulic acid on thyroid dysfunction against propyl-thiouracil induced hypothyroid rats. Endocrine 2024; 86:215-232. [PMID: 38637405 DOI: 10.1007/s12020-024-03818-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Accepted: 04/02/2024] [Indexed: 04/20/2024]
Abstract
PURPOSE Hypothyroidism is an endocrine disorder characterised by decreased T3, T4 and increased TSH levels. This study aims to examine the potential effects of Ferulic acid (FA) on rats with hypothyroidism induced by propylthiouracil through the estimation of biochemical parameters and histopathological studies. METHODS Twenty-five female wistar rats were allocated into five groups: Control group [1% CMC, p.o.], Disease group [PTU-50 mg/kg, p.o.], [Levothyroxine (LT4) group - 20 µg/kg, p.o. + PTU-50 mg/kg, p.o.], [FA -25 mg/kg, p.o. + PTU-50 mg/kg, p.o.] and [FA 50 mg/kg, p.o. + PTU-50 mg/kg, p.o.]. On 15th day blood was collected and serum was separated for estimation of biochemical parameters, liver and kidney homogenate was utilised for the estimation of oxidative stress markers and the thyroid gland was dissected to examine histological features. RESULTS PTU administration for 14 days showed a substantial decline in T3 and T4 and increases in TSH levels. PTU-administered rats significantly increased TC, TG and LDL levels, and decreased HDL levels. AST, ALT, urea, creatinine, and IL-6 were determined and these levels were significantly altered in PTU-induced hypothyroid group. In hypothyroid rats MDA, NO, GSH and SOD levels were significantly altered. However, treatment with FA for 14 days attenuated PTU-induced alterations. Furthermore, FA improves the histological changes of the thyroid gland. CONCLUSION In conclusion, FA treatment showed a protective effect against hypothyroidism by stimulating the thyroid hormones through the activation of thyroid peroxidase enzyme and improving thyroid function. In addition, FA diminished the increase in lipids, liver and kidney markers, oxidative stress and inflammation.
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Affiliation(s)
- Suma Rongala
- Department of Pharmacology, Shri Vishnu College of Pharmacy (SVCP) - Vishnupur, West Godavari, Bhimavaram, 534202, Andhra Pradesh, India
| | - Aravinda Sai Kolusu
- Department of Pharmacology, Shri Vishnu College of Pharmacy (SVCP) - Vishnupur, West Godavari, Bhimavaram, 534202, Andhra Pradesh, India
| | - Madhuri Suma Jakkamsetti
- Department of Pharmacology, Shri Vishnu College of Pharmacy (SVCP) - Vishnupur, West Godavari, Bhimavaram, 534202, Andhra Pradesh, India
| | - Sujit Kumar Mohanty
- Department of Pharmaceutical Chemistry, Shri Vishnu College of Pharmacy (SVCP) - Vishnupur, West Godavari, Bhimavaram, 534202, Andhra Pradesh, India
| | - Pavan Kumar Samudrala
- Department of Pharmacology, Shri Vishnu College of Pharmacy (SVCP) - Vishnupur, West Godavari, Bhimavaram, 534202, Andhra Pradesh, India
| | - Bhanu Prakash Arakareddy
- Department of Pharmacology, Shri Vishnu College of Pharmacy (SVCP) - Vishnupur, West Godavari, Bhimavaram, 534202, Andhra Pradesh, India.
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Kolure R, Vinaitheerthan N, Thakur S, Godela R, Doli SB, Santhepete Nanjundaiah M. Protective effect of Enicostemma axillare - Swertiamarin on oxidative stress against nicotine-induced liver damage in SD rats. ANNALES PHARMACEUTIQUES FRANÇAISES 2024; 82:792-799. [PMID: 38579927 DOI: 10.1016/j.pharma.2024.03.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Revised: 03/11/2024] [Accepted: 03/31/2024] [Indexed: 04/07/2024]
Abstract
OBJECTIVE The current investigation was aimed to determine the hepatoprotective benefits of Swertiamarin (ST) administration against nicotine-induced hepatotoxicity in SD rats. MATERIAL AND METHODS A total of 48 adult male SD rats were allocated into six groups using a fully randomised approach. As a control, group I was given oral (PO) normal saline. For 65 days, the animals in groups II, III, IV, V and VI received 2.5mg/kg/day of nicotine intraperitoneally (IP), 100mg/kg/day of ST orally (PO), 200mg/kg/day of ST orally (PO), 2.5mg/kg/day of nicotine (IP)+100mg/kg/day of ST (PO), and 2.5mg/kg/day of nicotine (IP)+200mg/kg/day of ST (PO), respectively. Animals were killed on 66thday, liver tissue was removed and used for histopathological analysis as well as biochemical testing (oxidative stress parameters and liver function enzymes). RESULTS When compared to control animals, the animals in group II showed a substantial rise in their aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, and creatinine levels (P˂0.001). Furthermore, compared to control animals, these animals displayed enhanced hepatic oxidative stress as indicated by significantly higher Malondialdehyde (MDA) levels (P˂0.001) and lower levels of Catalase (CAT), Glutathione (GSH), Glutathione peroxidase (GSH-Px) and Superoxide dismutase (SOD) (P˂0.001). Further, more histological anomalies were seen in the liver of nicotine-treated rats compared to control rats, including significant vacuolization, poor tissue architecture, the growth of pycnotic nuclei, and dilated sinusoids. Contrary to nicotine-treated rats, the co-administration of ST and nicotine was observed to prevent the abnormalities caused by nicotine (groups V and VI). CONCLUSION The results of the current study show that nicotine can seriously harm liver tissue and that swertiamarin can prevent the harmful effects of nicotine on rat liver. Future research is necessary to delve deeply into the mechanisms behind swertiamarin protective impact against nicotine-induced hepatotoxicity.
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Affiliation(s)
- Rajini Kolure
- Department of Pharmacology, St. Pauls College of Pharmacy, Turkayamjal, 501510 Hyderabad, Telangana, India.
| | - Nachammai Vinaitheerthan
- Department of Pharmacology, JSS College of Pharmacy (JSS Academy of Higher Education & Research), 570015 Mysuru, Karnataka, India.
| | - Sneha Thakur
- Department of Pharmacognosy, St. Pauls College of Pharmacy, Turkayamjal, Hyderabad, 501510 Telangana, India.
| | - Ramreddy Godela
- Department of Pharmaceutical Analysis, GITAM School of Pharmacy, GITAM (Deemed to be University), Rudraram, 502329 Telangana, India.
| | - Sherisha Bhavani Doli
- Department of Chemistry, Bhaskar Pharmacy College, Moinabad, 500075 Telangana, India.
| | - Manjula Santhepete Nanjundaiah
- Department of Pharmacology, JSS College of Pharmacy (JSS Academy of Higher Education & Research), 570015 Mysuru, Karnataka, India.
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Ungureanu LB, Ghiciuc CM, Amalinei C, Ungureanu C, Petrovici CG, Stănescu RȘ. Antioxidants as Protection against Reactive Oxygen Stress Induced by Formaldehyde (FA) Exposure: A Systematic Review. Biomedicines 2024; 12:1820. [PMID: 39200284 PMCID: PMC11352058 DOI: 10.3390/biomedicines12081820] [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: 07/11/2024] [Revised: 08/01/2024] [Accepted: 08/09/2024] [Indexed: 09/02/2024] Open
Abstract
BACKGROUND AND OBJECTIVES Formaldehyde induces oxidative stress and is carcinogenic, particularly squamous cell carcinoma of the nasopharyngeal area. Around us, in exhaust gases, cigarette smoke, and various industrial products, FA primarily affects the respiratory tract and other organs like the cornea, liver, kidneys, brain, and cardiovascular system. This study aims to determine if antioxidants can mitigate FA's harmful effects. MATERIALS AND METHODS Several databases, including PubMed, Science Direct, Springer, and Wiley, were systematically searched. Research publications on antioxidants mitigating FA-induced oxidative damage were included, but reviews and articles lacking complete texts were excluded. SYRCLE's risk of bias tool for animal studies has been used. Tables were used for data synthesis. Out of 8790 articles, 35 publications detailing tissue homogenate for biochemical analysis, standard hematoxylin-eosin staining, and immunohistochemistry markers for histopathological and immunohistochemical diagnosis were selected. Most studies were case-control studies, utilizing rat or mouse models. Additionally, one cohort study on industrial workers was analyzed. CONCLUSIONS Antioxidants, including plant extracts, vitamins, and pigments, can prevent or heal FA-induced lesions. However, human studies, particularly biopsies, remain challenging, and animal trials are limited. Further research is needed to confirm FA's long-term effects and optimize antioxidant dosages.
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Affiliation(s)
- Loredana Beatrice Ungureanu
- Morphopathology, Department of Morpho-Functional Sciences I, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania; (L.B.U.); (C.U.)
| | - Cristina Mihaela Ghiciuc
- Pharmacology, Clinical Pharmacology and Algeziology, Department of Morpho-Functional Sciences II, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania
| | - Cornelia Amalinei
- Histology, Department of Morpho-Functional Sciences I, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania
| | - Carmen Ungureanu
- Morphopathology, Department of Morpho-Functional Sciences I, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania; (L.B.U.); (C.U.)
| | - Cristina Gabriela Petrovici
- Infectious Disease, Department of Medical II, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania;
| | - Raluca Ștefania Stănescu
- Biochemistry, Department of Morpho-Functional Sciences II, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania;
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Shrivastav D, Kumbhakar SK, Srivastava S, Singh DD. Natural product-based treatment potential for type 2 diabetes mellitus and cardiovascular disease. World J Diabetes 2024; 15:1603-1614. [PMID: 39099809 PMCID: PMC11292323 DOI: 10.4239/wjd.v15.i7.1603] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Revised: 04/22/2024] [Accepted: 05/16/2024] [Indexed: 07/08/2024] Open
Abstract
BACKGROUND Type 2 diabetes (T2D) is a metabolic disease of impaired glucose utilization and a major cause of cardiovascular disease (CVD). The pathogenesis of both diseases shares common risk factors and mechanisms, and both are significant contributors to global morbidity and mortality. Supplements of natural products for T2D mellitus (T2DM) and CVD can be seen as a potential preventive and effective therapeutic strategy. AIM To critically evaluate the therapeutic potential of natural products in T2D and coronary artery disease (CAD). METHODS By using specific keywords, we strategically searched the PubMed database. Randomized controlled trials (RCTs) were searched as the primary focus that examined the effect of natural products on glycemic control, oxidative stress, and antioxidant levels. We focused on outcomes such as low blood glucose levels, adjustment on markers of oxidative stress and antioxidants. After screening full-length papers, we included 9 RCTs in our review that met our inclusion criteria. RESULTS In the literature search on the database, we found that various natural products like plant secondary metabolites play a diverse role in the management of CAD. American ginseng, sesame oil and cocoa flavanols proved effective in lowering blood glucose levels and controlling blood pressure, which are key factors in managing T2DM and CVD. In diabetic patients Melissa officinalis effectively reduce inflammation and shows diabetes prevention. Both fish oil and flaxseed oil reduced insulin levels and inflammatory markers, suggesting benefits for both conditions. The lipid profile and endothelial function were enhanced by Nigella sativa oil and Terminalia chebula, which is significant for the management of cardiovascular risk factors in T2DM. Additionally Bilberry extract also showed promise for improving glycemic control in patients with T2DM. CONCLUSION The high level of antioxidant, anti-inflammatory, and anti-angiogenic properties found in natural products makes them promising therapeutic options for the management of CAD, with the potential benefit of lowering the risk of CAD.
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Affiliation(s)
- Dharmsheel Shrivastav
- Amity Institute of Biotechnology, Amity University Rajasthan, Jaipur 303002, Rajasthan, India
| | - Satyam Kumar Kumbhakar
- Department of Biotechnology, Govt Veer Surendra Say P.G. College, Gariaband 493889, Chhattisgarh, India
| | - Shivangi Srivastava
- Department of Life Science, Chhatrapati Shahu ji Maharaj University, Kanpur 208024, Uttar Pradesh, India
| | - Desh Deepak Singh
- Amity Institute of Biotechnology, Amity University Rajasthan, Jaipur 303002, Rajasthan, India
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Bhuia MS, Chowdhury R, Shill MC, Chowdhury AK, Coutinho HDM, Antas E Silva D, Raposo A, Islam MT. Therapeutic Promises of Ferulic Acid and its Derivatives on Hepatic damage Related with Oxidative Stress and Inflammation: A Review with Mechanisms. Chem Biodivers 2024; 21:e202400443. [PMID: 38757848 DOI: 10.1002/cbdv.202400443] [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: 02/22/2024] [Revised: 05/03/2024] [Accepted: 05/17/2024] [Indexed: 05/18/2024]
Abstract
Ferulic acid (FA) is a naturally occurring phenolic compound commonly found in the plant Ferula communis. This study aims to investigate the hepatoprotective effect of FA and its derivatives (methyl ferulic acid and trans-ferulic acid) against oxidative stress and inflammation-related hepatotoxicity due to toxicants based on the results of different non-clinical and preclinical tests. For this, data was collected from different reliable electronic databases such as PubMed, Google Scholar, and ScienceDirect, etc. The results of this investigation demonstrated that FA and its derivatives have potent hepatoprotective effects against oxidative stress and inflammation-related damage. The findings also revealed that these protective effects are due to the antioxidant and anti-inflammatory effects of the chemical compound. FA and its analogues significantly inhibit free radical generation and hinder the effects of proinflammatory markers and inflammatory enzymes, resulting in diminished cytotoxic and apoptotic hepatocyte death. The compounds also prevent intracellular lipid accumulation and provide protective effects.
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Affiliation(s)
- Md Shimul Bhuia
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, 8100, Bangladesh
- Phytochemistry and Biodiversity Research Laboratory, BioLuster Research Center, Gopalganj, 8100, Dhaka, Bangladesh
| | - Raihan Chowdhury
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, 8100, Bangladesh
| | - Manik Chandra Shill
- Department of Pharmaceutical Sciences, North South University, Bashundhara, Dhaka, 1229, Bangladesh
| | | | | | - Davi Antas E Silva
- Departament of Physiology and Pathology, Federal University of Paraíba, Campus I Lot. Cidade Universitaria, João Pessoa, PB, 58051-900, Brazil
| | - António Raposo
- CBIOS (Research Center for Biosciences and Health Technologies), Universidade Lusófona de Humanidades e Tecnologias, Campo Grande 376, 1749-024, Lisboa, Portugal
| | - Muhammad Torequl Islam
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, 8100, Bangladesh
- Phytochemistry and Biodiversity Research Laboratory, BioLuster Research Center, Gopalganj, 8100, Dhaka, Bangladesh
- Pharmacy Discipline, Khulna University, Khulna, 9208, Bangladesh
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Hu Z, Sun Y, Liu S, Xiang Y, Li M, Li Y, Li Y, Liu X, Fu M. Dietary additive ferulic acid alleviated oxidative stress, inflammation, and apoptosis induced by chronic exposure to avermectin in the liver of common carp (Cyprinus carpio). Toxicon 2024; 244:107755. [PMID: 38740097 DOI: 10.1016/j.toxicon.2024.107755] [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: 03/05/2024] [Revised: 04/23/2024] [Accepted: 05/10/2024] [Indexed: 05/16/2024]
Abstract
Avermectin (AVM) has been utilized extensively in agricultural production since it is a low-toxicity pesticide. However, the pollution caused by its residues to fisheries aquaculture has been neglected. As an abundant polyphenolic substance in plants, ferulic acid (FA) possesses anti-inflammatory and antioxidant effects. The goal of the study is to assess the FA's ability to reduce liver damage in carp brought on by AVM exposure. Four groups of carp were created at random: the control group; the AVM group; the FA group; and the FA + AVM group. On day 30, and the liver tissues of carp were collected and examined for the detection of four items of blood lipid as well as the activity of the antioxidant enzymes catalase (CAT), glutathione (GSH) and malondialdehyde (MDA) in carp liver tissues by biochemical kits, and the transcript levels of indicators of oxidative stress, inflammation and apoptosis by qPCR. The results showed that liver injury, inflammation, oxidative stress, and apoptosis were attenuated in the FA + AVM group compared to the AVM group. In summary, dietary addition of FA could ameliorate the hepatotoxicity caused by AVM in carp by alleviating oxidative stress, inflammation, apoptosis in liver tissues.
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Affiliation(s)
- Zunhan Hu
- Jiangsu Key Laboratory of Marine Bioresources and Environment, Co-Innovation Center of Jiangsu Marine Bio-Industry Technology, Jiangsu Marine Pharmaceutical Resources Development Engineering Research Center, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China
| | - Ying Sun
- Jiangsu Key Laboratory of Marine Bioresources and Environment, Co-Innovation Center of Jiangsu Marine Bio-Industry Technology, Jiangsu Marine Pharmaceutical Resources Development Engineering Research Center, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China
| | - Shujuan Liu
- Jiangsu Key Laboratory of Marine Bioresources and Environment, Co-Innovation Center of Jiangsu Marine Bio-Industry Technology, Jiangsu Marine Pharmaceutical Resources Development Engineering Research Center, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China
| | - Yannan Xiang
- Jiangsu Key Laboratory of Marine Bioresources and Environment, Co-Innovation Center of Jiangsu Marine Bio-Industry Technology, Jiangsu Marine Pharmaceutical Resources Development Engineering Research Center, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China
| | - Mengxin Li
- Jiangsu Key Laboratory of Marine Bioresources and Environment, Co-Innovation Center of Jiangsu Marine Bio-Industry Technology, Jiangsu Marine Pharmaceutical Resources Development Engineering Research Center, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China
| | - Ying Li
- Jiangsu Key Laboratory of Marine Bioresources and Environment, Co-Innovation Center of Jiangsu Marine Bio-Industry Technology, Jiangsu Marine Pharmaceutical Resources Development Engineering Research Center, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China
| | - Yuanyuan Li
- Jiangsu Key Laboratory of Marine Bioresources and Environment, Co-Innovation Center of Jiangsu Marine Bio-Industry Technology, Jiangsu Marine Pharmaceutical Resources Development Engineering Research Center, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China
| | - Xiguang Liu
- Neurosurgery Department, Institute of Neuroscience, The First People's Hospital of Lianyungang, Lianyungang, 222000, China.
| | - Mian Fu
- Jiangsu Key Laboratory of Marine Bioresources and Environment, Co-Innovation Center of Jiangsu Marine Bio-Industry Technology, Jiangsu Marine Pharmaceutical Resources Development Engineering Research Center, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China.
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Bouyahya A, Bakrim S, Aboulaghras S, El Kadri K, Aanniz T, Khalid A, Abdalla AN, Abdallah AA, Ardianto C, Ming LC, El Omari N. Bioactive compounds from nature: Antioxidants targeting cellular transformation in response to epigenetic perturbations induced by oxidative stress. Biomed Pharmacother 2024; 174:116432. [PMID: 38520868 DOI: 10.1016/j.biopha.2024.116432] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2023] [Revised: 03/09/2024] [Accepted: 03/15/2024] [Indexed: 03/25/2024] Open
Abstract
Oxidative stress results from a persistent imbalance in oxidation levels that promotes oxidants, playing a crucial role in the early and sustained phases of DNA damage and genomic and epigenetic instability, both of which are intricately linked to the development of tumors. The molecular pathways contributing to carcinogenesis in this context, particularly those related to double-strand and single-strand breaks in DNA, serve as indicators of DNA damage due to oxidation in cancer cases, as well as factors contributing to epigenetic instability through ectopic expressions. Oxidative stress has been considered a therapeutic target for many years, and an increasing number of studies have highlighted the promising effectiveness of natural products in cancer treatment. In this regard, we present significant research on the therapeutic targeting of oxidative stress using natural molecules and underscore the essential role of oxidative stress in cancer. The consequences of stress, especially epigenetic instability, also offer significant therapeutic prospects. In this context, the use of natural epi-drugs capable of modulating and reorganizing the epigenetic network is beginning to emerge remarkably. In this review, we emphasize the close connections between oxidative stress, epigenetic instability, and tumor transformation, while highlighting the role of natural substances as antioxidants and epi-drugs in the anti-tumoral context.
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Affiliation(s)
- Abdelhakim Bouyahya
- Laboratory of Human Pathologies Biology, Department of Biology, Faculty of Sciences, Mohammed V University in Rabat, Rabat 10106, Morocco.
| | - Saad Bakrim
- Geo-Bio-Environment Engineering and Innovation Laboratory, Molecular Engineering, Biotechnology and Innovation Team, Polydisciplinary Faculty of Taroudant, Ibn Zohr University, Agadir 80000, Morocco
| | - Sara Aboulaghras
- Laboratory of Human Pathologies Biology, Department of Biology, Faculty of Sciences, Mohammed V University in Rabat, Rabat 10106, Morocco
| | - Kawtar El Kadri
- Laboratory of Human Pathologies Biology, Department of Biology, Faculty of Sciences, Mohammed V University in Rabat, Rabat 10106, Morocco
| | - Tarik Aanniz
- Biotechnology Lab (MedBiotech), Bioinova Research Center, Rabat Medical & Pharmacy School, Mohammed V University in Rabat, Morocco
| | - Asaad Khalid
- Substance Abuse and Toxicology Research Center, Jazan University, Jazan PO Box: 114, Saudi Arabia.
| | - Ashraf N Abdalla
- Department of Pharmacology and Toxicology, College of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia
| | - Ahmed A Abdallah
- Department of Anatomy, Faculty of Medicine, Umm Alqura University, Makkah 21955, Saudi Arabia
| | - Chrismawan Ardianto
- Department of Pharmacy Practice, Faculty of Pharmacy, Universitas Airlangga, Surabaya, Indonesia.
| | - Long Chiau Ming
- Department of Pharmacy Practice, Faculty of Pharmacy, Universitas Airlangga, Surabaya, Indonesia; School of Medical and Life Sciences, Sunway University, Sunway City, Malaysia; Pengiran Anak Puteri Rashidah Sa'adatul Bolkiah Institute of Health Sciences, Universiti Brunei Darussalam, Gadong, Brunei Darussalam.
| | - Nasreddine El Omari
- High Institute of Nursing Professions and Health Techniques of Tetouan, Tetouan, Morocco
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11
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Kim YY, Hur G, Jang HJ, Jeong S, Lee SW, Lee SJ, Rho MC, Kim SH, Lee S. Ferulic Acid Derivatives Ameliorate Intestine Barrier Destruction by Alleviating Inflammatory Responses in Dextran Sulfate Sodium-Induced Inflammatory Bowel Disease. TOXICS 2024; 12:268. [PMID: 38668491 PMCID: PMC11055104 DOI: 10.3390/toxics12040268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Revised: 03/29/2024] [Accepted: 04/02/2024] [Indexed: 04/29/2024]
Abstract
Inflammatory bowel disease (IBD), a chronic disorder affecting the colon and rectum, involves the overproduction of pro-inflammatory cytokines causing damage to tight junctions (TJ) in the intestinal epithelial cells and chronic inflammation. The current mainstay of treatment, sulfasalazine, often causes adverse effects, thereby necessitating the exploration of alternative herbal medicines with fewer side effects. Portulaca oleracea L. (P. oleracea), a traditional medicinal herb, contains feruloyl amide compounds. We synthesized new compounds by conjugating ferulic acid (FA) with (±)-octopamine. Our study focused on novel FA derivatives that demonstrate protective effects against the intestinal epithelial barrier and inflammatory responses. In lipopolysaccharide-induced cells, C1 and C1a inhibited the production of inflammatory mediators. In Caco-2 cells, these compounds maintained the TJ protein expression, thereby demonstrating their protective effects on the epithelial barrier. In a mouse model of dextran sulfate sodium-induced IBD, a treatment with these compounds ameliorated features including a body weight reduction, colon shortening, an increased disease activity index, and histopathological changes. Furthermore, C1a demonstrated greater efficacy than C1 at the same concentration. These findings suggest that the novel FA derivative (C1a) effectively alleviates clinical signs and inflammatory mediators in IBD, making these compounds potential candidates as natural medicines for the treatment of IBD.
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Affiliation(s)
- Yeon-Yong Kim
- Functional Biomaterials Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup 56212, Republic of Korea; (Y.-Y.K.); (G.H.); (S.J.); (S.W.L.); (S.-J.L.); (M.-C.R.)
| | - Gayeong Hur
- Functional Biomaterials Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup 56212, Republic of Korea; (Y.-Y.K.); (G.H.); (S.J.); (S.W.L.); (S.-J.L.); (M.-C.R.)
| | - Hyun-Jae Jang
- Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Republic of Korea;
| | - Seungwon Jeong
- Functional Biomaterials Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup 56212, Republic of Korea; (Y.-Y.K.); (G.H.); (S.J.); (S.W.L.); (S.-J.L.); (M.-C.R.)
| | - Seung Woong Lee
- Functional Biomaterials Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup 56212, Republic of Korea; (Y.-Y.K.); (G.H.); (S.J.); (S.W.L.); (S.-J.L.); (M.-C.R.)
| | - Seung-Jae Lee
- Functional Biomaterials Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup 56212, Republic of Korea; (Y.-Y.K.); (G.H.); (S.J.); (S.W.L.); (S.-J.L.); (M.-C.R.)
| | - Mun-Chual Rho
- Functional Biomaterials Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup 56212, Republic of Korea; (Y.-Y.K.); (G.H.); (S.J.); (S.W.L.); (S.-J.L.); (M.-C.R.)
| | - Sang-Hyun Kim
- Cell and Matrix Research Institute, Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea
| | - Soyoung Lee
- Functional Biomaterials Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup 56212, Republic of Korea; (Y.-Y.K.); (G.H.); (S.J.); (S.W.L.); (S.-J.L.); (M.-C.R.)
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12
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Mahmoud MH, El-Gogary RI, Soliman ME, Kamel AO. Novel green-based polyglycerol polymeric nanoparticles loaded with ferulic acid: A promising approach for hepatoprotection. Int J Biol Macromol 2024; 264:130698. [PMID: 38458296 DOI: 10.1016/j.ijbiomac.2024.130698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Revised: 03/03/2024] [Accepted: 03/05/2024] [Indexed: 03/10/2024]
Abstract
In the pursuit of eco-friendly and sustainable materials, polyglycerol diacid polymers hold immense promise for drug delivery compared to those derived from fossil fuels. Harnessing this potential, we aimed to prepare nanoparticles (NPs) derived from sustainable polymers, loaded with ferulic acid (FA), a natural polyphenolic compound known for its shielding effect against liver-damaging agents, including carbon tetrachloride (CCl4). Glycerol was esterified with renewable monomers, such as succinic acid, adipic acid, and/or FA, resulting in the creation of a novel class of polyglycerol diacid polymers. Characterization via Fourier-transform infrared spectroscopy and nuclear magnetic resonance confirmed the successful synthesis of these polymers with <7 % residual monomers. FA-loaded NPs were fabricated using the newly synthesized polymers. To further augment their potential, the NPs were coated with chitosan. The chitosan-coated NPs boasted an optimal PS of 290 ± 5.03 nm, showing superior physical stability, and a commendable EE% of 58.79 ± 0.43%w/v. The cytotoxicity was examined on fibroblast cells using the SRB assay. In-vivo experiments employing a CCl4-induced liver injury model yielded compelling evidence of the heightened hepatoprotective effects conferred by chitosan-coated particles. This demonstrates the benefits of incorporating sustainable polymers into innovative composites for efficient drug delivery, indicating their potential for creating versatile platforms for various therapeutic applications.
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Affiliation(s)
- Mariam H Mahmoud
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, 11566, Egypt
| | - Riham I El-Gogary
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, 11566, Egypt
| | - Mahmoud E Soliman
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, 11566, Egypt; Egypt Japan University of Science and Technology, Egypt
| | - Amany O Kamel
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, 11566, Egypt.
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13
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Sawie HG, Ahmed OM, Shabana ME, Elqattan GM, EL-Kassaby MI, Abou- Seif HS. Ferulic acid attenuated diethylnitrosamine-provoked hepato-renal damage and malfunction by suppressing oxidative stress, abating inflammation and upregulating nuclear factor erythroid related factor-2 signaling. EGYPTIAN PHARMACEUTICAL JOURNAL 2024; 23:16-27. [DOI: 10.4103/epj.epj_79_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Accepted: 06/26/2023] [Indexed: 08/09/2024]
Abstract
Background
Diethylnitrosamine (DEN) is a potent environmental toxin that can reach humans through the food chain. It induces proliferative, degenerative and cancerous lesions in the liver and kidneys.
Objective
The principal goal of the existing research was to assess the preventive impacts of ferulic acid (FA) versus DEN- provoked hepato-renal damage and malfunction.
Materials and methods
Adult male rats were divided into four groups: group 1 (normal control) animals orally received saline every day for 14 weeks; group 2 (DEN) animals intraperitoneally received DEN (150 mg/kg twice a week) for 2 weeks; group 3 (DEN + FA) animals were injected intraperitoneally twice a week with DEN for 2 weeks besides to oral administration of FA (100 mg/kg/day) for 14 weeks; group 4 (FA) animals were given a similar dose of FA for a similar period.
Results
The results revealed that FA treatment reversed the DEN-mediated elevation in serum values of the liver enzymes activities as well as urea and creatinine levels; it also augmented the hepato-renal antioxidant system that overcame DEN-induced oxidative stress deteriorations. Moreover, FA markedly reduced the DEN-induced elevated hepato-renal levels of immuno-inflammatory markers (IL-1β and TNF-α) as well as downregulated the inflammatory mediators (Bcl-2, NF-κB, and nuclear factor erythroid related factor-2 (Nrf-2)), reflecting its protective potential.
Conclusion
The existing results elucidate that ferulic acid could prevent and ameliorate DEN-induced hepato-renal toxicological changes and can restore livers and kidneys’ functions; this effect could be mechanized through activation of anti-inflammatory and antioxidant systems, as well as regulation of NF-κB, Bcl2, and nuclear factor erythroid related factor-2 expression.
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Affiliation(s)
- Hussein G. Sawie
- Medical Physiology Department, Medical Research and Clinical Studies Institute, the National Research Centre
| | - Osama M. Ahmed
- Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef
| | - Marwa E. Shabana
- Pathology Department, Medical Research and Clinical Studies Institute, the National Research Centre, Cairo, Egypt
| | - Ghada M. Elqattan
- Medical Physiology Department, Medical Research and Clinical Studies Institute, the National Research Centre
| | - Mahitab I. EL-Kassaby
- Medical Physiology Department, Medical Research and Clinical Studies Institute, the National Research Centre
| | - Howida S. Abou- Seif
- Medical Physiology Department, Medical Research and Clinical Studies Institute, the National Research Centre
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14
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Ma H, Lou K, Shu Q, Song X, Xu H. Aldehyde dehydrogenase 2 deficiency reinforces formaldehyde-potentiated pro-inflammatory responses and glycolysis in macrophages. J Biochem Mol Toxicol 2024; 38:e23518. [PMID: 37638564 DOI: 10.1002/jbt.23518] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Revised: 03/05/2023] [Accepted: 08/17/2023] [Indexed: 08/29/2023]
Abstract
Aldehyde dehydrogenase 2 (ALDH2) deficiency caused by genetic variant is present in more than 560 million people of East Asian descent, which can be identified by apparent facial flushing from acetaldehyde accumulation after consuming alcohol. Recent findings indicated that ALDH2 also played a critical role in detoxification of formaldehyde (FA). Our previous studies showed that FA could enhance macrophagic inflammatory responses through the induction of HIF-1α-dependent glycolysis. In the present study, pro-inflammatory responses and glycolysis promoted by 0.5 mg/m3 FA were found in mice with Aldh2 gene knockout, which was confirmed in the primary macrophages isolated from Aldh2 gene knockout mice treated with 50 μM FA. FA at 50 and 100 μM also induced stronger dose-dependent increases of pro-inflammatory responses and glycolysis in RAW264.7 murine macrophages with knock-down of ALDH2, and the enhanced effects induced by 50 μM FA was alleviated by inhibition of HIF-1α in RAW264.7 macrophages with ALDH2 knock-down. Collectively, these results clearly demonstrated that ALDH2 deficiency reinforced pro-inflammatory responses and glycolysis in macrophages potentiated by environmentally relevant concentration of FA, which may increase the susceptibility to inflammation and immunotoxicity induced by environmental FA exposure.
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Affiliation(s)
- Huijuan Ma
- Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, East China University of Science and Technology, Shanghai, China
| | - Kaiyan Lou
- Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, East China University of Science and Technology, Shanghai, China
| | - Qi Shu
- Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, East China University of Science and Technology, Shanghai, China
| | - Xiaodong Song
- Medical Laboratory Department, Hua Shan Hospital North, Fudan University, Shanghai, China
| | - Huan Xu
- Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, East China University of Science and Technology, Shanghai, China
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15
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Guzmán-López EG, Reina M, Hernández-Ayala LF, Galano A. Rational Design of Multifunctional Ferulic Acid Derivatives Aimed for Alzheimer's and Parkinson's Diseases. Antioxidants (Basel) 2023; 12:1256. [PMID: 37371986 DOI: 10.3390/antiox12061256] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2023] [Revised: 05/31/2023] [Accepted: 06/06/2023] [Indexed: 06/29/2023] Open
Abstract
Ferulic acid has numerous beneficial effects on human health, which are frequently attributed to its antioxidant behavior. In this report, many of them are reviewed, and 185 new ferulic acid derivatives are computationally designed using the CADMA-Chem protocol. Consequently, their chemical space was sampled and evaluated. To that purpose, selection and elimination scores were used, which are built from a set of descriptors accounting for ADME properties, toxicity, and synthetic accessibility. After the first screening, 12 derivatives were selected and further investigated. Their potential role as antioxidants was predicted from reactivity indexes directly related to the formal hydrogen atom transfer and the single electron transfer mechanisms. The best performing molecules were identified by comparisons with the parent molecule and two references: Trolox and α-tocopherol. Their potential as polygenic neuroprotectors was investigated through the interactions with enzymes directly related to the etiologies of Parkinson's and Alzheimer's diseases. These enzymes are acetylcholinesterase, catechol-O-methyltransferase, and monoamine oxidase B. Based on the obtained results, the most promising candidates (FA-26, FA-118, and FA-138) are proposed as multifunctional antioxidants with potential neuroprotective effects. The findings derived from this investigation are encouraging and might promote further investigations on these molecules.
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Affiliation(s)
- Eduardo Gabriel Guzmán-López
- Departamento de Química, Universidad Autónoma Metropolitana-Iztapalapa, Av. Ferrocarril San Rafael Atlixco 186, Col. Leyes de Reforma 1A Sección, Alcaldía Iztapalapa, Mexico City 09310, Mexico
| | - Miguel Reina
- Departamento de Química Inorgánica y Nuclear, Facultad de Química, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico
| | - Luis Felipe Hernández-Ayala
- Departamento de Química, Universidad Autónoma Metropolitana-Iztapalapa, Av. Ferrocarril San Rafael Atlixco 186, Col. Leyes de Reforma 1A Sección, Alcaldía Iztapalapa, Mexico City 09310, Mexico
| | - Annia Galano
- Departamento de Química, Universidad Autónoma Metropolitana-Iztapalapa, Av. Ferrocarril San Rafael Atlixco 186, Col. Leyes de Reforma 1A Sección, Alcaldía Iztapalapa, Mexico City 09310, Mexico
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16
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Mehmood A, Zeb A, Ateeq MK. In vivo antidiabetic effects of phenolic compounds of spinach, mustard, and cabbage leaves in mice. Heliyon 2023; 9:e16616. [PMID: 37292279 PMCID: PMC10245046 DOI: 10.1016/j.heliyon.2023.e16616] [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: 10/13/2022] [Revised: 05/16/2023] [Accepted: 05/22/2023] [Indexed: 06/10/2023] Open
Abstract
Leafy vegetables are considered to have health-promoting potentials, mainly attributed to bioactive phenolic compounds. The antidiabetic effects of spinach, mustard, and cabbage were studied by feeding their phenolic-rich aqueous extracts to alloxan-induced diabetic mice. The antioxidant, biochemical, histopathological, and hematological indices of the control, diabetic, and treated mice were studied. Phenolic compounds present in the extracts were identified and quantified using HPLC-DAD. Results showed ten, nineteen, and eleven phenolic compounds in spinach, mustard, and cabbage leave aqueous extracts, respectively. The body weight, tissue total glutathione (GSH) contents, fasting blood sugar, liver function tests, renal function tests, and lipid profile of the mice were affected by diabetes and were significantly improved by the extract treatments. Likewise, hematological indices and tissues histological studies also showed recovery from diabetic stress in treated mice. The study's findings highlight that the selected leafy vegetables potentially mitigate diabetic complications. Among the studied vegetables, cabbage extract was comparatively more active in ameliorating diabetic stress.
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Affiliation(s)
- Arif Mehmood
- Department of Biotechnology, University of Malakand, Chakdara, Khyber Pakhtunkhwa, Pakistan
| | - Alam Zeb
- Department of Biochemistry, University of Malakand, Chakdara, Khyber Pakhtunkhwa, Pakistan
| | - Muhammad Khalil Ateeq
- Department of Basic Sciences, University of Veterinary and Animals Sciences, Lahore, Pakistan
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17
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He Y, Wang H, Fang X, Zhang W, Zhang J, Qian J. Semicarbazide-based fluorescent probe for detection of Cu 2+ and formaldehyde in different channels. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2023; 299:122818. [PMID: 37167742 DOI: 10.1016/j.saa.2023.122818] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Revised: 04/19/2023] [Accepted: 05/02/2023] [Indexed: 05/13/2023]
Abstract
Two fluorescent sensors with the receptor semicarbazide respectively at 7- (CAA) and 3-position (CAB) of coumarin were designed and synthesized. CAA exhibits fluorescence turn-on response to Cu2+ by triggering the intramolecular charge transfer (ICT) process via Cu2+-catalyzed hydrolysis, and can detect formaldehyde (FA) at different channel by inhibiting the photo-induced electron transfer (PET). However, CAB displays quite different responses: the photophysical properties hardly changed in the presence of FA; while a three-stage fluorescence response of fast quenching, steady increasing and slowly decreasing was found upon addition of Cu2+. The high selectivity enabled CAA a good candidate for quantification of Cu2+ and formaldehyde as well as bioimaging Cu2+ in living cells. Good linear relationships between the fluorescence intensity and analyte concentration were observed in the range of 0.1-30 μM for Cu2+ and 1.0-50 μM for FA, and their detection limits (LOD) were calculated to be 0.43 μM and 1.92 μM (3δ/k), respectively.
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Affiliation(s)
- Yuting He
- Shanghai Key Laboratory of Functional Materials Chemistry, School of Chemistry & Molecular Engineering, East China University of Science and Technology, Shanghai 200237, China
| | - Hao Wang
- Shanghai Key Laboratory of Functional Materials Chemistry, School of Chemistry & Molecular Engineering, East China University of Science and Technology, Shanghai 200237, China
| | - Xinhang Fang
- Shanghai Key Laboratory of Functional Materials Chemistry, School of Chemistry & Molecular Engineering, East China University of Science and Technology, Shanghai 200237, China
| | - Weibing Zhang
- Shanghai Key Laboratory of Functional Materials Chemistry, School of Chemistry & Molecular Engineering, East China University of Science and Technology, Shanghai 200237, China
| | - Jingyuan Zhang
- Department of Chemistry, Faculty of Science, University of Alberta, Edmonton, Alberta t6g2r3, Canada
| | - Junhong Qian
- Shanghai Key Laboratory of Functional Materials Chemistry, School of Chemistry & Molecular Engineering, East China University of Science and Technology, Shanghai 200237, China.
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18
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Marcano-Gómez EC, de Souza ABF, Machado-Junior PA, Rodríguez-Herrera AJ, Castro TDF, da Silva SPG, Vieira RG, Talvani A, Nogueira KDOPC, de Oliveira LAM, Bezerra FS. N-acetylcysteine modulates redox imbalance and inflammation in macrophages and mice exposed to formaldehyde. Free Radic Res 2023; 57:444-459. [PMID: 37987619 DOI: 10.1080/10715762.2023.2284636] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Accepted: 11/04/2023] [Indexed: 11/22/2023]
Abstract
This study aimed to evaluate the protective role of N-acetylcysteine (NAC) in cells and mice exposed to formaldehyde. For the in vitro study, J774A.1 macrophages cells were incubated for 8, 16 and 24 h with formaldehyde or NAC to assess cell viability and reactive oxygen species (ROS). In the in vivo study, C57BL/6 mice (n = 48) were divided into 6 groups: control (CG), vehicle (VG) that received saline by orogastric gavage, a group exposed to formaldehyde 1% (FG) and formaldehyde exposed groups that received NAC at doses of 100, 150 and 200 mg/Kg (FN100, FN150 and FN200) for a period of 5 days. In vitro, formaldehyde promoted a decrease in cell viability and increased ROS, while NAC reduced formaldehyde-induced ROS production. Animals exposed to formaldehyde presented higher leukocyte counts in the blood and in the bronchoalveolar lavage fluid, and promoted secretion of inflammatory markers IL-6, IL-15, and IL-10. The exposure to formaldehyde also promoted redox imbalance and oxidative damage characterized by increased activities of superoxide dismutase, catalase, decreased GSH/GSSG ratio, as well as it increased levels of protein carbonyls and lipid peroxidation. NAC administration after formaldehyde exposure attenuated oxidative stress markers, secretion of inflammatory mediators and lung inflammation. In conclusion, both in in vitro and in vivo models, NAC administration exerted protective effects, which modulated the inflammatory response and redox imbalance, thus preventing the development airway injury induced by formaldehyde exposure.
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Affiliation(s)
- Elena Cecilia Marcano-Gómez
- Laboratory of Experimental Pathophysiology, Department of Biological Sciences and Center of Research in Biological Sciences, Federal University of Ouro Preto (UFOP), Ouro Preto, Brazil
| | - Ana Beatriz Farias de Souza
- Laboratory of Experimental Pathophysiology, Department of Biological Sciences and Center of Research in Biological Sciences, Federal University of Ouro Preto (UFOP), Ouro Preto, Brazil
| | - Pedro Alves Machado-Junior
- Laboratory of Experimental Pathophysiology, Department of Biological Sciences and Center of Research in Biological Sciences, Federal University of Ouro Preto (UFOP), Ouro Preto, Brazil
| | - Andrea Jazel Rodríguez-Herrera
- Laboratory of Experimental Pathophysiology, Department of Biological Sciences and Center of Research in Biological Sciences, Federal University of Ouro Preto (UFOP), Ouro Preto, Brazil
| | - Thalles de Freitas Castro
- Laboratory of Experimental Pathophysiology, Department of Biological Sciences and Center of Research in Biological Sciences, Federal University of Ouro Preto (UFOP), Ouro Preto, Brazil
| | - Sirlaine Pio Gomes da Silva
- Laboratory of Immunobiology of Inflammation, Department of Biological Sciences, Institute of Exact and Biological Sciences, Federal University of Ouro Preto (UFOP), Ouro Preto, Brazil
| | - Ramony Gonzaga Vieira
- Laboratory of Neurobiology and Biomaterials, Department of Biological Sciences, Institute of Exact and Biological Sciences, Federal University of Ouro Preto (UFOP), Ouro Preto, Brazil
| | - André Talvani
- Laboratory of Immunobiology of Inflammation, Department of Biological Sciences, Institute of Exact and Biological Sciences, Federal University of Ouro Preto (UFOP), Ouro Preto, Brazil
| | - Katiane de Oliveira Pinto Coelho Nogueira
- Laboratory of Neurobiology and Biomaterials, Department of Biological Sciences, Institute of Exact and Biological Sciences, Federal University of Ouro Preto (UFOP), Ouro Preto, Brazil
| | - Laser Antônio Machado de Oliveira
- Laboratory of Neurobiology and Biomaterials, Department of Biological Sciences, Institute of Exact and Biological Sciences, Federal University of Ouro Preto (UFOP), Ouro Preto, Brazil
| | - Frank Silva Bezerra
- Laboratory of Experimental Pathophysiology, Department of Biological Sciences and Center of Research in Biological Sciences, Federal University of Ouro Preto (UFOP), Ouro Preto, Brazil
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19
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Ermis A, Aritici Colak G, Acikel-Elmas M, Arbak S, Kolgazi M. Ferulic Acid Treats Gastric Ulcer via Suppressing Oxidative Stress and Inflammation. Life (Basel) 2023; 13:life13020388. [PMID: 36836745 PMCID: PMC9959638 DOI: 10.3390/life13020388] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 01/19/2023] [Accepted: 01/24/2023] [Indexed: 02/04/2023] Open
Abstract
(1) Background: The aim of the present study was to evaluate the gastroprotective potential of ferulic acid (FA) on indomethacin-induced gastric ulcers in rats with macroscopic and microscopic examinations along with biochemical assays. (2) Methods: After 24 h starvation, the ulcer was induced in male Sprague-Dawley rats by subcutaneous indomethacin (25 mg/kg) injection. Fifteen minutes after ulcer induction, rats were treated with either tween 80 or FA. FA was given by oral gavage at 100 mg/kg, 250 mg/kg, and 500 mg/kg. In the fourth hour, rats were euthanized and collected gastric samples were evaluated macroscopically and microscopically. Antioxidant parameters including malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and inflammatory parameters comprising of myeloperoxidase (MPO), Tumor Necrosis Factor (TNF)-α, Interleukin (IL)-1β, IL-6 and Nuclear Factor Kappa-B (NF-κB) p65 levels were also determined. (3) Results: Indomethacin injection significantly increased the macroscopic and microscopic scores. In addition, it increased the gastric MDA, MPO, TNF-α, IL-1β, IL-6, and NF-κB p65 levels but reduced SOD and GSH content. Treatment with FA significantly improved the gastric injury macroscopically and microscopically. Moreover, FA displayed a marked decrease in the gastric levels of MDA, MPO, TNF-α, IL-1β, IL-6, and NF-κB p65 and a significant increase in SOD and GSH compared to the INDO group. Ultimately, 250 mg/kg FA was determined as the most effective dose. (4) Conclusion: Our results revealed that FA has a gastroprotective effect against indomethacin-induced gastric ulcers in rats due to its antioxidant and anti-inflammatory properties. As a result, FA may be a potential treatment choice for gastric ulcers.
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Affiliation(s)
- Aleyna Ermis
- Department of Nutrition and Dietetics, Faculty of Health Science, Acibadem Mehmet Ali Aydinlar University, Icerenkoy Mah., Kayisdagi Cad. No: 32, Atasehir, Istanbul 34752, Turkey
| | - Gozde Aritici Colak
- Department of Nutrition and Dietetics, Faculty of Health Science, Acibadem Mehmet Ali Aydinlar University, Icerenkoy Mah., Kayisdagi Cad. No: 32, Atasehir, Istanbul 34752, Turkey
| | - Merve Acikel-Elmas
- Department of Histology and Embryology, School of Medicine, Acibadem Mehmet Ali Aydinlar University, Icerenkoy Mah., Kayisdagi Cad. No: 32, Atasehir, Istanbul 34752, Turkey
| | - Serap Arbak
- Department of Histology and Embryology, School of Medicine, Acibadem Mehmet Ali Aydinlar University, Icerenkoy Mah., Kayisdagi Cad. No: 32, Atasehir, Istanbul 34752, Turkey
| | - Meltem Kolgazi
- Department of Physiology, School of Medicine, Acibadem Mehmet Ali Aydinlar University, Icerenkoy Mah., Kayisdagi Cad. No: 32, Atasehir, Istanbul 34752, Turkey
- Correspondence:
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20
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Ojeda-Hernández DD, Canales-Aguirre AA, Matias-Guiu JA, Matias-Guiu J, Gómez-Pinedo U, Mateos-Díaz JC. Chitosan–Hydroxycinnamic Acids Conjugates: Emerging Biomaterials with Rising Applications in Biomedicine. Int J Mol Sci 2022; 23:ijms232012473. [PMID: 36293330 PMCID: PMC9604192 DOI: 10.3390/ijms232012473] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 10/13/2022] [Accepted: 10/15/2022] [Indexed: 11/16/2022] Open
Abstract
Over the past thirty years, research has shown the huge potential of chitosan in biomedical applications such as drug delivery, tissue engineering and regeneration, cancer therapy, and antimicrobial treatments, among others. One of the major advantages of this interesting polysaccharide is its modifiability, which facilitates its use in tailor-made applications. In this way, the molecular structure of chitosan has been conjugated with multiple molecules to modify its mechanical, biological, or chemical properties. Here, we review the conjugation of chitosan with some bioactive molecules: hydroxycinnamic acids (HCAs); since these derivatives have been probed to enhance some of the biological effects of chitosan and to fine-tune its characteristics for its application in the biomedical field. First, the main characteristics of chitosan and HCAs are presented; then, the currently employed conjugation strategies between chitosan and HCAs are described; and, finally, the studied biomedical applications of these derivatives are discussed to present their limitations and advantages, which could lead to proximal therapeutic uses.
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Affiliation(s)
- Doddy Denise Ojeda-Hernández
- Laboratory of Neurobiology, Institute of Neurosciences, IdISSC, Hospital Clínico San Carlos, Universidad Complutense de Madrid, 28040 Madrid, Spain
| | - Alejandro A. Canales-Aguirre
- Preclinical Evaluation Unit, Medical and Pharmaceutical Biotechnology Unit, CIATEJ-CONACyT, Guadalajara 44270, Mexico
| | - Jordi A. Matias-Guiu
- Department of Neurology, Institute of Neurosciences, IdISSC, Hospital Clínico San Carlos, Universidad Complutense de Madrid, 28040 Madrid, Spain
| | - Jorge Matias-Guiu
- Laboratory of Neurobiology, Institute of Neurosciences, IdISSC, Hospital Clínico San Carlos, Universidad Complutense de Madrid, 28040 Madrid, Spain
- Department of Neurology, Institute of Neurosciences, IdISSC, Hospital Clínico San Carlos, Universidad Complutense de Madrid, 28040 Madrid, Spain
| | - Ulises Gómez-Pinedo
- Laboratory of Neurobiology, Institute of Neurosciences, IdISSC, Hospital Clínico San Carlos, Universidad Complutense de Madrid, 28040 Madrid, Spain
- Correspondence: (U.G.-P.); (J.C.M.-D.)
| | - Juan Carlos Mateos-Díaz
- Department of Industrial Biotechnology, CIATEJ-CONACyT, Zapopan 45019, Mexico
- Correspondence: (U.G.-P.); (J.C.M.-D.)
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Chemical Profile of Cyperus laevigatus and Its Protective Effects against Thioacetamide-Induced Hepatorenal Toxicity in Rats. Molecules 2022; 27:molecules27196470. [PMID: 36235007 PMCID: PMC9573427 DOI: 10.3390/molecules27196470] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Revised: 09/21/2022] [Accepted: 09/27/2022] [Indexed: 11/17/2022] Open
Abstract
Cyperus species represent a group of cosmopolitan plants used in folk medicine to treat several diseases. In the current study, the phytochemical profile of Cyperus laevigatus ethanolic extract (CLEE) was assessed using UPLC-QTOF-MS/MS. The protective effect of CLEE at 50 and 100 mg /kg body weight (b.w.) was evaluated on hepatorenal injuries induced by thioacetamide (100 mg/kg) via investigation of the extract's effects on oxidative stress, inflammatory markers and histopathological changes in the liver and kidney. UPLC-QTOF-MS/MS analysis of CLEE resulted in the identification of 94 compounds, including organic and phenolic acids, flavones, aurones, and fatty acids. CLEE improved the antioxidant status in the liver and kidney, as manifested by enhancement of reduced glutathione (GSH) and coenzyme Q10 (CoQ10), in addition to the reduction in malondialdehyde (MDA), nitric oxide (NO), and 8-hydroxy-2'-deoxyguanosine (8OHdG). Moreover, CLEE positively affected oxidative stress parameters in plasma and thwarted the depletion of hepatorenal ATP content by thioacetamide (TAA). Furthermore, treatment of rats with CLEE alleviated the significant increase in plasma liver enzymes, kidney function parameters, and inflammatory markers. The protective effect of CLEE was confirmed by a histopathological study of the liver and kidney. Our results proposed that CLEE may reduce TAA-hepatorenal toxicity via its antioxidant and anti-inflammatory properties suppressing oxidative stress.
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Villanueva MP, Gioia C, Sisti L, Martí L, Llorens-Chiralt R, Verstichel S, Celli A. Valorization of Ferulic Acid from Agro-Industrial by-Products for Application in Agriculture. Polymers (Basel) 2022; 14:polym14142874. [PMID: 35890651 PMCID: PMC9325307 DOI: 10.3390/polym14142874] [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: 05/31/2022] [Revised: 07/08/2022] [Accepted: 07/11/2022] [Indexed: 02/04/2023] Open
Abstract
The use of bioplastic mulch in agriculture has increased dramatically in the last years throughout the world. Nowadays, biodegradable materials for mulching films strive to constitute a reliable and more sustainable alternative to classical materials such as polyethylene (PE). The main challenge is to improve their durability in the soil to meet the required service length for crop farming by using benign and sustainable antioxidant systems. Here, we report the design and fabrication of biodegradable materials based on polybutylene (succinate adipate) (PBSA) for mulching applications, incorporating a fully biobased polymeric antioxidant deriving from ferulic acid, which can be extracted from an industrial by-product. Poly-dihydro (ethylene ferulate) (PHEF) from ferulic acid was synthesized by a two-step polymerization process. It is characterized by improved thermal stability in comparison with ferulic acid monomer and therefore suitable for common industrial processing conditions. Different blends of PBSA and PHEF obtained by melt mixing or by reactive extrusion were prepared and analyzed to understand the effect of the presence of PHEF. The results demonstrate that PHEF, when processed by reactive extrusion, presents a remarkable antioxidant effect, even in comparison with commercial additives, preserving a high level of the mechanical properties of the PBSA matrix without affecting the biodegradable character of the blend.
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Affiliation(s)
- Maria Pilar Villanueva
- AIMPLAS, Plastics Technological Centre, Gustave Eiffel, 4, 46980 Paterna, Valencia, Spain; (M.P.V.); (L.M.); (R.L.-C.)
| | - Claudio Gioia
- Department of Civil, Chemical, Environmental and Materials Engineering, University of Bologna, Via Terracini 28, 40131 Bologna, Bologna, Italy; (L.S.); (A.C.)
- Correspondence:
| | - Laura Sisti
- Department of Civil, Chemical, Environmental and Materials Engineering, University of Bologna, Via Terracini 28, 40131 Bologna, Bologna, Italy; (L.S.); (A.C.)
| | - Laura Martí
- AIMPLAS, Plastics Technological Centre, Gustave Eiffel, 4, 46980 Paterna, Valencia, Spain; (M.P.V.); (L.M.); (R.L.-C.)
| | - Raquel Llorens-Chiralt
- AIMPLAS, Plastics Technological Centre, Gustave Eiffel, 4, 46980 Paterna, Valencia, Spain; (M.P.V.); (L.M.); (R.L.-C.)
| | | | - Annamaria Celli
- Department of Civil, Chemical, Environmental and Materials Engineering, University of Bologna, Via Terracini 28, 40131 Bologna, Bologna, Italy; (L.S.); (A.C.)
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Xu J, Jin X, Ye Z, Wang D, Zhao H, Tong Z. Opposite Roles of Co-enzyme Q10 and Formaldehyde in Neurodegenerative Diseases. Am J Alzheimers Dis Other Demen 2022; 37:15333175221143274. [PMID: 36455136 PMCID: PMC10624093 DOI: 10.1177/15333175221143274] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/04/2024]
Abstract
Most of neurodegenerative diseases (NDD) have no cure. The common etiology of neurodegenerations is unclear. Air pollutant-gaseous formaldehyde is notoriously known to induce demyelination and cognitive impairments. Unexpectedly, an amount of formaldehyde has been detected in the brains. Multiple factors can induce the generation and accumulation of endogenous formaldehyde. Excessive formaldehyde can induce oxidative stress to generate H2O2; in turn, H2O2 promote formaldehyde production. Clinical investigations have shown that an abnormal high level of formaldehyde but low level of coenzyme Q10 (coQ10) was observed in patients with NDD. Further studies have proven that excessive formaldehyde directly inactivates coQ10, reduces the ATP generation, enhances oxidative stress, initiates inflammation storm, induces demyelination; subsequently, it results in neurodegeneration. Although the low water solubility of coQ10 limits its clinical application, nanomicellar water-soluble coQ10 exhibits positive therapeutical effects. Hence, nanopackage of coQ10 may be a promising strategy for treating NDD.
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Affiliation(s)
- Jinan Xu
- Institute of Ningbo, Wenzhou Medical University, Wenzhou, China
- Key Laboratory of Alzheimer’s Disease of Zhejiang Province, Institute of Aging, Oujiang Laboratory, School of Mental Health, Wenzhou Medical University, Wenzhou, China
| | - Xingjiang Jin
- Key Laboratory of Alzheimer’s Disease of Zhejiang Province, Institute of Aging, Oujiang Laboratory, School of Mental Health, Wenzhou Medical University, Wenzhou, China
| | - Zuting Ye
- Key Laboratory of Alzheimer’s Disease of Zhejiang Province, Institute of Aging, Oujiang Laboratory, School of Mental Health, Wenzhou Medical University, Wenzhou, China
| | - Dandan Wang
- Key Laboratory of Alzheimer’s Disease of Zhejiang Province, Institute of Aging, Oujiang Laboratory, School of Mental Health, Wenzhou Medical University, Wenzhou, China
| | - Hang Zhao
- Key Laboratory of Alzheimer’s Disease of Zhejiang Province, Institute of Aging, Oujiang Laboratory, School of Mental Health, Wenzhou Medical University, Wenzhou, China
| | - Zhiqian Tong
- Institute of Ningbo, Wenzhou Medical University, Wenzhou, China
- Key Laboratory of Alzheimer’s Disease of Zhejiang Province, Institute of Aging, Oujiang Laboratory, School of Mental Health, Wenzhou Medical University, Wenzhou, China
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Mohammed N, Ahmed SA, Hegazy NI, Kashishy K. Ameliorative effects of hesperidin and N-acetylcysteine against formaldehyde-induced-hemato- and genotoxicity. Toxicol Res (Camb) 2021; 10:992-1002. [PMID: 34733484 PMCID: PMC8557673 DOI: 10.1093/toxres/tfab083] [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: 03/09/2021] [Revised: 07/26/2021] [Accepted: 08/01/2021] [Indexed: 11/14/2022] Open
Abstract
This study investigated the hemato- and genotoxic effects of formaldehyde (FA) and the possible mitigating role of hesperidin (HP) and N-acetylcysteine (NAC), each alone and in combination. Sixty-four adult male albino rats were divided into eight equal groups; the study was conducted for 8 weeks; Group I (negative control: received no medication), Group II (positive control: received distilled water), Group III (received HP 50 mg/kg/day), Group IV (received NAC 50 mg/kg/day), Group V (received FA 10 mg/kg/day), Group VI (FA + HP), Group VII (FA + NAC), and Group VIII (FA + HP + NAC). Groups VI, VII, VIII received the same previously mentioned doses and for the same duration. All treatments were given by intraperitoneal administration. At the end of the study, complete blood count, oxidative stress, histopathological changes, immunohistochemical staining of inducible nitric oxide synthase, and proliferating cell nuclear antigen and genotoxicity by comet assay in the bone marrow of treated rats were assessed. FA administration caused significant hematotoxicity represented by elevated white blood cell numbers and serum malondialdehyde levels and reduced red blood cell numbers, platelets, and serum superoxide dismutase values. Histologically, it induced an increase in fat cell numbers in bone marrow tissue with a widening of marrow spaces and decreased cellularity of hematopoietic cells, megakaryocytes, and granulocytes. FA exposure significantly decreased immunoreactivity for proliferating cell nuclear antigen, whereas the immunoreactivity for inducible nitric oxide synthase was increased. Genotoxicity, as measured by comet assay, revealed a significant increase in comet% and tail length in FA-treated group when compared with other groups. The cotreatment with HP and NAC revealed their ability to protect against hematological changes, oxidative damage, histopathological, and immunohistochemical changes, and genotoxicity induced by FA.
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Affiliation(s)
- Nourhan Mohammed
- Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Sahar A Ahmed
- Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Nagah I Hegazy
- Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Kamal Kashishy
- Department of Pathology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
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Preclinical and Clinical Antioxidant Effects of Natural Compounds against Oxidative Stress-Induced Epigenetic Instability in Tumor Cells. Antioxidants (Basel) 2021; 10:antiox10101553. [PMID: 34679688 PMCID: PMC8533336 DOI: 10.3390/antiox10101553] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 09/16/2021] [Accepted: 09/22/2021] [Indexed: 01/17/2023] Open
Abstract
ROS (reactive oxygen species) are produced via the noncomplete reduction in molecular oxygen in the mitochondria of higher organisms. The produced ROS are placed in various cell compartments, such as the mitochondria, cytoplasm, and endoplasmic reticulum. In general, there is an equilibrium between the synthesis of ROS and their reduction by the natural antioxidant defense system, called the redox system. Therefore, when this balance is upset, the excess ROS production can affect different macromolecules, such as proteins, lipids, nucleic acids, and sugars, which can lead to an electronic imbalance than oxidation of these macromolecules. Recently, it has also been shown that ROS produced at the cellular level can affect different signaling pathways that participate in the stimulation of transcription factors linked to cell proliferation and, consequently, to the carcinogenesis process. Indeed, ROS can activate the pathway of tyrosine kinase, MAP kinase, IKK, NF-KB, phosphoinositol 3 phosphate, and hypoxia-inducible factor (HIF). The activation of these signaling pathways directly contributes to the accelerated proliferation process and, as a result, the appearance of cancer. In addition, the use of antioxidants, especially natural ones, is now a major issue in the approach to cancer prevention. Some natural molecules, especially phytochemicals isolated from medicinal plants, have now shown interesting preclinical and clinical results.
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26
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Bouyahya A, Guaouguaou FE, El Omari N, El Menyiy N, Balahbib A, El-Shazly M, Bakri Y. Anti-inflammatory and analgesic properties of Moroccan medicinal plants: Phytochemistry, in vitro and in vivo investigations, mechanism insights, clinical evidences and perspectives. J Pharm Anal 2021; 12:35-57. [PMID: 35573886 PMCID: PMC9073245 DOI: 10.1016/j.jpha.2021.07.004] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2020] [Revised: 06/14/2021] [Accepted: 07/08/2021] [Indexed: 12/13/2022] Open
Abstract
Moroccan medicinal plants exhibit several pharmacological properties such as antimicrobial, anticancer, antidiabetic, analgesic, and anti-inflammatory effects, which are related to the presence of numerous bioactive compounds, including phenolic acids, flavonoids, and terpenoids. In the present review, we systematically evaluate previously published reports on the anti-inflammatory and analgesic effects of Moroccan medicinal plants. The in vitro investigations revealed that Moroccan medicinal plants inhibit several enzymes related to inflammatory processes, whereas in vivo studies noted significant anti-inflammatory and analgesic effects as demonstrated using different experimental models. Various bioactive compounds exhibiting in vitro and in vivo anti-inflammatory and analgesic effects, with diverse mechanisms of action, have been identified. Some plants and their bioactive compounds reveal specific secondary metabolites that possess important anti-inflammatory effects in clinical investigations. Our review proposes the potential applications of Moroccan medicinal plants as sources of anti-inflammatory and analgesic agents.
Anti-inflammatory and analgesic effects of Moroccan medicinal plants were highlighted. Chemical nature of Moroccan medicinal plants with anti-inflammatory and analgesic effects was reported. Insights into anti-inflammatory mechanisms of bioactive compounds were highlighted. Toxicological investigations of Moroccan medicinal plants were reviewed.
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27
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Zhou Q, Gu R, Xue B, Li P, Gu Q. Phenyl lactic acid alleviates Samonella Typhimurium-induced colitis via regulating microbiota composition, SCFA production and inflammatory responses. Food Funct 2021; 12:5591-5606. [PMID: 34017972 DOI: 10.1039/d1fo00166c] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Colitis caused by non-typhoidal Salmonella (NST) infection is increasingly serious and widespread, so new effective treatment strategies with little or no side-effects are urgently needed. Our previous research found that phenyl lactic acid (PLA) derived from Lactobacillus plantarum ZJ316 can effectively inhibit Salmonella enterica Typhimurium (S. Typhimurium). In this study, we further investigated the protective effects of this PLA against S. Typhimurium-induced colitis in mice. An infection model was established using female C57BL/6J mice by oral administration of 109 CFU mL-1 of S. Typhimurium, and PLA was supplied for 10 days after infection. In colitic mice, PLA administration reduced the disease activity index, prevented the colon shortening and spleen enlargement, decreased liver enzyme (AST and ALT) activities, and alleviated the colonic tissue damage. RT-qPCR analysis showed that PLA significantly down-regulated the levels of NF-κB, TLR4 and pro-inflammatory cytokines (IFN-γ, IL-1β and TNF-α), but stimulated the mRNA expression of the anti-inflammatory cytokine IL-10. Changes in intestinal microecology were analyzed by 16S rRNA sequencing. PLA modulated colonic microbiota dysbiosis by increasing the abundance of Lactobacillus, Butyricicoccus and Roseburia, and reducing Salmonella and Alloprevotella at the genus level. In addition, PLA significantly increased the concentrations of short-chain fatty acids (SCFAs) in the colon, especially propionic acid and butyric acid. These findings revealed that PLA has potential benefits on alleviating S. Typhimurium-induced colitis mainly through intestinal microbiota regulation and inflammation elimination, providing a new perspective for the NTS infection treatment strategy.
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Affiliation(s)
- Qingqing Zhou
- Key Laboratory for Food Microbial Technology of Zhejiang Province, College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Rongcheng Gu
- Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan 48824, USA
| | - Bingyao Xue
- Key Laboratory for Food Microbial Technology of Zhejiang Province, College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Ping Li
- Key Laboratory for Food Microbial Technology of Zhejiang Province, College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Qing Gu
- Key Laboratory for Food Microbial Technology of Zhejiang Province, College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
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Du K, Fang X, Li Z. Ferulic acid suppresses interleukin-1β-induced degeneration of chondrocytes isolated from patients with osteoarthritis through the SIRT1/AMPK/PGC-1α signaling pathway. IMMUNITY INFLAMMATION AND DISEASE 2021; 9:710-720. [PMID: 34078001 PMCID: PMC8342228 DOI: 10.1002/iid3.424] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 03/08/2021] [Accepted: 03/12/2021] [Indexed: 12/21/2022]
Abstract
Background Interleukin‐1β (IL‐1β) is involved in osteoarthritis pathogenesis and mediates a series of toxic processes including the production of matrix metalloproteinase and inflammatory regulators which are suppressed by activation of silent information regulator 1 (SIRT1). We aimed to determine the effects of ferulic acid (FA) on IL‐1β‐induced osteoarthritis chondrocyte degeneration. Methods We examined the effects of FA on osteoarthritis chondrocyte viability and SIRT1 activation. The impact of FA on IL‐1β‐induced osteoarthritis chondrocyte toxicity was determined by prostaglandin E2 (PGE2), nitrite, IL‐6, components of the extracellular matrix, and markers of oxidative stress. Finally, we determined whether these effects were mediated through SIRT1 by inhibiting SIRT1 activity using SIRT1 inhibitor Sirtinol. Results We found that FA activated SIRT1/AMPK/PGC‐1α signaling pathway and attenuated IL‐1β‐induced osteoarthritis chondrocyte degeneration by suppressing the production of IL‐6, PGE2, nitrite, Collagen I, Runx‐2, MMP‐1, MMP‐3, and MMP‐13, enhancing Collagen II and Aggrecan expression and inhibiting oxidative stress. Inhibition of SIRT1 by Sirtinol attenuated the protective effects of FA. Conclusion Our findings reveal that FA prevents IL‐1β‐induced osteoarthritis chondrocyte toxicity, which suggests that FA may be a potential therapy for osteoarthritis and warrants further investigation for its clinical application.
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Affiliation(s)
- Kewei Du
- Department of Orthopedics, Shidong Hospital Affiliated to University of Shanghai for Science and Technology, Shanghai, China
| | - Xuchen Fang
- Department of Orthopedics, Shidong Hospital Affiliated to University of Shanghai for Science and Technology, Shanghai, China
| | - Ziqiang Li
- Department of Orthopedics, Shidong Hospital Affiliated to University of Shanghai for Science and Technology, Shanghai, China
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Cao L, Li Z, Yang Z, Wang M, Zhang W, Ren Y, Li L, Hu J, Sun Z, Nie S. Ferulic acid positively modulates the inflammatory response to septic liver injury through the GSK-3β/NF-κB/CREB pathway. Life Sci 2021; 277:119584. [PMID: 33961853 DOI: 10.1016/j.lfs.2021.119584] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 04/16/2021] [Accepted: 04/25/2021] [Indexed: 12/12/2022]
Abstract
AIMS Ferulic acid (FA) is a component found in plants that has free radical scavenging and liver-protective properties. Acute liver injury (ALI) is a serious complication of sepsis and is closely associated with changes in the levels of inflammatory factors. This study was taken to examine the role of FA in cecal ligation and perforation (CLP)-induced murine ALI and lipopolysaccharide (LPS)-induced cellular ALI models. MATERIALS AND METHODS An in vivo ALI model was established by performing CLP surgery on C57BL/6 mice. After the ALI model was established, mice were examined for liver injury, including HE staining to observe tissue sections, the percentage of liver/body weight and inflammatory factor levels. Myeloperoxidase (MPO), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were measured in liver or serum using commercial kits. An in vitro ALI model was established using LPS-stimulated RAW264.7 cells. Cell viability was measured by MTT method and the intracellular levels of IL-10, IL-1β, IL-6, IL-12 and TNF-α inflammatory factors were measured using kits. The expression of GSK-3β, NF-κB and CREB was measured by western blot or immunofluorescence. KEY FINDINGS FA pretreatment significantly reduced liver/body weight ratio, decreased MPO, AST and ALT activity, alleviated the inflammatory responses and improved CLP-induced histopathological changes in liver. In addition, in vitro results showed that FA could dose-dependently increase the viability of RAW264.7 cells and decrease the levels of pro-inflammatory factors. SIGNIFICANCE In conclusion, our data suggest that FA can ameliorate ALI-induced inflammation via the GSK-3β/NF-κB/CREB pathway, suggesting that FA can be used to protect the liver against ALI.
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Affiliation(s)
- Liping Cao
- Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, PR China; Nanjing University of Chinese Medicine, Nanjing 210023, PR China
| | - Zhenghong Li
- Department of Nephrology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, PR China
| | - Zhizhou Yang
- Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, PR China
| | - Mengmeng Wang
- Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, PR China
| | - Wei Zhang
- Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, PR China
| | - Yi Ren
- Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, PR China
| | - Liang Li
- Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, PR China
| | - Junxian Hu
- Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, PR China
| | - Zhaorui Sun
- Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, PR China.
| | - Shinan Nie
- Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, PR China.
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Illam SP, Narayanankutty A, Kandiyil SP, Raghavamenon AC. Variations in natural polyphenols determine the anti-inflammatory potential of virgin coconut oils. J Food Sci 2021; 86:1620-1628. [PMID: 33864246 DOI: 10.1111/1750-3841.15705] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 02/18/2021] [Accepted: 03/02/2021] [Indexed: 11/30/2022]
Abstract
Virgin coconut oil (VCO), an edible oil prepared from fresh coconut kernel by natural or mechanical means without undergoing chemical refining, has been in the limelight of research as functional food oil. The phenolic components in VCO have been accredited with these pharmacological benefits. The present study compared the phenolic constituents of freshly prepared fermentation processed (FVCO) and hot-pressed VCO (HVCO) and their anti-inflammatory efficacies. The biochemical analysis documented quantitative variation in the phenolic content, being higher in HVCO than FVCO (40.03 ± 5.8 µg and 25.55 ± 5.8 µg/mL of oil, respectively). In vitro studies observed nitric oxide radical scavenging efficacy (IC50 value of 14.84 ± 0.81 µg/mL) for HVCO polyphenols, which shows higher inhibition efficacy than FVCO (29.41 ± 1.7 µg/mL). In dextran and formalin mediated acute and chronic inflammation in mice, HVCO displayed more protective efficacy (40.5 and 46.4% inhibition) than FVCO (33.3 and 43.8% inhibition), which is similar to the standard diclofenac (55.6 and 59.8% inhibition). The study, thus, concludes that compared to FVCO, HVCO is a more active anti-inflammatory agent. PRACTICAL APPLICATION: Virgin coconut oil, a widely used edible oil in South Asian countries, has been shown to have health benefits possibly exerted by the natural phenolics it contains. However, different modes of preparations of VCO determine the phenolic combinations and efficacy as well. Our study compared two different VCO preparations and suggests that the VCO prepared by the traditional way (HVCO) is pharmacologically potent than that prepared by simple fermentation process (FVCO) in reducing inflammation. The efficacy is attributed to the variations in phenolic profile revealed by LC-MS analysis. Hence, the current study suggests HVCO as a potential food supplement that can reduce the incidence of degenerative diseases.
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ÖZTÜRK Ş, DURMAZ B, MEMMEDOV H, OKTAY LM, GÜNEL SN, OLUKMAN M, SÖZMEN EY. Ferulik asitin lipopolisakkaridaz ile induklenmiş insan lösemi monositik hücrelerinde sitokin salınımına etkisi. EGE TIP DERGISI 2021. [DOI: 10.19161/etd.887360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
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Hasan I, Pervin M, Kobir MA, Sagor SH, Karim MR. Effect of formaldehyde and urea contaminated feed exposure into the liver of young and adult pigeons ( Columba livia). Vet World 2021; 14:769-776. [PMID: 33935426 PMCID: PMC8076463 DOI: 10.14202/vetworld.2021.769-776] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Accepted: 02/15/2021] [Indexed: 12/03/2022] Open
Abstract
Background and Aim: Nowadays, toxic chemical contaminants in food are a major food safety problem in Bangladesh. Among toxic food contaminants, formalin is used to preserve fruit, vegetables, and fish, where urea is used for the whitening of rice and puffed rice. The purpose of this study was to determine the biochemical and histopathological effects on the liver of young and adult pigeons after exposure to formalin and urea contaminated feed. Materials and Methods: A total of 15 young and 15 adult pigeons were divided into control group, formaldehyde exposed group (2.5 mL formalin/kg feed), and urea exposed (1 g/kg feed) group. Each group consisted of five pigeons. After the experimentation procedures, the blood samples were collected for biochemical study, and the liver tissue was collected for histomorphological study. The statistical analysis was performed using the Student’s t-test, and p<0.05 was considered as statistically significant. Results: The aspartate transaminase serum hepatic enzyme was significantly increased in both formalin and urea exposed young and adult pigeons than the control pigeons. In control pigeons, parenchymal hepatocytes and non-parenchymal cells are regularly arranged. However, histological observation of the liver of formalin and urea exposed young, and adult pigeons showed coagulation necrosis with infiltration of many inflammatory cells around the central and portal veins. The necrotic areas are more extensive with massive infiltration of inflammatory cells in the liver of formalin-treated pigeons than the urea treated pigeons. Conclusion: The present study results show that low concentrations of formalin and urea in feed induced liver lesions in pigeons in different extents and indicate that exposure to toxic chemicals may affect homeostasis of the liver and cause liver injury or act as a co-factor for liver disease.
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Affiliation(s)
- Imam Hasan
- Department of Anatomy and Histology, Faculty of Veterinary Science, Bangladesh Agricultural University, Mymensingh-2202, Bangladesh
| | - Munmun Pervin
- Department of Pathology, Faculty of Veterinary Science, Bangladesh Agricultural University, Mymensingh-2202, Bangladesh
| | - Md Alamgir Kobir
- Department of Anatomy and Histology, Faculty of Veterinary Science, Bangladesh Agricultural University, Mymensingh-2202, Bangladesh
| | - Sakib Hossain Sagor
- Department of Medicine, Faculty of Veterinary Science, Bangladesh Agricultural University, Mymensingh-2202, Bangladesh
| | - Mohammad Rabiul Karim
- Department of Anatomy and Histology, Faculty of Veterinary Science, Bangladesh Agricultural University, Mymensingh-2202, Bangladesh
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Protein-phenolic aggregates with anti-inflammatory activity recovered from maize nixtamalization wastewaters (nejayote). Lebensm Wiss Technol 2020. [DOI: 10.1016/j.lwt.2020.109881] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Zhang L, Meng B, Li L, Wang Y, Zhang Y, Fang X, Wang D. Boletus aereus protects against acute alcohol-induced liver damage in the C57BL/6 mouse via regulating the oxidative stress-mediated NF-κB pathway. PHARMACEUTICAL BIOLOGY 2020; 58:905-914. [PMID: 32915675 PMCID: PMC7534317 DOI: 10.1080/13880209.2020.1812672] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Revised: 08/09/2020] [Accepted: 08/15/2020] [Indexed: 06/11/2023]
Abstract
CONTEXT Alcoholic liver disease, caused by abuse and consumption of alcohol, exhibits high morbidity and mortality. Boletus aereus Bull. (Boletaceae) (BA) shows antioxidant, anti-inflammatory and antimicrobial effects. OBJECTIVES To investigate the hepatoprotective effects of BA using an acute alcohol-induced hepatotoxicity mice model. MATERIALS AND METHODS The composition of BA fruit body was first systematically analyzed. Subsequently, a C57BL/6 mice model of acute alcohol-induced liver injury was established by intragastrically administration of alcohol, which was intragastrically received with BA powder at 200 mg/kg and 800 mg/kg for 2 weeks, 60 mg/kg silybin treatment was used as positive control group. By employing the pathological examination, ELISA, RT-PCR and western blot, the regulation of BA on oxidative stress signals was investigated. RESULTS The LD50 of BA was much higher than 4 g/kg/p.o. In acute alcohol-damaged mice, BA reduced the levels of alanine aminotransferase (>18.3%) and aspartate aminotransferase (>27.6%) in liver, increased the activity of liver alcohol dehydrogenase (>35.0%) and serum acetaldehyde dehydrogenase (>18.9%). BA increased the activity of superoxide dismutase (>13.4%), glutathione peroxidase (>11.0%) and 800 mg/kg BA strongly reduced chemokine (C-X-C motif) ligand 13 (14.9%) and chitinase-3 like-1 protein (13.4%) in serum. BA reversed mRNA over-expression (>70%) and phosphor-stimulated expression (>45.0%) of an inhibitor of nuclear factor κ-B kinase (NF-κB, an inhibitor of nuclear factor κ-B α and nuclear factor κ-B in the liver. CONCLUSIONS BA is effective in ameliorating alcohol-induced liver injury through regulating oxidative stress-mediated NF-κB signalling, which provides a scientific basis for further research on its clinical applications.
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Affiliation(s)
- Luping Zhang
- Gastroenterology and Endoscopy Center, The First Bethune Hospital of Jilin University, Jilin University, Changchun, China
| | - Bo Meng
- Gastroenterology and Endoscopy Center, The First Bethune Hospital of Jilin University, Jilin University, Changchun, China
- Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, China
| | - Lanzhou Li
- Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, China
| | - Yanzhen Wang
- Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, China
- School of Pharmacy Food Science, Zhuhai College of Jilin University, Zhuhai, China
| | - Yuanzhu Zhang
- Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, China
| | - Xuexun Fang
- Gastroenterology and Endoscopy Center, The First Bethune Hospital of Jilin University, Jilin University, Changchun, China
- Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, China
| | - Di Wang
- Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, China
- School of Pharmacy Food Science, Zhuhai College of Jilin University, Zhuhai, China
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Bernardini L, Barbosa E, Charão MF, Goethel G, Muller D, Bau C, Steffens NA, Santos Stein C, Moresco RN, Garcia SC, Souza Vencato M, Brucker N. Oxidative damage, inflammation, genotoxic effect, and global DNA methylation caused by inhalation of formaldehyde and the purpose of melatonin. Toxicol Res (Camb) 2020; 9:778-789. [PMID: 33447362 PMCID: PMC7786178 DOI: 10.1093/toxres/tfaa079] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Revised: 09/09/2020] [Accepted: 10/05/2020] [Indexed: 12/13/2022] Open
Abstract
Formaldehyde (FA) exposure has been proven to increase the risk of asthma and cancer. This study aimed to evaluate for 28 days the FA inhalation effects on oxidative stress, inflammation process, genotoxicity, and global DNA methylation in mice as well as to investigate the potential protective effects of melatonin. For that, analyses were performed on lung, liver and kidney tissues, blood, and bone marrow. Bronchoalveolar lavage was used to measure inflammatory parameters. Lipid peroxidation (TBARS), protein carbonyl (PCO), non-protein thiols (NPSH), catalase activity (CAT), comet assay, micronuclei (MN), and global methylation were determined. The exposure to 5-ppm FA resulted in oxidative damage to the lung, presenting a significant increase in TBARS and NO levels and a decrease in NPSH levels, besides an increase in inflammatory cells recruited for bronchoalveolar lavage. Likewise, in the liver tissue, the exposure to 5-ppm FA increased TBARS and PCO levels and decreased NPSH levels. In addition, FA significantly induced DNA damage, evidenced by the increase of % tail moment and MN frequency. The pretreatment of mice exposed to FA applying melatonin improved inflammatory and oxidative damage in lung and liver tissues and attenuated MN formation in bone marrow cells. The pulmonary histological study reinforced the results observed in biochemical parameters, demonstrating the potential beneficial role of melatonin. Therefore, our results demonstrated that FA exposure with repeated doses might induce oxidative damage, inflammatory, and genotoxic effects, and melatonin minimized the toxic effects caused by FA inhalation in mice.
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Affiliation(s)
- Letícia Bernardini
- Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, RS 97105-900, Brazil
| | - Eduardo Barbosa
- Graduate Program on Toxicology and Analytical Toxicology, University Feevale, Novo Hamburgo, RS 93525-075, Brazil
| | - Mariele Feiffer Charão
- Graduate Program on Toxicology and Analytical Toxicology, University Feevale, Novo Hamburgo, RS 93525-075, Brazil
| | - Gabriela Goethel
- Graduate Program in Pharmaceutical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil
| | - Diana Muller
- Department of Genetics, Instituto de Biociências, Federal University of Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil
| | - Claiton Bau
- Department of Genetics, Instituto de Biociências, Federal University of Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil
| | - Nadine Arnold Steffens
- Graduate Program in Pharmaceutical Sciences, Federal University of Santa Maria, Santa Maria, RS 97105-900, Brazil
| | - Carolina Santos Stein
- Graduate Program in Pharmaceutical Sciences, Federal University of Santa Maria, Santa Maria, RS 97105-900, Brazil
| | - Rafael Noal Moresco
- Graduate Program in Pharmaceutical Sciences, Federal University of Santa Maria, Santa Maria, RS 97105-900, Brazil
| | - Solange Cristina Garcia
- Graduate Program in Pharmaceutical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil
| | - Marina Souza Vencato
- Departament of Morphology, Federal University of Santa Maria, Santa Maria, RS 97105-900, Brazil
| | - Natália Brucker
- Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, RS 97105-900, Brazil
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Ex vivo penetration analysis and anti-inflammatory efficacy of the association of ferulic acid and UV filters. Eur J Pharm Sci 2020; 156:105578. [PMID: 32998032 DOI: 10.1016/j.ejps.2020.105578] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 09/03/2020] [Accepted: 09/24/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND Unprotected chronic exposure to ultraviolet (UV) radiation generates many harmful effects to human skin and sunscreens are essential to health, however, traditional products do not provide enough protection against cutaneous oxidative stress, a process amplified by UV radiation. Therefore, the development of multifunctional photoprotective formulations seems to be a more efficacious approach, since these enable the absorption/reflection of UV radiation and maintain the cutaneous homeostasis. OBJECTIVES In the present study, ferulic acid (FA), a well-known antioxidant, has been combined with two UV filters, bemotrizinol and ethylhexyl triazone, and the safety and efficacy of this formulation has been assessed combining ex vivo and in vivo methods. METHODS Skin permeation assays were performed by applying the formulation in the volar forearm of participants, after which consecutive samples of the stratum corneum were collected by tape stripping, and the quantification of FA, bemotrizinol and ethylhexyl triazone was performed by high-performance liquid chromatography (HPLC). Also, the FA anti-inflammatory action in combination with the UV filters was probed through a method employing Laser Doppler flowmetry to measure the vasodilatory response to methyl nicotinate topical application. RESULTS Skin permeation assay was able to characterize the penetration depth of each substance. It should also be noted that a specific HPLC analytical method was developed in this study to enable the rapid simultaneous quantification of the three substances. Results from Laser Doppler flowmetry showed that the FA was able to mitigate the vasodilatory response. CONCLUSIONS FA proved to be a valuable resource in a multifunction sunscreen, not only providing an increase in the SPF of sunscreens, previously published, but also decreasing the extent of inflammation.
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Oztan O, Tutkun L, Turksoy VA, Deniz S, Dip A, Iritas SB, Eravci DB, Alaguney ME. The relationship between impaired lung functions and cytokine levels in formaldehyde exposure. ARCHIVES OF ENVIRONMENTAL & OCCUPATIONAL HEALTH 2020; 76:248-254. [PMID: 32895023 DOI: 10.1080/19338244.2020.1816883] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Exposure to formaldehyde (FA) causes detrimental effects on respiratory system. Inflammation is one of the mechanisms responsible for these effects. Our aim is to demonstrate the possible effect of formaldehyde on inflammation biomarkers and pulmonary function tests. One hundred ninety-eight male workers in a fiber production factory are included. Eighty two of them were not exposed to FA. Thirty nine workers were exposed to FA for 4 h or more in a work shift and 77 workers were exposed less than 4 h. Statistically significant differences were found for FA, TNF-α, and IL-6 levels and pulmonary function test parameters (FEV1 and FVC) between no exposure and exposure groups. The results revealed a correlation between decrement in pulmonary function tests and an increase in cytokine levels concordant with the duration of FA exposure. The results may emphasize that FA exposure shows its effect on pulmonary system via inflammatory pathways.
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Affiliation(s)
- Ozgur Oztan
- Department of Medical Management, HLC Medical Center, Ankara, Turkey
| | - Lutfiye Tutkun
- Department of Nutrition and Dietetics, Health Science Faculty Gazi University, Ankara, Turkey
| | - Vugar Ali Turksoy
- Department of Public Health, Yozgat Bozok University Faculty of Medicine, Yozgat, Turkey
| | | | - Aybike Dip
- Ministry of Justice, The Council of Forensic Medicine, Adana, Turkey
| | | | - Deniz Boz Eravci
- Center for Labour and Social Security Training and Research, Ankara, Turkey
| | - Mehmet Erdem Alaguney
- Department Of Occupational Medicine, Konya Training and Research Hospital, Health Sciences University, Konya, Turkey
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Liu Y, Wang Z, Kong F, Teng L, Zheng X, Liu X, Wang D. Triterpenoids Extracted From Antrodia cinnamomea Mycelia Attenuate Acute Alcohol-Induced Liver Injury in C57BL/6 Mice via Suppression Inflammatory Response. Front Microbiol 2020; 11:1113. [PMID: 32719658 PMCID: PMC7350611 DOI: 10.3389/fmicb.2020.01113] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2020] [Accepted: 05/04/2020] [Indexed: 12/12/2022] Open
Abstract
Excessive alcohol consumption causes liver injury–induced mortality. Here we systematically analyzed the structure of triterpenoids extracted from Antrodia cinnamomea mycelia (ACT) and investigated their protective effects against acute alcohol-induced liver injury in mice. Liquid chromatography–mass spectrometry and liquid chromatography with tandem mass spectrometry were performed to determine the structures of ACT constituents. Alcohol-induced liver injury was generated in C57BL/6 mice by oral gavage of 13 g/kg white spirit (a wine at 56% ABV). Mice were treated with either silibinin or ACT for 2 weeks. Liver injury markers and pathological signaling were then quantified with enzyme-linked immunosorbent assays, antibody array assays, and Western blots, and pathological examinations were performed using hematoxylin-eosin staining and periodic acid–Schiff staining. Triterpenoids extracted from A. cinnamomea mycelia contain 25 types of triterpenoid compounds. A 2-weeks alcohol consumption treatment caused significant weight loss, liver dyslipidemia, and elevation of alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase, and alkaline phosphatase activities in the serum and/or liver. These effects were markedly reversed after 2-weeks ACT administration. Triterpenoids extracted from A. cinnamomea mycelia alleviated the organ structural changes and inflammatory infiltration of alcohol-damaged tissues. Triterpenoids extracted from A. cinnamomea mycelia inhibited proinflammatory cytokine levels and enhanced anti-inflammatory cytokine levels. Acute alcohol treatment promoted inflammation with significant correlations to hypoxia-inducible factor 1α (HIF-1α), which was reduced by ACT and was partially related to modulation of the protein kinase B (Akt)/70-kDa ribosomal protein S6 kinase phosphorylation (p70S6K) and Wnt/β-catenin signaling pathways. In conclusion, ACT protected against acute alcohol-induced liver damage in mice mainly through its suppression of the inflammatory response, which may be related to HIF-1α signaling.
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Affiliation(s)
- Yange Liu
- School of Life Sciences, Jilin University, Changchun, China.,School of Basic Medical Sciences, Nanchang University, Nanchang, China
| | - Zhuqian Wang
- School of Life Sciences, Jilin University, Changchun, China
| | - Fange Kong
- School of Life Sciences, Jilin University, Changchun, China
| | - Lesheng Teng
- School of Life Sciences, Jilin University, Changchun, China
| | - Xiaoyi Zheng
- Division of Nephrology, Stanford University School of Medicine, Stanford, CA, United States
| | - Xingkai Liu
- Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Jilin University, Changchun, China
| | - Di Wang
- School of Life Sciences, Jilin University, Changchun, China
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Erseçkin V, Mert H, İrak K, Yildirim S, Mert N. Nephroprotective effect of ferulic acid on gentamicin-induced nephrotoxicity in female rats. Drug Chem Toxicol 2020; 45:663-669. [PMID: 32354291 DOI: 10.1080/01480545.2020.1759620] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Ferulic acid is a kind of phenolic compound that can be found in various fruits and vegetables. This study aims to investigate the effect of ferulic acid on nephrotoxicity induced by gentamicin (GM). In this study, rats were separated into 4 groups such that each containing 8 randomly selected rats: Control group, Ferulic Acid (FA) group, Gentamicin (GM) group and Gentamicin + Ferulic acid (GM + FA) group. Blood samples were collected after 24 hours following the 8-day trial period, and kidneys were taken out for histopathological evaluation. Serum urea, creatinine, uric acid and LDH analyses were performed in autoanalyzer while Malondialdehyde (MDA), Advanced Oxidized Protein Products (AOPP), Glutathione (GSH), Superoxide dismutase (SOD), Catalase (CAT), Interleukin 6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α) analyses were performed in ELISA, and kidney tissues were also examined histopathologically. Urea (p < .001), creatinine (p < .001), MDA (p < .01), AOPP (p < .001), IL-6 (p < .01) and TNF-α (p < .001) levels were found to be statistically and significantly lowered in GM + FA group when compared to GM group. As a result, ferulic acid has reduced the inflammation in nephrotoxicity induced by GM, causing decreased oxidative stress. In this study, anti-inflammatory features of ferulic acid have come to the forefront rather than the antioxidant features. It can be said that ferulic acid reduces nephrotoxic damage and has protective properties for kidneys.
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Affiliation(s)
- Vasfiye Erseçkin
- Department of Biochemistry, Faculty of Veterinary Medicine, Van Yuzuncu Yil University, Van, Turkey
| | - Handan Mert
- Department of Biochemistry, Faculty of Veterinary Medicine, Van Yuzuncu Yil University, Van, Turkey
| | - Kıvanç İrak
- Department of Biochemistry, Faculty of Veterinary Medicine, Siirt University, Siirt, Turkey
| | - Serkan Yildirim
- Department of Biochemistry, Faculty of Veterinary Medicine, Atatürk University, Erzurum, Turkey
| | - Nihat Mert
- Department of Biochemistry, Faculty of Veterinary Medicine, Van Yuzuncu Yil University, Van, Turkey
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Yi J, Zhu M, Qiu F, Zhou Y, Shu P, Liu N, Wei C, Xiang S. TNFAIP1 Mediates Formaldehyde-Induced Neurotoxicity by Inhibiting the Akt/CREB Pathway in N2a Cells. Neurotox Res 2020; 38:184-198. [PMID: 32335808 DOI: 10.1007/s12640-020-00199-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2019] [Revised: 03/20/2020] [Accepted: 03/31/2020] [Indexed: 02/07/2023]
Abstract
Formaldehyde (FA) is a common air pollutant. Exposure to exogenous FA can cause damage to the nervous system, such as learning and memory impairment, balance dysfunction, and sleep disorders. Excessive production of endogenous FA also causes memory impairment and is thought to be associated with Alzheimer's disease (AD). Tumor necrosis factor alpha-induced protein 1 (TNFAIP1) plays a crucial role in neurodevelopment and neurological diseases. However, the role of TNFAIP1 in FA-induced neurotoxicity is unclear. Herein, using a mouse neuroblastoma cell line (N2a cells), we explored the mechanism of TNFAIP1 in FA-induced neurotoxicity, the involvement of the Akt/CREB signaling pathway, and how the expression of TNFAIP1 is regulated by FA. We found that exposure to 100 μM or 200 μM FA for 24 h led to decreased cell viability, increased cell apoptosis and neurite retraction, increased reactive oxygen species (ROS) levels, upregulated protein expression of TNFAIP1 and decreased the levels of phosphorylated Akt and CREB in the Akt/CREB pathway. Knockdown of TNFAIP1 using a TNFAIP1 small interfering RNA (siRNA) expression vector prevented FA from inhibiting the Akt/CREB pathway, thus reducing cell apoptosis and restoring cell viability and neurite outgrowth. Clearance of ROS by vitamin E (Vit E) repressed the FA-mediated upregulation of TNFAIP1 expression. These results suggest that FA increases the expression of TNFAIP1 by inducing oxidative stress and that upregulated TNFAIP1 then inhibits the Akt/CREB pathway, consequently leading to cell apoptosis and neurite retraction. Therefore, TNFAIP1 is a potential target for alleviating FA-induced neurotoxicity and related neurological disorders.
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Affiliation(s)
- Junzhi Yi
- State Key Laboratory of Developmental Biology of Freshwater Fish, School of Life Sciences, Hunan Normal University, Changsha, 410081, Hunan, China.,Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou, China
| | - Min Zhu
- State Key Laboratory of Developmental Biology of Freshwater Fish, School of Life Sciences, Hunan Normal University, Changsha, 410081, Hunan, China.,The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, School of Life Sciences, Hunan Normal University, Changsha, 410081, Hunan, China
| | - Feng Qiu
- State Key Laboratory of Developmental Biology of Freshwater Fish, School of Life Sciences, Hunan Normal University, Changsha, 410081, Hunan, China.,The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, School of Life Sciences, Hunan Normal University, Changsha, 410081, Hunan, China
| | - Yubo Zhou
- State Key Laboratory of Developmental Biology of Freshwater Fish, School of Life Sciences, Hunan Normal University, Changsha, 410081, Hunan, China.,The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, School of Life Sciences, Hunan Normal University, Changsha, 410081, Hunan, China
| | - Pan Shu
- The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, School of Life Sciences, Hunan Normal University, Changsha, 410081, Hunan, China
| | - Ning Liu
- School of Medicine, Hunan Normal University, Changsha, 410013, Hunan, China
| | - Chenxi Wei
- State Key Laboratory of Developmental Biology of Freshwater Fish, School of Life Sciences, Hunan Normal University, Changsha, 410081, Hunan, China. .,The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, School of Life Sciences, Hunan Normal University, Changsha, 410081, Hunan, China.
| | - Shuanglin Xiang
- State Key Laboratory of Developmental Biology of Freshwater Fish, School of Life Sciences, Hunan Normal University, Changsha, 410081, Hunan, China. .,The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, School of Life Sciences, Hunan Normal University, Changsha, 410081, Hunan, China.
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41
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Mahmoud AM, Hussein OE, Hozayen WG, Bin-Jumah M, Abd El-Twab SM. Ferulic acid prevents oxidative stress, inflammation, and liver injury via upregulation of Nrf2/HO-1 signaling in methotrexate-induced rats. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2020; 27:7910-7921. [PMID: 31889292 DOI: 10.1007/s11356-019-07532-6] [Citation(s) in RCA: 79] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/26/2019] [Accepted: 12/25/2019] [Indexed: 06/10/2023]
Abstract
Liver injury is one of the adverse effects of methotrexate (MTX). Ferulic acid (FA) is an antioxidant phytochemical that confers hepatoprotective efficacy; however, its effect against MTX hepatotoxicity remains unexplored. This study investigated the role of FA in modulating oxidative stress, inflammation, Nrf2/HO-1 signaling, and PPARγ in MTX-administered rats. Following oral FA supplementation for 15 days, rats received a single dose of MTX at day 16 and samples were collected at day 19. MTX provoked multiple histological manifestations, including degenerative changes, steatosis, inflammatory cells infiltration and hemorrhage, and altered serum transaminases, bilirubin, and albumin. Reactive oxygen species, lipid peroxidation, and nitric oxide were increased in the liver of rats that received MTX. FA prevented all histological alterations, ameliorated liver function markers, suppressed oxidative stress, and boosted antioxidants in MTX-induced rats. FA reduced serum TNF-α and IL-1β, and hepatic NF-κB p65, Bax, and caspase-3, whereas increased Bcl-2, Nrf2, NQO1, HO-1, and PPARγ. In conclusion, FA prevented MTX hepatotoxicity by activating Nrf2/HO-1 signaling and PPARγ, and attenuating oxidative stress, inflammation, and cell death.
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Affiliation(s)
- Ayman M Mahmoud
- Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef, 62514, Egypt.
| | - Omnia E Hussein
- Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef, 62514, Egypt
| | - Walaa G Hozayen
- Biochemistry Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt
| | - May Bin-Jumah
- Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Sanaa M Abd El-Twab
- Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef, 62514, Egypt
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Abstract
Fruits come in a wide variety of colors, shapes, and flavors. This chapter will cover selected fruits that are known to be healthy and highly nutritious. These fruits were chosen due to their common usage and availability. Since it is not possible to cover all health benefits or essential nutrients and important phytochemicals of the fruit composition, this chapter will focus on the key valuable constituents and their potential health effects.
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Affiliation(s)
- Sawsan G Mohammed
- Qatar Research Leadership Program (QRLP), Qatar Foundation, Doha, Qatar.
| | - M Walid Qoronfleh
- Research & Policy Department, World Innovation Summit for Health (WISH), Qatar Foundation, Doha, Qatar.
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43
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Yin P, Zhang Z, Li J, Shi Y, Jin N, Zou W, Gao Q, Wang W, Liu F. Ferulic acid inhibits bovine endometrial epithelial cells against LPS-induced inflammation via suppressing NK-κB and MAPK pathway. Res Vet Sci 2019; 126:164-169. [DOI: 10.1016/j.rvsc.2019.08.018] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Revised: 07/29/2019] [Accepted: 08/12/2019] [Indexed: 12/15/2022]
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44
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Niknezhad F, Sayad-Fathi S, Karimzadeh A, Ghorbani-Anarkooli M, Yousefbeyk F, Nasiri E. Improvement in histology, enzymatic activity, and redox state of the liver following administration of Cinnamomum zeylanicum bark oil in rats with established hepatotoxicity. Anat Cell Biol 2019; 52:302-311. [PMID: 31598360 PMCID: PMC6773892 DOI: 10.5115/acb.18.180] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2018] [Revised: 03/26/2019] [Accepted: 05/15/2019] [Indexed: 11/27/2022] Open
Abstract
Formaldehyde (FA) is an environmentally-available pollutant. Since the liver acts as a detoxifier in the human body, it is the first and most affected organ in individuals exposed to higher-than-normal amounts of FA. FA mainly alters oxidant/antioxidant status and initiates oxidative stress, and by means, causes functional damage to the liver. Thus, it is important to identify natural bioactive compounds with antioxidant properties in order to be used as food additives. Cinnamon (Cinnamomum zeylanicum) is a popular flavor and also a medicinal plant with a variety of beneficial effects. In the present original study, cinnamon essential oil (CEO) has been administrated at doses of 10, 20, and 100 mg/kg, orally, to hepatotoxicity rat models caused by FA (10 mg/kg, intraperitoneally). Liver enzymes and its histology were assessed and oxidative stress biomarkers in the liver tissue were also examined. CEO administration caused a significant increase in superoxide dismutase, glutathione peroxidase, and catalase and a prominent decrease in nitric oxide levels in the liver tissue. Also, in serum samples, CEO significantly reduced the elevated amounts of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. When assessed histologically, portal area and central vein fibrosis alongside with the hepatocytes' hypereosinophilia and swelling, focal inflammation, and necrotic areas were found to be prominently decreased in the CEO group. In conclusion, our study suggested that the CEO may have the potential for being used against FA-induced hepatotoxicity.
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Affiliation(s)
- Fatemeh Niknezhad
- Cellular and Molecular Research Center, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran
- Department of Anatomical Sciences, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Sara Sayad-Fathi
- Cellular and Molecular Research Center, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran
- Department of Anatomical Sciences, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Arezoo Karimzadeh
- Student Research Committee, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Marjan Ghorbani-Anarkooli
- Cellular and Molecular Research Center, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran
- Department of Anatomical Sciences, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Fatemeh Yousefbeyk
- Department of Pharmacognosy, School of Pharmacy, Guilan University of Medical Sciences, Rasht, Iran
| | - Ebrahim Nasiri
- Cellular and Molecular Research Center, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran
- Department of Anatomical Sciences, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
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Saha P, Talukdar AD, Nath R, Sarker SD, Nahar L, Sahu J, Choudhury MD. Role of Natural Phenolics in Hepatoprotection: A Mechanistic Review and Analysis of Regulatory Network of Associated Genes. Front Pharmacol 2019; 10:509. [PMID: 31178720 PMCID: PMC6543890 DOI: 10.3389/fphar.2019.00509] [Citation(s) in RCA: 61] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Accepted: 04/24/2019] [Indexed: 12/11/2022] Open
Abstract
The liver is not only involved in metabolism and detoxification, but also participate in innate immune function and thus exposed to frequent target Thus, they are the frequent target of physical injury. Interestingly, liver has the unique ability to regenerate and completely recoup from most acute, non-iterative situation. However, multiple conditions, including viral hepatitis, non-alcoholic fatty liver disease, long term alcohol abuse and chronic use of medications can cause persistent injury in which regenerative capacity eventually becomes dysfunctional resulting in hepatic scaring and cirrhosis. Despite the recent therapeutic advances and significant development of modern medicine, hepatic diseases remain a health problem worldwide. Thus, the search for the new therapeutic agents to treat liver disease is still in demand. Many synthetic drugs have been demonstrated to be strong radical scavengers, but they are also carcinogenic and cause liver damage. Present day various hepatic problems are encountered with number of synthetic and plant based drugs. Nexavar (sorafenib) is a chemotherapeutic medication used to treat advanced renal cell carcinoma associated with several side effects. There are a few effective varieties of herbal preparation like Liv-52, silymarin and Stronger neomin phages (SNMC) against hepatic complications. Plants are the huge repository of bioactive secondary metabolites viz; phenol, flavonoid, alkaloid etc. In this review we will try to present exclusive study on phenolics with its mode of action mitigating liver associated complications. And also its future prospects as new drug lead.
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Affiliation(s)
- Priyanka Saha
- Department of Life Science & Bioinformatics, Assam University, Silchar, India
| | - Anupam Das Talukdar
- Department of Life Science & Bioinformatics, Assam University, Silchar, India
| | - Rajat Nath
- Department of Life Science & Bioinformatics, Assam University, Silchar, India
| | - Satyajit D. Sarker
- Centre for Natural Products Discovery, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, United Kingdom
| | - Lutfun Nahar
- Centre for Natural Products Discovery, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, United Kingdom
| | - Jagajjit Sahu
- Department of Mycology and Plant Pathology, Institute of Agricultural Sciences, Banaras Hindu University, Varanasi, India
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Zhao Y, Ge J, Li X, Guo Q, Zhu Y, Song J, Zhang L, Ding S, Yang X, Li R. Vasodilatory effect of formaldehyde via the NO/cGMP pathway and the regulation of expression of K ATP, BK Ca and L-type Ca 2+ channels. Toxicol Lett 2019; 312:55-64. [PMID: 30974163 DOI: 10.1016/j.toxlet.2019.04.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2019] [Revised: 03/28/2019] [Accepted: 04/06/2019] [Indexed: 12/12/2022]
Abstract
Formaldehyde (FA), a well-known toxic gas molecule similar to nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S), is widely produced endogenously via numerous biochemical pathways, and has a number of physiological roles in the biosystem. We attempted to investigate the vasorelaxant effects of FA and their underlying mechanisms. We found that FA induced vasorelaxant effects on rat aortic rings in a concentration-dependent manner. The NO/cyclic guanosine 5' monophosphate (cGMP) pathway was up-regulated when the rat aortas were treated with FA. The expression of large-conductance Ca2+-activated K+ (BKCa) channel subunits α and β of the rat aortas was increased by FA. Similarly, the levels of ATP-sensitive K+ (KATP) channel subunits Kir6.1 and Kir6.2 were also up-regulated when the rat aortas were incubated with FA. In contrast, levels of the L-type Ca2+ channel (LTCC) subunits, Cav1.2 and Cav1.3, decreased dramatically with increasing concentrations of FA. We demonstrated that the regulation of FA on vascular contractility may be via the up-regulation of the NO/cGMP pathway and the modulation of ion channels, including the upregulated expression of the KATP and BKCa channels and the inhibited expression of LTCCs. Further study is needed to explore the in-depth mechanisms of FA induced vasorelaxation.
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Affiliation(s)
- Yun Zhao
- Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, 152 Luoyu Road, Wuhan 430079, PR China
| | - Jing Ge
- Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, 152 Luoyu Road, Wuhan 430079, PR China
| | - Xiaoxiao Li
- Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, 152 Luoyu Road, Wuhan 430079, PR China
| | - Qing Guo
- Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, 152 Luoyu Road, Wuhan 430079, PR China; School of Public Health, Huazhong University of Science and Technology, Hangkong Road, Wuhan, 430030, PR China
| | - Yuqing Zhu
- Centre of Stem Cell and Regenerative medicine, School of Medicine, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, PR China
| | - Jing Song
- Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, 152 Luoyu Road, Wuhan 430079, PR China
| | - Luoping Zhang
- Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA, 94720, USA
| | - Shumao Ding
- Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, 152 Luoyu Road, Wuhan 430079, PR China
| | - Xu Yang
- Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, 152 Luoyu Road, Wuhan 430079, PR China.
| | - Rui Li
- Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, 152 Luoyu Road, Wuhan 430079, PR China.
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He C, Jiang S, Yao H, Zhang L, Yang C, Zhan D, Lin G, Zeng Y, Xia Y, Lin Z, Liu G, Lin Y. Endoplasmic reticulum stress mediates inflammatory response triggered by ultra-small superparamagnetic iron oxide nanoparticles in hepatocytes. Nanotoxicology 2018; 12:1198-1214. [PMID: 30422028 DOI: 10.1080/17435390.2018.1530388] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Ultra-small superparamagnetic iron oxide nanoparticles (USPIO-NPs) are widely used as clinical magnetic resonance imaging contrast agents for hepatic diseases diagnosis. USPIO-NPs often damage the hepatocytes and affect the function of liver but its mechanism of action remains unclear. In the present study, USPIO-NPs caused higher cytotoxicity and lactate dehydrogenase (LDH) leakage in hepatic L02 cells than SPIO-NPs. Subsequently, USPIO-NPs affected more genes' expression than SPIO-NPs analyzed through microarray and bioinformatics analysis. The affected genes were involved in several biological processes, including calcium ion homeostasis, inflammatory response-related leukocyte chemotaxis, and migration. In addition, the level of endoplasmic reticulum (ER) calcium ion was increased by USPIO-NPs. USPIO-NPs also upregulated the genes related to acute-phase inflammation, including IL1B, IL6, IL18, TNFSF12, TNFRSF12, SAA1, SAA2, JAK1, STAT5B, and CXCL14. Furthermore, interleukin-6 (IL-6) secretion was elevated by USPIO-NPs as detected using ELISA. On the other hand, USPIO-NPs changed the morphology of ER and triggered the ER stress and unfolded protein response PERK/ATF4 pathway. Furthermore, blocking ER stress with inhibitor or ATF4 small interfering RNA counteracted IL-6-related acute-phase inflammation and cytotoxicity caused by USPIO-NPs. Taken together, we found that the USPIO-NPs could trigger stronger IL-6-related acute-phase inflammation than SPIO-NPs in hepatocytes. We demonstrated, for the first time, that IL-6-related acute-phase inflammation caused by NPs was regulated by PERK/ATF4 signaling. The PERK/ATF4 pathway explored in this study could be a candidate for diagnostic and therapeutic target against NPs-induced liver injury and cytotoxicity, which would be helpful for USPIO-NPs medical application.
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Affiliation(s)
- Chengyong He
- a State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health , Xiamen University , Xiamen , China
| | - Shengwei Jiang
- a State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health , Xiamen University , Xiamen , China
| | - Huan Yao
- a State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health , Xiamen University , Xiamen , China
| | - Liyin Zhang
- a State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health , Xiamen University , Xiamen , China
| | - Chuanli Yang
- a State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health , Xiamen University , Xiamen , China
| | - Denglin Zhan
- a State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health , Xiamen University , Xiamen , China
| | - Gan Lin
- a State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health , Xiamen University , Xiamen , China
| | - Yun Zeng
- a State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health , Xiamen University , Xiamen , China
| | - Yankai Xia
- b State Key Laboratory of Cellular Stress Biology, School of Life Sciences , Xiamen University , Xiamen , China
| | - Zhongning Lin
- a State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health , Xiamen University , Xiamen , China
| | - Gang Liu
- a State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health , Xiamen University , Xiamen , China.,c State Key Laboratory of Reproductive Medicine, Institute of Applied Toxicology, School of Public Health , Nanjing Medical University , Nanjing , China
| | - Yuchun Lin
- a State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health , Xiamen University , Xiamen , China
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Flavonoids, Sterols and Lignans from Cochlospermum vitifolium and Their Relationship with Its Liver Activity. Molecules 2018; 23:molecules23081952. [PMID: 30081608 PMCID: PMC6222972 DOI: 10.3390/molecules23081952] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2018] [Revised: 08/02/2018] [Accepted: 08/03/2018] [Indexed: 12/25/2022] Open
Abstract
The sterols β-sitostenone (1), stigmast-4,6,8(14),22-tetraen-3-one (2), β-sitosterol (3) and stigmasterol (4), the aromatic derivatives antiarol (5) and gentisic acid (6), the phenylpropanes coniferyl alcohol (7), epoxyconiferyl alcohol (8) and ferulic acid (9), the apocarotenoid vomifoliol (10), the flavonoids naringenin (11), 7,4′-dimethoxytaxifolin (7,4′-dimethoxydihydroquercetin, 12), aromadendrin (13), kaempferol (14), taxifolin (dihydroquercetin, 15), prunin (naringenin-7-O-β-d-glucoside, 16), populnin (kaempferol-7-O-β-d-glucoside, 17) and senecin (aromadendrin-7-O-β-d-glucoside, 18) and the lignans kobusin (19) and pinoresinol (20), were isolated from the dried bark of Cochlospermum vitifolium Spreng (Cochlospermaceae), a Mexican medicinal plant used to treat jaundice, liver ailments and hepatitis C. Fourteen of these compounds were isolated for the first time from this plant and from the Cochlospermum genus. Compounds 3–4, 6–7, 9–11, 13–17 and 20 have previously exhibited diverse beneficial liver activities. The presence of these compounds in C. vitifolium correlates with the use of this Mexican medicinal plant.
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Guo J, Zhao Y, Jiang X, Li R, Xie H, Ge L, Xie B, Yang X, Zhang L. Exposure to Formaldehyde Perturbs the Mouse Gut Microbiome. Genes (Basel) 2018; 9:E192. [PMID: 29614050 PMCID: PMC5924534 DOI: 10.3390/genes9040192] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2018] [Revised: 03/20/2018] [Accepted: 03/28/2018] [Indexed: 12/11/2022] Open
Abstract
Exposure to Formaldehyde (FA) results in many pathophysiological symptoms, however the underlying mechanisms are not well understood. Given the complicated modulatory role of intestinal microbiota on human health, we hypothesized that interactions between FA and the gut microbiome may account for FA's toxicity. Balb/c mice were allocated randomly to three groups: a control group, a methanol group (0.1 and 0.3 ng/mL MeOH subgroups), and an FA group (1 and 3 ng/mL FA subgroups). Groups of either three or six mice were used for the control or experiment. We applied high-throughput sequencing of 16S ribosomal RNA (rRNA) gene approaches and investigated possible alterations in the composition of mouse gut microbiota induced by FA. Changes in bacterial genera induced by FA exposure were identified. By analyzing KEGG metabolic pathways predicted by PICRUSt software, we also explored the potential metabolic changes, such as alpha-Linolenic acid metabolism and pathways in cancer, associated with FA exposure in mice. To the best of our knowledge, this preliminary study is the first to identify changes in the mouse gut microbiome after FA exposure, and to analyze the relevant potential metabolisms. The limitation of this study: this study is relatively small and needs to be further confirmed through a larger study.
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Affiliation(s)
- Junhui Guo
- Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, China.
- Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA 94720, USA.
- School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, Wuhan 430070, China.
| | - Yun Zhao
- Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, China.
| | - Xingpeng Jiang
- School of Computer, Central China Normal University, Wuhan 430079, China.
| | - Rui Li
- Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, China.
| | - Hao Xie
- School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, Wuhan 430070, China.
| | - Leixin Ge
- Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, China.
| | - Bo Xie
- Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, China.
| | - Xu Yang
- Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, China.
| | - Luoping Zhang
- Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA 94720, USA.
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Upregulation of PPAR-γ mediates the renoprotective effect of omega-3 PUFA and ferulic acid in gentamicin-intoxicated rats. Biomed Pharmacother 2018; 99:504-510. [DOI: 10.1016/j.biopha.2018.01.036] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2017] [Revised: 01/03/2018] [Accepted: 01/03/2018] [Indexed: 12/24/2022] Open
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