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Feng H, Wu T, Chin J, Ding R, Long C, Wang G, Yan D, Ma X, Yue R. Tangzu granule alleviate neuroinflammation in diabetic peripheral neuropathy by suppressing pyroptosis through P2X7R /NLRP3 signaling pathway. JOURNAL OF ETHNOPHARMACOLOGY 2025; 337:118792. [PMID: 39251151 DOI: 10.1016/j.jep.2024.118792] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/01/2024] [Revised: 09/01/2024] [Accepted: 09/04/2024] [Indexed: 09/11/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus, mainly manifested as paresthesia. Tangzu granule (TZG) is derived from famous traditional Chinese medicine decoctions and optimized by long-term temporary practice. TZG has good efficacy in improving numbness, pain and pruritus of the lower extremities of DPN patients. However, the overall regulatory mechanisms underlying its effects on DPN remain unclear. AIM OF THE STUDY This study aims to explore the potential mechanism of TZG for treating DPN. MATERIALS AND METHODS Sprague-Dawley (SD) rats were used to establish an in vivo model of DPN with streptozotocin (STZ) injection and high-fat diet (HFD) feeding. Additionally, sciatic glial RSC96 cells were induced with high glucose in vitro. SD rats in intervention group received TZG treatment for 12 weeks. After 12 weeks of treatment, sciatic nerve function was evaluated by intelligent hot plate meter and neuro electrophysiology detector. The morphological changes of sciatic nerve cells were observed by hematoxylin-eosin staining and transmission electron microscope. IL-1β, IL-18 inflammatory cytokines, pyroptosis and P2X7R/NLRP3 signaling pathway were observed by Western blotting, immunofluorescence staining and ELISA. RESULTS TZG improved nerve conduction velocity and sciatic neuropathy rational structural changes in DPN rats. It also inhibited RSC96 inflammatory response and cell death that induced by high glucose. This may be related to TZG inhibiting P2X7R, decreasing the activation of NLRP3 inflammasomes, down-regulating the levels of pyroptosis proteins such as caspase-1, cleaved caspase-1, gasdermin D (GSDMD), and GSDMD-N, and inhibiting the release of interleuki (IL)-18 and IL-1β inflammatory cytokines. CONCLUSIONS TZG inhibited pyroptosis through P2X7R/NLRP3 signaling pathway, alleviated neuroinflammation, and showed protective effect in the treatment of DPN.
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Affiliation(s)
- Haoyue Feng
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
| | - Tingchao Wu
- Chengdu Second People׳s Hospital, Chengdu, Sichuan, China.
| | - Jiawei Chin
- School of Integrative Medicine, Mae Fah Luang University, Chiangrai, Thailand.
| | - Rui Ding
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
| | - Caiyi Long
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
| | - Gang Wang
- Zigong First People's Hospital, Zigong, Sichuan, China.
| | - Dawei Yan
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
| | - Xitao Ma
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
| | - Rensong Yue
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
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Hwang J, Jung JS, Kim D, Kwon M, Yong J, Yoon H, Park KM. Therapeutic Potential of Dimethyl Sulfoxide via Subconjunctival Injection in a Diabetic Retinopathy Rat Model. In Vivo 2025; 39:132-145. [PMID: 39740902 PMCID: PMC11705140 DOI: 10.21873/invivo.13811] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Revised: 10/25/2024] [Accepted: 10/29/2024] [Indexed: 01/02/2025]
Abstract
BACKGROUND/AIM Diabetic retinopathy (DR), a complication of diabetes, causes damage to retinal blood vessels and can lead to vision impairment. Persistent high blood glucose levels contribute to this damage, and despite ongoing research, effective treatment options for DR remain limited. Dimethyl sulfoxide (DMSO) has shown anti-inflammatory and antioxidant properties in both in vivo and in vitro studies; however, its potential as an anti-inflammatory agent in the context of DR has not yet been explored. This study aimed to assess the effects of subconjunctival injection of DMSO on the progression of DR. MATERIALS AND METHODS DR was induced in rats using intraperitoneal injections of streptozotocin (55 mg/kg), confirmed by measuring blood glucose levels and electroretinography (ERG). The rats were divided into five groups: a normal control group (CON), a DR control group receiving PBS injections (DMSO 0), and three DR groups receiving different concentrations of DMSO (98%, 50%, and 10%). Retinal function was evaluated using ERG at weeks 10 and 14, and histological analysis at week 16. RESULTS The DMSO 50 group had significantly higher B-wave amplitude in ERG compared to the DMSO 0 group (p<0.05). Flicker response amplitudes were also significantly greater in the DMSO 50 and DMSO 10 groups compared to DMSO 0 (p<0.05). Histological examination revealed thinner retinal layers in the DMSO 0 group compared to the CON group, while the DMSO-treated groups showed improved retinal thickness. CONCLUSION Subconjunctival injection of 50% DMSO appears to improve retinal function in a rat model of DR.
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Affiliation(s)
- Jiyi Hwang
- Laboratory of Veterinary Ophthalmology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic for Korea
| | - Ji Seung Jung
- Laboratory of Veterinary Ophthalmology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic for Korea
| | - Donghee Kim
- Laboratory of Veterinary Ophthalmology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic for Korea
| | - Myeongjee Kwon
- Laboratory of Veterinary Ophthalmology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic for Korea
| | - Jungyeon Yong
- Laboratory of Veterinary Ophthalmology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic for Korea
| | - Haerin Yoon
- Laboratory of Veterinary Ophthalmology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic for Korea
| | - Kyung-Mee Park
- Laboratory of Veterinary Ophthalmology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic for Korea
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Allamreddy S, Arora M, Ganugula R, Friend R, Basu R, Kumar MNVR. Prospects for the convergence of polyphenols with pharmaceutical drugs in type 2 diabetes: Challenges, risks, and strategies. Pharmacol Rev 2025; 77:100003. [PMID: 39952688 DOI: 10.1124/pharmrev.124.001074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Revised: 08/26/2024] [Accepted: 09/09/2024] [Indexed: 09/28/2024] Open
Abstract
Type 2 diabetes mellitus (T2DM) is a complex disease that can lead to a variety of life-threatening secondary health conditions. Current treatment strategies primarily revolve around tight glucose control, which is difficult to achieve and often turns out to be dangerous because of possible hypoglycemic events. Numerous long-term studies have demonstrated that complex pathways, including low-grade inflammation due to fluctuating glucose levels, are involved in the progression of the disease and the development of secondary health conditions. Growing clinical evidence supports the effectiveness of using multiple medications, possibly in combination with insulin, to effectively manage T2DM. Despite the huge, largely untapped potential therapeutic benefit of polyphenols, there remains a general skepticism of the practice. However, for any evidence-based clinical intervention, the balance of benefits and risks takes center stage and is governed by biopharmaceutics principles. In this article, we outline the current clinical perspectives on pharmaceutical drug combinations, rationale for early initiation of insulin, and advantages of novel dosage forms to meet the pathophysiological changes of T2DM, emphasizing the need for further clinical studies to substantiate these approaches. We also make the case for traditional medicines and their combinations with pharmaceutical drugs and outline the inherent challenges in doing so, while also providing recommendations for future research and clinical practice. SIGNIFICANCE STATEMENT: Type 2 diabetes is associated with life-threatening secondary health conditions that are often difficult to treat. This review provides an in-depth account of preventing/delaying secondary health conditions through combination therapies and emphasizes the role of effective delivery strategies in realizing the translation of such combinations. This review builds the case for the importance of polyphenols in diabetes, determines the reasons for skepticism, and discusses potential combinations with pharmaceutical drugs.
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Affiliation(s)
- S Allamreddy
- The Center for Convergent Bioscience and Medicine (CCBM), University of Alabama, Tuscaloosa, Alabama; Department of Translational Science and Medicine, College of Community Health Sciences, University of Alabama, Tuscaloosa, Alabama; Alabama Life Research Institute, University of Alabama, Tuscaloosa, Alabama
| | - M Arora
- The Center for Convergent Bioscience and Medicine (CCBM), University of Alabama, Tuscaloosa, Alabama; Department of Translational Science and Medicine, College of Community Health Sciences, University of Alabama, Tuscaloosa, Alabama; Alabama Life Research Institute, University of Alabama, Tuscaloosa, Alabama; Department of Biological Sciences, University of Alabama, Tuscaloosa, Alabama
| | - R Ganugula
- The Center for Convergent Bioscience and Medicine (CCBM), University of Alabama, Tuscaloosa, Alabama; Department of Translational Science and Medicine, College of Community Health Sciences, University of Alabama, Tuscaloosa, Alabama; Alabama Life Research Institute, University of Alabama, Tuscaloosa, Alabama; Department of Biological Sciences, University of Alabama, Tuscaloosa, Alabama
| | - R Friend
- Department of Family, Internal, and Rural Medicine, College of Community Health Sciences, University of Alabama, Tuscaloosa, Alabama
| | - R Basu
- Division of Endocrinology, Diabetes, and Metabolism, School of Medicine, Marnix E. Heersink School of Medicine, University of Alabama, Birmingham, Alabama
| | - M N V Ravi Kumar
- The Center for Convergent Bioscience and Medicine (CCBM), University of Alabama, Tuscaloosa, Alabama; Department of Translational Science and Medicine, College of Community Health Sciences, University of Alabama, Tuscaloosa, Alabama; Alabama Life Research Institute, University of Alabama, Tuscaloosa, Alabama; Department of Biological Sciences, University of Alabama, Tuscaloosa, Alabama; Department of Chemical and Biological Engineering, University of Alabama, Tuscaloosa, Alabama; Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, Alabama; Nephrology Research and Training Center, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
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Freitas M, Ribeiro D, Janela JS, Varela CL, Costa SC, da Silva ET, Fernandes E, Roleira FMF. Plant-derived and dietary phenolic cinnamic acid derivatives: Anti-inflammatory properties. Food Chem 2024; 459:140080. [PMID: 38986205 DOI: 10.1016/j.foodchem.2024.140080] [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: 04/17/2024] [Revised: 06/02/2024] [Accepted: 06/10/2024] [Indexed: 07/12/2024]
Abstract
Cinnamic acids are aromatic acids primarily found in plants and plant-derived food. Phenolic cinnamic acids, with one or more hydroxyl groups in the aromatic ring, often contribute to the biological activities attributed to these compounds. The presence of hydroxyl groups and a carboxyl group makes cinnamic acids very hydrophilic, preventing them from crossing biological membranes and exerting their biological activities. To alleviate this condition, a panel of synthetic modifications have been made leading to a diverse set of phenolic cinnamic structures. In this review, an overview of the natural phenolic cinnamic acid derivatives and their plant sources (more than 200) is described. The synthetic approaches to obtain the referred derivatives (more than 200) namely esters and amides are reviewed. Further, their anti-inflammatory activity (more than 70 compounds) is scrutinized. Finally, future directions will be indicated to translate the research on phenolic cinnamic derivatives into potentially effective anti-inflammatory drugs.
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Affiliation(s)
- Marisa Freitas
- LAQV, REQUIMTE, University of Porto, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, 4050-313 Porto, Portugal.
| | - Daniela Ribeiro
- LAQV, REQUIMTE, University of Porto, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, 4050-313 Porto, Portugal; Faculdade de Ciências Agrárias e do Ambiente da Universidade dos Açores, Portugal.
| | - João S Janela
- Univ Coimbra, CERES, Faculty of Pharmacy, Laboratory of Pharmaceutical Chemistry, Azinhaga de Santa Comba, Pólo III - Pólo das Ciências da Saúde, 3000-548 Coimbra, Portugal.
| | - Carla L Varela
- Univ Coimbra, CERES, Coimbra, Portugal; Univ Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Clinic Academic Center of Coimbra (CACC), Coimbra, Portugal; Univ Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), Coimbra, Portugal.
| | - Saul C Costa
- Univ Coimbra, Faculty of Pharmacy, Laboratory of Pharmaceutical Chemistry, Azinhaga de Santa Comba, Pólo III - Pólo das Ciências da Saúde, 3000-548 Coimbra, Portugal.
| | - Elisiário Tavares da Silva
- Univ Coimbra, CERES, Faculty of Pharmacy, Laboratory of Pharmaceutical Chemistry, Azinhaga de Santa Comba, Pólo III - Pólo das Ciências da Saúde, 3000-548 Coimbra, Portugal.
| | - Eduarda Fernandes
- LAQV, REQUIMTE, University of Porto, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, 4050-313 Porto, Portugal.
| | - Fernanda M F Roleira
- Univ Coimbra, CERES, Faculty of Pharmacy, Laboratory of Pharmaceutical Chemistry, Azinhaga de Santa Comba, Pólo III - Pólo das Ciências da Saúde, 3000-548 Coimbra, Portugal.
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Shang Y, Yan CY, Li H, Liu N, Zhang HF. Tiliroside protects against diabetic nephropathy in streptozotocin-induced diabetes rats by attenuating oxidative stress and inflammation. World J Diabetes 2024; 15:2220-2236. [PMID: 39582560 PMCID: PMC11580572 DOI: 10.4239/wjd.v15.i11.2220] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 08/17/2024] [Accepted: 09/23/2024] [Indexed: 10/16/2024] Open
Abstract
BACKGROUND Diabetic nephropathy (DN), affecting half of diabetic patients and contributing significantly to end-stage kidney disease, poses a substantial medical challenge requiring dialysis or transplantation. The nuanced onset and clinical progression of kidney disease in diabetes involve consistent renal function decline and persistent albuminuria. AIM To investigate Tiliroside's (Til) protective effect against diabetic nephropathy (DN) in rats under diabetic conditions. METHODS Five groups of six rats each were included in this study: Rats treated with DMSO by intraperitoneal injection as controls, those treated with STZ by intraperitoneal injection, those treated with STZ + Til (25 mg/kg body weight [bwt]) or Til (50 mg/kg bwt), and those treated with anti-diabetic medication glibenclamide (600 μg/kg bwt). Biochemical markers, fasting blood glucose, food intake, kidney weight, antioxidant enzymes, inflammatory and fibrotic markers, and renal injury were monitored in different groups. Molecular docking analysis was performed to identify the interactions between Til and its targeted biomarkers. RESULTS Til significantly reduced biochemical markers, fasting blood glucose, food intake, and kidney weight and elevated antioxidant enzymes in diabetic rats. It also mitigated inflammatory and fibrotic markers, lessened renal injury, and displayed inhibitory potential against crucial markers associated with DN as demonstrated by molecular docking analysis. CONCLUSION These findings suggest Til's potential as a therapeutic agent for DN treatment, highlighting its promise for future drug development.
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Affiliation(s)
- Yan Shang
- Department of Nephrology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan 030032, Shanxi Province, China
| | - Cai-Yun Yan
- Department of Nephrology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan 030032, Shanxi Province, China
| | - Hui Li
- Department of Nephrology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan 030032, Shanxi Province, China
| | - Na Liu
- Department of Nephrology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan 030032, Shanxi Province, China
| | - Hui-Feng Zhang
- Department of Nephrology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan 030032, Shanxi Province, China
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Khatun MM, Bhuia MS, Chowdhury R, Sheikh S, Ajmee A, Mollah F, Al Hasan MS, Coutinho HDM, Islam MT. Potential utilization of ferulic acid and its derivatives in the management of metabolic diseases and disorders: An insight into mechanisms. Cell Signal 2024; 121:111291. [PMID: 38986730 DOI: 10.1016/j.cellsig.2024.111291] [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: 05/22/2024] [Revised: 06/28/2024] [Accepted: 07/05/2024] [Indexed: 07/12/2024]
Abstract
Metabolic diseases are abnormal conditions that impair the normal metabolic process, which involves converting food into energy at a cellular level, and cause difficulties like obesity and diabetes. The study aimed to investigate how ferulic acid (FA) and its derivatives could prevent different metabolic diseases and disorders and to understand the specific molecular mechanisms responsible for their therapeutic effects. Information regarding FA associations with metabolic diseases and disorders was compiled from different scientific search engines, including Science Direct, Wiley Online, PubMed, Scopus, Web of Science, Springer Link, and Google Scholar. This review revealed that FA exerts protective effects against metabolic diseases such as diabetes, diabetic retinopathy, neuropathy, nephropathy, cardiomyopathy, obesity, and diabetic hypertension, with beneficial effects on pancreatic cancer. Findings also indicated that FA improves insulin secretion by increasing Ca2+ influx through the L-type Ca2+ channel, thus aiding in diabetes management. Furthermore, FA regulates the activity of inflammatory cytokines (TNF-α, IL-18, and IL-1β) and antioxidant enzymes (CAT, SOD, and GSH-Px) and reduces oxidative stress and inflammation, which are common features of metabolic diseases. FA also affects various signaling pathways, including the MAPK/NF-κB pathways, which play an important role in the progression of diabetic neuropathy and other metabolic disorders. Additionally, FA regulates apoptosis markers (Bcl-2, Bax, and caspase-3) and exerts its protective effects on cellular destruction. In conclusion, FA and its derivatives may act as potential medications for the management of metabolic diseases.
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Affiliation(s)
- Mst Muslima Khatun
- 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
| | - 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; Phytochemistry and Biodiversity Research Laboratory, BioLuster Research Center, Gopalganj 8100, Dhaka, Bangladesh
| | - Salehin Sheikh
- Phytochemistry and Biodiversity Research Laboratory, BioLuster Research Center, Gopalganj 8100, Dhaka, Bangladesh
| | - Afiya Ajmee
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh
| | - Faysal Mollah
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh
| | - Md Sakib Al Hasan
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh
| | - Henrique D M Coutinho
- Department of Biological Chemistry, Regional University of Cariri, Crato, CE 63105-000, Brazil.
| | - 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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Rusli N, Ng CF, Makpol S, Wong YP, Mohd Isa IL, Remli R. Antioxidant Effect in Diabetic Peripheral Neuropathy in Rat Model: A Systematic Review. Antioxidants (Basel) 2024; 13:1041. [PMID: 39334700 PMCID: PMC11428735 DOI: 10.3390/antiox13091041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Revised: 08/20/2024] [Accepted: 08/22/2024] [Indexed: 09/30/2024] Open
Abstract
Oxidative stress is a contributing factor that leads to the vascular complications of diabetes mellitus. Diabetic peripheral neuropathy (DPN) is one of the microvascular complications with rising concern as the disease progresses despite strict glucose control and monitoring. Thus, there is an ongoing need for an early intervention that is effective in halting or slowing the progression of DPN where antioxidants have been proposed as potential therapeutic agents. This systematic review aims to evaluate the existing evidence on the antioxidant effect in DPN and provide insight on the role of antioxidants in the progression of DPN in a rat model. A comprehensive literature search was conducted on Web of Science, EBSCOhost, and Scopus to identify the effects and role of antioxidants in DPN. Data extraction was performed and SYRCLE's risk of bias (RoB) tool was used for risk assessment. This systematic review was written following the PRISMA 2020 statements. From the literature search, 1268 articles were screened, and a total of 101 full-text articles were further screened before 33 were analyzed. These findings collectively suggest that antioxidants can play a crucial role in managing and potentially reversing the effects of diabetic neuropathy by targeting oxidative stress and improving nerve function.
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Affiliation(s)
- Noradliyanti Rusli
- Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras 56000, Malaysia
| | - Chen Fei Ng
- Department of Neurology, Sunway Medical Centre, Subang Jaya 47500, Malaysia
| | - Suzana Makpol
- Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras 56000, Malaysia
| | - Yin Ping Wong
- Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras 56000, Malaysia
| | - Isma Liza Mohd Isa
- Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras 56000, Malaysia
- CÚRAM, SFI Research Centre for Medical Devices, School of Medicine, University of Galway, H91 TK33 Galway, Ireland
| | - Rabani Remli
- Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras 56000, Malaysia
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Pyrzynska K. Ferulic Acid—A Brief Review of Its Extraction, Bioavailability and Biological Activity. SEPARATIONS 2024; 11:204. [DOI: 10.3390/separations11070204] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2025] Open
Abstract
Ferulic acid is a widespread phenolic compound that occurs in seeds and leaves, both in its free form and conjugated to polysaccharides, carbohydrates, glycoproteins and lignins in the plant cell walls. It exhibits various biological activities, like antioxidant, anticarcinogenic, anti-inflammatory, hepatoprotective, antimicrobial, and antiviral activity, and it modulates enzyme activity. Given these wide potential health benefits, ferulic acid has attracted considerable research interest and may be considered a biomolecule with strong prospects as a functional food ingredient. Great attempts have been made to enhance its extraction process and recovery from natural matrices and agro-industrial wastes for its various applications relating to human health and nutrition. This review presents the recently available information on the extraction methods for quantifying ferulic acid in different samples, along with its bioavailability and stability in processing foods and biological activities.
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Affiliation(s)
- Krystyna Pyrzynska
- Department of Chemistry, University of Warsaw, Pasteur Str. 1, 02-093 Warsaw, Poland
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Figueredo KC, Guex CG, Graiczik J, Reginato FZ, Engelmann AM, Andrade CMD, Timmers LFSM, Bauermann LDF. Caffeic acid and ferulic acid can improve toxicological damage caused by iron overload mediated by carbonic anhydrase inhibition. Drug Chem Toxicol 2024; 47:147-155. [PMID: 36444844 DOI: 10.1080/01480545.2022.2152043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 11/04/2022] [Accepted: 11/06/2022] [Indexed: 11/30/2022]
Abstract
The iron ion is an essential element for most forms of life, however, it can damage biological systems when found in free form. Chelation therapy is very important, but it is precarious. Caffeic and ferulic acid are antioxidant compounds with many properties described in research such as anti-inflammatory, antiobesogenic, antithrombotic, vasodilator, and anti-tumor. The aim of the study was to evaluate presenting an in silico approach on the toxicity and bioavailability of caffeic and ferulic acid, subsequently, evaluating them in an iron overload model in vivo and providing a pharmacophoric model through molecular docking. The predictive in silico test did not show relevant toxicity of the compounds, therefore, the in vivo test was performed. The rats received dextran iron and the test groups received caffeic and ferulic acid orally for six weeks. Biochemical, hematological parameters, and tissue oxidative stress marker were analyzed. The experimental model showed increased serum iron levels and changes in several serum parameters such as glucose (215.8 ± 20.3 mg/dL), ALT (512.2 ± 128.7 U/L), creatine kinase (186.8 ± 30.1 U/L), and creatine kinase isoform MB (373.3 ± 69.7 U/L). Caffeic acid and, to a lessed degree, ferullic acid, attenuated the effects of iron overload on the rat serum biochemical parameters. Docking showed a pharmacophoric model where carbonic anhydrase interacted with the test molecules and caffeic acid showed less energy expenditure in this interaction. The results illustrate a new therapeutic action of phenolic compounds on iron overload. The possible interference of carbonic anhydrase in iron metabolism needs to be elucidated.
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Affiliation(s)
| | - Camille Gaube Guex
- Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, Brazil
| | - James Graiczik
- Graduate Program in Pharmacy, University of Federal University of Santa Maria, Santa Maria, Brazil
| | | | | | | | | | - Liliane De Freitas Bauermann
- Graduate Program in Pharmaceutical Sciences, Federal University of Santa Maria, Santa Maria, Brazil
- Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, Brazil
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10
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Eissa RG, Eissa NG, Eissa RA, Diab NH, Abdelshafi NA, Shaheen MA, Elsabahy M, Hammad SK. Oral proniosomal amitriptyline and liraglutide for management of diabetic neuropathy: Exceptional control over hyperglycemia and neuropathic pain. Int J Pharm 2023; 647:123549. [PMID: 37890645 DOI: 10.1016/j.ijpharm.2023.123549] [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: 06/14/2023] [Revised: 09/19/2023] [Accepted: 10/23/2023] [Indexed: 10/29/2023]
Abstract
Exploitation of nanocarriers provides a compartment for enclosing drugs to protect them from degradation and potentiate their therapeutic efficiency. In the current study, amitriptyline- and liraglutide-loaded proniosomes were constructed for management of diabetic neuropathy, a serious complication associated with diabetes, that triggers spontaneous pain in patients and results in impaired quality of life. The developed therapeutic proniosomes were extensively characterized via dynamic light scattering, scanning electron microscopy, transmission electron microscopy, and Fourier transform-infrared spectroscopy. High entrapment efficiency could be attained for both drugs in the proniosomes, and the reconstituted amitriptyline- and liraglutide-loaded niosomes possessed spherical morphology and particle sizes of 585.3 nm and 864.4 nm, respectively. In a diabetic neuropathy rat model, oral administration of the developed amitriptyline- and liraglutide-loaded proniosomes significantly controlled blood glucose levels, reduced neuropathic pain, oxidative stress and inflammatory markers, and improved histological structure of the sciatic nerve as compared to the oral and subcutaneous administration of amitriptyline and liraglutide, respectively. Loading of the tricyclic antidepressant amitriptyline and the antidiabetic peptide liraglutide into proniosomes resulted in exceptional control over hyperglycemia and neuropathic pain, and thus could provide an auspicious delivery system for management of neuropathic pain and control of blood glucose levels.
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Affiliation(s)
- Rana G Eissa
- Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt
| | - Noura G Eissa
- Department of Pharmaceutics, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt; Badr University in Cairo Research Center, Badr University in Cairo, Badr City, Cairo 11829, Egypt
| | - Rana A Eissa
- Badr University in Cairo Research Center, Badr University in Cairo, Badr City, Cairo 11829, Egypt
| | - Nadeen H Diab
- Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt
| | - Nahla A Abdelshafi
- Department of Pharmaceutical Analytical Chemistry, School of Pharmacy, Badr University in Cairo, Badr City, Cairo 11829, Egypt
| | - Mohamed A Shaheen
- Department of Histology & Cell Biology, Faculty of Medicine, Zagazig University, Zagazig 44519, Egypt
| | - Mahmoud Elsabahy
- Badr University in Cairo Research Center, Badr University in Cairo, Badr City, Cairo 11829, Egypt; Department of Chemistry, Texas A&M University, College Station, TX 77842, USA.
| | - Sally K Hammad
- Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt
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Bhuia MS, Rokonuzzman M, Hossain MI, Ansari SA, Ansari IA, Islam T, Al Hasan MS, Mubarak MS, Islam MT. Anxiolytic- like Effects by trans-Ferulic Acid Possibly Occur through GABAergic Interaction Pathways. Pharmaceuticals (Basel) 2023; 16:1271. [PMID: 37765079 PMCID: PMC10535412 DOI: 10.3390/ph16091271] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Revised: 09/02/2023] [Accepted: 09/05/2023] [Indexed: 09/29/2023] Open
Abstract
Numerous previous studies reported that ferulic acid exerts anxiolytic activity. However, the mechanisms have yet to be elucidated. The current study aimed to investigate the anxiolytic effect of trans-ferulic acid (TFA), a stereoisomer of ferulic acid, and evaluated its underlying mechanism using in vivo and computational studies. For this, different experimental doses of TFA (25, 50, and 75 mg/kg) were administered orally to Swiss albino mice, and various behavioral methods of open field, hole board, swing box, and light-dark tests were carried out. Diazepam (DZP), a positive allosteric modulator of the GABAA receptor, was employed as a positive control at a dose of 2 mg/kg, and distilled water served as a vehicle. Additionally, molecular docking was performed to estimate the binding affinities of the TFA and DZP toward the GABAA receptor subunits of α2 and α3, which are associated with the anxiolytic effect; visualizations of the ligand-receptor interaction were carried out using various computational tools. Our findings indicate that TFA dose-dependently reduces the locomotor activity of the animals in comparison with the controls, calming their behaviors. In addition, TFA exerted the highest binding affinity (-5.8 kcal/mol) to the α2 subunit of the GABAA receptor by forming several hydrogen and hydrophobic bonds. Taken together, our findings suggest that TFA exerts a similar effect to DZP, and the compound exerts moderate anxiolytic activity through the GABAergic interaction pathway. We suggest further clinical studies to develop TFA as a reliable anxiolytic agent.
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Affiliation(s)
- Md. Shimul Bhuia
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh; (M.S.B.); (M.R.); (M.I.H.); (T.I.); (M.S.A.H.)
| | - Md. Rokonuzzman
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh; (M.S.B.); (M.R.); (M.I.H.); (T.I.); (M.S.A.H.)
| | - Md. Imran Hossain
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh; (M.S.B.); (M.R.); (M.I.H.); (T.I.); (M.S.A.H.)
| | - Siddique Akber Ansari
- Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia;
| | - Irfan Aamer Ansari
- Department of Drug Science and Technology, University of Turin, 10124 Turin, Italy;
| | - Tawhida Islam
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh; (M.S.B.); (M.R.); (M.I.H.); (T.I.); (M.S.A.H.)
| | - Md. Sakib Al Hasan
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh; (M.S.B.); (M.R.); (M.I.H.); (T.I.); (M.S.A.H.)
| | | | - Muhammad Torequl Islam
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh; (M.S.B.); (M.R.); (M.I.H.); (T.I.); (M.S.A.H.)
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Alkholifi FK, Aodah AH, Foudah AI, Alam A. Exploring the Therapeutic Potential of Berberine and Tocopherol in Managing Diabetic Neuropathy: A Comprehensive Approach towards Alleviating Chronic Neuropathic Pain. Biomedicines 2023; 11:1726. [PMID: 37371821 DOI: 10.3390/biomedicines11061726] [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: 05/13/2023] [Revised: 06/12/2023] [Accepted: 06/13/2023] [Indexed: 06/29/2023] Open
Abstract
Diabetic neuropathy (DN) causes sensory dysfunction, such as numbness, tingling, or burning sensations. Traditional medication may not ease pain and discomfort, but natural remedies such as Berberine (BR) and vitamin E or Tocopherol (TOC) have therapeutic potential to reduce inflammation while improving nerve function. Novel substances offer a more potent alternative method for managing severe chronic neuropathic pain that does not react to standard drug therapy by targeting various pathways that regulate it. Rats with diabetic control received oral doses of BR + TOC that showed significant changes in serum insulin levels compared to DN controls after 90 days, suggesting a decrease in sensitivity to painful stimuli partly by modulating the oxidative stress of the inflammatory pathway such as TNF-α suppression or stimulation of TNF-α depending on the amount of dose consumed by them. NF-kB also played its role here. Administering doses of BR and TOC reduced heightened levels of NF-kB and AGEs, effectively counteracting inflammation-targeted key factors in diabetes, promising possibilities for the benefits of these molecules revealed through in vivo investigation. In summary, treating neuropathy pain with a more comprehensive and organic approach can involve harnessing the powerful capabilities of BR and TOC. These compounds have been found to not only considerably decrease inflammation but also provide effective nerve protection while enhancing overall nerve function. With their multifunctional impacts on various neuropathic pain pathways in the body, these naturally occurring substances offer an exciting possibility for those who encounter high levels of neuropathic distress that do not respond well to conventional medication-centred therapies.
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Affiliation(s)
- Faisal K Alkholifi
- Department of Pharmacology & Toxicology, College of Pharmacy, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | - Alhussain H Aodah
- Department of Pharmaceutics, College of Pharmacy, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | - Ahmed I Foudah
- Department of Pharmacognosy, College of Pharmacy, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | - Aftab Alam
- Department of Pharmacognosy, College of Pharmacy, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
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Khan A, Shal B, Ullah Khan A, Ullah Shah K, Saniya Zahra S, ul Haq I, ud Din F, Ali H, Khan S. Neuroprotective mechanism of Ajugarin-I against Vincristine-Induced neuropathic pain via regulation of Nrf2/NF-κB and Bcl2 signalling. Int Immunopharmacol 2023; 118:110046. [PMID: 36989890 DOI: 10.1016/j.intimp.2023.110046] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 02/13/2023] [Accepted: 03/13/2023] [Indexed: 03/29/2023]
Abstract
Vincristine (VCR) is a well-known chemotherapeutic agent that frequently triggers neuropathic pain. Ajugarin-I (Aju-I) isolated from Ajuga bracteosa exerts antioxidant, anti-inflammatory, and neuroprotective properties. The present study was designed to investigate the ameliorative potential of Aju-I against VCR-induced neuropathic pain and explored the underlying mechanism involved. The neuroprotective potential of Aju-I was first confirmed against hydrogen peroxide (H2O2)-induced cytotoxicity and oxidative stress in PC12 cells. For neuropathic pain induction, vincristine was given intraperitoneally (i.p.) into adult male albino mice (BALB/c) of the same age (8-12 weeks old) for 10 days (days 1-10). Aju-I (1 and 5 mg/kg) doses were administered from day 11 to 21 intraperitoneally (i.p.) after the neuropathic induction. Initially, behavioral tests such as thermal hyperalgesia, mechanical allodynia, and cold allodynia were performed to investigate the antinociceptive potential of Ajugarin-I (1 and 5 mg/kg, b.w). The nuclear factor-erythroid factor 2-related factor 2(Nrf2), nuclear factor-κB (NF-κB), BCL2-associated × protein (Bax), and B-cell-lymphoma-2 (Bcl-2) signaling proteins were determined by immunohistochemistry and western blot. Additionally, inflammatory cytokines, antioxidant, and oxidative stress parameters were also measured in the spinal cord and sciatic nerve. The behavioral results demonstrated that Aju-I (5 mg/kg) markedly alleviated VCR-induced neuropathic pain behaviors including hyperalgesia and allodynia. It reversed the histological alterations caused by VCR in the sciatic nerve, spinal cord, and brain. It significantly alleviated oxidative stress and inflammation by regulating the immunoreactivity of Nrf2/NF-κB signaling. It suppressed apoptosis by regulating the immunoreactivity of Bcl-2/Bax and Caspase-3. The flow cytometry and comet analysis also confirmed its anti-apoptotic potential. It considerably improved the antioxidant status and mitigated VCR-induced inflammatory cytokines. High-performance liquid chromatography (HPLC) analysis indicated that Aju-I crosses the blood-brain barrier (BBB) and penetrated the brain tissue. These findings suggest that Aju-I treatment inhibited vincristine-induced neuropathy via regulation of Nrf2/NF-κB and Bcl2 signaling.
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Zhang D, Jing B, Chen ZN, Li X, Shi HM, Zheng YC, Chang SQ, Gao L, Zhao GP. Ferulic acid alleviates sciatica by inhibiting neuroinflammation and promoting nerve repair via the TLR4/NF-κB pathway. CNS Neurosci Ther 2023; 29:1000-1011. [PMID: 36601662 PMCID: PMC10018085 DOI: 10.1111/cns.14060] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Revised: 11/14/2022] [Accepted: 12/02/2022] [Indexed: 01/06/2023] Open
Abstract
INTRODUCTION Sciatica causes intense pain. No satisfactory therapeutic drugs exist to treat sciatica. This study aimed to probe the potential mechanism of ferulic acid in sciatica treatment. METHODS Thirty-two SD rats were randomly divided into 4 groups: sham operation, chronic constriction injury (CCI), mecobalamin, and ferulic acid. We conducted RNA sequencing, behavioral tests, ELISA, PCR, western blotting, and immunofluorescence analysis. TAK-242 and JSH23 were administered to RSC96 and GMI-R1 cells to explore whether ferulic acid can inhibit apoptosis and alleviate inflammation. RESULTS RNA sequencing showed that TLR4/NF-κB pathway is involved in the mechanism of sciatica. CCI induced cold and mechanical hyperalgesia; destroyed the sciatic nerve structure; increased IL-1β, IL-6, TNF-α, IL-8, and TGF-β protein levels and IL-1β, IL-6, TNF-α, TGF-β, TLR4, and IBA-1 mRNA levels; and decreased IL-10 and INF-γ protein levels and IL-4 mRNA levels. Immunohistochemistry showed that IBA-1, CD32, IL-1β, iNOS, nNOS, COX2, and TLR4 expression was increased while S100β and Arg-1 decreased. CCI increased TLR4, IBA-1, IL-1β, iNOS, Myd88, p-NF-κB, and p-p38MAPK protein levels. Treatment with mecobalamin and ferulic acid reversed these trends. Lipopolysaccharide (LPS) induced RSC96 cell apoptosis by reducing Bcl-2 and Bcl-xl protein and mRNA levels and increasing Bax and Bad mRNA and IL-1β, TLR4, Myd88, p-NF-κB, and p-p38MAPK protein levels, while ferulic acid inhibited cell apoptosis by decreasing IL-1β, TLR4, Myd88, p-NF-κB, and p-p38MAPK levels and increasing Bcl-2 and Bcl-xl levels. In GMI-R1 cells, Ferulic acid attenuated LPS-induced M1 polarization by decreasing the M1 polarization markers IL-1β, IL-6, iNOS, and CD32 and increasing the M2 polarization markers CD206, IL-4, IL-10 and Arg-1. After LPS treatment, IL-1β, iNOS, TLR4, Myd88, p-p38MAPK, and p-NF-κB levels were obviously increased, and Arg-1 expression was reduced, while ferulic acid reversed these changes. CONCLUSION Ferulic acid can promote injured sciatic nerve repair by reducing neuronal cell apoptosis and inflammatory infiltration though the TLR4/NF-κB pathway.
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Affiliation(s)
- Di Zhang
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Bei Jing
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Zhen-Ni Chen
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Xin Li
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Hui-Mei Shi
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Ya-Chun Zheng
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Shi-Quan Chang
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Li Gao
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Guo-Ping Zhao
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, China
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15
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Bajaj S, Gupta S. Nutraceuticals: A Promising Approach Towards Diabetic Neuropathy. Endocr Metab Immune Disord Drug Targets 2023; 23:581-595. [PMID: 36263482 DOI: 10.2174/1871530323666221018090024] [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: 02/05/2022] [Revised: 05/16/2022] [Accepted: 05/25/2022] [Indexed: 11/22/2022]
Abstract
BACKGROUND Various nutraceuticals from different sources have various beneficial actions and have been reported for many years. The important findings from the research conducted using various nutraceuticals exhibiting significant physiological and pharmacological activities have been summarized. METHODS An extensive investigation of literature was done using several worldwide electronic scientific databases like PUBMED, SCOPUS, Science Direct, Google Scholar, etc. The entire manuscript is available in the English language that is used for our various compounds of interest. These databases were thoroughly reviewed and summarized. RESULTS Nutraceuticals obtained from various sources play a vital role in the management of peripheral neuropathy associated with diabetes. Treatment with nutraceuticals has been beneficial as an alternative in preventing the progression. In particular, in vitro and in vivo studies have revealed that a variety of nutraceuticals have significant antioxidant and anti-inflammatory properties that may inhibit the early diabetes-driven molecular mechanisms that induce DPN. CONCLUSION Nutraceuticals obtained from different sources like a plant, an animal, and marine have been properly utilized for the safety of health. In our opinion, this review could be of great interest to clinicians, as it offers a complementary perspective on the management of DPN. Trials with a well-defined patient and symptom selection have shown robust pharmacological design as pivotal points to let these promising compounds become better accepted by the medical community.
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Affiliation(s)
- Sakshi Bajaj
- Department of Pharmaceutical Sciences, M.M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala, Haryana-133207, India
| | - Sumeet Gupta
- Department of Pharmaceutical Sciences, M.M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala, Haryana-133207, India
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Ye L, Hu P, Feng LP, Huang LL, Wang Y, Yan X, Xiong J, Xia HL. Protective Effects of Ferulic Acid on Metabolic Syndrome: A Comprehensive Review. Molecules 2022; 28:molecules28010281. [PMID: 36615475 PMCID: PMC9821889 DOI: 10.3390/molecules28010281] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 11/27/2022] [Accepted: 12/14/2022] [Indexed: 12/31/2022] Open
Abstract
Metabolic syndrome (MetS) is a complex disease in which protein, fat, carbohydrates and other substances are metabolized in a disorderly way. Ferulic acid (FA) is a phenolic acid found in many vegetables, fruits, cereals and Chinese herbs that has a strong effect on ameliorating MetS. However, no review has summarized the mechanisms of FA in treating MetS. This review collected articles related to the effects of FA on ameliorating the common symptoms of MetS, such as diabetes, hyperlipidemia, hypertension and obesity, from different sources involving Web of Science, PubMed and Google Scholar, etc. This review summarizes the potential mechanisms of FA in improving various metabolic disorders according to the collected articles. FA ameliorates diabetes via the inhibition of the expressions of PEPCK, G6Pase and GP, the upregulation of the expressions of GK and GS, and the activation of the PI3K/Akt/GLUT4 signaling pathway. The decrease of blood pressure is related to the endothelial function of the aortas and RAAS. The improvement of the lipid spectrum is mediated via the suppression of the HMG-Co A reductase, by promoting the ACSL1 expression and by the regulation of the factors associated with lipid metabolism. Furthermore, FA inhibits obesity by upregulating the MEK/ERK pathway, the MAPK pathway and the AMPK signaling pathway and by inhibiting SREBP-1 expression. This review can be helpful for the development of FA as an appreciable agent for MetS treatment.
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Affiliation(s)
- Lei Ye
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Pan Hu
- Chengdu Institute of Chinese Herbal Medicine, Chengdu 610016, China
- Correspondence: (P.H.); (H.-L.X.); Tel.: +86-182-2442-7340 (P.H.); +86-135-6889-9011 (H.-L.X.)
| | - Li-Ping Feng
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Li-Lu Huang
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Yi Wang
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Xin Yan
- Chengdu Institute of Chinese Herbal Medicine, Chengdu 610016, China
| | - Jing Xiong
- Chengdu Institute of Chinese Herbal Medicine, Chengdu 610016, China
| | - Hou-Lin Xia
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
- Correspondence: (P.H.); (H.-L.X.); Tel.: +86-182-2442-7340 (P.H.); +86-135-6889-9011 (H.-L.X.)
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17
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Zhang D, Jing B, Chen Z, Li X, Shi H, Zheng Y, Chang S, Zhao G. Ferulic acid alleviates sciatica by inhibiting peripheral sensitization through the RhoA/p38MAPK signalling pathway. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 106:154420. [PMID: 36115115 DOI: 10.1016/j.phymed.2022.154420] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Revised: 08/18/2022] [Accepted: 08/26/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND Nonsteroidal anti-inflammatory drugs are used to relieve sciatica, but their effects are not satisfactory. PURPOSE This study aimed to explore the therapeutic effects of ferulic acid on sciatica. METHODS Thirty-two SD rats were randomly divided into 4 groups, i.e., sham operation group, chronic constriction injury (CCI) group, mecobalamin group, and ferulic acid group. We conducted behavioural tests, ELISA, PCR, Western blots, and immunofluorescence analysis. Specific inhibitors were used in cell experiments to explore the related mechanisms. RESULTS Thermal hyperalgesia was induced after CCI operation, and ferulic acid relieved thermal hyperalgesia. In addition, ferulic acid decreased the IL1β, IL6, TNF-α, and CRP mRNA levels; the IBA-1, iNOS, IL1β, RhoA, RhoA-GTP, COX2, Rock1, TRPV1, TRPA1, and p-p38MAPK levels in dorsal root ganglion (DRG) neurons; and the LPS, CRP, substance P (SP), and prostaglandin E2 (PGE2) levels in serum, and these levels were higher in the CCI group. In the cell experiments, LPS induced M1 polarization of GMI-R1 cells via the RhoA/Rock pathway. Ferulic acid attenuated LPS-induced M1 polarization by decreasing the levels of M1 polarization markers, including IL1β, IL6, TNF-α, iNOS, and CD32, and increased M2 polarization by increasing the levels of M2 polarization markers, including CD206 and Arg-1. LPS treatment clearly increased the iNOS, IL1β, RhoA, Rock1, Rock2 and p-p38 MAPK levels and reduced Arg-1 expression, and ferulic acid reversed these changes. CONCLUSION Ferulic acid can inhibit peripheral sensitization by reducing the levels of inflammatory factors, TRPA1 and TRPV1 through the RhoA/p38 MAPK pathway to alleviate sciatica.
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Affiliation(s)
- Di Zhang
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, China.
| | - Bei Jing
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Zhenni Chen
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Xin Li
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Huimei Shi
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Yachun Zheng
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Shiquan Chang
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Guoping Zhao
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, China.
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Li X, Wu J, Xu F, Chu C, Li X, Shi X, Zheng W, Wang Z, Jia Y, Xiao W. Use of Ferulic Acid in the Management of Diabetes Mellitus and Its Complications. Molecules 2022; 27:molecules27186010. [PMID: 36144745 PMCID: PMC9503003 DOI: 10.3390/molecules27186010] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Revised: 09/05/2022] [Accepted: 09/13/2022] [Indexed: 12/06/2022] Open
Abstract
Diabetes mellitus, a metabolic disease mainly characterized by hyperglycemia, is becoming a serious social health problem worldwide with growing prevalence. Many natural compounds have been found to be effective in the prevention and treatment of diabetes, with negligible toxic effects. Ferulic acid (FA), a phenolic compound commonly found in medicinal herbs and the daily diet, was proved to have several pharmacological effects such as antihyperglycemic, antihyperlipidemic and antioxidant actions, which are beneficial to the management of diabetes and its complications. Data from PubMed, EM-BASE, Web of Science and CNKI were searched with the keywords ferulic acid and diabetes mellitus. Finally, 28 articles were identified after literature screening, and the research progress of FA for the management of DM and its complications was summarized in the review, in order to provide references for further research and medical applications of FA.
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Affiliation(s)
- Xu Li
- Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, China
| | - Jingxian Wu
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Fanxing Xu
- Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, China
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Chun Chu
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Xiang Li
- School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Xinyi Shi
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Wen Zheng
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Zhenzhong Wang
- Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, China
| | - Ying Jia
- Faculty of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang 110016, China
- Correspondence: (Y.J.); (W.X.)
| | - Wei Xiao
- Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, China
- Correspondence: (Y.J.); (W.X.)
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Ghazipour AM, Pourheydar B, Naderi R. The effect of tropisetron on peripheral diabetic neuropathy: possible protective actions against inflammation and apoptosis. Cell Stress Chaperones 2022; 27:513-521. [PMID: 35972643 PMCID: PMC9485520 DOI: 10.1007/s12192-022-01287-9] [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: 02/04/2022] [Revised: 06/21/2022] [Accepted: 06/22/2022] [Indexed: 11/03/2022] Open
Abstract
Diabetic peripheral neuropathy (DPN) is a common nerve disorder of diabetes. The aim of this study was to explore the protective effects of tropisetron in DPN. Type 1 diabetes was created by a single injection of streptozotocin (50 mg/kg, ip). Tropisetron (3 mg/kg, ip) was administered daily for 2 weeks. Our analysis showed that nerve fibers and their myelin sheaths were thinned with decreased myelinated fiber number in diabetic animals. The intensity of Bcl-2 staining decreased and the intensity of Bax staining increased in the sciatic nerves of diabetic rats by using immunohistochemical staining. Furthermore, diabetes significantly increased tumor necrosis factor-alpha, interleukin 1-β (TNFα and IL-1β) and Bax/Bcl-2 ratio in sciatic nerves of rats. However, intraperitoneal injection of tropisetron significantly reversed these alterations induced by diabetes. These findings suggest that tropisetron attenuates diabetes-induced peripheral nerve injury through its anti-inflammatory and anti-apoptotic effects, and may provide a novel therapeutic strategy to ameliorate the process of peripheral neuropathy in diabetes.
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Affiliation(s)
| | - Bagher Pourheydar
- Neurophysiology Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran
- Department of Anatomical Sciences, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Roya Naderi
- Neurophysiology Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran.
- Department of Physiology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
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Dhaliwal J, Dhaliwal N, Akhtar A, Kuhad A, Chopra K. Tetramethylpyrazine Attenuates Cognitive Impairment Via Suppressing Oxidative Stress, Neuroinflammation, and Apoptosis in Type 2 Diabetic Rats. Neurochem Res 2022; 47:2431-2444. [PMID: 35665448 DOI: 10.1007/s11064-022-03640-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 05/14/2022] [Accepted: 05/17/2022] [Indexed: 10/18/2022]
Abstract
Cognitive dysfunction is an important complication observed in type 2 diabetes mellitus (T2DM) patients. Tetramethylpyrazine (TMP) is known to exhibit anti-diabetic and neuroprotective properties. Therefore, the present study aimed to investigate the possible therapeutic effects of TMP against type 2 diabetes-associated cognitive impairment in rats. High-fat diet (HFD) followed by a low dose of streptozotocin (35 mg/kg) was used to induce diabetes in Sprague-Dawley rats. TMP (20, 40, and 80 mg/kg) and Pioglitazone (10 mg/kg) were administered for 4 weeks. The Morris water maze (MWM) and novel objective recognition task (NOR) tests were used to assess memory function. Fasting blood glucose (FBG), lipid profile, HOMA-IR, glycosylated hemoglobin (HbA1c), and glucose tolerance were measured. Acetylcholinesterase (AChE) and choline acetytransferase (ChAT) activity, acetylcholine (ACh) levels, oxidative stress, apoptotic (Bcl-2, Bax, caspase-3), and inflammatory markers (TNF-α, IL-1β, and NF-kβ) were assessed. BDNF, p-AKT, and p-CREB levels were also measured. In the present work, we observed that treatment of diabetic rats with TMP alleviated learning and memory deficits, improved insulin sensitivity, and attenuated hyperglycemia and dyslipidemia. Furthermore, treatment with TMP increased BDNF, p-Akt, and p-CREB levels, normalized cholinergic dysfunction, and suppressed oxidative, inflammatory, and apoptotic markers in the hippocampus. Collectively, our results suggest that the TMP may be an effective neuroprotective agent in alleviating type 2 diabetes-associated cognitive deficits.
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Affiliation(s)
- Jatinder Dhaliwal
- Pharmacology Division, University Institute of Pharmaceutical Sciences (UIPS), Panjab University, Chandigarh, 160014, India
| | - Navneet Dhaliwal
- Pharmacology Division, University Institute of Pharmaceutical Sciences (UIPS), Panjab University, Chandigarh, 160014, India
| | - Ansab Akhtar
- Pharmacology Division, University Institute of Pharmaceutical Sciences (UIPS), Panjab University, Chandigarh, 160014, India
| | - Anurag Kuhad
- Pharmacology Division, University Institute of Pharmaceutical Sciences (UIPS), Panjab University, Chandigarh, 160014, India
| | - Kanwaljit Chopra
- Pharmacology Division, University Institute of Pharmaceutical Sciences (UIPS), Panjab University, Chandigarh, 160014, India.
- Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences (UIPS), UGC Centre of Advanced Studies, Panjab University, Chandigarh, 160 014, India.
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21
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Ullah R, Badshah W, Ali G, Ullah A, Khan SU, Ahmad N, Shahid M, Naveed M, Ullah S, Bangash SA, Althobaiti YS. Cassia artemisiodes attenuates nociceptive and diabetes-induced neuropathic pain modalities apropos antioxidant and anti-inflammatory mechanisms. Biomed Pharmacother 2022; 149:112834. [PMID: 35339108 DOI: 10.1016/j.biopha.2022.112834] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Revised: 03/15/2022] [Accepted: 03/16/2022] [Indexed: 11/02/2022] Open
Abstract
Cassia plants have a considerable position in conventional systems of medicine. The possible anti-nociceptive, anti-inflammatory, and anti-neuropathic properties of Cassia artemisiodes (CAD) extract were tested using the standard animal models. In this study, in vitro antioxidant, cyclooxygenase (COX-1 and 2), and 5-lipoxygenase (5-LOX) inhibitory assays were performed. The anti-inflammatory activity was evaluated using carrageenan, histamine, and serotonin-induced paw edema models. Antipyretic activity, thermally and chemically-induced nociception, and naloxone antagonistic activities were carried out. The CAD extract was tested for anti-neuropathic activity in the streptozotocin-induced diabetic neuropathy model. Suppressing the effect of CAD extract on the mRNA level of inducible nitric oxide synthase (iNOS), COX-2, and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) was determined by performing RT-PCR. The CAD extract inhibited COX-2 and 5-LOX enzymes, paw inflammation, and reduced nociceptive behaviors. The mRNA gene expression of iNOS, COX-2, and inflammatory cytokines was reduced significantly with increased DPPH scavenging activity. The extract significantly reduced the diabetes-induced neuropathic pain. In a nutshell, these results recommended that the CAD extract has anti-nociceptive and anti-neuropathic activities due to inhibition of inflammatory and oxidative signaling.
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Affiliation(s)
- Rahim Ullah
- Faculty of Life Science, Department of Pharmacy Sarhad University of Science and Information Technology, Peshawar, Khyber Pakhtunkhwa, Pakistan; Department of Pharmacy, University of Peshawar, Peshawar 25120, Khyber Pakhtunkhwa, Pakistan.
| | - Waseem Badshah
- Department of Pharmacy, Abdul Wali Khan University, Mardan, Khyber Pakhtunkhwa, Pakistan.
| | - Gowhar Ali
- Department of Pharmacy, University of Peshawar, Peshawar 25120, Khyber Pakhtunkhwa, Pakistan; The Ken and Ruth Davee Department of Neurology and Clinical Neurosciences Northwestern University Feinberg School of Medicine, Tarry Building, Room 13-715 300 East Superior St., Chicago IL 60611, USA.
| | - Aman Ullah
- College of Pharmaceutical Sciences, Shifa Tameer-e-Millat University, Islamabad 44000, Pakistan.
| | - Saleem Ullah Khan
- Department of Pharmacy, Abdul Wali Khan University, Mardan, Khyber Pakhtunkhwa, Pakistan.
| | - Nisar Ahmad
- Faculty of Pharmacy, Grand Asian University Sialkot, Punjab, Pakistan.
| | - Muhammad Shahid
- Department of Pharmacy, Institute of Integrative Biosciences, CECOS University of IT and Emerging Sciences, Peshawar, Khyber Pakhtunkhwa, Pakistan.
| | - Muhammad Naveed
- Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
| | - Sami Ullah
- Department of Pharmacy, University of Peshawar, Peshawar 25120, Khyber Pakhtunkhwa, Pakistan.
| | - Sudhair Abbas Bangash
- Faculty of Life Science, Department of Pharmacy Sarhad University of Science and Information Technology, Peshawar, Khyber Pakhtunkhwa, Pakistan.
| | - Yusuf S Althobaiti
- Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia; Addiction and Neuroscience Research Unit, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
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22
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Garcia-Gonzalez MA, Vallejo-Ruiz V, Atonal-Flores F, Flores-Hernandez J, Torres-Ramírez O, Diaz-Fonsecae A, Perez Vizcaino F, Lopez-Lopez JG. Sildenafil prevents right ventricular hypertrophy and improves heart rate variability in rats with pulmonary hypertension secondary to experimental diabetes. Clin Exp Hypertens 2022; 44:355-365. [DOI: 10.1080/10641963.2022.2050743] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Affiliation(s)
- Miguel Angel Garcia-Gonzalez
- Departamento de Farmacia, Benemerita Universidad Autonoma de Puebla, Laboratorio de Farmacia Clinica, Edificio FCQ10, Ciudad Universitaria, Col. Jardines de San Manuel, Puebla, Mexico
| | - Veronica Vallejo-Ruiz
- Instituto Mexicano del Seguro Social, Centro de Investigación Biomédica de Oriente, Laboratorio de Biología Molecular, Puebla, Mexico
| | - Fausto Atonal-Flores
- Departamento de Fisiología, Benemérita Universidad Autónoma de Puebla, Facultad de Medicina, Metepec, Mexico
| | - Jorge Flores-Hernandez
- Laboratorio de Neuromodulación, Benemerita Universidad Autonoma de Puebla, Fisiología, Puebla,Mexico
| | - Oswaldo Torres-Ramírez
- Departamento de Farmacia, Benemérita Universidad Autónoma de Puebla, Facultad de Ciencias Químicas, Puebla, Mexico
| | - Alfonso Diaz-Fonsecae
- Departamento de Farmacia, Benemérita Universidad Autónoma de Puebla, Facultad de Ciencias Químicas, Puebla, Mexico
| | - Francisco Perez Vizcaino
- Departamento de Farmacología y Toxicología, Universidad Complutense de Madrid, Escuela de Medicina, Puebla,Mexico
| | - Jose Gustavo Lopez-Lopez
- Departamento de Farmacia, Benemerita Universidad Autonoma de Puebla, Laboratorio de Farmacia Clinica, Edificio FCQ10, Ciudad Universitaria, Col. Jardines de San Manuel, Puebla, Mexico
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23
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Shoaib A, Azmi L, Pal S, Alqahtani SS, Rahamathulla M, Hani U, Alshehri S, Ghoneim MM, Shakeel F. Integrating nanotechnology with naturally occurring phytochemicals in neuropathy induced by diabetes. J Mol Liq 2022. [DOI: 10.1016/j.molliq.2021.118189] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
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24
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The Use of Bioactive Compounds in Hyperglycemia- and Amyloid Fibrils-Induced Toxicity in Type 2 Diabetes and Alzheimer’s Disease. Pharmaceutics 2022; 14:pharmaceutics14020235. [PMID: 35213966 PMCID: PMC8879577 DOI: 10.3390/pharmaceutics14020235] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 01/14/2022] [Accepted: 01/19/2022] [Indexed: 12/29/2022] Open
Abstract
It has become increasingly apparent that defective insulin signaling may increase the risk for developing Alzheimer’s disease (AD), influence neurodegeneration through promotion of amyloid formation or by increasing inflammatory responses to intraneuronal β-amyloid. Recent work has demonstrated that hyperglycemia is linked to cognitive decline, with elevated levels of glucose causing oxidative stress in vulnerable tissues such as the brain. The ability of β-amyloid peptide to form β-sheet-rich aggregates and induce apoptosis has made amyloid fibrils a leading target for the development of novel pharmacotherapies used in managing and treatment of neuropathological conditions such as AD-related cognitive decline. Additionally, deposits of β-sheets folded amylin, a glucose homeostasis regulator, are also present in diabetic patients. Thus, therapeutic compounds capable of reducing intracellular protein aggregation in models of neurodegenerative disorders may prove useful in ameliorating type 2 diabetes mellitus symptoms. Furthermore, both diabetes and neurodegenerative conditions, such as AD, are characterized by chronic inflammatory responses accompanied by the presence of dysregulated inflammatory biomarkers. This review presents current evidence describing the role of various small bioactive molecules known to ameliorate amyloidosis and subsequent effects in prevention and development of diabetes and AD. It also highlights the potential efficacy of peptide–drug conjugates capable of targeting intracellular targets.
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25
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Singh SSB, Patil KN. Trans-ferulic acid attenuates hyperglycemia-induced oxidative stress and modulates glucose metabolism by activating AMPK signaling pathway in vitro. J Food Biochem 2022; 46:e14038. [PMID: 34981525 DOI: 10.1111/jfbc.14038] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 11/04/2021] [Accepted: 11/08/2021] [Indexed: 12/15/2022]
Abstract
Adenosine monophosphate-activated protein kinase (AMPK) is a potent metabolic regulator and an attractive target for antidiabetic activators. Here we report for the first that, trans-ferulic acid (TFA) is a potent dietary bioactive molecule of hydroxycinnamic acid derivative for the activation of AMPK with a maximum increase in phosphorylation (2.71/2.67 ± 0.10; p < .001 vs. high glucose [HG] control) in hyperglycemia-induced human liver cells (HepG2) and rat skeletal muscle cells (L6), where HG suppresses the AMPK pathway. It was also observed that TFA increased activation of AMPK in a dose- and time-dependent manner and also increased the phosphorylation of acetyl-CoA carboxylase (ACC), suggesting that it may promotes fatty acid oxidation; however, pretreatment with compound C reversed the effect. In addition, TFA reduced the level of intracellular reactive oxygen species (ROS) and nitric oxide (NO) induced by hyperglycemia and subsequently increased the level of glutathione. Interestingly, TFA also upregulated the glucose transporters, GLUT2 and GLUT4, and inhibited c-Jun N-terminal protein kinase (JNK1/2) by decreasing the phosphorylation level in tested cells under HG condition. Our studies provide critical insights into the mechanism of action of TFA as a potential natural activator of AMPK under hyperglycemia. PRACTICAL APPLICATIONS: Hydroxycinnamic acid derivatives possess various pharmacological properties and are found to be one of the most ubiquitous groups of plant metabolites in almost all dietary sources. However, the tissue-specific role and its mechanism under hyperglycemic condition remain largely unknown. The present study showed that TFA is a potent activator of AMPK under HG condition and it could be used as a therapeutic agent against hyperglycemia in type 2 diabetes.
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Affiliation(s)
- Sangeetha S B Singh
- Department of Protein Chemistry and Technology, Council of Scientific & Industrial Research-Central Food Technological Research Institute (CSIR-CFTRI), Mysore, India.,Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
| | - K Neelakanteshwar Patil
- Department of Protein Chemistry and Technology, Council of Scientific & Industrial Research-Central Food Technological Research Institute (CSIR-CFTRI), Mysore, India.,Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
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26
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Hu Y, Wang J, Zeng S, Chen M, Zou G, Li Y, Zhu L, Xu J. Association Between Serum Albumin Levels and Diabetic Peripheral Neuropathy Among Patients with Type 2 Diabetes: Effect Modification of Body Mass Index. Diabetes Metab Syndr Obes 2022; 15:527-534. [PMID: 35228809 PMCID: PMC8881928 DOI: 10.2147/dmso.s347349] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Accepted: 01/18/2022] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND The role of serum albumin in the risk of diabetic peripheral neuropathy (DPN) remains unclear. This study aimed to explore the relationship between serum albumin level and DPN, and to examine any possible effect modifiers among patients with type 2 diabetes mellitus. METHODS This cross-sectional study was conducted in Jiangxi, China, from May 2012 to December 2014. Serum albumin levels were determined in 523 subjects, and the association between serum albumin level and DPN was evaluated using linear regression models (odds ratio [OR] and corresponding 95% confidence interval [CI]). RESULTS There was a significant inverse association between serum albumin level (per 1 g/L increment, OR 0.95 [95% CI 0.92-0.98]) and the risk of DPN. Accordingly, when serum albumin was assessed as quartiles, a significantly lower risk of DPN was found in participants in quartile 4 (OR 0.49 [95% CI 0.25-0.95]), compared with those in quartile 1. Consistently, higher albumin levels (≥35 g/L) were associated with decreased odds for DPN (OR 0.36 [95% CI 0.17-0.74]) compared with lower levels. Furthermore, the albumin-DPN association was significantly stronger in patients with a relatively high body mass index (BMI; ≥24 kg/m2; OR 0.91 [95% CI 0.85-0.98]) than in those with a low BMI (<24 kg/m2; OR 0.99 [95% CI 0.94-1.04]; P for interaction = 0.042). CONCLUSION These data suggest that serum albumin level could be a novel risk factor for DPN among patients with type 2 diabetes and relatively high BMI (>24 kg/m2).
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Affiliation(s)
- Ying Hu
- Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China
- Jiangxi Clinical Research Center for Endocrine and Metabolic Disease, Nanchang, Jiangxi, 330006, People's Republic of China
- Jiangxi Branch of National Clinical Research Center for Metabolic Disease, Nanchang, JIangxi, 330006, People's Republic of China
| | - Jiancheng Wang
- Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China
- Jiangxi Clinical Research Center for Endocrine and Metabolic Disease, Nanchang, Jiangxi, 330006, People's Republic of China
- Jiangxi Branch of National Clinical Research Center for Metabolic Disease, Nanchang, JIangxi, 330006, People's Republic of China
| | - Sha Zeng
- Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China
- Jiangxi Clinical Research Center for Endocrine and Metabolic Disease, Nanchang, Jiangxi, 330006, People's Republic of China
- Jiangxi Branch of National Clinical Research Center for Metabolic Disease, Nanchang, JIangxi, 330006, People's Republic of China
| | - Mengxia Chen
- Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China
- Jiangxi Clinical Research Center for Endocrine and Metabolic Disease, Nanchang, Jiangxi, 330006, People's Republic of China
- Jiangxi Branch of National Clinical Research Center for Metabolic Disease, Nanchang, JIangxi, 330006, People's Republic of China
| | - Guilin Zou
- Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China
- Jiangxi Clinical Research Center for Endocrine and Metabolic Disease, Nanchang, Jiangxi, 330006, People's Republic of China
- Jiangxi Branch of National Clinical Research Center for Metabolic Disease, Nanchang, JIangxi, 330006, People's Republic of China
| | - Yuxia Li
- Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China
- Jiangxi Clinical Research Center for Endocrine and Metabolic Disease, Nanchang, Jiangxi, 330006, People's Republic of China
- Jiangxi Branch of National Clinical Research Center for Metabolic Disease, Nanchang, JIangxi, 330006, People's Republic of China
| | - Lingyan Zhu
- Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China
- Jiangxi Clinical Research Center for Endocrine and Metabolic Disease, Nanchang, Jiangxi, 330006, People's Republic of China
- Jiangxi Branch of National Clinical Research Center for Metabolic Disease, Nanchang, JIangxi, 330006, People's Republic of China
| | - Jixiong Xu
- Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China
- Jiangxi Clinical Research Center for Endocrine and Metabolic Disease, Nanchang, Jiangxi, 330006, People's Republic of China
- Jiangxi Branch of National Clinical Research Center for Metabolic Disease, Nanchang, JIangxi, 330006, People's Republic of China
- Correspondence: Jixiong Xu; Jiancheng Wang, Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang University, No. 17, Yongwaizheng Street, Nanchang, Jiangxi, 330006, People’s Republic of China,Tel/Fax +86-791-86836960, Email ;
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27
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Chen Y, Qie X, Quan W, Zeng M, Qin F, Chen J, Adhikari B, He Z. Omnifarious fruit polyphenols: an omnipotent strategy to prevent and intervene diabetes and related complication? Crit Rev Food Sci Nutr 2021:1-37. [PMID: 34792409 DOI: 10.1080/10408398.2021.2000932] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Diabetes mellitus is a metabolic syndrome which cannot be cured. Recently, considerable interest has been focused on food ingredients to prevent and intervene in complications of diabetes. Polyphenolic compounds are one of the bioactive phytochemical constituents with various biological activities, which have drawn increasing interest in human health. Fruits are part of the polyphenol sources in daily food consumption. Fruit-derived polyphenols possess the anti-diabetic activity that has already been proved either from in vitro studies or in vivo studies. The mechanisms of fruit polyphenols in treating diabetes and related complications are under discussion. This is a comprehensive review on polyphenols from the edible parts of fruits, including those from citrus, berries, apples, cherries, mangoes, mangosteens, pomegranates, and other fruits regarding their potential benefits in preventing and treating diabetes mellitus. The signal pathways of characteristic polyphenols derived from fruits in reducing high blood glucose and intervening hyperglycemia-induced diabetic complications were summarized.
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Affiliation(s)
- Yao Chen
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China.,International Joint Laboratory on Food Safety, Jiangnan University, Wuxi, Jiangsu, China
| | - Xuejiao Qie
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China.,International Joint Laboratory on Food Safety, Jiangnan University, Wuxi, Jiangsu, China
| | - Wei Quan
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China.,International Joint Laboratory on Food Safety, Jiangnan University, Wuxi, Jiangsu, China
| | - Maomao Zeng
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China.,International Joint Laboratory on Food Safety, Jiangnan University, Wuxi, Jiangsu, China
| | - Fang Qin
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China.,International Joint Laboratory on Food Safety, Jiangnan University, Wuxi, Jiangsu, China
| | - Jie Chen
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China.,International Joint Laboratory on Food Safety, Jiangnan University, Wuxi, Jiangsu, China
| | - Benu Adhikari
- School of Science, RMIT University, Melbourne, Victoria, Australia
| | - Zhiyong He
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China.,International Joint Laboratory on Food Safety, Jiangnan University, Wuxi, Jiangsu, China
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28
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Lal R, Dhaliwal J, Dhaliwal N, Dharavath RN, Chopra K. Activation of the Nrf2/HO-1 signaling pathway by dimethyl fumarate ameliorates complete Freund's adjuvant-induced arthritis in rats. Eur J Pharmacol 2021; 899:174044. [PMID: 33745959 DOI: 10.1016/j.ejphar.2021.174044] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Revised: 03/08/2021] [Accepted: 03/15/2021] [Indexed: 12/13/2022]
Abstract
The nuclear factor erythroid 2-related factor (Nrf2) signaling pathway has recently emerged as a novel therapeutic target in treating various diseases. Therefore, the present study aimed to assess the protective role of the Nrf2 activator, dimethyl fumarate (DMF) in the complete Freund's adjuvant (CFA)- induced arthritis model. DMF (25, 50, and 100 mg/kg) and dexamethasone (2 mg/kg) were orally administered for 14 days. Pain-related tests, paw volume, and arthritic scores were measured weekly. Serum TNF-α, IL-1β, cyclic citrullinated peptide (CCP), C-reactive protein (CRP), and rheumatoid factor (RF) levels were estimated. Nitrite, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione (GSH), catalase (CAT), and myeloperoxidase (MPO) levels were also evaluated. NF-κB, Nrf2, HO-1, and COX-2 levels were estimated in the joint tissue. DMF treatment exerted anti-arthritic activity by enhancing the nociceptive threshold, improving arthritis scores, and reducing paw edema. Also, DMF suppressed changes in oxidative stress markers and inflammatory mediators and enhanced Nrf2 and HO-1 levels in CFA-injected rats. These findings indicate that the anti-arthritic activity of DMF may be mediated by the activation of the Nrf2/HO-1 pathway, which reduced oxidative damage and inflammation.
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Affiliation(s)
- Roshan Lal
- Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences (UIPS), Panjab University, Chandigarh, 160014, India
| | - Jatinder Dhaliwal
- Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences (UIPS), Panjab University, Chandigarh, 160014, India
| | - Navneet Dhaliwal
- Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences (UIPS), Panjab University, Chandigarh, 160014, India
| | - Ravinder Naik Dharavath
- Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences (UIPS), Panjab University, Chandigarh, 160014, India
| | - Kanwaljit Chopra
- Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences (UIPS), Panjab University, Chandigarh, 160014, India.
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