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Banjan B, Raju R, Keshava Prasad TS, Abhinand CS. Computational identification of potential bioactive compounds from Triphala against alcoholic liver injury by targeting alcohol dehydrogenase. Mol Divers 2025; 29:623-638. [PMID: 38743308 DOI: 10.1007/s11030-024-10879-9] [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: 03/14/2024] [Accepted: 04/15/2024] [Indexed: 05/16/2024]
Abstract
Alcoholic liver injury resulting from excessive alcohol consumption is a significant social concern. Alcohol dehydrogenase (ADH) plays a critical role in the conversion of alcohol to acetaldehyde, leading to tissue damage. The management of alcoholic liver injury encompasses nutritional support and, in severe cases liver transplantation, but potential adverse effects exist, and effective medications are currently unavailable. Natural products with their potential benefits and historical use in traditional medicine emerge as promising alternatives. Triphala, a traditional polyherbal formula demonstrates beneficial effects in addressing diverse health concerns, with a notable impact on treating alcoholic liver damage through enhanced liver metabolism. The present study aims to identify potential active phytocompounds in Triphala targeting ADH to prevent alcoholic liver injury. Screening 119 phytocompounds from the Triphala formulation revealed 62 of them showing binding affinity to the active site of the ADH1B protein. Promising lipid-like molecule from Terminalia bellirica, (4aS, 6aR, 6aR, 6bR, 7R, 8aR, 9R, 10R, 11R, 12aR, 14bS)-7, 10, 11-trihydroxy-9-(hydroxymethyl)-2, 2, 6a, 6b, 9, 12a-hexamethyl-1, 3, 4, 5, 6, 6a, 7, 8, 8a, 10, 11, 12, 13, 14b-tetradecahydropicene-4a-carboxylic acid showed high binding efficiency to a competitive ADH inhibitor, 4-Methylpyrazole. Pharmacokinetic analysis further confirmed the drug-likeness and non-hepatotoxicity of the top-ranked compound. Molecular dynamics simulation and MM-PBSA studies revealed the stability of the docked complexes with minimal fluctuation and consistency of the hydrogen bonds throughout the simulation. Together, computational investigations suggest that (4aS, 6aR, 6aR, 6bR, 7R, 8aR, 9R, 10R, 11R, 12aR, 14bS)-7, 10, 11-trihydroxy-9-(hydroxymethyl)-2, 2, 6a, 6b, 9, 12a-hexamethyl-1, 3, 4, 5, 6, 6a, 7, 8, 8a, 10, 11, 12, 13, 14b-tetradecahydropicene-4a-carboxylic acid from the Triphala formulation holds promise as an ADH inhibitor, suggesting an alternative therapy for alcoholic liver injury.
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Affiliation(s)
- Bhavya Banjan
- Centre for Integrative Omics Data Science, Yenepoya (Deemed to be University), Mangalore, 575018, India
| | - Rajesh Raju
- Centre for Integrative Omics Data Science, Yenepoya (Deemed to be University), Mangalore, 575018, India
| | - Thottethodi Subrahmanya Keshava Prasad
- Center for Systems Biology and Molecular Medicine (CSBMM), Yenepoya Research Centre, Yenepoya (Deemed to be University), Deralakatte, Mangalore, Karnataka, 575018, India
| | - Chandran S Abhinand
- Center for Systems Biology and Molecular Medicine (CSBMM), Yenepoya Research Centre, Yenepoya (Deemed to be University), Deralakatte, Mangalore, Karnataka, 575018, India.
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Fayed RH, Ali SE, Yassin AM, Madian K, Bawish BM. Terminalia bellirica and Andrographis paniculata dietary supplementation in mitigating heat stress-induced behavioral, metabolic and genetic alterations in broiler chickens. BMC Vet Res 2024; 20:388. [PMID: 39227945 PMCID: PMC11370032 DOI: 10.1186/s12917-024-04233-2] [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: 05/24/2024] [Accepted: 08/12/2024] [Indexed: 09/05/2024] Open
Abstract
BACKGROUND Heat stress (HS) is one of the most significant environmental stressors on poultry production and welfare worldwide. Identification of innovative and effective solutions is necessary. This study evaluated the effects of phytogenic feed additives (PHY) containing Terminalia bellirica and Andrographis paniculata on behavioral patterns, hematological and biochemical parameters, Oxidative stress biomarkers, and HSP70, I-FABP2, IL10, TLR4, and mTOR genes expression in different organs of broiler chickens under chronic HS conditions. A total of 208 one-day-old Avian-480 broiler chicks were randomly allocated into four treatments (4 replicate/treatment, 52 birds/treatment): Thermoneutral control treatment (TN, fed basal diet); Thermoneutral treatment (TN, fed basal diet + 1 kg/ton feed PHY); Heat stress treatment (HS, fed basal diet); Heat stress treatment (HS, fed basal diet + 1 kg/ton feed PHY). RESULTS The findings of the study indicate that HS led to a decrease in feeding, foraging, walking, and comfort behavior while increasing drinking and resting behavior, also HS increased red, and white blood cells (RBCs and WBCs) counts, and the heterophile/ lymphocyte (H/L) ratio (P < 0.05); while both mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) were decreased (P < 0.05). In addition, HS negatively impacted lipid, protein, and glucose levels, liver and kidney function tests, and oxidative biomarkers by increasing malondialdehyde (MDA) levels and decreasing reduced glutathion (GSH) activity (P < 0.05). Heat stress (HS) caused the upregulation in HSP70, duodenal TLR4 gene expression, and the downregulation of I-FABP2, IL10, mTOR in all investigated tissues, and hepatic TLR4 (P < 0.05) compared with the TN treatment. Phytogenic feed additives (PHY) effectively mitigated heat stress's negative impacts on broilers via an improvement of broilers' behavior, hematological, biochemical, and oxidative stress biomarkers with a marked decrease in HSP70 expression levels while all tissues showed increased I-FABP2, IL10, TLR4, and mTOR (except liver) levels (P < 0.05). CONCLUSION Phytogenic feed additives (PHY) containing Terminalia bellirica and Andrographis paniculata have ameliorated the HS-induced oxidative stress and improved the immunity as well as the gut health and welfare of broiler chickens.
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Affiliation(s)
- Rabie H Fayed
- Department of Veterinary Hygiene and Management, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt
| | - Sara E Ali
- Department of Physiology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt
| | - Aya M Yassin
- Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt.
| | - K Madian
- Department of Poultry Diseases, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt
| | - Basma M Bawish
- Department of Veterinary Hygiene and Management, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt
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Borges ALS, Bittar VP, Justino AB, Carrillo MSP, Duarte RFM, Silva NBS, Gonçalves DS, Prado DG, Araújo IAC, Martins MM, Motta LC, Martins CHG, Botelho FV, Silva NM, de Oliveira A, Romão W, Espíndola FS. Exploring the composition and properties of Centella asiatica metabolites and investigating their impact on BSA glycation, LDL oxidation and α-amylase inhibition. J Pharm Biomed Anal 2024; 245:116143. [PMID: 38678859 DOI: 10.1016/j.jpba.2024.116143] [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: 12/21/2023] [Revised: 03/26/2024] [Accepted: 03/31/2024] [Indexed: 05/01/2024]
Abstract
Centella asiatica (L.) Urb. is a small herbaceous plant belonging to the Apiaceae family that is rich in triterpenes, such as asiaticoside and madecassoside. Centella asiatica finds broad application in promoting wound healing, addressing skin disorders, and boosting both memory and cognitive function. Given its extensive therapeutic potential, this study aimed not only to investigate the Centella asiatica ethanolic extract but also to analyze the biological properties of its organic fractions, such as antioxidant antiglycation capacity, which are little explored. We also identified the main bioactive compounds through spectrometry analysis. The ethanolic extract (EE) was obtained through a static maceration for seven days, while organic fractions (HF: hexane fraction; DF: dichloromethane fraction; EAF: ethyl acetate fraction; BF: n-butanol fraction and HMF: hydromethanolic fraction) were obtained via liquid-liquid fractionation. The concentration of phenolic compounds, flavonoids, and tannins in each sample was quantified. Additionally, the antiglycation (BSA/FRU, BSA/MGO, and ARG/MGO models) and antioxidant (FRAP, ORAC, and DPPH) properties, as well as the ability to inhibit LDL oxidation and hepatic tissue peroxidation were evaluated. The inhibition of enzyme activity was also analyzed (α-amylase, α-glycosidase, acetylcholinesterase, and butyrylcholinesterase). We also evaluated the antimicrobial and cytotoxicity against RAW 264.7 macrophages. The main compounds present in the most bioactive fractions were elucidated through ESI FT-ICR MS and HPLC-ESI-MS/MS analysis. In the assessment of antioxidant capacity (FRAP, ORAC, and DPPH), the EAF and BF fractions exhibited notable results, and as they are the phenolic compounds richest fractions, they also inhibited LDL oxidation, protected the hepatic tissue from peroxidation and inhibited α-amylase activity. Regarding glycation models, the EE, EAF, BF, and HMF fractions demonstrated substantial activity in the BSA/FRU model. However, BF was the only fraction that presented non-cytotoxic activity in RAW 264.7 macrophages at all tested concentrations. In conclusion, this study provides valuable insights into the antioxidant, antiglycation, and enzymatic inhibition capacities of the ethanolic extract and organic fractions of Centella asiatica. The findings suggest that further in vivo studies, particularly focusing on the butanol fraction (BF), may be promising routes for future research and potential therapeutic applications.
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Affiliation(s)
- Ana Luiza Silva Borges
- Laboratory of Biochemistry and Molecular Biology in Institute of Biotechnology, Federal University of Uberlândia, Uberlândia, MG 38400-902, Brazil
| | - Vinícius Prado Bittar
- Laboratory of Biochemistry and Molecular Biology in Institute of Biotechnology, Federal University of Uberlândia, Uberlândia, MG 38400-902, Brazil
| | - Allisson Benatti Justino
- Laboratory of Biochemistry and Molecular Biology in Institute of Biotechnology, Federal University of Uberlândia, Uberlândia, MG 38400-902, Brazil
| | - Maria Sol Peña Carrillo
- Laboratory of Biochemistry and Molecular Biology in Institute of Biotechnology, Federal University of Uberlândia, Uberlândia, MG 38400-902, Brazil
| | - Rener Francisco Mateus Duarte
- Laboratory of Biochemistry and Molecular Biology in Institute of Biotechnology, Federal University of Uberlândia, Uberlândia, MG 38400-902, Brazil
| | - Nagela Bernadelli Sousa Silva
- Laboratory of Antimicrobial Testing, Institute of Biomedical Sciences, University of Uberlândia, Campus Umuarama, Uberlândia, MG 38405-320, Brazil
| | - Daniela Silva Gonçalves
- Laboratory of Antimicrobial Testing, Institute of Biomedical Sciences, University of Uberlândia, Campus Umuarama, Uberlândia, MG 38405-320, Brazil
| | - Diego Godina Prado
- Nucleus of Research in Natural Products (NuPPeN), Federal University of Uberlândia, Uberlândia, MG 38400-902, Brazil
| | - Iasmin Aparecida Cunha Araújo
- Laboratory of Immunoparasitology, Institute for Biomedical Sciences, Federal University of Uberlandia, Uberlândia, MG 38400-902, Brazil
| | - Mário Machado Martins
- Laboratory of Nanobiotechnology "Dr. Luiz Ricardo Goulart Filho", in Institute of Biotechnology, Federal University of Uberlândia, Uberlândia, MG 38400-902, Brazil
| | - Larissa Campos Motta
- Laboratory of Petroleum and Forensics, of the Center of Competence in Petroleum Chemistry - NCQP, Federal University of Espírito Santo (UFES), Vitória, ES 29075-910, Brazil
| | - Carlos Henrique Gomes Martins
- Laboratory of Antimicrobial Testing, Institute of Biomedical Sciences, University of Uberlândia, Campus Umuarama, Uberlândia, MG 38405-320, Brazil
| | - Françoise Vasconcelos Botelho
- Laboratory of Biochemistry and Molecular Biology in Institute of Biotechnology, Federal University of Uberlândia, Uberlândia, MG 38400-902, Brazil
| | - Neide Maria Silva
- Laboratory of Immunoparasitology, Institute for Biomedical Sciences, Federal University of Uberlandia, Uberlândia, MG 38400-902, Brazil
| | - Alberto de Oliveira
- Nucleus of Research in Natural Products (NuPPeN), Federal University of Uberlândia, Uberlândia, MG 38400-902, Brazil
| | - Wanderson Romão
- Laboratory of Petroleum and Forensics, of the Center of Competence in Petroleum Chemistry - NCQP, Federal University of Espírito Santo (UFES), Vitória, ES 29075-910, Brazil; Federal Institute of Education, Science, and Technology of Espírito Santo, Vila Velha, 29106-010, Brazil
| | - Foued Salmen Espíndola
- Laboratory of Biochemistry and Molecular Biology in Institute of Biotechnology, Federal University of Uberlândia, Uberlândia, MG 38400-902, Brazil.
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Rana HK, Singh AK, Pandey AK. Therapeutic Potential of Morin Hydrate Against Rifampicin Induced Hepato and Renotoxicity in Albino Wistar Rats: Modulation of Organ Function, Oxidative Stress and Inflammatory Response. Indian J Clin Biochem 2024; 39:197-206. [PMID: 38577136 PMCID: PMC10987459 DOI: 10.1007/s12291-023-01145-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Accepted: 07/21/2023] [Indexed: 04/06/2024]
Abstract
Tuberculosis (TB) is a challenging public health issue, particularly in poor and developing countries. Rifampicin (RIF) is one of the most common first-line anti-TB drugs but it is known for its adverse effects on the hepato-renal system. The present study investigated the efficacy of morin hydrate (MH) in protecting hepato-renal damage inflicted by RIF in rats. RIF (50 mg/kg), and a combination of RIF (50 mg/kg) and MH (50 mg/kg) were administered orally for 4 weeks in rats. Silymarin (50 mg/kg) was used as a positive control. Increased levels of serological parameters such as AST, ALT, ALP, LDH, GGT, bilirubin, triglyceride, total cholesterol, urea, uric acid, creatinine, TNF-α, IFN-γ, IL-6 along with the decreased level of IL-10, total protein and albumin were used as markers of hepatic and renal injury. Oxidative damage in the tissues was measured by the increase in lipid peroxidation and decline in GSH, SOD and catalase activities. Histopathology of liver slices was used to study hepatic architecture. Four-week RIF treatment produced altered serological parameters with an increase in pro-inflammatory cytokines in serum suggesting hepatotoxicity and nephrotoxicity. The antioxidant status of the liver and kidney (increased lipid peroxidation and decline in GSH, SOD and catalase) was compromised. Cellular damage and necrosis were observed in liver slices. MH supplementation with RIF improved hepato-renal functions by restoring the serum and tissue markers towards normal values. Histological observations authenticated the results. MH supplementation also reduced the production of pro-inflammatory cytokines. Thus, the results revealed that MH provides protection against RIF-induced hepato-renal injury.
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Affiliation(s)
- Harvesh Kumar Rana
- Department of Biochemistry, University of Allahabad, Prayagraj (Allahabad), 211002 India
- Present Address: Department of Zoology, Feroze Gandhi College, Raebareli, 229001 India
| | - Amit Kumar Singh
- Department of Biochemistry, University of Allahabad, Prayagraj (Allahabad), 211002 India
- Present Address: Department of Botany, BMK Government. Girls College, Balod, Chhattisgarh 491226 India
| | - Abhay Kumar Pandey
- Department of Biochemistry, University of Allahabad, Prayagraj (Allahabad), 211002 India
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Rana HK, Singh AK, Kumar R, Pandey AK. Antitubercular drugs: possible role of natural products acting as antituberculosis medication in overcoming drug resistance and drug-induced hepatotoxicity. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:1251-1273. [PMID: 37665346 DOI: 10.1007/s00210-023-02679-z] [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: 06/07/2023] [Accepted: 08/16/2023] [Indexed: 09/05/2023]
Abstract
Mycobacterium tuberculosis (Mtb) is a pathogenic bacterium which causes tuberculosis (TB). TB control programmes are facing threats from drug resistance. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mtb strains need longer and more expensive treatment with many medications resulting in more adverse effects and decreased chances of treatment outcomes. The World Health Organization (WHO) has emphasised the development of not just new individual anti-TB drugs, but also novel medication regimens as an alternative treatment option for the drug-resistant Mtb strains. Many plants, as well as marine creatures (sponge; Haliclona sp.) and fungi, have been continuously used to treat TB in various traditional treatment systems around the world, providing an almost limitless supply of active components. Natural products, in addition to their anti-mycobacterial action, can be used as adjuvant therapy to increase the efficacy of conventional anti-mycobacterial medications, reduce their side effects, and reverse MDR Mtb strain due to Mycobacterium's genetic flexibility and environmental adaptation. Several natural compounds such as quercetin, ursolic acid, berberine, thymoquinone, curcumin, phloretin, and propolis have shown potential anti-mycobacterial efficacy and are still being explored in preclinical and clinical investigations for confirmation of their efficacy and safety as anti-TB medication. However, more high-level randomized clinical trials are desperately required. The current review provides an overview of drug-resistant TB along with the latest anti-TB medications, drug-induced hepatotoxicity and oxidative stress. Further, the role and mechanisms of action of first and second-line anti-TB drugs and new drugs have been highlighted. Finally, the role of natural compounds as anti-TB medication and hepatoprotectants have been described and their mechanisms discussed.
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Affiliation(s)
- Harvesh Kumar Rana
- Department of Biochemistry, University of Allahabad, Prayagraj (Allahabad), 211002, India
- Department of Zoology, Feroze Gandhi College, Raebareli, 229001, India
| | - Amit Kumar Singh
- Department of Biochemistry, University of Allahabad, Prayagraj (Allahabad), 211002, India
- Department of Botany, BMK Government. Girls College, Balod, Chhattisgarh, 491226, India
| | - Ramesh Kumar
- Department of Biochemistry, University of Allahabad, Prayagraj (Allahabad), 211002, India
- Department of Biochemistry, Central University of Punjab, Bathinda, Punjab, 151401, India
| | - Abhay K Pandey
- Department of Biochemistry, University of Allahabad, Prayagraj (Allahabad), 211002, India.
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Ezhilarasan D, Shree Harini K, Karthick M, Selvaraj C. Ethyl gallate concurrent administration protects against acetaminophen-induced acute liver injury in mice: An in vivo and in silico approach. Chem Biol Drug Des 2024; 103:e14369. [PMID: 37817304 DOI: 10.1111/cbdd.14369] [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: 07/31/2023] [Revised: 09/13/2023] [Accepted: 09/25/2023] [Indexed: 10/12/2023]
Abstract
Acetaminophen (APAP) in high doses causes acute liver injury and acute liver failure. Ethyl gallate (EG) is a natural polyphenol, possessing antioxidant, anti-inflammatory, and anti-microbial properties. Therefore, in this study, we evaluated the protective role of EG against APAP-induced acute liver injury in mice. Acute liver injury was induced by a single dose of APAP (400 mg/kg., i.p.). In separate groups, EG (10 mg/kg), EG (20 mg/kg), and N-acetylcysteine (NAC; 1200 mg/kg., i.p.) were administered concurrently with APAP. The mice were sacrificed after 24 h of treatment. Liver marker enzymes of hepatotoxicity, antioxidant markers, inflammatory markers, and histopathological studies were done. APAP administration caused a significant elevation of marker enzymes of hepatotoxicity and lipid peroxidation. APAP administration also decreased enzymic and nonenzymic antioxidants. Acute APAP intoxication induced nuclear factor κ B, tumor necrosis factor-α, interleukin-1, p65, and p52 and downregulated IκB gene expressions. Our histopathological studies have confirmed the presence of centrilobular necrosis, 24 h after APAP intoxication. All the above abnormalities were significantly inhibited in groups of mice that were concurrently administered with APAP + EG and APAP + NAC. Our in silico analysis further confirms that hydroxyl groups of EG interact with the above inflammatory proteins at the 3,4,5-trihydroxybenzoic acid region. These effects of EG against APAP-induced acute liver injury could be attributed to its antioxidative, free radical scavenging, and anti-inflammatory potentials. Therefore, this study suggests that EG can be an efficient therapeutic approach to protect the liver from APAP intoxication.
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Affiliation(s)
- Devaraj Ezhilarasan
- Department of Pharmacology, Hepatology and Molecular Medicine Lab, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Chennai, India
| | - Karthik Shree Harini
- Department of Pharmacology, Hepatology and Molecular Medicine Lab, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Chennai, India
| | - Munusamy Karthick
- Department of Pharmacology, Hepatology and Molecular Medicine Lab, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Chennai, India
| | - Chandrabose Selvaraj
- Department of Pharmacology, Hepatology and Molecular Medicine Lab, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Chennai, India
- Laboratory for Artificial Intelligence and Molecular Modelling, Center for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, Chennai, India
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Ganguly R, Singh SV, Jaiswal K, Kumar R, Pandey AK. Modulatory effect of caffeic acid in alleviating diabetes and associated complications. World J Diabetes 2023; 14:62-75. [PMID: 36926656 PMCID: PMC10011896 DOI: 10.4239/wjd.v14.i2.62] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2022] [Revised: 11/04/2022] [Accepted: 12/14/2022] [Indexed: 02/14/2023] Open
Abstract
Diabetes mellitus (DM) is one of the most common metabolic disorders characterized by elevated blood glucose levels. Prolonged uncontrolled hyperglycemia often leads to multi-organ damage including diabetic neuropathy, nephropathy, retinopathy, cardiovascular disorders, and diabetic foot ulcers. Excess production of free radicals causing oxidative stress in tissues is often considered to be the primary cause of onset and progression of DM and associated complications. Natural polyphenols can be used to induce or inhibit the expression of antioxidant enzymes such as glutathione peroxidase, heme oxygenase-1, superoxide dismutase, and catalase that are essential in maintaining redox balance, and ameliorate oxidative stress. Caffeic acid (CA) is a polyphenolderived from hydroxycinnamic acid and possesses numerous physiological properties includ-ing antioxidant, anti-inflammatory, anti-atherosclerotic, immune-stimulatory, cardioprotective, antiproliferative, and hepatoprotective activities. CA acts as a regulatory compound affecting numerous biochemical pathways and multiple targets. These include various transcription factors such as nuclear factor-B, tumor necrosis factor-α, interleukin-6, cyclooxygenase-2, and nuclear factor erythroid 2-related factor 2. Therefore, this review summarizes the pharmacological properties, molecular mechanisms, and pharmacokinetic profile of CA in mitigating the adverse effects of DM and associated complications. The bioavailability, drug delivery, and clinical trials of CA have also been discussed.
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Affiliation(s)
- Risha Ganguly
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, India
| | - Shiv Vardan Singh
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, India
| | - Kritika Jaiswal
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, India
| | - Ramesh Kumar
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, India
| | - Abhay K Pandey
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, India
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Singh AK, Singh SV, Kumar R, Kumar S, Senapati S, Pandey AK. Current therapeutic modalities and chemopreventive role of natural products in liver cancer: Progress and promise. World J Hepatol 2023; 15:1-18. [PMID: 36744169 PMCID: PMC9896505 DOI: 10.4254/wjh.v15.i1.1] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Revised: 07/02/2022] [Accepted: 12/21/2022] [Indexed: 01/16/2023] Open
Abstract
Liver cancer is a severe concern for public health officials since the clinical cases are increasing each year, with an estimated 5-year survival rate of 30%-35% after diagnosis. Hepatocellular carcinoma (HCC) constitutes a significant subtype of liver cancer (approximate75%) and is considered primary liver cancer. Treatment for liver cancer mainly depends on the stage of its progression, where surgery including, hepatectomy and liver transplantation, and ablation and radiotherapy are the prime choice. For advanced liver cancer, various drugs and immunotherapy are used as first-line treatment, whereas second-line treatment includes chemotherapeutic drugs from natural and synthetic origins. Sorafenib and lenvatinib are first-line therapies, while regorafenib and ramucirumab are second-line therapy. Various metabolic and signaling pathways such as Notch, JAK/ STAT, Hippo, TGF-β, and Wnt have played a critical role during HCC progression. Dysbiosis has also been implicated in liver cancer. Drug-induced toxicity is a key obstacle in the treatment of liver cancer, necessitating the development of effective and safe medications, with natural compounds such as resveratrol, curcumin, diallyl sulfide, and others emerging as promising anticancer agents. This review highlights the current status of liver cancer research, signaling pathways, therapeutic targets, current treatment strategies and the chemopreventive role of various natural products in managing liver cancer.
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Affiliation(s)
- Amit Kumar Singh
- Department of Botany, Government Naveen Girls College, Balod (Hemchand Yadav University), Durg, Chattisgarh, India
- Department of Biochemistry, University of Allahabad, Prayagraj 211002, Uttar Pradesh, India
| | - Shiv Vardan Singh
- Department of Biochemistry, University of Allahabad, Prayagraj 211002, Uttar Pradesh, India
| | - Ramesh Kumar
- Department of Biochemistry, University of Allahabad, Prayagraj 211002, Uttar Pradesh, India
- Department of Biochemistry, School of Basic and Applied Sciences, Central University of Punjab, Bathinda 151401, Punjab, India
| | - Shashank Kumar
- Department of Biochemistry, School of Basic and Applied Sciences, Central University of Punjab, Bathinda 151401, Punjab, India
| | - Sabyasachi Senapati
- Department of Human Genetics and Molecular Medicine, Central University of Punjab, Bathinda 151401, Punjab, India
| | - Abhay K Pandey
- Department of Biochemistry, University of Allahabad, Prayagraj 211002, Uttar Pradesh, India.
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Deepika, Maurya PK. Ellagic acid: insight into its protective effects in age-associated disorders. 3 Biotech 2022; 12:340. [PMID: 36340805 PMCID: PMC9633905 DOI: 10.1007/s13205-022-03409-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Accepted: 10/23/2022] [Indexed: 11/06/2022] Open
Abstract
The disparity in the free radical generation and the production of antioxidants to counteract its effect is known as oxidative stress. Oxidative stress causes damage to the macromolecules such as lipids, carbohydrates, proteins, and DNA and RNA. The oxidative damage to the cellular components leads to a process of aging and various age-associated disorders. The literature survey for this review was done using PubMed, Google Scholar, and Science Direct. The papers showing the studies related to aging and age-associated disorders have been selected for reviewing this paper. Ellagic acid has been used as the keyword, and more emphasis has been put on papers from the last 10 years. However, some papers with significant studies prior to 10 years have also been considered. Almost 250 papers have been studied for reviewing this paper, and about 135 papers have been cited. Ellagic acid (EA) is present in high quantities in pomegranate and various types of berries. It is known to possess the antioxidant potential and protects from the harmful effects of free radicals. Various studies have shown its effect to protect cardiovascular, neurodegenerative, cancer, and diabetes. The present review focuses on the protective effect of ellagic acid in age-associated disorders. The effect of EA has been studied in various chronic disorders but the scope of this review is limited to cancer, diabetes, cardiovascular and neurodegenerative disorders. All the disease aspects have not been addressed in this particular review.
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Affiliation(s)
- Deepika
- Department of Biochemistry, Central University of Haryana, Mahendragarh, 123031 India
| | - Pawan Kumar Maurya
- Department of Biochemistry, Central University of Haryana, Mahendragarh, 123031 India
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Ganguly R, Gupta A, Pandey AK. Role of baicalin as a potential therapeutic agent in hepatobiliary and gastrointestinal disorders: A review. World J Gastroenterol 2022; 28:3047-3062. [PMID: 36051349 PMCID: PMC9331529 DOI: 10.3748/wjg.v28.i26.3047] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Revised: 03/21/2022] [Accepted: 05/22/2022] [Indexed: 02/06/2023] Open
Abstract
Baicalin is a natural bioactive compound derived from Scutellaria baicalensis, which is extensively used in traditional Chinese medicine. A literature survey demonstrated the broad spectrum of health benefits of baicalin such as antioxidant, anticancer, anti-inflammatory, antimicrobial, cardio-protective, hepatoprotective, renal protective, and neuroprotective properties. Baicalin is hydrolyzed to its metabolite baicalein by the action of gut microbiota, which is further reconverted to baicalin via phase 2 metabolism in the liver. Many studies have suggested that baicalin exhibits therapeutic potential against several types of hepatic disorders including hepatic fibrosis, xenobiotic-induced liver injury, fatty liver disease, viral hepatitis, cholestasis, ulcerative colitis, hepatocellular and colorectal cancer. During in vitro and in vivo examinations, it has been observed that baicalin showed a protective role against liver and gut-associated abnormalities by modifying several signaling pathways such as nuclear factor-kappa B, transforming growth factor beta 1/SMAD3, sirtuin 1, p38/mitogen-activated protein kinase/Janus kinase, and calcium/calmodulin-dependent protein kinase kinaseβ/adenosine monophosphate-activated protein kinase/acetyl-coenzyme A carboxylase pathways. Furthermore, baicalin also regulates the expression of fibrotic genes such as smooth muscle actin, connective tissue growth factor, β-catenin, and inflammatory cytokines such as interferon gamma, interleukin-6 (IL-6), tumor necrosis factor-alpha, and IL-1β, and attenuates the production of apoptotic proteins such as caspase-3, caspase-9 and B-cell lymphoma 2. However, due to its low solubility and poor bioavailability, widespread therapeutic applications of baicalin still remain a challenge. This review summarized the hepatic and gastrointestinal protective attributes of baicalin with an emphasis on the molecular mechanisms that regulate the interaction of baicalin with the gut microbiota.
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Affiliation(s)
- Risha Ganguly
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, Uttar Pradesh, India
| | - Ashutosh Gupta
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, Uttar Pradesh, India
| | - Abhay K Pandey
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, Uttar Pradesh, India
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Ganguly R, Kumar R, Pandey AK. Baicalin provides protection against fluoxetine-induced hepatotoxicity by modulation of oxidative stress and inflammation. World J Hepatol 2022; 14:729-743. [PMID: 35646277 PMCID: PMC9099103 DOI: 10.4254/wjh.v14.i4.729] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Revised: 09/17/2021] [Accepted: 03/27/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Fluoxetine is one of the most widely prescribed anti-depressant drugs belonging to the category of selective serotonin reuptake inhibitors. Long-term fluoxetine treatment results in hepatotoxicity. Baicalin, a natural compound obtained from the Chinese herb Scutellaria baicalensis is known to have antioxidant, hepatoprotective and anti-inflammatory effects. However, the beneficial effects of baicalin against fluoxetine-induced hepatic damage have not previously been reported.
AIM To evaluate the protective action of baicalin in fluoxetine-induced liver toxicity and inflammation.
METHODS Male albino Wistar rats were divided into seven groups. Group 1 was the normal control. Oral fluoxetine was administered at 10 mg/kg body weight to groups 2, 3, 4 and 5. In addition, groups 3 and 4 were also co-administered oral baicalin (50 mg/kg and 100 mg/kg, respectively) while group 5 received silymarin (100 mg/kg), a standard hepatoprotective compound for comparison. Groups 6 and 7 were used as a positive control for baicalin (100 mg/kg) and silymarin (100 mg/kg), respectively. All treatments were carried out for 28 d. After sacrifice of the rats, biomarkers of oxidative stress [superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione-S-transferase (GST), advanced oxidation protein products (AOPP), malondialdehyde (MDA)], and liver injury [alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total protein, albumin, bilirubin] were studied in serum and tissue using standard protocols and diagnostic kits. Inflammatory markers [tumor necrosis factor (TNF-α), interleukin (IL)-6, IL-10 and interferon (IFN)-γ] in serum were evaluated using ELISA-based kits. The effect of baicalin on liver was also analyzed by histopathological examination of tissue sections.
RESULTS Fluoxetine-treated rats showed elevated levels of the serum liver function markers (total bilirubin, ALT, AST, and ALP) and inflammatory markers (TNF-α, IL-6, IL-10 and IFN-γ), with a decline in total protein and albumin levels. Biochemical markers of oxidative stress such as SOD, CAT, GST, GSH, MDA and AOPP in the liver tissue homogenate were also altered indicating a surge in reactive oxygen species leading to oxidative damage. Histological examination of liver tissue also showed degeneration of hepatocytes. Concurrent administration of baicalin (50 and 100 mg/kg) restored the biomarkers of oxidative stress, inflammation and hepatic damage in serum as well as in liver tissues to near normal levels.
CONCLUSION These findings suggested that long-term treatment with fluoxetine leads to oxidative stress via the formation of free radicals that consequently cause inflammation and liver damage. Concurrent treatment with baicalin alleviated fluoxetine-induced hepatotoxicity and liver injury by regulating oxidative stress and inflammation.
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Affiliation(s)
- Risha Ganguly
- Department of Biochemistry, University of Allahabad, Prayagraj 211002, India
| | - Ramesh Kumar
- Department of Biochemistry, University of Allahabad, Prayagraj 211002, India
| | - Abhay K Pandey
- Department of Biochemistry, University of Allahabad, Prayagraj 211002, India
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Sharifi-Rad J, Quispe C, Castillo CMS, Caroca R, Lazo-Vélez MA, Antonyak H, Polishchuk A, Lysiuk R, Oliinyk P, De Masi L, Bontempo P, Martorell M, Daştan SD, Rigano D, Wink M, Cho WC. Ellagic Acid: A Review on Its Natural Sources, Chemical Stability, and Therapeutic Potential. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:3848084. [PMID: 35237379 PMCID: PMC8885183 DOI: 10.1155/2022/3848084] [Citation(s) in RCA: 71] [Impact Index Per Article: 23.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Accepted: 01/31/2022] [Indexed: 12/18/2022]
Abstract
Ellagic acid (EA) is a bioactive polyphenolic compound naturally occurring as secondary metabolite in many plant taxa. EA content is considerable in pomegranate (Punica granatum L.) and in wood and bark of some tree species. Structurally, EA is a dilactone of hexahydroxydiphenic acid (HHDP), a dimeric gallic acid derivative, produced mainly by hydrolysis of ellagitannins, a widely distributed group of secondary metabolites. EA is attracting attention due to its antioxidant, anti-inflammatory, antimutagenic, and antiproliferative properties. EA displayed pharmacological effects in various in vitro and in vivo model systems. Furthermore, EA has also been well documented for its antiallergic, antiatherosclerotic, cardioprotective, hepatoprotective, nephroprotective, and neuroprotective properties. This review reports on the health-promoting effects of EA, along with possible mechanisms of its action in maintaining the health status, by summarizing the literature related to the therapeutic potential of this polyphenolic in the treatment of several human diseases.
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Affiliation(s)
| | - Cristina Quispe
- Facultad de Ciencias de la Salud, Universidad Arturo Prat, Avda. Arturo Prat 2120, Iquique 1110939, Chile
| | | | - Rodrigo Caroca
- Biotechnology and Genetic Engineering Group, Science and Technology Faculty, Universidad del Azuay, Av. 24 de Mayo 7-77, Cuenca, Ecuador
- Universidad del Azuay, Grupos Estratégicos de Investigación en Ciencia y Tecnología de Alimentos y Nutrición Industrial (GEICA-UDA), Av. 24 de Mayo 7-77, Apartado 01.01.981, Cuenca, Ecuador
| | - Marco A. Lazo-Vélez
- Universidad del Azuay, Grupos Estratégicos de Investigación en Ciencia y Tecnología de Alimentos y Nutrición Industrial (GEICA-UDA), Av. 24 de Mayo 7-77, Apartado 01.01.981, Cuenca, Ecuador
| | | | | | - Roman Lysiuk
- Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
| | - Petro Oliinyk
- Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
| | - Luigi De Masi
- National Research Council (CNR), Institute of Biosciences and Bioresources (IBBR), Via Università 133, 80055 Portici, Naples, Italy
| | - Paola Bontempo
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Via L. De Crecchio 7, 80138 Naples, Italy
| | - Miquel Martorell
- Department of Nutrition and Dietetics, Faculty of Pharmacy, and Centre for Healthy Living, University of Concepción, 4070386 Concepción, Chile
| | - Sevgi Durna Daştan
- Department of Biology, Faculty of Science, Sivas Cumhuriyet University, 58140 Sivas, Turkey
- Beekeeping Development Application and Research Center, Sivas Cumhuriyet University, 58140 Sivas, Turkey
| | - Daniela Rigano
- Department of Pharmacy, University of Naples “Federico II”, Via D. Montesano, 49 80131 Naples, Italy
| | - Michael Wink
- Heidelberg University, Institute of Pharmacy and Molecular Biotechnology, INF 329, D-69120 Heidelberg, Germany
| | - William C. Cho
- Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong
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Gupta A, Marquess AR, Pandey AK, Bishayee A. Jackfruit ( Artocarpus heterophyllus Lam.) in health and disease: a critical review. Crit Rev Food Sci Nutr 2022; 63:6344-6378. [PMID: 35144492 DOI: 10.1080/10408398.2022.2031094] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Artocarpus heterophyllus Lam. (Family Moraceae), is a tropical tree, native to India and common in Asia, Africa, and several regions in South America. The fruit is commonly known as jackfruit which is one of the largest edible fruits in the world. Jackfruits comprises a wide range of nutrients, including minerals, carbohydrates, volatile compounds, proteins, and vitamins. The fruit, bark, leaves, and roots are endowed with therapeutic attributes and are utilized in the many traditional medicinal systems for the management of various ailments. Fruit and seeds are commonly used to prepare various food items, including sauce, ice creams, jams, jellies, and marmalades. Due to unique texture, jackfruit is becoming a popular meat substitute. Based on preclinical studies, jackfruit exhibits antimicrobial, antioxidant, anti-melanin, antidiabetic, anti-inflammatory, immunomodulatory, antiviral, anthelmintic, wound-healing, and antineoplastic activities. Clinical studies reveal that the leaves possess antidiabetic action in healthy and insulin-independent diabetic individuals. Despite numerous health benefits, regrettably, jackfruit has not been properly utilized in a marketable scale in areas where it is produced. This review delivers an updated, comprehensive, and critical evaluation on the nutritional value, phytochemical profiling, pharmacological attributes and underlying mechanisms of action to explore the full potential of jackfruit in health and disease.
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Affiliation(s)
- Ashutosh Gupta
- Department of Biochemistry, University of Allahabad, Prayagraj, Uttar Pradesh, India
| | - Alexis R Marquess
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, Florida, USA
| | - Abhay Kumar Pandey
- Department of Biochemistry, University of Allahabad, Prayagraj, Uttar Pradesh, India
| | - Anupam Bishayee
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, Florida, USA
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Gupta A, Atkinson AN, Pandey AK, Bishayee A. Health-promoting and disease-mitigating potential of Verbascum thapsus L. (common mullein): A review. Phytother Res 2022; 36:1507-1522. [PMID: 35088467 DOI: 10.1002/ptr.7393] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Revised: 11/28/2021] [Accepted: 01/12/2022] [Indexed: 12/14/2022]
Abstract
Medicinal plants represent rich sources of traditional medicines and numerous currently used medicines are either directly or indirectly derived from plants. Verbascum thapsus L. (great mullein or common mullein), a medicinal herb indigenous to northern Africa, western and central Asia, and Europe, has been brought to the Americas and Australia. It has been used as a medicine for lung, skin and throat disorders and has a long history of therapeutic importance, particularly as an astringent and calming agent. Presently, the dried leaves, flowers, various plant extracts and flower oil are used in several formulations within Indian traditional medicine. An extract taken from the roots is useful in minimizing toothache, and it also relieves stiffness and seizures. V. thapsus contains a wide variety of phytoconstituents, such as flavonoids, iridoid, phenylethanoid and phenylpropanoid glycosides, saponins, as well as vitamin C and minerals. The most valuable constituents are coumarin and hesperidin, which possess healing properties. Emerging literature based on experimental studies on V. thapsus demonstrates various biological and pharmacological properties, including antiviral, antioxidant, analgesic, sedative, anti-inflammatory, hypnotic, antibacterial, antifungal, as well as anticancer activities. The present review provides an updated, comprehensive, and critical evaluation of various health-promoting and disease-mitigating properties of V. thapsus.
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Affiliation(s)
- Ashutosh Gupta
- Department of Biochemistry, University of Allahabad, Prayagraj, Uttar Pradesh, India
| | - Alexa N Atkinson
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, Florida, USA
| | - Abhay Kumar Pandey
- Department of Biochemistry, University of Allahabad, Prayagraj, Uttar Pradesh, India
| | - Anupam Bishayee
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, Florida, USA
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15
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Zhao L, Mehmood A, Soliman MM, Iftikhar A, Iftikhar M, Aboelenin SM, Wang C. Protective Effects of Ellagic Acid Against Alcoholic Liver Disease in Mice. Front Nutr 2021; 8:744520. [PMID: 34595202 PMCID: PMC8478122 DOI: 10.3389/fnut.2021.744520] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Accepted: 08/19/2021] [Indexed: 12/14/2022] Open
Abstract
Ellagic acid, a natural polyphenolic compound commonly present in vegetables, fruits, nuts, and other edible plants, exerts many pharmacological activities. The present project was designed to explore the hepatoprotective effect of ellagic acid against alcohol-induced liver disease (ALD) and the correlation among alcohol, oxidative stress, inflammation, and gut microbiota. Fifty percent (v/v) alcohol (10 mL/kg bw daily) was orally administrated for 4 weeks in mice along with ellagic acid (50 and 100 mg/kg bw). Alcohol administration significantly (p < 0.05) increased the activities of alanine aminotransferase and serum aspartate aminotransferase, levels of triglyceride, low density lipoprotein, free fatty acid, and total cholesterol, and decreased contents of the high-density lipoprotein in model group compared with the control group, which were further improved by ellagic acid (50 or 100 mg/kg bw). Furthermore, daily supplementation of ellagic acid alleviated hepatic antioxidant activities (glutathione peroxidase, catalase, malondialdehyde, superoxide dismutase, and glutathione), proinflammatory cytokines levels (IL-6, IL-1β, and TNF-α), genes expressions (Tlr4, Myd88, Cd14, Cox2, Nos2, and Nfκb1), and histopathological features in alcohol-induced liver injured mice. Additionally, results also revealed that ellagic acid supplementation improved alcohol-induced gut microbiota dysbiosis. In conclusion, ellagic acid mitigated oxidative stress, inflammatory response, steatosis, and gut microbiota dysbiosis in ALD mice. Our results suggested that ellagic acid could be applied as an ideal dietary therapy against ALD.
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Affiliation(s)
- Liang Zhao
- Beijing Advance Innovation Center for Food Nutrition and Human Health, Beijing Engineering and Technology Research Center of Food Additives, Beijing Technology and Business University, Beijing, China
| | - Arshad Mehmood
- Beijing Advance Innovation Center for Food Nutrition and Human Health, Beijing Engineering and Technology Research Center of Food Additives, Beijing Technology and Business University, Beijing, China
| | - Mohamed Mohamed Soliman
- Clinical Laboratory Sciences Department, Turabah University College, Taif University, Taif, Saudi Arabia
| | - Asra Iftikhar
- Department of Pharmacy, Faculty of Pharmaceutical Sciences, The University of Faisalabad, Faisalabad, Pakistan
| | - Maryam Iftikhar
- Beijing Advance Innovation Center for Food Nutrition and Human Health, Beijing Engineering and Technology Research Center of Food Additives, Beijing Technology and Business University, Beijing, China
| | | | - Chengtao Wang
- Beijing Advance Innovation Center for Food Nutrition and Human Health, Beijing Engineering and Technology Research Center of Food Additives, Beijing Technology and Business University, Beijing, China
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Gupta A, Singh AK, Kumar R, Jamieson S, Pandey AK, Bishayee A. Neuroprotective Potential of Ellagic Acid: A Critical Review. Adv Nutr 2021; 12:1211-1238. [PMID: 33693510 PMCID: PMC8321875 DOI: 10.1093/advances/nmab007] [Citation(s) in RCA: 74] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Revised: 09/02/2020] [Accepted: 01/19/2021] [Indexed: 02/06/2023] Open
Abstract
Ellagic acid (EA) is a dietary polyphenol present in various fruits, vegetables, herbs, and nuts. It exists either independently or as part of complex structures, such as ellagitannins, which release EA and several other metabolites including urolithins following absorption. During the past few decades, EA has drawn considerable attention because of its vast range of biological activities as well as its numerous molecular targets. Several studies have reported that the oxidative stress-lowering potential of EA accounts for its broad-spectrum pharmacological attributes. At the biochemical level, several mechanisms have also been associated with its therapeutic action, including its efficacy in normalizing lipid metabolism and lipidemic profile, regulating proinflammatory mediators, such as IL-6, IL-1β, and TNF-α, upregulating nuclear factor erythroid 2-related factor 2 and inhibiting NF-κB action. EA exerts appreciable neuroprotective activity by its free radical-scavenging action, iron chelation, initiation of several cell signaling pathways, and alleviation of mitochondrial dysfunction. Numerous in vivo studies have also explored the neuroprotective attribute of EA against various neurotoxins in animal models. Despite the increasing number of publications with experimental evidence, a critical analysis of available literature to understand the full neuroprotective potential of EA has not been performed. The present review provides up-to-date, comprehensive, and critical information regarding the natural sources of EA, its bioavailability, metabolism, neuroprotective activities, and underlying mechanisms of action in order to encourage further studies to define the clinical usefulness of EA for the management of neurological disorders.
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Affiliation(s)
- Ashutosh Gupta
- Department of Biochemistry, University of Allahabad, Prayagraj, Uttar Pradesh, India
| | - Amit Kumar Singh
- Department of Biochemistry, University of Allahabad, Prayagraj, Uttar Pradesh, India
| | - Ramesh Kumar
- Department of Biochemistry, University of Allahabad, Prayagraj, Uttar Pradesh, India
| | - Sarah Jamieson
- Lake Erie College of Osteopathic Medicine, Bradenton, FL, USA
| | - Abhay Kumar Pandey
- Department of Biochemistry, University of Allahabad, Prayagraj, Uttar Pradesh, India
| | - Anupam Bishayee
- Lake Erie College of Osteopathic Medicine, Bradenton, FL, USA
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Singh AK, Rana HK, Singh V, Chand Yadav T, Varadwaj P, Pandey AK. Evaluation of antidiabetic activity of dietary phenolic compound chlorogenic acid in streptozotocin induced diabetic rats: Molecular docking, molecular dynamics, in silico toxicity, in vitro and in vivo studies. Comput Biol Med 2021; 134:104462. [PMID: 34148008 DOI: 10.1016/j.compbiomed.2021.104462] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 04/28/2021] [Accepted: 04/28/2021] [Indexed: 12/17/2022]
Abstract
BACKGROUND Chlorogenic acid is amongst the well-known polyphenolic compounds being used in human food and beverages. Its presence has been reported in tea leaves, roasted green beans, coffee, cocoa, berry fruits, apples, citrus fruits, and pears. OBJECTIVE The present study aims to elucidate the effectiveness of chlorogenic acid on in silico and in vitro inhibition of glucose metabolising enzymes (α-amylase and α-glucosidase) and on blood-based markers associated with diabetic complications in vivo. METHODS Docking and molecular dynamics studies were performed using GLIDE (Schrodinger, LLC, NY, 2019-2) and Maestro-Desmond Interoperability Tools, version 4.1 (Schrödinger, NY, 2015), respectively. α-Amylase and α-glucosidase inhibitory activities of chlorogenic acid were measured in vitro. Diabetes was induced in adult Wistar rats by injecting streptozotocin (50 mg/kg). Biochemical assays were performed using standard kits. RESULT The in silico studies for α-amylase and α-glucosidase with chlorogenic acid suggested that the ligand was stable and strongly bound with the above-mentioned proteins. During in vitro studies, chlorogenic acid inhibited both the enzymes in a dose-dependent manner (5-30 μg/mL). In addition, chlorogenic acid treatment for 28 days significantly suppressed the increase in blood glucose, total cholesterol, triglyceride, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, γ-glutamyl transferase, alkaline phosphatase, total bilirubin, creatinine, urea, uric acid, and feed intake levels in diabetic rats. Chlorogenic acid also caused significant improvement in body weight, serum HDL-cholesterol, total protein, and albumin levels leading to betterment in atherogenic indices related to diabetes-associated cardiovascular risks. CONCLUSION The findings indicated that chlorogenic acid inhibited α-amylase and α-glucosidase and significantly decreased diabetes associated hyperglycemia, hyperlipidemia, and hepatorenal damage, making it a possible functional food ingredient and drug candidate for the management of diabetes and related complications.
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Affiliation(s)
- Amit Kumar Singh
- Department of Biochemistry, University of Allahabad, Prayagraj, 211002, India
| | - Harvesh Kumar Rana
- Department of Biochemistry, University of Allahabad, Prayagraj, 211002, India
| | - Vishal Singh
- Bioinformatics Division, Indian Institute of Information Technology Allahabad, Prayagraj, 211015, India
| | - Tara Chand Yadav
- Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, 247667, India
| | - Pritish Varadwaj
- Bioinformatics Division, Indian Institute of Information Technology Allahabad, Prayagraj, 211015, India
| | - Abhay Kumar Pandey
- Department of Biochemistry, University of Allahabad, Prayagraj, 211002, India.
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Gupta A, Singh AK, Loka M, Pandey AK, Bishayee A. Ferulic acid-mediated modulation of apoptotic signaling pathways in cancer. ADVANCES IN PROTEIN CHEMISTRY AND STRUCTURAL BIOLOGY 2021; 125:215-257. [PMID: 33931140 DOI: 10.1016/bs.apcsb.2020.12.005] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Ferulic acid (4-hydroxy-3-methoxycinnamic acid, FA), a hydroxycinnamic acid derived from various seeds, nuts, leaves, and fruits, exists in a free form as well as is covalently conjugated with polysaccharides, glycoproteins, polyamines, lignin, and hydroxy fatty acids of plant cell walls. It exhibits a variety of pharmacological effects, such as antioxidant, anti-inflammatory, vasodilatory, antithrombotic, antimicrobial, anti-allergic, antiviral, hepatoprotective, and anticancer activities. FA induces the expression of cell cycle-related proteins, such as p53 and p21, and reduces cyclin D1 and cyclin E levels. Moreover, FA triggers apoptosis and autophagic cell death depending on intracellular reactive oxygen species production in various cancer cell lines. The potential apoptotic action of FA is mediated by altered expression of procaspase-3, procaspase-8, procaspase-9, poly (ADP ribose) polymerase, Bcl-2, and Bax. It blocks the activation of both the canonical Smad and noncanonical extracellular-signal-regulated kinase/Akt (protein kinase B) pathways in various cancer cells. However, due to low solubility and permeability, its availability to biological systems is limited. Therefore, encapsulation of FA into chitosan tripolyphosphate nanoparticles may enhance its cytocompatibility, solubility, and anticancer potential. The nanohybrids of FA and double layered hydroxide exhibit cellular delivery properties of intercalated molecules on cancer cell lines. This chapter summarizes the anticancer efficacy of FA with an emphasis on the role of apoptosis, and underlying molecular mechanisms involving various signaling pathways in tumor cells.
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Affiliation(s)
- Ashutosh Gupta
- Department of Biochemistry, University of Allahabad, Prayagraj, Uttar Pradesh, India
| | - Amit Kumar Singh
- Department of Biochemistry, University of Allahabad, Prayagraj, Uttar Pradesh, India
| | - Mariam Loka
- Lake Erie College of Osteopathic Medicine, Bradenton, FL, United States
| | - Abhay Kumar Pandey
- Department of Biochemistry, University of Allahabad, Prayagraj, Uttar Pradesh, India.
| | - Anupam Bishayee
- Lake Erie College of Osteopathic Medicine, Bradenton, FL, United States.
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Antioxidant, anti-inflammatory and hepatoprotective activities of Terminalia bellirica and its bioactive component ellagic acid against diclofenac induced oxidative stress and hepatotoxicity. Toxicol Rep 2020; 8:44-52. [PMID: 33391996 PMCID: PMC7772792 DOI: 10.1016/j.toxrep.2020.12.010] [Citation(s) in RCA: 56] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Revised: 11/07/2020] [Accepted: 12/10/2020] [Indexed: 12/19/2022] Open
Abstract
Long term usage and overdose of diclofenac (DCF), an anti-inflammatory drug is known to cause oxidative stress and liver injury. The present study reports the antioxidant, anti-inflammatory and hepatoprotective activities of Terminalia bellirica (Tb) fruit aqueous and ethyl acetate extracts and its bioactive compound ellagic acid (EA) against DCF-induced toxicity. in vitro antioxidant activities were measured by ABTS and FRAP assays while anti‐inflammatory activity was assessed by the albumin denaturation method. The adverse effects of DCF and hepatoprotective potential of Tb extracts and EA were assessed in serum and liver tissue of rats after oral administration for 21 days. Silymarin was used as standard hepatoprptective agent for comparison. Hepatic markers analyzed in serum included ALP, GPT, GOT, LDH, γ-glutamyl transferase, total protein, creatinine, and uric acid while superoxide dismutase (SOD) and catalase (CAT) were analyzed in liver tissue. The EA exhibited superior ABTS radical scavenging, FRAP, and anti-inflammatory activities as compared to fruit extracts. DCF treatment led to rise in the levels of most of the serum hepatic markers with decline in total serum protein as well as SOD and CAT in liver tissue. The supplementation of extracts, EA and silymarin in DCF treated rats significantly reduced the adverse effects of DCF on serum and tissue markers. Histopathology of the liver indicated that extracts and EA significantly decreased the degree of liver fibrosis. The hepatoprotective ability of EA was comparable to the silymarin but activity of Tb fruit extracts was little lower. Among fruit extracts ethyl acetate extract exhibited better activity than aqueous extract. The results revealed that ellagic acid and T. bellirica fruit extracts have potential to mitigate oxidative stress and hepatotoxicity produced by long term use of diclofenac.
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