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16.10.2023 | Original Article

Systems pharmacology and multi-scale mechanism of Enicostema axillare bioactives in treating Alzheimer disease

verfasst von: Madhana Vigneshwari Gopal Samy, Sasidharan Perumal

Erschienen in: Inflammopharmacology

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Abstract

As a progressive neurological disease with increased morbidity and mortality, Alzheimer Disease (AD) is characterized by neuron damage that controls memory and mental functions. Enicostema axillare (EA), an herb with a history of combativeness and effectiveness in treating Rheumatoid Arthritis, Cancer, and Diabetes, is used in Indian folk medicine from a holistic point of view. Though the herb is used for many illnesses, the molecular mechanism of its bioactive on AD has not been deciphered by intricate research. A unique pharmacology approach based on ADME drug screening and targeting, pathway enrichment (GO and KEGG), and network pharmacology, was established to explore the molecular mechanisms of E. axillare (EA) bioactive compounds for the treatment of AD. In brief, we bring to light the three active compounds of EA and seven potential molecular targets of AD, which are mainly implicated in four signaling pathways, i.e., MAPK, Apoptosis, neurodegeneration, and the TNF pathway. Moreover, the network analysis of the active compounds, molecular targets, and their pathways reveals the pharmacological nature of the compounds. Further, molecular docking studies were carried out to explore the interactions between the EA bioactive compounds and the targets and examine the binding affinity. The outcome of the work reflects the potential therapeutic effects of the compounds for treating AD through the modulation of the key proteins, which further corroborates the reliability of our network pharmacology analysis. This study not only helps in understanding the molecular mechanism of the drugs but also helps in finding and sorting new drugs for the treatment of AD, and other complex diseases through modern medicine.
Literatur
Zurück zum Zitat Ahmad SS, Sinha M, Ahmad K, Khalid M, Choi I (2020) Study of caspase 8 inhibition for the management of Alzheimer’s disease: a molecular docking and dynamics simulation. Molecules 25(9):2071 PubMedPubMedCentralCrossRef Ahmad SS, Sinha M, Ahmad K, Khalid M, Choi I (2020) Study of caspase 8 inhibition for the management of Alzheimer’s disease: a molecular docking and dynamics simulation. Molecules 25(9):2071 PubMedPubMedCentralCrossRef
Zurück zum Zitat Ahmad S, Ahmed SB, Khan A, Wasim M, Tabassum S, Haider S, Ahmed F, Batool Z, Khaliq S, Rafiq H, Tikmani P, Gilani AU (2023) Natural remedies for Alzheimer's disease: A systematic review of randomized controlled trials. Metab Brain Dis 38(1):17–44 PubMedCrossRef Ahmad S, Ahmed SB, Khan A, Wasim M, Tabassum S, Haider S, Ahmed F, Batool Z, Khaliq S, Rafiq H, Tikmani P, Gilani AU (2023) Natural remedies for Alzheimer's disease: A systematic review of randomized controlled trials. Metab Brain Dis 38(1):17–44 PubMedCrossRef
Zurück zum Zitat Allen M, Kachadoorian M, Quicksall Z, Zou F, Chai HS, Younkin C et al (2014) Association of MAPT haplotypes with Alzheimer’s disease risk and MAPT brain gene expression levels. Alzheimer’s Res Ther 6(4):39 CrossRef Allen M, Kachadoorian M, Quicksall Z, Zou F, Chai HS, Younkin C et al (2014) Association of MAPT haplotypes with Alzheimer’s disease risk and MAPT brain gene expression levels. Alzheimer’s Res Ther 6(4):39 CrossRef
Zurück zum Zitat Atanasov AG, Zotchev SB, Dirsch VM, Supuran CT, International Natural Product Sciences Taskforce (2021) Natural products in drug discovery: advances and opportunities. Nat Rev Drug Discov 20(3):200–216 PubMedPubMedCentralCrossRef Atanasov AG, Zotchev SB, Dirsch VM, Supuran CT, International Natural Product Sciences Taskforce (2021) Natural products in drug discovery: advances and opportunities. Nat Rev Drug Discov 20(3):200–216 PubMedPubMedCentralCrossRef
Zurück zum Zitat Ayaz M, Sadiq A, Junaid M, Ullah F, Ovais M, Ullah I, Shahid M (2019) Flavonoids as Prospective Neuroprotectants and Their Therapeutic Propensity in Aging Associated Neurological Disorders. Front Aging Neurosci 11 Ayaz M, Sadiq A, Junaid M, Ullah F, Ovais M, Ullah I, Shahid M (2019) Flavonoids as Prospective Neuroprotectants and Their Therapeutic Propensity in Aging Associated Neurological Disorders. Front Aging Neurosci 11
Zurück zum Zitat Bakoyiannis I, Daskalopoulou A, Pergialiotis V, Perrea D (2019) Phytochemicals and cognitive health: Are flavonoids doing the trick. Biomed Pharmacother 109:1488–1497 PubMedCrossRef Bakoyiannis I, Daskalopoulou A, Pergialiotis V, Perrea D (2019) Phytochemicals and cognitive health: Are flavonoids doing the trick. Biomed Pharmacother 109:1488–1497 PubMedCrossRef
Zurück zum Zitat Barone E, Di Domenico F, Cenini G, Sultana R, Coccia R, Preziosi P et al (2011) Oxidative and nitrosative modifications of biliverdin reductase-A in the brain of subjects with Alzheimer’s disease and amnestic mild cognitive impairment. J Alzheimer’s Dis 25(4):623–633 CrossRef Barone E, Di Domenico F, Cenini G, Sultana R, Coccia R, Preziosi P et al (2011) Oxidative and nitrosative modifications of biliverdin reductase-A in the brain of subjects with Alzheimer’s disease and amnestic mild cognitive impairment. J Alzheimer’s Dis 25(4):623–633 CrossRef
Zurück zum Zitat Bellenguez C, Grenier-Boley B, Lambert JC (2020) Genetics of Alzheimer’s disease: where we are, and where we are going. Curr Opin Neurobiol 61:40–48 PubMedCrossRef Bellenguez C, Grenier-Boley B, Lambert JC (2020) Genetics of Alzheimer’s disease: where we are, and where we are going. Curr Opin Neurobiol 61:40–48 PubMedCrossRef
Zurück zum Zitat Berger SI, Iyengar R (2009) Network analyses in systems pharmacology. J Bioinform 25(19):2466–2472 CrossRef Berger SI, Iyengar R (2009) Network analyses in systems pharmacology. J Bioinform 25(19):2466–2472 CrossRef
Zurück zum Zitat Bui TT, Nguyen TH (2017) Natural product for the treatment of Alzheimer’s disease. J Basic Clin Physiol Pharmacol 28(5):413–423 PubMedCrossRef Bui TT, Nguyen TH (2017) Natural product for the treatment of Alzheimer’s disease. J Basic Clin Physiol Pharmacol 28(5):413–423 PubMedCrossRef
Zurück zum Zitat Butterfield DA, Di Domenico F, Barone E (2014) Elevated risk of type 2 diabetes for development of Alzheimer disease: a key role for oxidative stress in brain. Biochem Biophys Acta 1842(9):1693–1706 PubMed Butterfield DA, Di Domenico F, Barone E (2014) Elevated risk of type 2 diabetes for development of Alzheimer disease: a key role for oxidative stress in brain. Biochem Biophys Acta 1842(9):1693–1706 PubMed
Zurück zum Zitat Cai FF, Bian YQ, Wu R, Sun Y, Chen XL, Yang MD et al (2019) Yinchenhao decoction suppresses rat liver fibrosis involved in an apoptosis regulation mechanism based on network pharmacology and transcriptomic analysis. Biomed Pharmacother 114:108863 PubMedCrossRef Cai FF, Bian YQ, Wu R, Sun Y, Chen XL, Yang MD et al (2019) Yinchenhao decoction suppresses rat liver fibrosis involved in an apoptosis regulation mechanism based on network pharmacology and transcriptomic analysis. Biomed Pharmacother 114:108863 PubMedCrossRef
Zurück zum Zitat Castro RE, Santos MMM, Glória PMC, Ribeiro CJ, Ferreira DM, Xavier JM et al (2010) Cell death targets and potential modulators in alzheimer’s disease. Curr Pharm Des 16(25):2851–2864 PubMedCrossRef Castro RE, Santos MMM, Glória PMC, Ribeiro CJ, Ferreira DM, Xavier JM et al (2010) Cell death targets and potential modulators in alzheimer’s disease. Curr Pharm Des 16(25):2851–2864 PubMedCrossRef
Zurück zum Zitat Chae HS, Xu R, Won JY, Chin YW, Yim H (2019) Molecular targets of genistein and its related flavonoids to exert anticancer effects. Int J Mol Sci 20(10):2420 PubMedPubMedCentralCrossRef Chae HS, Xu R, Won JY, Chin YW, Yim H (2019) Molecular targets of genistein and its related flavonoids to exert anticancer effects. Int J Mol Sci 20(10):2420 PubMedPubMedCentralCrossRef
Zurück zum Zitat Chin-Chan M, Navarro-Yepes J, Quintanilla-Vega B (2015) Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases. Front Cell Neurosci 9:124 PubMedPubMedCentralCrossRef Chin-Chan M, Navarro-Yepes J, Quintanilla-Vega B (2015) Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases. Front Cell Neurosci 9:124 PubMedPubMedCentralCrossRef
Zurück zum Zitat Chang YJ, Linh NH, Shih YH, Yu HM, Li MS, Chen YR (2016) Alzheimer’s amyloid-β sequesters caspase-3 in vitro via Its C-terminal tail. ACS Chem Neurosci 7(8):1097–1106 PubMedCrossRef Chang YJ, Linh NH, Shih YH, Yu HM, Li MS, Chen YR (2016) Alzheimer’s amyloid-β sequesters caspase-3 in vitro via Its C-terminal tail. ACS Chem Neurosci 7(8):1097–1106 PubMedCrossRef
Zurück zum Zitat Chang R, Yee KL, Sumbria RK (2017) Tumor necrosis factor α Inhibition for Alzheimer’s disease. J Cent Nerv Syst 9:1179573517709278 Chang R, Yee KL, Sumbria RK (2017) Tumor necrosis factor α Inhibition for Alzheimer’s disease. J Cent Nerv Syst 9:1179573517709278
Zurück zum Zitat Chaudhuri RK, Singh AK, Ghosal S (1975) Chemical constituents of gentianaceae XVIII Structure of Enicoflavine Monoterpene alkaloid from Enecostimma hyssopifolium. Chem Ind London 3:127–128 Chaudhuri RK, Singh AK, Ghosal S (1975) Chemical constituents of gentianaceae XVIII Structure of Enicoflavine Monoterpene alkaloid from Enecostimma hyssopifolium. Chem Ind London 3:127–128
Zurück zum Zitat Chopra RN, Nayar SL, Chopra IC (1956) Glossary of Indian medicinal plants. CSIR, New Delhi, pp 107 Chopra RN, Nayar SL, Chopra IC (1956) Glossary of Indian medicinal plants. CSIR, New Delhi, pp 107
Zurück zum Zitat Deore SI, Khadabadi SS, Bhagure L, Ghorpade DS (2008) In vitro antimicrobial and antioxidant studies on Enicostemma axillare Raynal leaves. Nat prod radiance 7(5):409–412 Deore SI, Khadabadi SS, Bhagure L, Ghorpade DS (2008) In vitro antimicrobial and antioxidant studies on Enicostemma axillare Raynal leaves. Nat prod radiance 7(5):409–412
Zurück zum Zitat de Andrade Teles RB, Diniz TC, Costa Pinto TC, de Oliveira Junior RG, Gama E Silva M, de Lavor EM, Fernandes AWC, de Oliveira AP, de Almeida Ribeiro FPR, da Silva AAM, Cavalcante TCF, Quintans Junior LJ,  da Silva Almeida JRG (2018) Flavonoids as Therapeutic Agents in Alzheimer's and Parkinson's Diseases: A Systematic Review of Preclinical Evidences. Oxid Med Cell Longev 2018:7043213 PubMedPubMedCentralCrossRef de Andrade Teles RB, Diniz TC, Costa Pinto TC, de Oliveira Junior RG, Gama E Silva M, de Lavor EM, Fernandes AWC, de Oliveira AP, de Almeida Ribeiro FPR, da Silva AAM, Cavalcante TCF, Quintans Junior LJ,  da Silva Almeida JRG (2018) Flavonoids as Therapeutic Agents in Alzheimer's and Parkinson's Diseases: A Systematic Review of Preclinical Evidences. Oxid Med Cell Longev 2018:7043213 PubMedPubMedCentralCrossRef
Zurück zum Zitat De la Rosa A, Olaso-Gonzalez G, Arc-Chagnaud C, Millan F, Salvador-Pascual A, García-Lucerga C, Gomez-Cabrera MC (2020) Physical exercise in the prevention and treatment of Alzheimer’s disease. J Sport Health Sci 9:394–404 De la Rosa A, Olaso-Gonzalez G, Arc-Chagnaud C, Millan F, Salvador-Pascual A, García-Lucerga C, Gomez-Cabrera MC (2020) Physical exercise in the prevention and treatment of Alzheimer’s disease. J Sport Health Sci 9:394–404
Zurück zum Zitat Devi S, Kumar V, Singh SK, Dubey AK, Kim JJ (2021) Flavonoids: Potential Candidates for the Treatment of Neurodegenerative Disorders. Biomedicines 9(2):99 PubMedPubMedCentralCrossRef Devi S, Kumar V, Singh SK, Dubey AK, Kim JJ (2021) Flavonoids: Potential Candidates for the Treatment of Neurodegenerative Disorders. Biomedicines 9(2):99 PubMedPubMedCentralCrossRef
Zurück zum Zitat Dolan H, Crain B, Troncoso J, Resnick SM, Zonderman AB, Obrien RJ (2010) Atherosclerosis, dementia, and Alzheimer disease in the Baltimore longitudinal study of aging cohort. Ann Neurol 68(2):231–240 PubMedPubMedCentral Dolan H, Crain B, Troncoso J, Resnick SM, Zonderman AB, Obrien RJ (2010) Atherosclerosis, dementia, and Alzheimer disease in the Baltimore longitudinal study of aging cohort. Ann Neurol 68(2):231–240 PubMedPubMedCentral
Zurück zum Zitat Du Y, Du Y, Zhang Y, Huang Z, Fu M, Li J et al (2019) MKP-1 reduces Aβ generation and alleviates cognitive impairments in Alzheimer’s disease models. Signal Transduct Target Ther 4:58 PubMedPubMedCentralCrossRef Du Y, Du Y, Zhang Y, Huang Z, Fu M, Li J et al (2019) MKP-1 reduces Aβ generation and alleviates cognitive impairments in Alzheimer’s disease models. Signal Transduct Target Ther 4:58 PubMedPubMedCentralCrossRef
Zurück zum Zitat Duong MT, Nasrallah IM, Wolk DA, Chang CCY, Chang TY (2021) Cholesterol atherosclerosis and APOE in vascular contributions to cognitive impairment and dementia (VCID): potential mechanisms and therapy. Front Aging Neurosci 13:647990 PubMedPubMedCentralCrossRef Duong MT, Nasrallah IM, Wolk DA, Chang CCY, Chang TY (2021) Cholesterol atherosclerosis and APOE in vascular contributions to cognitive impairment and dementia (VCID): potential mechanisms and therapy. Front Aging Neurosci 13:647990 PubMedPubMedCentralCrossRef
Zurück zum Zitat Fish PV, Steadman D, Bayle ED, Whiting P (2019) New approaches for the treatment of Alzheimer’s disease. Bioorg Med Chem Lett 29(2):125–133 PubMedCrossRef Fish PV, Steadman D, Bayle ED, Whiting P (2019) New approaches for the treatment of Alzheimer’s disease. Bioorg Med Chem Lett 29(2):125–133 PubMedCrossRef
Zurück zum Zitat Ghosal S, Singh AK, Sharma PV, Chaudhuri RK (1974) Chemical constituents of Gentianaceae IX. Natural occurrence of erythrocentaurin in E. hyssopifolium and Swertia lawii. J Pharm Sci 63:944–745 PubMedCrossRef Ghosal S, Singh AK, Sharma PV, Chaudhuri RK (1974) Chemical constituents of Gentianaceae IX. Natural occurrence of erythrocentaurin in E. hyssopifolium and Swertia lawii. J Pharm Sci 63:944–745 PubMedCrossRef
Zurück zum Zitat Hicks DA, Nalivaeva NN, Turner AJ (2012) Lipid rafts and Alzheimer’s disease: protein-lipid interactions and perturbation of signaling. Front Physiol 3:189 PubMedPubMedCentralCrossRef Hicks DA, Nalivaeva NN, Turner AJ (2012) Lipid rafts and Alzheimer’s disease: protein-lipid interactions and perturbation of signaling. Front Physiol 3:189 PubMedPubMedCentralCrossRef
Zurück zum Zitat Hiebl V, Ladurner A, Latkolik S, Dirsch VM (2018) Natural products as modulators of the nuclear receptors and metabolic sensors LXR. FXR and RXR Biotechnol Adv 36(6):1657–1698 PubMedCrossRef Hiebl V, Ladurner A, Latkolik S, Dirsch VM (2018) Natural products as modulators of the nuclear receptors and metabolic sensors LXR. FXR and RXR Biotechnol Adv 36(6):1657–1698 PubMedCrossRef
Zurück zum Zitat Hole KL, Williams RJ (2021) Flavonoids as an Intervention for Alzheimer’s Disease Progress and Hurdles Towards Defining a Mechanism of Action. Brain Plast 6:167–192 PubMedPubMedCentralCrossRef Hole KL, Williams RJ (2021) Flavonoids as an Intervention for Alzheimer’s Disease Progress and Hurdles Towards Defining a Mechanism of Action. Brain Plast 6:167–192 PubMedPubMedCentralCrossRef
Zurück zum Zitat Honório KM, Moda TL, Andricopulo AD (2013) Pharmacokinetic properties and in silico ADME modeling in drug discovery. Med Chem 9(2):163–176 PubMedCrossRef Honório KM, Moda TL, Andricopulo AD (2013) Pharmacokinetic properties and in silico ADME modeling in drug discovery. Med Chem 9(2):163–176 PubMedCrossRef
Zurück zum Zitat Hopkins AL (2008) Network pharmacology: the next paradigm in drug discovery. Nat Chem Biol 4(11):682–690 PubMedCrossRef Hopkins AL (2008) Network pharmacology: the next paradigm in drug discovery. Nat Chem Biol 4(11):682–690 PubMedCrossRef
Zurück zum Zitat Hussain G, Rasul A, Anwar H, Aziz N, Razzaq A, Wei W et al (2018a) Role of plant derived alkaloids and their mechanism in neurodegenerative disorders. Int J Biol Sci 14(3):341–357 PubMedPubMedCentralCrossRef Hussain G, Rasul A, Anwar H, Aziz N, Razzaq A, Wei W et al (2018a) Role of plant derived alkaloids and their mechanism in neurodegenerative disorders. Int J Biol Sci 14(3):341–357 PubMedPubMedCentralCrossRef
Zurück zum Zitat Hussain R, Zubair H, Pursell S, Shahab M (2018b) neurodegenerative diseases: regenerative mechanisms and novel therapeutic approaches. Brain Sci 8(9):177 PubMedPubMedCentralCrossRef Hussain R, Zubair H, Pursell S, Shahab M (2018b) neurodegenerative diseases: regenerative mechanisms and novel therapeutic approaches. Brain Sci 8(9):177 PubMedPubMedCentralCrossRef
Zurück zum Zitat Itakura M, Nakajima H, Kubo T, Semi Y, Kume S, Higashida S et al (2015) Glyceraldehyde-3-phosphate dehydrogenase aggregates accelerate amyloid-β amyloidogenesis in Alzheimer disease. J Biol Chem 290(43):26072–26087 PubMedPubMedCentralCrossRef Itakura M, Nakajima H, Kubo T, Semi Y, Kume S, Higashida S et al (2015) Glyceraldehyde-3-phosphate dehydrogenase aggregates accelerate amyloid-β amyloidogenesis in Alzheimer disease. J Biol Chem 290(43):26072–26087 PubMedPubMedCentralCrossRef
Zurück zum Zitat Jaishree VS, Badami M, Kumar R, Tamizhmani T (2009) Antinociceptive activity of swertiamarin isolated from Enicostemma axillare. J Phytomedicine 16:227–232 PubMedCrossRef Jaishree VS, Badami M, Kumar R, Tamizhmani T (2009) Antinociceptive activity of swertiamarin isolated from Enicostemma axillare. J Phytomedicine 16:227–232 PubMedCrossRef
Zurück zum Zitat Jamal S, Grover A, Grover S (2019) Machine learning from molecular dynamics trajectories to predict caspase-8 inhibitors against Alzheimer’s disease. Front Pharmacol 10:780 PubMedPubMedCentralCrossRef Jamal S, Grover A, Grover S (2019) Machine learning from molecular dynamics trajectories to predict caspase-8 inhibitors against Alzheimer’s disease. Front Pharmacol 10:780 PubMedPubMedCentralCrossRef
Zurück zum Zitat Ji HF, Li XJ, Zhang HY (2009) Natural products and drug discovery, Can thousands of years of ancient medical knowledge lead us to new and powerful drug combinations in the fight against cancer and dementia. EMBO Rep 10(3):194–200 PubMedPubMedCentralCrossRef Ji HF, Li XJ, Zhang HY (2009) Natural products and drug discovery, Can thousands of years of ancient medical knowledge lead us to new and powerful drug combinations in the fight against cancer and dementia. EMBO Rep 10(3):194–200 PubMedPubMedCentralCrossRef
Zurück zum Zitat Jiang RW, Wong K, Chan Y, Xu H, But PPH, Shaw PC (2005) Isolation of iridoid and secoiridiod glycosides and comparative study on Radix gentiane and related adulterants by HPLC analysis. Phytochem 66:2674–2680 CrossRef Jiang RW, Wong K, Chan Y, Xu H, But PPH, Shaw PC (2005) Isolation of iridoid and secoiridiod glycosides and comparative study on Radix gentiane and related adulterants by HPLC analysis. Phytochem 66:2674–2680 CrossRef
Zurück zum Zitat Kamm MA (2002) Review article: the complexity of drug development for irritable bowel syndrome. Aliment Pharmacol Ther 16(3):343–351 PubMedCrossRef Kamm MA (2002) Review article: the complexity of drug development for irritable bowel syndrome. Aliment Pharmacol Ther 16(3):343–351 PubMedCrossRef
Zurück zum Zitat Kim N, Lee HJ (2020) Target enzymes considered for the treatment of alzheimer’s disease and parkinson’s disease. Biomed Res Int 2010:728 Kim N, Lee HJ (2020) Target enzymes considered for the treatment of alzheimer’s disease and parkinson’s disease. Biomed Res Int 2010:728
Zurück zum Zitat Kirtikar KR, Basu BD (1999) Indian medicinal plants. 2nd edn. Bishen Sing, Dehradun, Mahendra Pal Sing Publication, pp 1655–1656 Kirtikar KR, Basu BD (1999) Indian medicinal plants. 2nd edn. Bishen Sing, Dehradun, Mahendra Pal Sing Publication, pp 1655–1656
Zurück zum Zitat Lane CA, Hardy J, Schott JM (2018) Alzheimer’s disease. Eur Neurol 25(1):59–70 CrossRef Lane CA, Hardy J, Schott JM (2018) Alzheimer’s disease. Eur Neurol 25(1):59–70 CrossRef
Zurück zum Zitat Lazarev VF, Tsolaki M, Mikhaylova ER, Benken KA, Shevtsov MA, Nikotina AD et al (2021) Extracellular GAPDH promotes Alzheimer’s disease progression by enhancing amyloid-β aggregation and cytotoxicity. Aging Dis 12(5):1223–1237 PubMedPubMedCentralCrossRef Lazarev VF, Tsolaki M, Mikhaylova ER, Benken KA, Shevtsov MA, Nikotina AD et al (2021) Extracellular GAPDH promotes Alzheimer’s disease progression by enhancing amyloid-β aggregation and cytotoxicity. Aging Dis 12(5):1223–1237 PubMedPubMedCentralCrossRef
Zurück zum Zitat Lee JK, Kim NJ (2017) Recent advances in the inhibition of p38 MAPK as a potential strategy for the treatment of Alzheimer’s disease. Molecules 22(8):1287 PubMedPubMedCentralCrossRef Lee JK, Kim NJ (2017) Recent advances in the inhibition of p38 MAPK as a potential strategy for the treatment of Alzheimer’s disease. Molecules 22(8):1287 PubMedPubMedCentralCrossRef
Zurück zum Zitat Li J, Sun M, Cui X, Li C (2022) Protective Effects of Flavonoids against Alzheimer's Disease: Pathological Hypothesis, Potential Targets, and Structure-Activity Relationship. Int J Mol Sci 23(17):10020 PubMedPubMedCentralCrossRef Li J, Sun M, Cui X, Li C (2022) Protective Effects of Flavonoids against Alzheimer's Disease: Pathological Hypothesis, Potential Targets, and Structure-Activity Relationship. Int J Mol Sci 23(17):10020 PubMedPubMedCentralCrossRef
Zurück zum Zitat Li S, Zhang B (2013) Traditional Chinese medicine network pharmacology: theory, methodology and application. Chin J Nat Med 11(2):110–120 PubMedCrossRef Li S, Zhang B (2013) Traditional Chinese medicine network pharmacology: theory, methodology and application. Chin J Nat Med 11(2):110–120 PubMedCrossRef
Zurück zum Zitat Liang JW, Wang MY, Olounfeh KM, Zhao N, Wang S, Meng FH (2019) Network pharmacology-based identification of potential targets of the flower of Trollius chinensis Bunge acting on anti-inflammatory effects. Sci Rep 9(1):8109 PubMedPubMedCentralCrossRef Liang JW, Wang MY, Olounfeh KM, Zhao N, Wang S, Meng FH (2019) Network pharmacology-based identification of potential targets of the flower of Trollius chinensis Bunge acting on anti-inflammatory effects. Sci Rep 9(1):8109 PubMedPubMedCentralCrossRef
Zurück zum Zitat Lubitz I, Ricny J, Atrakchi-Baranes D, Shemesh C, Kravitz E, Liraz-Zaltsman S et al (2016) High dietary advanced glycation end products are associated with poorer spatial learning and accelerated Aβ deposition in an Alzheimer mouse model. Aging Cell 15(2):309–316 PubMedPubMedCentralCrossRef Lubitz I, Ricny J, Atrakchi-Baranes D, Shemesh C, Kravitz E, Liraz-Zaltsman S et al (2016) High dietary advanced glycation end products are associated with poorer spatial learning and accelerated Aβ deposition in an Alzheimer mouse model. Aging Cell 15(2):309–316 PubMedPubMedCentralCrossRef
Zurück zum Zitat Luo TT, Lu Y, Yan SK, Xiao X, Rong XL, Guo J (2020) Network pharmacology in research of chinese medicine formula: methodology application and prospective. J Integr Med 26(1):72–80 Luo TT, Lu Y, Yan SK, Xiao X, Rong XL, Guo J (2020) Network pharmacology in research of chinese medicine formula: methodology application and prospective. J Integr Med 26(1):72–80
Zurück zum Zitat Meng-Zhen S, Ju L, Lan-Chun Z, Cai-Feng D, Shu-da Y, Hao-Fei Y et al (2022) Potential therapeutic use of plant flavonoids in AD and PD. Heliyon 8(11):e11440 PubMedPubMedCentralCrossRef Meng-Zhen S, Ju L, Lan-Chun Z, Cai-Feng D, Shu-da Y, Hao-Fei Y et al (2022) Potential therapeutic use of plant flavonoids in AD and PD. Heliyon 8(11):e11440 PubMedPubMedCentralCrossRef
Zurück zum Zitat Minocha T, Birla H, Obaid AA, Rai V, Sushma P, Shivamallu C, Moustafa M, Al-Shehri M, Al-Emam A, Tikhonova MA, Yadav SK, Poeggeler B, Singh D, Singh SK (2022) Flavonoids as Promising Neuroprotectants and Their Therapeutic Potential against Alzheimer's Disease. Oxid Med Cell longev 2022:6038996 PubMedPubMedCentralCrossRef Minocha T, Birla H, Obaid AA, Rai V, Sushma P, Shivamallu C, Moustafa M, Al-Shehri M, Al-Emam A, Tikhonova MA, Yadav SK, Poeggeler B, Singh D, Singh SK (2022) Flavonoids as Promising Neuroprotectants and Their Therapeutic Potential against Alzheimer's Disease. Oxid Med Cell longev 2022:6038996 PubMedPubMedCentralCrossRef
Zurück zum Zitat Mummery CJ, Börjesson-Hanson A, Blackburn DJ et al (2023) Tau-targeting antisense oligonucleotide MAPTRx in mild Alzheimer’s disease: a phase 1b, randomized, placebo-controlled trial. Nat Med 29:1437–1447 PubMedPubMedCentralCrossRef Mummery CJ, Börjesson-Hanson A, Blackburn DJ et al (2023) Tau-targeting antisense oligonucleotide MAPTRx in mild Alzheimer’s disease: a phase 1b, randomized, placebo-controlled trial. Nat Med 29:1437–1447 PubMedPubMedCentralCrossRef
Zurück zum Zitat Murali B, Upadhyaya UM, Goyal RK (2002) Effect of chronic treatment with Enicostemma littorale in non-insulin-dependent diabetic (NIDDM) rats. J  ethnopharmacology 81(2):199–204 CrossRef Murali B, Upadhyaya UM, Goyal RK (2002) Effect of chronic treatment with Enicostemma littorale in non-insulin-dependent diabetic (NIDDM) rats. J  ethnopharmacology 81(2):199–204 CrossRef
Zurück zum Zitat Noori T, Dehpour AR, Sureda A, Sobarzo-Sanchez E, Shirooie S (2021) Role of natural products for the treatment of Alzheimer’s disease. Eur J Pharmacol 898:73974 CrossRef Noori T, Dehpour AR, Sureda A, Sobarzo-Sanchez E, Shirooie S (2021) Role of natural products for the treatment of Alzheimer’s disease. Eur J Pharmacol 898:73974 CrossRef
Zurück zum Zitat OBrien RJ, Wong PC (2011) Amyloid precursor protein processing and Alzheimer’s disease. Annu Rev Neurosci 34:185–204 PubMedCrossRef OBrien RJ, Wong PC (2011) Amyloid precursor protein processing and Alzheimer’s disease. Annu Rev Neurosci 34:185–204 PubMedCrossRef
Zurück zum Zitat Pandey SN, Rangra NK, Singh S, Arora S, Gupta V (2021)Evolving Role of Natural Products from Traditional Medicinal Herbs in the Treatment of Alzheimer's Disease. ACS Chem Neurosci 12(15):2718–2728 PubMedCrossRef Pandey SN, Rangra NK, Singh S, Arora S, Gupta V (2021)Evolving Role of Natural Products from Traditional Medicinal Herbs in the Treatment of Alzheimer's Disease. ACS Chem Neurosci 12(15):2718–2728 PubMedCrossRef
Zurück zum Zitat Perry RT, Collins JS, Wiener H, Acton R, Go RC (2001) The role of TNF and its receptors in Alzheimer’s disease. Neurobiol Aging 22(6):873–883 PubMedCrossRef Perry RT, Collins JS, Wiener H, Acton R, Go RC (2001) The role of TNF and its receptors in Alzheimer’s disease. Neurobiol Aging 22(6):873–883 PubMedCrossRef
Zurück zum Zitat Perumal S, Gopal Samy MV, Subramanian D (2021a) Developmental toxicity, antioxidant, and marker enzyme assessment of swertiamarin in zebrafish ( Danio rerio). J Biochem Mol Toxicol 35(9):e22843 PubMedCrossRef Perumal S, Gopal Samy MV, Subramanian D (2021a) Developmental toxicity, antioxidant, and marker enzyme assessment of swertiamarin in zebrafish ( Danio rerio). J Biochem Mol Toxicol 35(9):e22843 PubMedCrossRef
Zurück zum Zitat Perumal S, Gopal Samy MV, Subramanian D (2021b) Selenium nanoparticle synthesis from endangered medicinal herb ( Enicostema axillare). Bioprocess Biosyst Eng 44(9):1853–1863 PubMedCrossRef Perumal S, Gopal Samy MV, Subramanian D (2021b) Selenium nanoparticle synthesis from endangered medicinal herb ( Enicostema axillare). Bioprocess Biosyst Eng 44(9):1853–1863 PubMedCrossRef
Zurück zum Zitat Perumal S, Gopal Samy MV, Subramanian D (2022a) In vitro and in silico screening of novel typhoid drugs from endangered herb ( Enicostema axillare). J Biomol Struct Dyn 41:2926–2936 PubMedCrossRef Perumal S, Gopal Samy MV, Subramanian D (2022a) In vitro and in silico screening of novel typhoid drugs from endangered herb ( Enicostema axillare). J Biomol Struct Dyn 41:2926–2936 PubMedCrossRef
Zurück zum Zitat Perumal S, Gopal Samy MV, Subramanian D (2022b) Effect of novel therapeutic medicine swertiamarin from Enicostema axillare in zebrafish infected with Salmonella typhi. Chem Biol Drug Des 100(6):1033–1041 PubMedCrossRef Perumal S, Gopal Samy MV, Subramanian D (2022b) Effect of novel therapeutic medicine swertiamarin from Enicostema axillare in zebrafish infected with Salmonella typhi. Chem Biol Drug Des 100(6):1033–1041 PubMedCrossRef
Zurück zum Zitat Rehker J, Rodhe J, Nesbitt RR, Boyle EA, Martin BK, Lord J et al (2017) Caspase-8, association with Alzheimer’s disease and functional analysis of rare variants. PLoS One 12(10):e0185777 PubMedPubMedCentralCrossRef Rehker J, Rodhe J, Nesbitt RR, Boyle EA, Martin BK, Lord J et al (2017) Caspase-8, association with Alzheimer’s disease and functional analysis of rare variants. PLoS One 12(10):e0185777 PubMedPubMedCentralCrossRef
Zurück zum Zitat Rushworth JV, Hooper NM (2010) Lipid rafts: linking Alzheimer’s amyloid-β production, aggregation, and toxicity at neuronal membranes. J Alzheimer’s Dis 2011:603052 Rushworth JV, Hooper NM (2010) Lipid rafts: linking Alzheimer’s amyloid-β production, aggregation, and toxicity at neuronal membranes. J Alzheimer’s Dis 2011:603052
Zurück zum Zitat Sasidharan P, Jayachitra A (2017) Direct shoot bud regeneration from shoot tip explants of Enicostema axillare: an important medicinal plant. Agroforest Syst 91:471–477 CrossRef Sasidharan P, Jayachitra A (2017) Direct shoot bud regeneration from shoot tip explants of Enicostema axillare: an important medicinal plant. Agroforest Syst 91:471–477 CrossRef
Zurück zum Zitat Sharma P, Dwivedee BP, Bisht D, Dash AK, Kumar D (2019) The chemical constituents and diverse pharmacological importance of Tinospora cordifolia. Heliyon 5(9):e02437 PubMedPubMedCentralCrossRef Sharma P, Dwivedee BP, Bisht D, Dash AK, Kumar D (2019) The chemical constituents and diverse pharmacological importance of Tinospora cordifolia. Heliyon 5(9):e02437 PubMedPubMedCentralCrossRef
Zurück zum Zitat Sharma M, Malim FM, Goswami A, Sharma N, Juvvalapalli SS, Chatterjee S et al (2022) Neuroprotective effect of swertiamarin in a rotenone model of Parkinson’s disease: role of neuroinflammation and alpha-synuclein accumulation. ACS Pharmacol Transl Sci 6(1):40–51 PubMedCrossRef Sharma M, Malim FM, Goswami A, Sharma N, Juvvalapalli SS, Chatterjee S et al (2022) Neuroprotective effect of swertiamarin in a rotenone model of Parkinson’s disease: role of neuroinflammation and alpha-synuclein accumulation. ACS Pharmacol Transl Sci 6(1):40–51 PubMedCrossRef
Zurück zum Zitat Shawky E (2019) Prediction of potential cancer-related molecular targets of North African plant constituents using network pharmacology-based analysis. J Ethnopharmacol 238:111826 PubMedCrossRef Shawky E (2019) Prediction of potential cancer-related molecular targets of North African plant constituents using network pharmacology-based analysis. J Ethnopharmacol 238:111826 PubMedCrossRef
Zurück zum Zitat Su JH, Zhao M, Anderson AJ, Srinivasan A, Cotman CW (2001) Activated caspase-3 expression in Alzheimer’s and aged control brain: correlation with Alzheimer pathology. Brain Res 898(2):350–357 PubMedCrossRef Su JH, Zhao M, Anderson AJ, Srinivasan A, Cotman CW (2001) Activated caspase-3 expression in Alzheimer’s and aged control brain: correlation with Alzheimer pathology. Brain Res 898(2):350–357 PubMedCrossRef
Zurück zum Zitat Tang M, Xie X, Yi P, Kang J, Liao J, Li W, Li F (2020) Integrating Network Pharmacology with Molecular Docking to Unravel the Active Compounds and Potential Mechanism of Simiao Pill Treating Rheumatoid Arthritis. Evid Based Complement Alternat Med 2020:5786053 PubMedPubMedCentralCrossRef Tang M, Xie X, Yi P, Kang J, Liao J, Li W, Li F (2020) Integrating Network Pharmacology with Molecular Docking to Unravel the Active Compounds and Potential Mechanism of Simiao Pill Treating Rheumatoid Arthritis. Evid Based Complement Alternat Med 2020:5786053 PubMedPubMedCentralCrossRef
Zurück zum Zitat Thomford NE, Senthebane DA, Rowe A, Munro D, Seele P, Maroyi A, Dzobo K (2018) Natural products for drug discovery in the 21st century: innovations for novel drug discovery. Int J Mol Sci 19(6):1578 PubMedPubMedCentralCrossRef Thomford NE, Senthebane DA, Rowe A, Munro D, Seele P, Maroyi A, Dzobo K (2018) Natural products for drug discovery in the 21st century: innovations for novel drug discovery. Int J Mol Sci 19(6):1578 PubMedPubMedCentralCrossRef
Zurück zum Zitat Tian G, Kong Q, Lai L, Ray-Chaudhury A, Lin CL (2010a) Increased expression of cholesterol 24S-hydroxylase results in disruption of glial glutamate transporter EAAT2 association with lipid rafts: a potential role in Alzheimer’s disease. J Neurochem 113(4):978–989 PubMedPubMedCentralCrossRef Tian G, Kong Q, Lai L, Ray-Chaudhury A, Lin CL (2010a) Increased expression of cholesterol 24S-hydroxylase results in disruption of glial glutamate transporter EAAT2 association with lipid rafts: a potential role in Alzheimer’s disease. J Neurochem 113(4):978–989 PubMedPubMedCentralCrossRef
Zurück zum Zitat Tian J, Shi J, Zhang X, Wang Y (2010b) Herbal therapy: a new pathway for the treatment of Alzheimer’s disease. Alzheimer’s Res Ther 2(5):30 CrossRef Tian J, Shi J, Zhang X, Wang Y (2010b) Herbal therapy: a new pathway for the treatment of Alzheimer’s disease. Alzheimer’s Res Ther 2(5):30 CrossRef
Zurück zum Zitat Tsaioun K, Blaauboer BJ, Hartung T (2016) Evidence-based absorption, distribution, metabolism, excretion (ADME) and its interplay with alternative toxicity methods. ALTEX 33(4): 343–358 PubMedCrossRef Tsaioun K, Blaauboer BJ, Hartung T (2016) Evidence-based absorption, distribution, metabolism, excretion (ADME) and its interplay with alternative toxicity methods. ALTEX 33(4): 343–358 PubMedCrossRef
Zurück zum Zitat Tzvetkov NT, Atanasov AG (2018) Natural product-based multitargeted ligands for Alzheimer’s disease treatment. Future Med Chem 10(15): 1745–1748 PubMedCrossRef Tzvetkov NT, Atanasov AG (2018) Natural product-based multitargeted ligands for Alzheimer’s disease treatment. Future Med Chem 10(15): 1745–1748 PubMedCrossRef
Zurück zum Zitat Ullah A, Munir S, Badshah SL, Khan N, Ghani L, Poulson BG et al (2020) Important flavonoids and their role as a therapeutic agent. Molecules 25(22):5243 PubMedPubMedCentralCrossRef Ullah A, Munir S, Badshah SL, Khan N, Ghani L, Poulson BG et al (2020) Important flavonoids and their role as a therapeutic agent. Molecules 25(22):5243 PubMedPubMedCentralCrossRef
Zurück zum Zitat Varier PS (1994) Indian medicinal plants. vol 2, Chennai, orient longman ltd, pp 374 Varier PS (1994) Indian medicinal plants. vol 2, Chennai, orient longman ltd, pp 374
Zurück zum Zitat Vishwakarma S, Rajani M, Bagul M, Goyal R (2004) A rapid method for the isolation of swertiamarin from Enicostemma littorale. Pharm Biol 42(6):400–403 CrossRef Vishwakarma S, Rajani M, Bagul M, Goyal R (2004) A rapid method for the isolation of swertiamarin from Enicostemma littorale. Pharm Biol 42(6):400–403 CrossRef
Zurück zum Zitat Ygland E, van Weste D, Englund E, Rademakers R, Wszolek K, Nilsson K et al (2018) Slowly progressive dementia caused by MAPT R406W mutations: LONGITUDINAL report on a new kindred and systematic review. Alzheimers Res Ther 10(1):2 PubMedPubMedCentralCrossRef Ygland E, van Weste D, Englund E, Rademakers R, Wszolek K, Nilsson K et al (2018) Slowly progressive dementia caused by MAPT R406W mutations: LONGITUDINAL report on a new kindred and systematic review. Alzheimers Res Ther 10(1):2 PubMedPubMedCentralCrossRef
Zurück zum Zitat Zhao J, Liu X, Xia W, Zhang Y, Wang C (2020) Targeting amyloidogenic processing of APP in Alzheimer’s disease. Front Mol Neurosci 413:137 CrossRef Zhao J, Liu X, Xia W, Zhang Y, Wang C (2020) Targeting amyloidogenic processing of APP in Alzheimer’s disease. Front Mol Neurosci 413:137 CrossRef
Zurück zum Zitat Zheng Q, Song B, Li G, Cai F, Wu M, Zhao Y et al (2022) USP25 inhibition ameliorates Alzheimer’s pathology through the regulation of APP processing and Aβ generation. J Clin Investig 132(5):e152170 PubMedPubMedCentralCrossRef Zheng Q, Song B, Li G, Cai F, Wu M, Zhao Y et al (2022) USP25 inhibition ameliorates Alzheimer’s pathology through the regulation of APP processing and Aβ generation. J Clin Investig 132(5):e152170 PubMedPubMedCentralCrossRef
Zurück zum Zitat Zhou M, Xu R, Kaelber DC, Gurney ME (2020) Tumor Necrosis factor (TNF) blocking agents are associated with lower risk for Alzheimer’s disease in patients with rheumatoid arthritis and psoriasis. PLoS One 15(3):e0229819 PubMedPubMedCentralCrossRef Zhou M, Xu R, Kaelber DC, Gurney ME (2020) Tumor Necrosis factor (TNF) blocking agents are associated with lower risk for Alzheimer’s disease in patients with rheumatoid arthritis and psoriasis. PLoS One 15(3):e0229819 PubMedPubMedCentralCrossRef
Metadaten
Titel
Systems pharmacology and multi-scale mechanism of Enicostema axillare bioactives in treating Alzheimer disease
verfasst von
Madhana Vigneshwari Gopal Samy
Sasidharan Perumal
Publikationsdatum
16.10.2023
Verlag
Springer International Publishing
Erschienen in
Inflammopharmacology
Print ISSN: 0925-4692
Elektronische ISSN: 1568-5608
DOI
https://doi.org/10.1007/s10787-023-01348-0